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Publisher: John Wiley and Sons   (Total: 1598 journals)

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Paediatric and Perinatal Epidemiology     Hybrid Journal   (Followers: 4, SJR: 1.429, h-index: 58)
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PAMM : Proceedings in Applied Mathematics and Mechanics     Free  
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Periodontology 2000     Hybrid Journal   (Followers: 4, SJR: 1.467, h-index: 74)
Permafrost and Periglacial Processes     Hybrid Journal   (Followers: 2, SJR: 1.741, h-index: 46)
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Pharmacotherapy The J. of Human Pharmacology and Drug Therapy     Hybrid Journal   (Followers: 21, SJR: 0.852, h-index: 78)
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Philosophy and Phenomenological Research     Hybrid Journal   (Followers: 20, SJR: 1.629, h-index: 11)
Philosophy Compass     Hybrid Journal   (Followers: 10, SJR: 0.282, h-index: 2)
Photochemistry and Photobiology     Hybrid Journal   (Followers: 1, SJR: 0.764, h-index: 96)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 2, SJR: 0.642, h-index: 42)
Phycological Research     Hybrid Journal   (Followers: 3, SJR: 0.405, h-index: 21)
physica status solidi (a)     Hybrid Journal   (Followers: 1, SJR: 0.81, h-index: 72)
physica status solidi (b)     Hybrid Journal   (Followers: 1, SJR: 0.852, h-index: 70)
physica status solidi (c)     Hybrid Journal   (Followers: 1, SJR: 0.471, h-index: 31)
Physica Status Solidi - Rapid Research Letters     Hybrid Journal   (Followers: 1, SJR: 1.166, h-index: 32)
Physik in unserer Zeit     Hybrid Journal   (Followers: 1)
Physik J.     Hybrid Journal  
Physiologia Plantarum     Hybrid Journal   (Followers: 1, SJR: 1.442, h-index: 95)
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Physiological Reports     Open Access   (Followers: 1)
Physiotherapy Research Intl.     Hybrid Journal   (Followers: 27, SJR: 0.396, h-index: 30)
Phytochemical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.959, h-index: 45)
Phytotherapy Research     Hybrid Journal   (Followers: 1, SJR: 0.82, h-index: 76)
Pigment Cell & Melanoma Research     Hybrid Journal   (Followers: 3, SJR: 2.572, h-index: 72)
Plant Biology     Hybrid Journal   (Followers: 11, SJR: 0.951, h-index: 52)
Plant Biotechnology J.     Open Access   (Followers: 9, SJR: 2.463, h-index: 58)
Plant Breeding     Hybrid Journal   (Followers: 15, SJR: 0.626, h-index: 49)
Plant Pathology     Hybrid Journal   (Followers: 7, SJR: 1.114, h-index: 50)
Plant Species Biology     Hybrid Journal   (Followers: 3, SJR: 0.509, h-index: 26)
Plant, Cell & Environment     Hybrid Journal   (Followers: 5, SJR: 2.821, h-index: 121)
Plasma Processes and Polymers     Hybrid Journal   (SJR: 1.231, h-index: 40)
Poe Studies     Partially Free   (Followers: 5)
POLAR: Political and Legal Anthropology Review     Hybrid Journal   (Followers: 11, SJR: 0.415, h-index: 3)
Policy & Internet     Hybrid Journal   (Followers: 9)
Policy Studies J.     Hybrid Journal   (Followers: 4, SJR: 1.362, h-index: 30)
Political Psychology     Hybrid Journal   (Followers: 17, SJR: 1.885, h-index: 45)
Political Science Quarterly     Hybrid Journal   (Followers: 32, SJR: 0.378, h-index: 26)
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Polymer Intl.     Hybrid Journal   (Followers: 3, SJR: 0.847, h-index: 67)
Polymers for Advanced Technologies     Hybrid Journal   (Followers: 3, SJR: 0.833, h-index: 57)
Population and Development Review     Hybrid Journal   (Followers: 4, SJR: 2.686, h-index: 56)
Population Space and Place     Hybrid Journal   (Followers: 2, SJR: 1.836, h-index: 33)
Poverty & Public Policy     Hybrid Journal   (Followers: 13)
Practical Diabetes     Hybrid Journal   (Followers: 7, SJR: 0.175, h-index: 3)
Practice Development in Health Care     Hybrid Journal   (Followers: 2)
Prenatal Diagnosis     Hybrid Journal   (Followers: 1, SJR: 1.262, h-index: 69)
Prescriber     Hybrid Journal   (Followers: 9)
Presidential Studies Quarterly     Hybrid Journal   (Followers: 3)
Preventive Cardiology     Hybrid Journal   (Followers: 3, SJR: 0.839, h-index: 23)
Proceedings of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 25, SJR: 0.169, h-index: 21)
Proceedings of the Aristotelian Society (hardback)     Hybrid Journal   (Followers: 3, SJR: 0.381, h-index: 16)
Process Safety Progress     Hybrid Journal   (Followers: 6, SJR: 0.387, h-index: 22)
Production and Operations Management     Hybrid Journal   (Followers: 5, SJR: 2.417, h-index: 62)
Progress In Cardiovascular Nursing     Hybrid Journal   (Followers: 1)
Progress in Neurology and Psychiatry     Hybrid Journal   (Followers: 5, SJR: 0.124, h-index: 3)
Progress in Photovoltaics: Research & Applications     Hybrid Journal   (Followers: 7, SJR: 4.314, h-index: 74)
Progress in Structural Engineering and Materials     Hybrid Journal   (Followers: 5)
Project Management J.     Hybrid Journal   (Followers: 33, SJR: 0.497, h-index: 8)
Propellants, Explosives, Pyrotechnics     Hybrid Journal   (Followers: 197, SJR: 0.765, h-index: 37)

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Journal Cover Phytotherapy Research
  [SJR: 0.82]   [H-I: 76]   [1 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0951-418X - ISSN (Online) 1099-1573
   Published by John Wiley and Sons Homepage  [1598 journals]
  • Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in
           Nonalcoholic Fatty Liver Disease through the AMPK/Nrf2 Pathway
    • Abstract: This study was designed to investigate the antioxidative, antiinflammatory and metabolism‐regulating effects of gastrodin (GSTD) in the treatment of nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) was used to induce steatosis in HL‐7702 cells; a high‐fat or high‐fat and high‐cholesterol diet was used to induce NAFLD in mice and rats. Our results showed that GSTD significantly increased hepatic superoxide dismutase (SOD) but decreased reactive oxygen species (ROS)/malondialdehyde (MDA) and reduced the mRNA levels of proinflammatory cytokines both in vitro and in vivo. GSTD promoted the phosphorylation of nuclear factor erythroid‐2‐related factor‐2 (Nrf2) at serine (Ser) 40, stimulated its nuclear translocation and increased hepatic expression of heme oxygenase‐1 (HO‐1). GSTD activated AMP‐activated protein kinase (AMPK), suppressed hepatic steatosis, lowered serum triglyceride (TG)/glucose and decreased body weight gain in animals with NAFLD. The stimulating effects of GSTD on the Nrf2 pathway as well as its antioxidative/antiinflammatory activities were abolished by compound C in OA‐treated HL‐7702 cells. In summary, our results demonstrate that GSTD activates the AMPK/Nrf2 pathway, ameliorates oxidative stress/proinflammatory response and improves lipid metabolism in NAFLD. Our findings may support the future clinical application of GSTD for the treatment of NAFLD to reduce hepatic steatosis, oxidative stress and proinflammatory response. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-04T01:56:32.859834-05:
      DOI: 10.1002/ptr.5541
       
  • Antidiabetic Effects of Simple Phenolic Acids: A Comprehensive Review
    • Authors: Ramachandran Vinayagam; Muthukumaran Jayachandran, Baojun Xu
      Abstract: Diabetes mellitus (DM) has become a major public health threat across the globe. Current antidiabetic therapies are based on synthetic drugs that very often have side effects. It has been widely acknowledged that diet plays an important role in the management of diabetes. Phenolic acids are widely found in daily foods such as fruits, vegetables, cereals, legumes, and wine and they provide biological, medicinal, and health properties. Simple phenolic acids have been shown to increase glucose uptake and glycogen synthesis, improve glucose and lipid profiles of certain diseases (obesity, cardiovascular diseases, DM, and its complication). The current review is an attempt to list out the antidiabetic effects of simple phenolic acids from medicinal plants and botanical foods. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-04T01:37:46.317524-05:
      DOI: 10.1002/ptr.5528
       
  • Neuroprotective Effect of Lycopene Against PTZ‐induced Kindling
           Seizures in Mice: Possible Behavioural, Biochemical and Mitochondrial
           Dysfunction
    • Authors: Manveen Bhardwaj; Anil Kumar
      Abstract: Oxidative stress and mitochondrial dysfunction are the major contributing factors in the pathophysiology of various neurological disorders. Recently, antioxidant therapies aimed at reducing oxidative stress gained a considerable attention in epilepsy treatment. Lycopene, a carotenoid antioxidant, has received scientific interest in recent years. So, the present study has been designed to evaluate the neuroprotective effect of lycopene against the pentylenetetrazol (PTZ)‐induced kindling epilepsy. Laca mice received lycopene (2.5, 5 and 10 mg/kg) and sodium valproate for a period of 29 days and PTZ (40 mg/kg i.p (Intraperitoneal)) injection on alternative days. Various behavioural (kindling score), biochemical parameters (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase and nitrite) and mitochondrial enzyme complex activities (I, II and IV) were assessed in the brain. Results depicted that repeated administration of a sub‐convulsive dose of PTZ (40 mg/kg) significantly increased kindling score, oxidative damage and impaired mitochondrial enzyme complex activities (I, II and IV) as compared with naive animals. Lycopene (5 and 10 mg/kg) and sodium valproate (100 mg/kg) treatment for a duration of 29 days significantly attenuated kindling score, reversed oxidative damage and restored mitochondrial enzyme complex activities (I, II and IV) as compared with control. Thus, present study demonstrates the neuroprotective potential of lycopene in PTZ‐induced kindling in mice. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-03T02:13:54.754361-05:
      DOI: 10.1002/ptr.5533
       
  • Medicinal Plants Traditionally Used for Treatment of Obesity and Diabetes
           Mellitus – Screening for Pancreatic Lipase and α‐Amylase
           Inhibition
    • Authors: Tina Buchholz; Matthias F. Melzig
      Abstract: In order to find new pancreatic lipase (PL) and α‐amylase inhibitors from natural sources for the treatment of obesity and related diseases as diabetes mellitus II, 23 medicinal plants with weight‐reducing, serum glucose‐reducing or related potential were investigated. Methanolic and water extracts of the plants were evaluated by using two in vitro test systems. Our findings have shown that the methanolic extract of Hibiscus sabdariffa L. (Malvaceae) showed high inhibitory activities to PL (IC50: 35.8 ± 0.8 µg/mL) and α‐amylase (IC50: 29.3 ± 0.5 µg/mL). Furthermore, the methanolic extract of Tamarindus indica L. (Leguminosae) showed a high anti‐lipase (IC50: 152.0 ± 7.0 µg/mL) and the aqueous extract a high anti‐amylase (IC50: 139.4 ± 9.0 µg/mL) activity. This work provides a priority list of interesting plants for further study with respect to the treatment of obesity and associated diseases. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-03T02:03:33.788966-05:
      DOI: 10.1002/ptr.5525
       
  • Effect of Resveratrol Treatment on the Pharmacokinetics of Diclofenac in
           Healthy Human Volunteers
    • Authors: Satish Kumar Bedada; Narsimha Reddy Yellu, Prasad Neerati
      Abstract: The purpose of the present study was to assess the effect of resveratrol (RSV) treatment on the pharmacokinetics of diclofenac (DIC) in healthy human volunteers. The open‐label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered daily for 10 days during treatment phase. A single dose of DIC 100 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after DIC dosing and analyzed by HPLC. Treatment with RSV significantly enhanced maximum plasma concentration (Cmax) (1.73 to 2.91 µg/mL), area under the curve (AUC) (5.05 to 9.95 µg h/mL), half life (T1/2) (1.12 to 1.76 h) and significantly decreased elimination rate constant (Kel) (0.71 to 0.41 h−1), apparent oral clearance (CL/F) (14.58 to 6.48 L/h) of DIC as compared to control. The geometric mean ratios for Cmax, AUC, T1/2, Kel and CL/F of DIC were 1.75, 2.12, 1.65, 0.61 and 0.47, respectively were outside the limits of 0.8–1.25, which indicates clinically significant interaction between DIC and RSV. The results suggest that the altered pharmacokinetics of DIC might be attributed to RSV mediated inhibition of CYP2C9 enzyme. Therefore, combination therapy of DIC along with RSV may represent a novel approach to reduce dosage and results in reduced gastrointestinal side effects of DIC. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-03T01:59:50.30235-05:0
      DOI: 10.1002/ptr.5539
       
  • Cardioprotective Efficacy of Red Wine Extract of Onion in Healthy
           Hypercholesterolemic Subjects
    • Abstract: The objective of this study was to evaluate the efficacy of the red wine extract of onion (RO) and red wine (RW) on alleviating the risk factors of cardiovascular disease. During in vitro studies, various antioxidant activities [trolox equivalent antioxidant capacity (TEAC), DPPH, and H2O2 scavenging ability] of RO and RW group were evaluated. Both RO and RW showed the maximum antioxidant capacity. During in vivo studies, 23 healthy hypercholesterolemic volunteers were randomly selected and assigned into two groups, who drunk 250 mL of RO (n = 11) or RW (n = 10) for 10 weeks. No significant changes were observed in anthropometric parameters (body weight, height, body mass, and BMI) in each group. Both RW and RO extracts elevated (p 
      PubDate: 2015-12-03T01:50:35.017383-05:
      DOI: 10.1002/ptr.5537
       
  • Camellia sinensis Ameliorates the Efficacy of Last Line Antibiotics
           Against Carbapenem Resistant Escherichia coli
    • Authors: Pallavi Thakur; Raman Chawla, Ankita Singh Chakotiya, Ankit Tanwar, Rajeev Goel, Alka Narula, Rajesh Arora, Rakesh Kumar Sharma
      Abstract: Aquo‐ethanolic extract of Camellia sinensis (PTRC‐31911‐A), standardized using Fourier transform infrared analysis, was found to have seven common functional groups in comparison with pre‐identified marker compound ‘quercetin’. Phyto‐chemical quantitation analysis revealed the presence of 10.65 µg/mg of flavonoids. The bioactivity fingerprint profile of PTRC‐31911‐A includes IC50 (Hydroxyl radical site specific scavenging) = 11.36 ± 0.5 µg/mL, IC80 (Hydroxyl radical non‐site specific scavenging) = 26.44 ± 0.5 µg/mL and IC50 (Superoxide ion scavenging) = 10.141 ± 0.5 µg/mL. The drug combination analysis of PTRC‐31911‐A with five third‐line antibiotics was carried out against carbapenem‐resistant Escherichia coli. The analysis of combination of PTRC‐31911‐A (6.25–1000 µg/mL) and antibiotics (6.25–1000 µg/mL) revealed synergistic behaviour (fractional inhibitory concentration indices 
      PubDate: 2015-12-01T07:33:37.199199-05:
      DOI: 10.1002/ptr.5535
       
  • Scutellaria radix Extract as a Natural UV Protectant for Human Skin
    • Abstract: Ultraviolet (UV) radiation induces oxidative injury and inflammation in human skin. Scutellaria radix (SR, the root of Scutellaria baicalensis Georgi) contains flavonoids with high UV absorptivity and antioxidant properties. The purpose of this study was to examine the potential use of SR extract as an additive in cosmetic products for UV protection. SR extract and its butanol (BuOH) fraction strongly absorbed UV radiation and displayed free radical scavenging activity against 2,2‐diphenyl‐1‐picrylhydrazyl radials and 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals. They also attenuated the UV‐induced death of HaCaT cells. Sunscreen creams, with or without supplementation of SR extract BuOH fraction, were tested in vivo in human trials to evaluate potential skin irritation and determine the sun protection factor (SPF). Both sunscreen creams induced no skin irritation. A sunscreen cream containing 24% ZnO showed an SPF value of 17.8, and it increased to 22.7 when supplemented with 5% SR extract BuOH fraction. This study suggests that SR‐derived materials are useful as safe cosmetic additives that provide UV protection. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-01T07:22:51.369948-05:
      DOI: 10.1002/ptr.5534
       
  • The Hypoglycemic and Synergistic Effect of Loganin, Morroniside, and
           Ursolic Acid Isolated from the Fruits of Cornus officinalis
    • Authors: Kai He; Shanghua Song, Zongyao Zou, Min Feng, Dezhen Wang, Yanzhi Wang, Xuegang Li, Xiaoli Ye
      Abstract: Hypoglycemic activity‐guided separation of ethanol extracts from the fruits of Cornus officinalis Sieb. et Zucc (CO) led to the isolation of loganin, morroniside, and ursolic acid. The antidiabetic capacity of CO extracts and related compounds was further investigated in diabetes mellitus mice. The results suggested that both CO extracts and pure compounds could ameliorate diabetes‐associated damages and complications. Oral administration of loganin and morroniside decreased fasting blood glucose levels in diabetes mellitus mice. Ursolic acid exhibited the highest reactive oxygen species scavenging activity and α‐glucosidase inhibitory activity. Notably, we noticed an interesting synergistic effect between loganin and ursolic acid. Given these favorable hypoglycemic properties, C. officinalis, a food and medicinal plant in China, may be used as a valuable food supplement for the treatment of diabetes mellitus. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-01T07:20:07.192094-05:
      DOI: 10.1002/ptr.5529
       
  • Pharmacokinetic Herb–Drug Interaction between Essential Oil of
           Aniseed (Pimpinella anisum L., Apiaceae) and Acetaminophen and Caffeine: A
           Potential Risk for Clinical Practice
    • Abstract: Aniseed (Pimpinella anisum L., Apiaceae) and its essential oil (EO) have been widely used. Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb–drug interaction between aniseed EO and acetaminophen and caffeine in mice. The chemical analysis (gas chromatography–mass spectrometry) of aniseed EO has confirmed trans‐anethole (87.96%) as the main component. The pharmacokinetic studies of intraperitoneally (i.p.) and orally applied acetaminophen (200 mg/kg) and caffeine (20 mg/kg) were performed in mice after 5 days of oral treatment with human equivalent dose of aniseed EO (0.3 mg/kg/day). The analysis of pharmacokinetic data showed that in the group treated by aniseed EO, the significant decrease in the peak plasma concentration of acetaminophen after oral application (p = 0.024) was revealed when compared with control group and the reduction of systemic exposure to the drug after oral application (74 ± 32% vs. 85 ± 35% in the control) was noted. The bioavailability of orally applied caffeine was also significantly decreased (p = 0.022) after the EO treatment in comparison with the control (57 ± 24% vs. 101 ± 29%). Therefore, the compromised therapeutic efficacy of acetaminophen and caffeine during the usage of aniseed EO preparations should be considered. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-01T07:18:44.5386-05:00
      DOI: 10.1002/ptr.5523
       
  • Taxodione and Extracts from Salvia austriaca Roots as Human Cholinesterase
           Inhibitors
    • Abstract: Taxodione, an abietane diterpenoid, was isolated from Salvia austriaca transformed roots grown in in vitro conditions. The compound is known to have antibacterial, cytotoxic and anti‐tumour properties. This study evaluates the ability of pure taxodione and extracts obtained from the S. austriaca hairy roots and roots from field‐grown plants to inhibit human acetylcholinesterase and butyrylcholinesterase. Both extracts were found to have similar actions against acetylcholinesterase. The IC50 for extracts from transformed and untransformed roots were 142.5 and 139.5 µg ml−1, respectively. The highest activity towards human acetylcholinesterase was demonstrated by taxodione (IC50 = 54.84 µg ml−1). With respect to BChE inhibition, the root extracts demonstrated stronger activity (IC50 = 23.6 µg ml−1: field‐grown plants and 41.6 µg ml−1: transformed roots) than taxodione (IC50 = 195.9 µg ml−1). Taxodione showed significant cytotoxicity against A549 cell line (IC50 = 9.1 µg ml−1), whereas the activities for the extracts from S. austriaca roots of field‐grown plants (IC50 = 75.7 µg ml−1) and hairy roots (IC50 = 86.2 µg ml−1) were lower. Computer modelling suggests that taxodione should not demonstrate cardiotoxic or genotoxic activity. It also indicates that taxodione should demonstrate very rapid transport from the body with very good blood–brain barrier penetration, but with no cumulative effect on the human body. The obtained results indicate that taxodione is a safe compound and may be used for further investigations in pharmacological activities. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-12-01T06:28:55.056061-05:
      DOI: 10.1002/ptr.5521
       
  • The Role of Curcumin Administration in Patients with Major Depressive
           Disorder: Mini Meta‐Analysis of Clinical Trials
    • Abstract: Major depression is a common, recurrent, and chronic disease that negatively affects the quality of life and increases the risk of mortality. Several studies have demonstrated that curcumin, the yellow‐pigmented substance of the turmeric, possesses antidepressant properties. The aim of this review is to meta‐analytically assess the antidepressant effect of curcumin in patients with major depressive disorders. We extensively searched the literature until August 2015. The random‐effect model was used to calculate the pooled standardized difference of means (SMD). Subgroup analyses were also performed to examine the effect of different study characteristics on the overall model. Six clinical trials met the inclusion criteria. Overall, curcumin administration showed a significantly higher reduction in depression symptoms [SMD = −0.34; 95% confidence interval (CI) = −0.56, −0.13; p = 0.002]. Subgroup analyses showed that curcumin had the highest effect when given to middle‐aged patients (SMD = −0.36; 95% CI = −0.59; −0.13; p = 0.002), for longer duration of administration (SMD = −0.40; 95% CI = −0.64, −0.16; p = 0.001), and at higher doses (SMD = −0.36; 95% CI = −0.59, −0.13; p = 0.002). The administration of new formulation of curcumin (BCM‐95) had non‐significantly higher effect on depression as compared with the conventional curcumin–piperine formula. We conclude that there is supporting evidence that curcumin administration reduces depressive symptoms in patients with major depression. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-27T02:40:51.38701-05:0
      DOI: 10.1002/ptr.5524
       
  • Microarray Expression Analysis for the Paradoxical Roles of Acanthopanax
           senticosus Harms in Treating α‐Synucleinopathies
    • Abstract: α‐Synuclein is a key player in the pathogenesis of neurodegenerative disorders with Lewy bodies. Our previous studies have also showed that Acanthopanax senticosus harms (AS) could significantly suppress α‐synuclein overexpression and toxicity. Identifying the RNAs related to α‐synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Microarray expression profiling of long non‐coding RNAs (lncRNAs) and mRNAs was undertaken in control non‐transgenic and human α‐synuclein transgenic mice. The effects of AS on central nervous system (CNS) in pathology and physiology were investigated based on the lncRNA/mRNA targets analysis. In total, 341 lncRNAs and 279 mRNAs were differentially expressed by α‐synuclein stimulus, among which 29 lncRNAs and 25 mRNAs were involved in the anti‐α‐synucleinopathies mechanism of AS. However, the levels of 19/29 lncRNAs and 12/25 mRNAs in AS group were similar to those in α‐synuclein group, which may cause potential neurotoxicity analogous to α‐synuclein. This study demonstrated that some of lncRNAs/mRNAs were involved in α‐synuclein related pathophysiology, and AS produced the bidirectional effects on CNS under pathological and physiological conditions. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-27T02:08:05.691797-05:
      DOI: 10.1002/ptr.5522
       
  • Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and
           their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T
           Lymphocyte (Jurkat) Cells via the Activation of c‐Jun
           n‐terminal Kinase Phosphorylation
    • Abstract: Infrared‐guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C. concolor. The structures of these compounds were elucidated by one‐dimensional and two‐dimensional nuclear magnetic resonance techniques, as well as high‐resolution mass spectrometry. The purified and characterized compounds were subjected to cytotoxicity assay. The sesquiterpene lactones desoxyjanerin and rhaserolide showed significant cytotoxic activities against five different cancer cell lines and the normal human embryonic kidney cell line. Rhaserolide was chosen to evaluate the possible mechanism of action. Western blot analysis revealed that rhaserolide could induce apoptosis in Jurkat cells via the activation of c‐Jun n‐terminal kinase phosphorylation. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-19T00:07:17.871705-05:
      DOI: 10.1002/ptr.5519
       
  • Protocatechuic Acid Restores Vascular Responses in Rats With Chronic
           Diabetes Induced by Streptozotocin
    • Authors: Yoswaris Semaming; Upa Kukongviriyapan, Bunkerd Kongyingyoes, Wipawee Thukhammee, Patchareewan Pannangpetch
      Abstract: Oxidative stress has been shown to play an important role in development of vascular dysfunction in diabetes. Protocatechuic acid (PCA) has been reported to exert antioxidant and anti‐hyperglycemic activities. Diabetes was induced in male Sprague–Dawley rats by a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The rats were maintained in a state of hyperglycemia for 12 weeks. Then, PCA (50 or 100 mg/kg/day) was administered orally or insulin (4 U/kg/day) was subcutaneous injected to the rats for 6 weeks. Blood pressure, vascular responses to vasoactive agents, vascular superoxide production, blood glucose, insulin, malondialdehyde, nitric oxide and antioxidant enzymes were examined. The diabetic rats showed weight loss, insulin deficiency, hyperglycemia, increased oxidative stress, decreased plasma nitric oxide, elevated blood pressure, increased vascular response to phenylephrine and decreased vascular responses to acetylcholine and sodium nitroprusside. PCA significantly decreased blood glucose and oxidative stress, and increased plasma nitric oxide in diabetic rats. Interestingly, PCA treatment restored blood pressure and vascular reactivity, and antioxidant enzyme activity diabetic rats. This study provides the first evidence of the efficacy of PCA in restoring the vascular reactivity of diabetic rats. The mechanism of action may be associated with an alleviation of oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-17T05:32:04.875039-05:
      DOI: 10.1002/ptr.5520
       
  • Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve
           Growth Factor‐Mediated Signaling
    • Abstract: The flower bud of Zingiber mioga Roscoe, known as ‘myoga’ or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal‐regulated kinases and cAMP response element‐binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-13T00:59:52.083213-05:
      DOI: 10.1002/ptr.5511
       
  • Nobiletin, a Polymethoxylated Flavone, Inhibits Glioma Cell Growth and
           Migration via Arresting Cell Cycle and Suppressing MAPK and Akt Pathways
    • Abstract: Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3',4'‐hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20–100 µm) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI‐annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin‐dependent kinase 2, cyclin‐dependent kinase 4, and E2 promoter‐binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen‐activated protein kinases, including p38, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen‐activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme. Copyright © 2015 John Wiley & Sons, Ltd.
      PubDate: 2015-11-12T00:10:30.557429-05:
      DOI: 10.1002/ptr.5517
       
  • Gymnemic Acid Stimulates In Vitro Splenic Lymphocyte Proliferation
    • Authors: Vineet Kumar Singh; Padmanabh Dwivedi, B. R. Chaudhary, Ramesh Singh
      Abstract: Gymnemic acid is a mixture of triterpenoid saponins of oleanane class, isolated from Gymnema sylvestre Wild R.Br (family: Asclepidaceae), an herbal plant used in traditional medicine to treat diabetes. Effect of gymnemic acid (0.1–20 µg/mL) on in vitro mitogen (concanavalin A and lipopolysaccharide)‐induced splenic lymphocyte proliferation was studied using rat as model. Significant (p 
      PubDate: 2015-11-09T00:50:52.353953-05:
      DOI: 10.1002/ptr.5514
       
  • TOC
    • Abstract: No abstract is available for this article.
       
  • Issue Information
    • Abstract: No abstract is available for this article.
       
  • The Hot‐Water Extract of Smilacis Chinae Rhizome Suppresses
           2,4‐Dinitrochlorobenzene and House Dust Mite‐Induced Atopic
           Dermatitis‐Like Skin Lesions in Mice
    • Abstract: Smilacis Chinae Rhizome (SCR) has been used as an oriental folk medicine for various biological activities. However, its effect on atopic dermatitis (AD) remains undetermined to date. We assessed the effect of orally administered hot‐water extract of SCR on AD‐like skin lesions in mice and its underlying mechanisms. AD‐like murine model was prepared by repeated alternate application of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4‐dinitrochlorobenzene (DNCB) for 4 weeks, topically to the ears. Daily oral administration of SCR for 3 and 4 weeks significantly reduced inflammatory ear thickening, with the effect being enhanced at the earlier start and longer period of administration. This effect was accompanied by a significant decrease in both Th2 and Th1 serum antibodies (total IgE, DFE‐specific IgE, and IgG2a). Histological analysis showed that SCR markedly decreased the epidermal/dermal ear thickening and the dermal infiltration of inflammatory cells. Furthermore, SCR suppressed DFE/DNCB‐induced expression of IL‐4, IL‐13, IL‐17, IL‐18, TSLP, and IFN‐γ genes in the ear tissue. Taken together, our observations demonstrate that chronic oral administration of SCR exerts beneficial effect in mouse AD model, suggesting that SCR has the therapeutic potential as an orally active treatment of AD by modulating both Th1 and Th2 responses. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Dihydro‐Resveratrol Ameliorates Lung Injury in Rats with
           Cerulein‐Induced Acute Pancreatitis
    • Abstract: Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro‐resveratrol, a prominent analog of trans‐resveratrol, against acute pancreatitis‐associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro‐inflammatory cytokines. When treated with dihydro‐resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro‐inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor‐kappaB (NF‐κB) activation was attenuated. This study is the first to report the oral administration of dihydro‐resveratrol ameliorated acute pancreatitis‐associated lung injury via an inhibitory modulation of pro‐inflammatory response, which was associated with a suppression of the NF‐κB signaling pathway.Copyright © 2016 John Wiley & Sons, Ltd.
       
  • [6]‐Shogaol, a Novel Chemopreventor in
           7,12‐Dimethylbenz[a]anthracene‐induced Hamster Buccal Pouch
           Carcinogenesis
    • Abstract: Oral cancer is a major cause of morbidity and mortality in developing countries. Despite advances in chemotherapy for the cancer management, the survival rate has not yet been improved. Dietary nutrient has been receiving a lot of attention and interest in the chemotherapeutic development. [6]‐Shogaol is a major bioactive compound identified in ginger that possesses many pharmacological properties. The aim of the present study is to investigate the effect of [6]‐shogaol on 7,12‐dimethylbenz[a]anthracene‐induced hamster buccal pouch (HBP) carcinogenesis. Oral squamous cell carcinoma induced in HBP by painting with 0.5% 7,12‐dimethylbenz(a)anthracene (DMBA), thrice in a week for 16 weeks. We observed 100% tumour incidence, decreased levels of lipid peroxidation, antioxidant, and phase II detoxification enzymes (GST, GR and GSH) in DMBA‐induced hamsters. Further, enhanced activity of phase I enzymes (cytochrome p450 and b5) and over‐expression of mutant p53, Bcl‐2 and decreased expression of wild type p53 and Bax were noticed in DMBA‐induced hamsters. Our results indicated that [6]‐shogaol (10, 20 and 40 mg/kg body weight) treated with DMBA‐painted hamsters, considerably reversed tumour incidence, improved antioxidant status, phase II detoxification enzymes, and also inhibit lipid peroxidation and phase I enzymes. Moreover, [6]‐shogaol inhibits mutant p53 and Bcl‐2 expression and significantly restored normal p53, Bax levels. Thus, we concluded that [6]‐shogaol prevents DMBA‐induced HBP carcinogenesis through its antioxidant as well as modulating apoptotic signals. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Possible Involvement of Nitric Oxide Modulatory Mechanisms in the
           Neuroprotective Effect of Centella asiatica Against Sleep Deprivation
           Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation
    • Abstract: Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72‐h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF‐alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti‐anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep‐deprived 72‐h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD‐induced anxiety‐like behaviour, oxidative damage and neuroinflammation in mice. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents
    • Abstract: Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non‐stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non‐stimulatory thermogenic agents include p‐synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The
      Authors Phytotherapy Research published by John Wiley & Sons Ltd.
       
  • Hydroxy‐Safflower Yellow A inhibits the TNFR1‐Mediated
           Classical NF‐κB Pathway by Inducing Shedding of TNFR1
    • Abstract: Hydroxy‐safflower yellow A (HSYA) is the major active component of safflower, a traditional Asia herbal medicine well known for its cardiovascular protective activities. The purpose of this study was to investigate the effect of HSYA on TNF‐α‐induced inflammatory responses in arterial endothelial cells (AECs) and to explore the mechanisms involved. The results showed that HSYA suppressed the up‐regulation of ICAM‐1 expression in TNF‐α‐stimulated AECs in a dose‐dependent manner. High concentration (120 μM) HSYA significantly inhibited the TNF‐α‐induced adhesion of RAW264.7 cells to AECs. HSYA blocked the TNFR1‐mediated phosphorylation and degradation of IκBα and also prevented the nuclear translocation of NF‐κB p65. Moreover, HSYA reduced the cell surface level of TNFR1 and increased the content of sTNFR1 in the culture media. TNF‐α processing inhibitor‐0 (TAPI‐0) prevented the HSYA inhibition of TNFR1‐induced IκBα degradation, implying the occurrence of TNFR1 shedding. Furthermore, HSYA induced phosphorylation of TNF‐α converting enzyme (TACE) at threonine 735, which is thought to be required for its activation. Conclusively, HSYA suppressed TNF‐α‐induced inflammatory responses in AECs, at least in part by inhibiting the TNFR1‐mediated classical NF‐κB pathway. TACE‐mediated TNFR1 shedding can be involved in this effect. Our study provides new evidence for the antiinflammatory and anti‐atherosclerotic effects of HSYA. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of
           Paeoniflorin Against ANIT Induced Cholestasis
    • Abstract: Cholestasis is a leading cause of hepatic accumulation of bile acids resulting in liver injury, fibrosis, and liver failure. Paeoniflorin displays bright prospects in liver protective effect. However, its molecular mechanism has not been well‐explored. This study was designed to assess the effects and possible mechanisms of paeoniflorin against alpha‐naphthylisothiocyanate‐induced liver injury. Ultraperformance liquid chromatography coupled with quadrupole time‐of‐flight combined with principle component analysis and partial least squares discriminant analysis were integrated to obtain differentiating metabolites for the pathways and clarify mechanisms of disease. The results indicated that paeoniflorin could remarkably downregulate serum biochemical indexes and alleviate the histological damage of liver tissue. Different expression of 14 metabolites demonstrated that paeoniflorin mainly regulated the dysfunctions of glycerophospholipid metabolism and primary bile acid biosynthesis. Moreover, several pathways such as arginine and proline metabolism, ether lipid metabolism, and arachidonic acid metabolism were also related to the efficacy. In conclusion, paeoniflorin has indicated favorable pharmacological effect on serum biochemical indexes and pathological observation on cholestatic model. And metabolomics is a promising approach to unraveling hepatoprotective effects by partially regulating the perturbed pathways, which provide insights into mechanisms of cholestasis. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and
           Affects Neurotransmission in Rats
    • Abstract: Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long‐term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4‐week‐old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose‐dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd. Administration of Passiflora incarnata extract in dose‐dependent manner reduces stress and improves spatial memory in young male Wistar rats. In biochemical examination the depletion of hippocampal glutamic acid, cortical serotonin and noradrenaline content along with an increase in their metabolites level and turnover were found.
       
  • Activation of Cellular Immunity in Herpes Simplex Virus Type
           1‐Infected Mice by the Oral Administration of Aqueous Extract of
           Moringa oleifera Lam. Leaves
    • Abstract: Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti‐herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV‐1) infection model. AqMOL (300 mg/kg) was administered orally to HSV‐1‐infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed‐type hypersensitivity (DTH) reaction to inactivated HSV‐1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)‐γ production by HSV‐1 antigen from splenocytes of HSV‐1‐infected mice at 4 days post‐infection. AqMOL administration was effective in elevating the ratio of CD11b+ and CD49b+ subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV‐1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Effects of Plants on Osteogenic Differentiation and Mineralization of
           Periodontal Ligament Cells: A Systematic Review
    • Abstract: This systematic review aimed to evaluate the effects of plants on osteogenic differentiation and mineralization of human periodontal ligament cells. The included studies were selected using five different electronic databases. The reference list of the included studies was crosschecked, and a partial gray literature search was undertaken using Google Scholar and ProQuest. The methodology of the selected studies was evaluated using GRADE. After a two‐step selection process, eight studies were identified. Six different types of plants were reported in the selected studies, which were Morinda citrifolia, Aloe vera, Fructus cnidii, Zanthoxylum schinifolium, Centella asiatica, and Epimedium species. They included five types of isolated plant components: acemannan, osthole, hesperetin, asiaticoside, and icariin. In addition, some active substances of these components were identified as polysaccharides, coumarins, flavonoids, and triterpenes. The studies demonstrated the potential effects of plants on osteogenic differentiation, cell proliferation, mineral deposition, and gene and protein expression. Four studies showed that periodontal ligament cells induce mineral deposition after plant treatment. Although there are few studies on the subject, current evidence suggests that plants are potentially useful for the treatment of periodontal diseases. However, further investigations are required to confirm the promising effect of these plants in regenerative treatments. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Immunomodulation in Middle‐Aged Humans Via the Ingestion of
           Physta® Standardized Root Water Extract of Eurycoma longifolia
           Jack—A Randomized, Double‐Blind, Placebo‐Controlled,
           Parallel Study
    • Abstract: This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta® to modulate human immunity in a middle‐aged Japanese population. This randomized, double‐blind, placebo‐controlled, parallel study was conducted for 4 weeks. Eighty‐four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty‐three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p 
       
  • Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics
           of Ribavirin and Its Major Metabolite in Rats
    • Abstract: The herb‐derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (PO) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, PO), glycyrrhizin (15 mg/kg, intraperitoneal [IP]), or oxymatrine (60 mg/kg, PO). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration‐time curve (AUC0–t) and the peak plasma concentration (Cmax) of ribavirin and ribavirin base by 31.2–44.5% and 48.9–50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0–t of both ribavirin and its metabolite by 35.3–37.6% and 38.6–39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax. Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Grapes (Vitis vinifera) as a Potential Candidate for the Therapy of the
           Metabolic Syndrome
    • Abstract: Metabolic syndrome is associated with several disorders, including hypertension, diabetes, hyperlipidemia as well as cardiovascular diseases and stroke. Plant‐derived polyphenols, compounds found in numerous plant species, play an important role as potential treatments for components of metabolic syndrome. Studies have provided evidence for protective effects of various polyphenol‐rich foods against metabolic syndrome. Fruits, vegetables, cereals, nuts, and berries are rich in polyphenolic compounds. Grapes (Vitis vinifera), especially grape seeds, stand out as rich sources of polyphenol potent antioxidants and have been reported helpful for inhibiting the risk factors involved in the metabolic syndrome such as hyperlipidemia, hyperglycemia, and hypertension. There are also many studies about gastroprotective, hepatoprotective, and anti‐obesity effects of grape polyphenolic compounds especially proanthocyanidins in the literature. The present study investigates the protective effects of grape seeds in metabolic syndrome. The results of this study show that grape polyphenols have significant effects on the level of blood glucose, lipid profile, blood pressure, as well as beneficial activities in liver and heart with various mechanisms. In addition, the pharmacokinetics of grape polyphenols is discussed. More detailed mechanistic investigations and phytochemical studies for finding the exact bioactive component(s) and molecular signaling pathways are suggested. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Protocatechuic Acid Attenuates Osteoclastogenesis by Downregulating
           JNK/c‐Fos/NFATc1 Signaling and Prevents Inflammatory Bone Loss in
           Mice
    • Abstract: Protocatechuic acid (PCA) plays a critical role in nutritional metabolism; it is a major metabolite of anthocyanins, which are flavonoids with a range of health benefits. PCA has a variety of biological activities including anti‐oxidant, antiinflammatory, anti‐apoptosis, and anti‐microbial activities. However, the pharmacological effect of PCA, especially on osteoclastogenesis, remains unknown. We examined the effect of PCA on receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation and bone resorption. PCA dose‐dependently inhibited RANKL‐induced osteoclast differentiation in mouse bone marrow macrophages (BMMs) and suppressed the bone‐resorbing activity of mature osteoclasts. At the molecular level, PCA suppressed RANKL‐induced phosphorylation of JNK among MAPKs only, without significantly affecting the early signaling pathway. PCA also suppressed RANKL‐stimulated expression of c‐Fos and nuclear factor of activated T cells c1 (NFATc1) at the mRNA and protein levels, without altering c‐Fos mRNA expression. Additionally, PCA down‐regulated the expression of downstream osteoclastogenesis‐related genes including β3‐integrin, DC‐STAMP, OC‐STAMP, Atp6v0d2, CTR, and CtsK. Mice treated with PCA efficiently recovered from lipopolysaccharide‐induced bone loss in vivo. Thus, PCA inhibits RANKL‐induced osteoclast differentiation and function by suppressing JNK signaling, c‐Fos stability, and expression of osteoclastic marker genes. These results suggest that PCA could be useful in treatment of inflammatory bone disorders. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Ginkgo Biloba Extract Attenuates Oxidative Stress and Apoptosis in Mouse
           Cochlear Neural Stem Cells
    • Abstract: In the organ or Corti, oxidative stress could result in damage to the hearing, and neural stem cells (NSCs) hold great therapeutic potential in treating hearing loss. Ginkgo biloba extract (GBE) has been widely shown to exhibit anti‐oxidative and anti‐apoptotic effects in treatments of neural damage and disorder. Using hydrogen peroxide to induced oxidative stress as a model, we investigated the anti‐oxidative role of GBE in isolated mouse cochlear NSCs. GBE treatment was found to significantly promote viability of NSCs, by markedly attenuating hydrogen peroxide induced oxidative stress. In addition, this anti‐oxidative function of GBE was also able to prevent mitochondrial depolarization and subsequent apoptosis. Moreover, the anti‐apoptotic role of GBE was mediated by antagonizing the intrinsic mitochondrial apoptotic pathway, where GBE could reverse the changes in key intrinsic apoptosis pathway factors including Bcl‐2, Bax, and Caspase‐3. Our data provided the first report on the beneficial role of GBE in protecting cochlear NSCs, by attenuating oxidative stress triggered intrinsic apoptosis, therefore supporting the potential therapeutic value of GBE in preventing oxidative stress‐related hearing loss. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Hydroxysafflor Yellow A Attenuates Bleomycin‐induced Pulmonary
           Fibrosis in Mice
    • Abstract: Hydroxysafflor yellow A (HSYA) is an active component of Carthamus tinctorius L., and we want to investigate whether HSYA attenuates pulmonary fibrosis induced by bleomycin (BLM) in mice. The mice received a BLM via oropharyngeal aspiration, and HSYA was intraperitoneally injected. Arterial blood gas analysis was performed. Morphological changes and hydroxyproline content were measured. mRNA expression of transforming growth factor‐β1 (TGF‐β1), connective tissue growth factor, α‐smooth muscle actin (α‐SMA), and collagen I was measured by real‐time polymerase chain reaction. α‐SMA‐positive cells in lung tissues were detected by immunohistochemical staining. A549 cell was cultured, and morphological changes were observed after TGF‐β1 and HSYA treatment. mRNA expression was detected by real‐time polymerase chain reaction. Phosphorylation of Smad3 was evaluated by western blotting. HSYA decreased the lung consolidation area and collagen deposition in mice with pulmonary fibrosis. The blood gas changes due to BLM were attenuated by HSYA. HSYA also alleviated the BLM‐induced increase of TGF‐β1, connective tissue growth factor, α‐SMA, and collagen I mRNA levels. HSYA treatment inhibited the increase of α‐SMA expression, Smad3 phosphorylation, the morphological changes in lung tissue. HSYA inhibits Smad3 phosphorylation and elevated expression of collagen I mRNA in epithelial–mesenchymal transition induced by TGF‐β1. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Anxiolytic Effect of Citrus aurantium L. on Patients with Chronic Myeloid
           Leukemia
    • Abstract: The bone marrow aspiration procedure is used in hematological diseases and consists of a painful, invasive procedure causing anxiety‐associated symptoms. The present study assessed the effect of Citrus aurantium L. essential oil on the treatment of anxiety, in the moment that precedes the collection of medullary material in patients with chronic myeloid leukemia (CML). Volunteers from both sexes were divided into groups receiving either the C. aurantium essential oil through inhalation, diazepam (10 mg), or the placebo. The evaluation was performed through psychometric scales [State‐Trait Anxiety Inventory (STAI)] and physiological measurements (blood pressure and cardiac and respiratory frequency). Inhalation of C. aurantium was associated with a decrease in the STAI‐S scores, suggesting an anxiolytic effect. In support of these results, a change in all the physiological measurements was observed in the group exposed to C. aurantium. In the diazepam group, only the diastolic pressure decreased, and no effect was observed in the placebo group. Therefore, the results showed that C. aurantium exhibits an anxiolytic effect and reduces the signs and symptoms associated with anxiety in patients with CML. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • c‐Jun N‐terminal Kinase‐Dependent Endoplasmic Reticulum
           Stress Pathway is Critically Involved in Arjunic Acid Induced Apoptosis in
           Non‐Small Cell Lung Cancer Cells
    • Abstract: Though arjunic acid, a triterpene isolated from Terminalia arjuna, was known to have antioxidant, antiinflammatory, and cytotoxic effects, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the molecular antitumor mechanism of arjunic acid was examined in A549 and H460 non‐small cell lung cancer (NSCLC) cells. Arjunic acid exerted cytotoxicity by 3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5‐diphenyl tetrazolium bromide (MTT) assay and significantly increased sub‐G1 population in A549 and H460 cells by cell cycle analysis. Consistently, arjunic acid cleaved poly (ADP‐ribose) polymerase (PARP), activated Bax, and phosphorylation of c‐Jun N‐terminal kinases (JNK), and also attenuated the expression of pro‐caspase‐3 and Bcl‐2 in A549 and H460 cells. Furthermore, arjunic acid upregulated the expression of endoplasmic reticulum (ER) stress proteins such as IRE1 α, ATF4, p‐eIF2α, and C/EBP homologous protein (CHOP) in A549 and H460 cells. Conversely, CHOP depletion attenuated the increase of sub‐G1 population by arjunic acid, and also JNK inhibitor SP600125 blocked the cytotoxicity and upregulation of IRE1 α and CHOP induced by arjunic acid in A549 and H460 cells. Overall, our findings suggest that arjunic acid induces apoptosis in NSCLC cells via JNK mediated ER stress pathway as a potent chemotherapeutic agent for NSCLC.
       
  • Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and
           Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD
           Modeling
    • Abstract: The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin‐induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p 
       
  • New Findings on the Effects of Tannic Acid: Inhibition of L‐Type
           Calcium Channels, Calcium Transient and Contractility in Rat Ventricular
           Myocytes
    • Abstract: Tannic acid (TA) is a group of water‐soluble polyphenolic compounds that occur mainly in plant‐derived feeds, food grains and fruits. Many studies have explored its biomedical properties, such as anticancer, antibacterial, antimutagenic, antioxidant, antidiabetic, antiinflammatory and antihypertensive activities. However, the effects of TA on the L‐type Ca2+ current (ICa‐L) of cardiomyocytes remain undefined. The present study examined the effects of TA on ICa‐L using the whole‐cell patch‐clamp technique and on intracellular Ca2+ handling and cell contractility in rat ventricular myocytes with the aid of a video‐based edge detection system. Exposure to TA resulted in a concentration‐ and voltage‐dependent blockade of ICa‐L, with the half maximal inhibitory concentration of 1.69 μM and the maximal inhibitory effect of 46.15%. Moreover, TA significantly inhibited the amplitude of myocyte shortening and peak value of Ca2+ transient and increased the time to 10% of the peak. These findings provide new experimental evidence for the cellular mechanism of action of TA and may help to expand clinical treatments for cardiovascular disease. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Plant Phenols as Antibiotic Boosters: In Vitro Interaction of Olive Leaf
           Phenols with Ampicillin
    • Abstract: The antimicrobial properties of olive leaf extract (OLE) have been well recognized in the Mediterranean traditional medicine. Few studies have investigated the antimicrobial properties of OLE. In this preliminary study, commercial OLE and its major phenolic secondary metabolites were evaluated in vitro for their antimicrobial activities against Escherichia coli and Staphylococcus aureus, both individually and in combination with ampicillin. Besides luteolin 7‐O‐glucoside, OLE and its major phenolic secondary metabolites were effective against both bacteria, with more activity on S. aureus. In combination with ampicillin, OLE, caffeic acid, verbascoside and oleuropein showed additive effects. Synergistic interaction was observed between ampicillin and hydroxytyrosol. The phenolic composition of OLE and the stability of olive phenols in assay medium were also investigated. While OLE and its phenolic secondary metabolites may not be potent enough as stand‐alone antimicrobials, their abilities to boost the activity of co‐administered antibiotics constitute an imperative future research area. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile
           of Luteolin‐7‐O‐glucoside Isolated from Trifolium
           alexandrinum L. in Ovariectomized Rats
    • Abstract: Luteolin‐7‐O‐glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin‐7‐O‐glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone‐specific alkaline phosphatase, plasma osteocalsin, type I procollagen N‐terminal, and C‐telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Rhodiola rosea L. and Alzheimer's Disease: From Farm to Pharmacy
    • Abstract: Rhodiola rosea L. (roseroot) is a common member of the family Crassulaceae, known as one of the most important popular medicinal plants in the northern region of Europe. The roots of R. rosea possess a wide range of pharmacological activities such as antioxidant, antiinflammatory, anticancer, cardioprotective, and neuroprotective effects that are because of the presence of different phytochemicals such as phenols and flavonoids. In addition, the presence of salidroside, rosavins, and p‐tyrosol are responsible for its beneficial effects for the treatment of on depression, fatigue, and cognitive dysfunction. A plethora of studies report that R. rosea has potent neuroprotective effects through the suppression of oxidative stress, neuroinflammation, and excitotoxicity in brain tissues and antagonism of oncogenic p21‐activated kinase. However, to our knowledge, no review articles have been published addressing the neuroprotective effects of R. rosea. Therefore, the present article aims at critically reviewing the available literature on the beneficial effects of R. rosea on as a therapeutic strategy for the treatment of Alzheimer's disease and other neurodegenerative diseases where oxidative stress plays a major role in disease development and progression. We also discuss the cultivation, phytochemistry, clinical impacts, and adverse effects of R. rosea to provide a broader insight on the therapeutic potential for this plant. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Listerine® Products: An Update on the Efficacy and Safety
    • Abstract: In the 19th century, the mouthwash Listerine® was formulated from four essential oils. Later, the oils were replaced by their marker substances. To keep them in solution, 24–27% ethanol was added as a vehicle. This is an update of our previous review on the efficacy and safety of Listerine®. Method: PubMed was searched for clinical studies on the therapeutic benefits and safety of Listerine® from the end of 2011 to the end of October 2015. Results: Sixteen studies were found and extracted. Three of the four 6‐month studies were of sound confirmatory design. Two of these investigated Listerine® and one Listerine Zero®. The evidence of effectiveness for Listerine®, based on the bulk of three confirmatory studies and numerous exploratory studies carried out so far, is strong, but only moderate for Listerine® Zero and poor for Listerine® Cool Blue. In the three safety studies identified, we found methodological flaws that biased the results. Conclusions: Evidence is accumulating that Listerine® is effective in improving oral health, but the absence of systematic toxicological studies means that an accurate safety assessment cannot be made. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Ginkgetin Blocks Constitutive STAT3 Activation and Induces Apoptosis
           through Induction of SHP‐1 and PTEN Tyrosine Phosphatases
    • Abstract: Ginkgetin, a biflavone from Ginkgo biloba leaves, is known to exhibit antiinflammatory, antifungal, neuroprotective, and antitumor activities, but its precise mechanism of action has not been fully elucidated. Because the aberrant activation of STAT3 has been linked with regulation of inflammation, proliferation, invasion, and metastasis of tumors, we hypothesized that ginkgetin modulates the activation of STAT3 in tumor cells. We found that ginkgetin clearly suppressed constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK1 and c‐Src kinases and nuclear translocation of STAT3 on both A549 and FaDu cells. Treatment with sodium pervanadate reversed the ginkgetin‐induced down‐modulation of STAT3, thereby indicating a critical role for a PTP. We also found that ginkgetin strongly induced the expression of the SHP‐1 and PTEN proteins and its mRNAs. Further, deletion of SHP‐1 and PTEN genes by siRNA suppressed the induction of SHP‐1 and PTEN, and reversed the inhibition of STAT3 activation. Ginkgetin induced apoptosis as characterized by an increased accumulation of cells in subG1 phase, positive Annexin V binding, loss of mitochondrial membrane potential, down‐regulation of STAT3‐regulated gene products, and cleavage of PARP. Overall, ginkgetin abrogates STAT3 signaling pathway through induction of SHP‐1 and PTEN proteins, thus attenuating STAT3 phosphorylation and tumorigenesis. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • The Integration of Chinese Material Medica into the Chinese Health Care
           Delivery System, an Update
    • Abstract: Integration of Traditional Chinese medicine, including Chinese material medica (CMM), into the national healthcare delivery system, is now an essential national policy in China and is increasing rapidly. This case study summarizes the profile of integration of CMM in China, describing markets, industries, management mechanisms, education, research and development, human resources and international cooperation related to Traditional Chinese medicine, and CMM in particular. It provides a basis for policies for integrating TM into national healthcare systems to save costs and improve the general health of the population. By the end of 2014, the overall sale value of CMM exceeded $US120bn, representing 31% of the total pharmaceutical industry markets in China. More than 200 CMM formulated drugs and 1100 prepared CMM are now on the national ‘Essential Drug List’ and the financial budget for CMM from the Chinese government in 2014 was approximately $US4.66bn, almost double that of 2011, indicating an increasing and long‐term commitment to integrated medicine in China. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration,
           Invasion, and In Vivo Invasive Growth Through Targeting C‐Met
    • Abstract: Breast cancer is a major health problem affecting the female population worldwide. The triple‐negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto‐oncogenic receptor tyrosine kinase c‐Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c‐Met is proposed as a promising candidate target for the control of TNBCs. Lichens‐derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen‐derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer‐guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone‐derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA‐MB‐231 cell proliferation, migration, and invasion, with minimal toxicity to non‐tumorigenic MCF‐10A mammary epithelial cells. Molecular modeling, Z'‐LYTE biochemical kinase assay and Western blot analysis identified c‐Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA‐MB‐231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen‐derived natural products are promising resources to discover novel c‐Met inhibitors useful to control TNBCs. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • 6‐Gingerol Mediates its Anti Tumor Activities in Human Oral and
           Cervical Cancer Cell Lines through Apoptosis and Cell Cycle Arrest
    • Abstract: 6‐Gingerol, a potent nutraceutical, has been shown to have antitumor activity in different tumors, although its mechanism of action is not well understood. In this study, we evaluated antitumor activities of 6‐gingerol on human oral (SCC4, KB) and cervical cancer (HeLa) cell lines with or without wortmannin, rapamycin, and cisplatin. Tumor cell proliferation was observed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H tetrazolium, inner salt assay, cell cycle analysis by propidium iodide labeling and flow cytometry, apoptosis by Annexin‐V binding assay, and caspase activity by chemiluminescence assay. 6‐Gingerol showed dose‐dependent cytotoxicity in all three cell lines. Combinations of 6‐gingerol with wortmannin and cisplatin showed additive effects, while with rapamycin, it showed 50% cytotoxicity that was equivalent to IC50 of 6‐gingerol alone. Treatment with 6‐gingerol resulted in G2‐phase arrest in KB and HeLa cells and S‐phase arrest in SCC4 cells. 6‐Gingerol, wortmannin, and rapamycin treatment showed almost two‐fold higher expression of caspase 3 in all cell lines. The results imply that 6‐gingerol either alone or in combination with PI‐3 K inhibitor and cisplatin may provide better therapeutic effects in oral and cervical carcinoma. Thus, 6‐gingerol appears to be a safe and potent chemotherapeutic/chemopreventive compound acting through cell cycle arrest and induction of apoptosis in human oral and cervical tumor cells. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • The Significance of Tinospora crispa in Treatment of Diabetes Mellitus
    • Abstract: Tinospora crispa is a medicinal plant belonging to the botanical family Menispermiaceae. The plant is widely distributed in Southeast Asia and the northeastern region of India. A related species Tinospora cordifolia is used in Ayurveda for treating a large spectrum of diseases. Traditional healers of Thailand, Malaysia, Guyana, Bangladesh and the southern Indian province of Kerala use this plant in the treatment of diabetes. Many diterpenes, triterpenes, phytosteroids, alkaloids and their glycosides have been isolated from T. crispa. Cell culture and animal studies suggest that the herb stimulates secretion of insulin from β‐cells. It also causes dose‐dependent and time‐dependent enhancement of glucose uptake in muscles. However, in view of the reported hepatotoxicity, this herb may be used with caution. This article reviews the animal studies and human clinical trials carried out using this herb. Areas of future research are also identified. Copyright © 2016 John Wiley & Sons, Ltd.
       
  • Binary and Tertiary Mixtures of Satureja hortensis and Origanum vulgare
           
    • Abstract: Essential oils possess strong antimicrobial activity, even against multiresistant Helicobacter pylori. Available therapies against H. pylori infection have multiple disadvantages, indicating a great need for a development of new therapeutics. The purpose of this study was to develop a potent natural product based anti‐H. pylori formulation. First, anti‐H. pylori activity of nine essential oils was determined, after which the most active oils were mixed in various ratios for further testing. Satureja hortensis, Origanum vulgare subsp. vulgare and O. vulgare subsp. hirtum essential oils expressed the highest activity (MIC = 2 μL mL−1). Their binary and ternary mixtures exhibited notably higher antimicrobial activity (MIC ≤ 2 μL mL−1). The most active was the mixture of S. hortensis and O. vulgare subsp. hirtum oils in volume ratio 2:1, which expressed 4 times higher activity than individual oils (MIC = 0.5 μL mL−1). According to GC‐MS, both oils in the mixture were characterized by high content of phenols (48–73%), with carvacrol as the main carrier of antimicrobial activity. Presented in vitro study pointed out binary mixture of S. hortensis and O. vulgare subsp. hirtum essential oils in volume ratio 2:1 as promising candidate for further in vivo studies targeting H. pylori infection. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Hedera nepalensis K. Koch: A Novel Source of Natural Cancer
           Chemopreventive and Anticancerous Compounds
    • Abstract: Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer‐cell lines: MCF‐7, MDA‐MB‐231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n‐hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n‐hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 μM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 μM. HPLC‐DAD‐based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Codonopsis lanceolata: A Review of Its Therapeutic Potentials
    • Abstract: Codonopsis lanceolata (Campanulaceae) is dicotyledonous herbaceous perennial plant, predominantly found in Central, East, and South Asia. This plant has been widely used in traditional medicine and is considered to have medicinal properties to treat diseases and symptoms such as bronchitis, coughs, spasm, psychoneurosis, cancer, obesity, hyperlipidemia, edema, hepatitis, colitis, and lung injury. C. lanceolata contains many biologically active compounds, including polyphenols, saponins, tannins, triterpene, alkaloids, and steroids, which contribute to its numerous pharmacological activities. Through systematic studies, the pharmacological actions of these compounds have been revealed. Therapeutic potentialities of C. lanceolata and its previously reported molecular mechanisms are described in this review. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T
           Cells and Metabolic Biomarkers in Type 2 Diabetes Patients
    • Abstract: The present study was undertaken to evaluate the effects of black tea intake on inflammatory cytokines and metabolic biomarkers in Type 2 diabetes mellitus (T2DM). Thirty patients with T2DM were randomly assigned either to a High Intake (HI) group, consuming three cups (600 mL) of black tea per day; and a Low Intake (LI) group, administered 1 cup (200 mL) per day, each during a 12‐week period. Intracellular cytokine expression, regulatory T cells (Treg), glycemic and lipid profiles were measured at baseline and following the tea intake period. Tea consumption correlated with major effects measured in peripheral blood of subjects that included significantly reduced glycated hemoglobin (HbA1c) levels, along with increased regulatory T cells CD3+ CD4+ CD25+ FOXP3, CD3+ CD4+ IL‐10+ cells (an immunosuppressive phenotype), reduced (pro‐inflammatory) CD3+ CD4+ IL‐17+ cells and reduced Th1‐associated CD3+ CD4+ IFN‐Υ+ cells. Tea consumption was also observed to abolish the significance of an inverse correlation between total serum cholesterol and representation of CD4+ IL‐4+ T cells, which may reflect protection against atopy‐related oxidative stress. Outcomes of this study describe both advantages and limitations to consumption of black tea as an aid to sustained health maintenance by persons at‐risk for TD2M and related obesity‐associated metabolic syndromes. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Sensitization of K562 Leukemia Cells to Doxorubicin by the Viscum album
           Extract
    • Abstract: Toxicity of conventional chemotherapeutics highlights the requirement for complementary or alternative medicines that would reduce side effects and improve their anticancer effectiveness. European mistletoe (Viscum album) has long been used as a complementary and alternative medicine supporting cancer therapy. The aim of this study was to investigate synergistic antitumor action of V. album extract and doxorubicin during co‐treatment of chemoresistant chronic myelogenic leukemia K562 cells. Combined treatment of leukemia cells led to inhibitory synergism at sub‐apoptotic doxorubicin concentrations and multifold reduction of cytotoxic effects in healthy control cells. Prolonged co‐treatment was associated with reduced G2/M accumulation and increased expression of early and late apoptotic markers. Our data indicate that V. album extract increases antileukemic effectiveness of doxorubicin against resistant K562 cells by preventing G2/M arrest and inducing apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Ramalin‐Mediated Apoptosis Is Enhanced by Autophagy Inhibition in
           Human Breast Cancer Cells
    • Abstract: Breast cancer, the most commonly diagnosed cancer in women worldwide, is treated in various ways. Ramalin is a chemical compound derived from the Antarctic lichen Ramalina terebrata and is known to exhibit antioxidant and antiinflammatory activities. However, its effect on breast cancer cells remains unknown. We examined the ability of ramalin to induce apoptosis and its mechanisms in MCF‐7 and MDA‐MB‐231 human breast cancer cell lines. Ramalin inhibited cell growth and induced apoptosis in both cell lines in a concentration‐dependent manner. By upregulating Bax and downregulating Bcl‐2, ramalin caused cytochrome c and apoptosis‐inducing factor to be released from the mitochondria into the cytosol, thus activating the mitochondrial apoptotic pathway. In addition, activated caspase‐8 and caspase‐9 were detected in both types of cells exposed to ramalin, whereas ramalin activated caspase‐3 only in the MDA‐MB‐231 cells. Ramalin treatment also increased the levels of LC3‐II and p62. Moreover, the inhibition of autophagy by 3‐methyladenine or Atg5 siRNA significantly enhanced ramalin‐induced apoptosis, which was accompanied by a decrease in Bcl‐2 levels and an increase in Bax levels. Therefore, autophagy appears to be activated as a protective mechanism against apoptosis in cancer cells exposed to ramalin. These findings suggest that ramalin is a potential anticancer agent for the treatment of patients with non‐invasive or invasive breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Cinnamomum verum Component 2‐Methoxycinnamaldehyde: A Novel
           Anticancer Agent with Both Anti‐Topoisomerase I and II Activities in
           Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo
    • Abstract: Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2‐methoxycinnamaldehyde (2‐MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2‐MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro‐apoptotic Bax and Bak genes and downregulation of anti‐apoptotic Bcl‐2 and Bcl‐XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase‐3 and ‐9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2‐MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor‐κB (NF‐κB) and both topoisomerase I and II activities. Further study reveals that the growth‐inhibitory effect of 2‐MCA was also evident in a nude mice model. Taken together, the data suggest that the growth‐inhibitory effect of 2‐MCA against A549 cells is accompanied by downregulations of NF‐κB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2‐MCA could be a potential agent for anticancer therapy. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in
           Healthy Human Volunteers
    • Abstract: The purpose of the present study was to investigate the effect of resveratrol (RSV) pretreatment on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy human volunteers. The open‐label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered once daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CHZ dosing at predetermined time intervals and analyzed by HPLC. RSV pretreatment significantly enhanced the maximum plasma concentration (Cmax), area under the curve (AUC) and half life (T1/2) and significantly decreased elimination rate constant (Kel), apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F) of CHZ as compared to that of control. In addition, RSV pretreatment significantly decreased the metabolite to parent (6‐OHCHZ/CHZ) ratios of Cmax, AUC and T1/2 and significantly increased the Kel ratio of 6‐OHCHZ/CHZ, which indicated the reduced formation of CHZ to 6‐OHCHZ. The results suggest that the altered CYP2E1 enzyme activity and pharmacokinetics of CHZ might be attributed to RSV mediated inhibition of CYP2E1 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CHZ. The inhibition of CYP2E1 by RSV may provide a novel approach for minimizing the hepatotoxicity of ethanol. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Baicalin Reverses Depressive‐Like Behaviours and Regulates Apoptotic
           Signalling Induced by Olfactory Bulbectomy
    • Abstract: Apoptosis is thought to be involved in neurological disorders including major depression. In this study, we examined whether the polyphenolic compound baicalin could decrease apoptosis in the olfactory bulbectomy (OBX) depression rat model. OBX rats exhibited decreased performance in depression‐like behavioural tests and showed evidence of increased oxidative stress, decreased synaptophysin expression, and hippocampal apoptosis. Treatment with baicalin (20 and 40 mg/kg) significantly reversed all of these changes. Baicalin modulated the levels or activity of malondialdehyde, superoxide dismutase, and glutathione peroxidase and prevented apoptotic protease‐activating factor‐1 expression, effectively suppressing caspase‐mediated apoptosis signalling cascades. Our results demonstrate that baicalin has potent antidepressant activity, likely because of its ability to suppress apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage
           and Cell Proliferation
    • Abstract: Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2O2‐induced and azoxymethane‐induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption.
       
  • Polyphenolic Secondary Metabolites Synergize the Activity of Commercial
           Antibiotics against Clinical Isolates of
           β‐Lactamase‐producing Klebsiella pneumoniae
    • Abstract: Emergence of worldwide antimicrobial resistance prompted us to study the resistance modifying potential of plant‐derived dietary polyphenols, mainly caffeic acid, ellagic acid, epigallocatechin‐3‐gallate (EGCG) and quercetin. These compounds were studied in logical combination with clinically significant antibiotics (ciprofloxacin/gentamicin/tetracycline) against Klebsiella pneumoniae, after conducting phenotypic screening of a large number of clinical isolates and selecting the relevant strains possessing extended‐spectrum β‐lactamase (ESBL) and K. pneumoniae carbapenemase (KPC)‐type carbapenemase enzymes only. The study demonstrated that EGCG and caffeic acid could synergize the activity of tested antibiotics within a major population of β‐lactamase‐producing K. pneumoniae. In spectrofluorimetric assay, ~17‐fold greater ciprofloxacin accumulation was observed within K. pneumoniae cells pre‐treated with EGCG in comparison with the untreated control, indicating its ability to synergize ciprofloxacin to restrain active drug‐efflux. Further, electron micrograph of ESBL‐producing K. pneumoniae clearly demonstrated the prospective efficacy of EGCG towards biofilm degradation. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Hypoglycemic and Hypolipidemic Effects of Aloe vera Extract Preparations:
           A Review
    • Abstract: Obesity is considered to be an epidemic disease, and it is associated with several metabolic disorders. Pharmacological treatments currently available are not effective for prolonged treatment duration. So, people are looking toward new therapeutic approach such as herbal ingredients. Since ancient periods, different herbs have been used for remedy purposes such as anti‐obesity, antidiabetes, and antiinflammatory. Among the several herbal ingredients, Aloe vera (Aloe barbadensis Miller) is widely used to curb the metabolic complications. Till date, reports are not available for the side effects of A. vera. Several researchers are used to different solvents such as aqueous solution, alcohol, ethanol, and chloroform for the A. vera extract preparations and studied their hypoglycemic and hypolipidemic effects in animal and human studies. Furthermore, little information was recorded with the active compounds extracted from the A. vera and their anti‐obesity and antidiabetic effects in clinical studies. In this review, we made an attempt to compile all the available literature by using different search engines (PubMed, Scopus, and Google Scholar) on the A. vera extract preparations and the possible mechanism of action involved in carbohydrate and lipid metabolism. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • β‐Bisabolene, a Sesquiterpene from the Essential Oil Extract of
           Opoponax (Commiphora guidottii), Exhibits Cytotoxicity in Breast Cancer
           Cell Lines
    • Abstract: The essential oils from Commiphora species have for centuries been recognized to possess medicinal properties. Here, we performed gas chromatography‐mass spectrometry on the essential oil from opoponax (Commiphora guidotti) and identified bisabolene isomers as the main constituents of this essential oil. Opoponax essential oil, a chemical component; β‐bisabolene and an alcoholic analogue, α‐bisabolol, were tested for their ability to selectively kill breast cancer cells. Only β‐bisabolene, a sesquiterpene constituting 5% of the essential oil, exhibited selective cytotoxic activity for mouse cells (IC50 in normal Eph4: >200 µg/ml, MG1361: 65.49 µg/ml, 4T1: 48.99 µg/ml) and human breast cancer cells (IC50 in normal MCF‐10A: 114.3 µg/ml, MCF‐7: 66.91 µg/ml, MDA‐MB‐231: 98.39 µg/ml, SKBR3: 70.62 µg/ml and BT474: 74.3 µg/ml). This loss of viability was because of the induction of apoptosis as shown by Annexin V‐propidium iodide and caspase‐3/7 activity assay. β‐bisabolene was also effective in reducing the growth of transplanted 4T1 mammary tumours in vivo (37.5% reduction in volume by endpoint). In summary, we have identified an anti‐cancer agent from the essential oil of opoponax that exhibits specific cytotoxicity to both human and murine mammary tumour cells in vitro and in vivo, and this warrants further investigation into the use of β‐bisabolene in the treatment of breast cancers. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Antifungal Saponins from the Maya Medicinal Plant Cestrum schlechtendahlii
           G. Don (Solanaceae)
    • Abstract: Bioassay‐guided fractionation of the crude extract (80% EtOH) of the leaves of Cestrum schlechtendahlii, a plant used by Q'eqchi' Maya healers for treatment of athlete's foot, resulted in the isolation and identification of two spirostanol saponins (1 and 2). Structure elucidation by MS, 1D‐NMR, and 2D‐NMR spectroscopic methods identified them to be the known saponin (25R)‐1β,2α‐dihydroxy‐5α‐spirostan‐3‐β‐yl‐O‐α‐l‐rhamnopyranosyl‐(1 → 2)‐β‐d‐galactopyranoside (1) and new saponin (25R)‐1β,2α‐dihydroxy‐5α‐spirostan‐3‐β‐yl‐O‐β‐d‐galactopyranoside (2). While 2 showed little or no antifungal activity at the highest concentration tested, 1 inhibited growth of Saccharomyces cerevisiae (minimum inhibitory concentration (MIC) of 15–25 μM), Candida albicans, Cryptococcus neoformans, and Fusarium graminearum (MIC of 132–198 μM). Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Protective Effects of Gastrodin Against Autophagy‐Mediated Astrocyte
           Death
    • Abstract: Gastrodin is an active ingredient derived from the rhizome of Gastrodia elata. This compound is usually used to treat convulsive illness, dizziness, vertigo, and headache. This study aimed to investigate the effect of gastrodin on the autophagy of glial cells exposed to lipopolysaccharides (LPS, 1 µg/mL). Autophagy is a form of programmed cell death, although it also promotes cell survival. In cultured astrocytes, LPS exposure induced excessive autophagy and apoptosis, which were significantly prevented by the pretreatment cells with gastrodin (10 μM). The protective effects of gastrodin via autophagy inhibition were verified by the decreased levels of LC3‐II, P62, and Beclin‐1, which are classical markers for autophagy. Furthermore, gastrodin protected astrocytes from apoptosis through Bcl‐2 and Bax signaling pathway. The treatment of astrocytes with rapamycin (500 nM), wortmannin (100 nM), and LY294002 (10 μM), which are inhibitors of mTOR and PI3K, respectively, eliminated the known effects of gastrodin on the inhibited Beclin‐1 expression. Furthermore, gastrodin blocked the down‐regulation of glutamine synthetase induced by LPS exposure in astrocytes. Our results suggest that gastrodin can be used as a preventive agent for the excessive autophagy induced by LPS. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Extract of Ziziphus jujuba Fruit (Jujube) Stimulates Expression of Enzymes
           Responsible for Heme Recycle via Anti‐oxidant Response Element in
           Cultured Murine Macrophages
    • Abstract: Jujube, the fruit of Ziziphus jujuba Mill., is a functional food and commonly used as a health supplement worldwide. To study the beneficial role of jujube in heme iron recycling during erythrophagocytosis, the expression of heme oxygenase‐1 (HO‐1), biliverdin reductase A and B, and ferroportin were determined in jujube‐treated cultured RAW 264.7 macrophages. Application of a chemically standardized jujube water extract in cultured RAW 264.7 cells for 24 h stimulated the expressions of HO‐1, biliverdin reductase A, biliverdin reductase B, and ferroportin in a concentration‐dependent manner, having the maximal responses from twofolds to threefolds. A plasmid containing anti‐oxidant response element, a regulator for HO‐1 transcription, was transfected into RAW 264.7 cells. Application of jujube water extract onto the transfected macrophages stimulated the anti‐oxidant response element‐mediated transcriptional activity by twofolds. These results supported the potential capacity of jujube by regulating expressions of heme iron recycling genes in cultured macrophages. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Inhibition of Helicobacter pylori and Its Associate Urease by Labdane
           Diterpenoids Isolated from Andrographis paniculata
    • Abstract: The present study was carried out to evaluate anti‐Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50, 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti‐H. pylori agents possessing urease inhibition. Copyright © 2015 John Wiley & Sons, Ltd.
       
  • Antitumor Activity of Total Flavonoids from Daphne genkwa in Colorectal
           Cancer
    • Abstract: Daphne genkwa Sieb.et Zucc. is a well‐known medicinal plant. This study was designed to investigate the anticancer effects of total flavonoids in D. genkwa (TFDG) in vitro and in vivo. HT‐29 and SW‐480 human colorectal cancer cells were cultured to investigate the anticancer activity of TFDG. In addition, the ApcMin/+ mouse model was applied in the in vivo experiment. Results of the cell experiment revealed that TFDG possessed significant inhibitory effects on HT‐29 and SW‐480 human colorectal cancer cells (both p 
       
 
 
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