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Journal Cover Phytotherapy Research
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   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  [1583 journals]
  • Resistance-modifying Activity in Vinblastine-resistant Human Breast Cancer
           Cells by Oligosaccharides Obtained from Mucilage of Chia Seeds (Salvia
    • Authors: Daniel G. Rosas-Ramírez; Mabel Fragoso-Serrano, Sonia Escandón-Rivera, Alba L. Vargas-Ramírez, Juan P. Reyes-Grajeda, Manuel Soriano-García
      Abstract: The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was used to purify the hydrolysis degradation products. All compounds were tested in eight different cancer cell lines and Vero cells. All compounds were noncytotoxic at the concentration tested against the drug-sensitive and multidrug-resistant cells (IC50 > 29.2 μM). For the all products, a moderate vinblastine-enhancing activity from 4.55-fold to 6.82-fold was observed. That could be significant from a therapeutic perspective. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-20T01:21:37.820246-05:
      DOI: 10.1002/ptr.5815
  • Hypoglycemic and Antihyperglycemic Activities of Nine Medicinal Herbs Used
           as Antidiabetic in the Region of Lubumbashi (DR Congo)
    • Authors: Bakari Amuri; Mwamba Maseho, Lumbu Simbi, Philippe Okusa, Pierre Duez, Kahumba Byanga
      Abstract: The aim of this study was to assess the hypoglycemic and antihyperglycemic activities of nine plants used as antidiabetic treatments in Lubumbashi and its surroundings. Those are Albizia adianthifolia, Azanza garckeana, Cassia occidentalis, Cassia sieberiana, Erythrina abyssinica, Gladiolus klattianus, Rauvolfia caffra, Strychnos spinosa, and Vitex madiensis. Aqueous extracts, obtained by decoction and maceration, were administered (500 mg/kg) per os to guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral glucose tolerance test (OGTT) conditions (glucose, 2 g/kg; follow-up over 210 min). For OGTT experiments, area under the curve of blood glucose levels, maximum glucose concentration (Cmax), and time to reach Cmax (Tmax) were used to compare test groups with the control conditions (glucose group). In hypoglycemic tests, only three species induced significant (p 
      PubDate: 2017-04-20T00:50:33.378578-05:
      DOI: 10.1002/ptr.5814
  • Effects of Avocado (Persea americana) on Metabolic Syndrome: A
           Comprehensive Systematic Review
    • Authors: Jamshid Tabeshpour; Bibi Marjan Razavi, Hossein Hosseinzadeh
      Abstract: Metabolic syndrome (MetS) is a clustering of risk factors including high blood glucose, dyslipidemia, hypertension, and obesity that lead to the increased risk of type 2 diabetes mellitus and cardiovascular diseases (CVDs), which are among leading causes of death in the world. Metabolic syndrome increases the risk of type 2 diabetes mellitus and CVDs by approximately five and three folds, respectively. Therefore, it is of vital importance to manage such conditions with herbal options which have less undesirable adverse effects and may be more efficacious in comparison with synthetic options. Avocado is a well-known source of carotenoids, minerals, phenolics, vitamins, and fatty acids. The lipid-lowering, antihypertensive, antidiabetic, anti-obesity, antithrombotic, antiatherosclerotic, and cardioprotective effects of avocado have been demonstrated in several studies. In this review, we aimed to find out avocado's pharmacological effects on different components of MetS. Moreover, this review report is performed on the MetS effects of peel, seed, flesh, and leaves of avocado. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-10T02:20:47.980408-05:
      DOI: 10.1002/ptr.5805
  • Auraptene Induces Apoptosis via Myeloid Cell Leukemia 1-Mediated
           Activation of Caspases in PC3 and DU145 Prostate Cancer Cells
    • Authors: Jae Chul Lee; Eun Ah Shin, Bonglee Kim, Bo-Im Kim, Mahsa Chitsazian-Yazdi, Mehrdad Iranshahi, Sung-Hoon Kim
      Abstract: Although auraptene, a prenyloxy coumarin from Citrus species, was known to have anti-oxidant, anti-bacterial, antiinflammatory, and anti-tumor activities, the underlying anti-tumor mechanism of auraptene in prostate cancers is not fully understood to date. Thus, in the present study, we have investigated the anti-tumor mechanism of auraptene mainly in PC3 and DU145 prostate cancer cells, because auraptene suppressed the viability of androgen-independent PC3 and DU145 prostate cancer cells better than androgen-sensitive LNCaP cells. Also, auraptene notably increased sub-G1 cell population and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells as features of apoptosis in two prostate cancer cells compared with untreated control. Consistently, auraptene cleaved poly(ADP-ribose) polymerase, activated caspase-9 and caspase-3, suppressed the expression of anti-apoptotic proteins, including Bcl-2 and myeloid cell leukemia 1 (Mcl-1), and also activated pro-apoptotic protein Bax in both prostate cancer cells. However, Mcl-1 overexpression reversed the apoptotic effect of auraptene to increase sub-G1 population and induce caspase-9/3 in both prostate cancer cells. Taken together, the results support scientific evidences that auraptene induces apoptosis in PC3 and DU145 prostate cancer cells via Mcl-1-mediated activation of caspases as a potent chemopreventive agent for prostate cancer prevention and treatment. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T05:41:46.587499-05:
      DOI: 10.1002/ptr.5810
  • Anticancer Properties of Solamargine: A Systematic Review
    • Authors: Fatemeh Kalalinia; Iman Karimi-Sani
      Abstract: Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and enough effective for cancer prevention. Solamargine, a steroidal alkaloid glycoside found in Solanum species such as Solanum nigrum, displayed several therapeutic activities. We aim to review the use of solamargine in experimental cancer studies. Articles published in biology journals between 1975 and 2017 were retrieved from PubMed, Scopus, and Web of Science using relevant keywords. The scientific papers mainly focusing on solamargine with therapeutic efficacies against cancers were identified and tabulated. In addition, the reliability of experimental findings was determined under “Risk of Bias” criteria. The author manually reviewed 33 articles; 27 articles were found concerning the anti-cancer potential in cancer cells. Solamargine has been found to possess anticancer activities via its effect on a variety of biological pathways including cell survival pathways, tumor suppressor pathways, caspase activation pathway, mitochondrial pathways, death receptor pathways, protein kinase pathways, and signal pathways, which promote invasion/migration and multi drug resistance. Solamargine can be an anticancer agent candidate when complementary scientific evidences become available. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T04:44:46.289808-05:
      DOI: 10.1002/ptr.5809
  • The Clinical Efficacy and Adverse Effects of Interferon Combined with
           Matrine in Chronic hepatitis B: A Systematic Review and Meta-Analysis.
    • Authors: Xiaotong Wang; Haixiong Lin, Ren Zhang
      Abstract: Currently, many studies have demonstrated certain beneficial effects of interferon (IFN) combined with matrine (Mat) for chronic hepatitis B (CHB) in China. However, the evidence from these randomized control trials is still controversial. Therefore, the aim of this meta-analysis was to explore the efficacy and safety of Mat combined with IFN for CHB. We performed a systematic search of seven databases to identify all randomized controlled trials that treated CHB with IFN or IFN plus Mat from their start date to September 30, 2015. The clinical efficacy and adverse effects were evaluated. Nine studies involving 1089 participants were included. Compared with IFN monotherapy, IFN 5 MU combined with Mat 150 mg augmented the hepatitis B e-antigen negative conversion rate after 3-month treatment [relative ratio (RR) = 1.41; 95% confidence interval (CI) (1.18, 1.69), p = 0.0002] and after 12-month treatment [RR = 1.96; 95% CI (1.21, 3.19), p = 0.006], hepatitis B virus DNA negative conversion rate after 3-month treatment [RR = 1.37; 95% CI (1.16, 1.62), p = 0.0002] and after 12-month treatment [RR = 1.96; 95% CI (1.21, 3.19), p = 0.006], hepatitis B virus e antibody (anti-HBe) conversion rate after 3-month treatment [RR = 1.47; 95% CI (1.19, 1.81), p = 0.0003], and AST level after 3-week treatment [weighted mean difference = −22; 95% CI (−40.41, −3.59), p = 0.02]. Furthermore, IFN 3 MU 3 months combined with Mat 150 mg after 2-month treatment reduced the risk of leucopenia and thrombocytopenia [RR = 0.55; 95% CI (0.36, 0.85), p = 0.007]. Unfortunately, all of the included trials were not in favor of hepatitis B surface antigen (HBsAg) negative conversion rate or influenza-like symptoms. Combination therapy with IFN plus Mat exhibited better clinical efficacy and fewer adverse effects than did IFN monotherapy in patients with CHB, except in the improvement of HBsAg negative conversion rate and influenza-like symptoms. Given the poor methodological quality of the evidence currently available, future high-quality, three-blinded randomized control trials are necessary to confirm these results. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T04:00:47.789595-05:
      DOI: 10.1002/ptr.5808
  • Epimedii Herba: A Promising Herbal Medicine for Neuroplasticity
    • Authors: Jae-Heung Cho; Jae-Young Jung, Beom-Joon Lee, Kyungjin Lee, Jae-Woo Park, Youngmin Bu
      Abstract: Epimedii Herba (EH) is an herbal medicine originating from several plants of the genus Epimedium. It is a major therapeutic option for kidney yang deficiency syndrome, which is closely related to androgen hormones and also has been used to treat hemiplegia following a stroke in traditional medicine of Korea and PR China. To date, many clinical and basic researches of EH have shown the activities on functional recovery from brain diseases. Recently, neuroplasticity, which is the spontaneous reaction of the brain in response to diseases, has been shown to accelerate functional recovery. In addition, androgen hormones including testosterone are known to be the representative of neuroplasticity factors in the brain recovery processes. In this review, we described the neuro-pharmacological activities of EH, focusing on neuroplasticity. Thirty-three kinds of papers from MEDLINE/PubMed, EMBASE, and CNKI were identified and analyzed. We categorized the results into five types based on neuroplasticity mechanisms and presented the definition of each category and briefly described the results of these papers. Altogether, we can suggest that neuroplasticity is a novel viewpoint for guiding future brain research of EH and provide the evidence for the development of new clinical applications using EH in the treatment of brain diseases. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-04-06T02:58:33.631475-05:
      DOI: 10.1002/ptr.5807
  • Effectiveness of Ageratina pichinchensis Extract in Patients with
           Vulvovaginal Candidiasis. A Randomized, Double-Blind, and Controlled Pilot
    • Authors: Ofelia Romero-Cerecero; Ana Laura Islas-Garduño, Alejandro Zamilpa, Jaime Tortoriello
      Abstract: Previous clinical studies have demonstrated the antifungal effectiveness of Ageratina pichinchensis extracts when topically administered to patients with dermatomycosis. The objective of this study was to evaluate the effectiveness and tolerability of a 7% standardized extract of A. pichinchensis (intravaginal) in patients with vulvovaginal candidiasis. The extract was standardized in terms of its encecalin content and administered during 6 days to patients with Candida albicans-associated vulvovaginitis. The positive control group was treated with Clotrimazole (100 mg). On day 7 of the study, a partial evaluation was carried out; it demonstrated that 94.1% of patients treated with Clotrimazole and 100% of those treated with the A. pichinchensis extract referred a decrease or absence of signs and symptoms consistent with vulvovaginal candidiasis. In the final evaluation, 2 weeks after concluding administration, 86.6% of patients in the control group and 81.2% (p = 0.65) of those treated with the A. pichinchensis extract demonstrated therapeutic success. Statistical analysis evidenced no significant differences between the two treatment groups. With the results obtained, it is possible to conclude that the standardized extract from A. pichinchensis, intravaginally administered, showed therapeutic and mycological effectiveness, as well as tolerability, in patients with vulvovaginal candidiasis, without noting statistical differences in patients treated with Clotrimazole. Copyright © 2017 John Wiley & Sons, Ltd.
      PubDate: 2017-03-16T03:41:56.934535-05:
      DOI: 10.1002/ptr.5802
  • Pterostilbene Inhibits Lipogenic Activity similar to Resveratrol or
           Caffeine but Differently Modulates Lipolysis in Adipocytes
    • Abstract: The anti-obesity effects of resveratrol shown in rodents are not transposed into an efficient therapy of human obesity. Consequently, the search for molecules mimicking or surpassing resveratrol actions is ongoing. The natural phenolic compound pterostilbene exhibits beneficial health effects and has the capacity to limit fat mass in animal models. In this study, we tested whether pterostilbene modulates triacylglycerol accumulation/breakdown. Prolonged exposure to pterostilbene or resveratrol inhibited adipocyte differentiation in 3T3-F442A preadipocytes. Acute effects on lipolysis, antilipolysis and lipogenesis were determined for pterostilbene in mouse adipocytes, and compared with resveratrol. Pterostilbene was also tested on glycerol release and glucose uptake in subcutaneous human adipocytes. Dose–response analyses did not reveal a clear lipolytic effect in both species. The antilipolytic effect of insulin was improved by pterostilbene at 1–10 μM in mouse fat cells only, while at 1 mM, the phenolic compound was antilipolytic in human fat cells in a manner not additive to insulin. Pterostilbene dose-dependently inhibited glucose incorporation into lipids similarly to resveratrol and caffeine. However, only the former did not inhibit insulin-stimulated glucose uptake. Indeed, pterostilbene abolished the insulin lipogenic effect without inhibiting its antilipolytic action and rapid activation of glucose uptake. Pterostilbene therefore exhibits a unique panel of direct interactions with adipocytes that relies on its reported anti-obesity and antidiabetic properties. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Tilianin on Proliferation, Migration and TGF-β/Smad Signaling
           in Rat Vascular Smooth Muscle Cells Induced with Angiotensin II
    • Abstract: Flavonoid Tilianin was isolated from Dracocephalum moldavica, and its pharmacological mechanism on proliferation, migration and the TGF-β/Smad signaling pathway in rat vascular smooth muscle cells (VSMCs) induced with Angiotensin II (Ang II) was systematically evaluated. Primary rat VSMCs were stimulated with Ang II to induce proliferation. The cells were then treated with Tilianin for 24 or 48 h. MTT assay and Transwell assays were used to evaluate the effects of Tilianin on proliferation and migration. The expression of intracellular proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by immunohistochemistry as verification of effects on proliferation and migration. The expression of TGF-β1, Smad2 and Smad3 mRNA was measured by qRT-PCR, and the expression of TGF-β1 and P-Smad2/3 protein was measured by Western blotting. The results show that Tilianin can inhibit proliferation and expression of intracellular PCNA in VSMCs induced with Ang II, in a dose-dependent manner. Tilianin also mediates a dose-dependent inhibition of migration and the expression of intracellular ICAM-1, VCAM-1, MMP-2 and MMP-9. Furthermore, TGF-β1, Smad2, Smad3, Smad2/3 and P-Smad2/3 in Ang II-induced VSMCs are suppressed by Tilianin. The inhibitory effects of Tilianin support its use in the suppression and treatment of atherosclerosis. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacognosy, Phytochemistry and Pharmacological Properties of Achillea
           millefolium L.: A Review
    • Abstract: Achillea millefoilum L. (Yarrow) is an important species of Asteraceae family with common utilization in traditional medicine of several cultures from Europe to Asia for the treatment of spasmodic gastrointestinal disorders, hepatobiliary, gynecological disorders, against inflammation and for wound healing. An extensive review of literature was made on A. millefoilum L. using ethno botanical text books, published articles in peer-reviewed journals, unpublished materials and scientific databases. The Plant List, International Plant Name Index and Kew Botanical Garden databases were used to authenticate the scientific names. Monoterpenes are the most representative metabolites constituting 90% of the essential oils in relation to the sesquiterpenes, and a wide range of chemical compounds have also been reported. Different pharmacological experiments in many in-vitro and in-vivo models have proved the potential of A. millefoilum with antiinflammatory, antiulcer, anticancer activities etc. lending support to the rationale behind numerous of its traditional uses. Due to the noteworthy pharmacological activities, A. millefoilum will be a better option for new drug discovery. The present review will comprehensively summarize the pharmacognosy, phytochemistry and ethnopharmacology of A. millefoilum reported to date, with emphasis on more in vitro, clinical and pathological studies needed to investigate the unexploited potential of this plant. Copyright © 2017 John Wiley & Sons, Ltd.
  • Morin Suppresses Astrocyte Activation and Regulates Cytokine Release in
           Bone Cancer Pain Rat Models
    • Abstract: As inflammatory and immune responses are involved in pathophysiology of debilitating neuropathic pain, reagents that can modulate these two responses may have therapeutic potential. Morin, derived from the moraceae family of plants, benefits inflammation-related diseases, but its antinociceptive effects on cancer pain remain elusive. In the present study, we investigated antinociceptive effects of morin on bone cancer pain using a rat model, where rats were subject to implantation of Walker 256 mammary gland carcinoma cells into the tibia. Morin (5–20 mg/kg) dose-dependently attenuated behavioral hypersensitivities, including mechanical allodynia and free movement pain, which was accompanied by downregulation of astrocyte marker glial fibrillary acidic protein in the spinal cord in cancer-bearing rats. Treatment with morin also induced reduction of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 and upregulation of an antiinflammatory cytokine IL-10. Furthermore, intrathecal injection of AM630 (an antagonist of cannabinoid receptor 2, CB2), but not naloxone (an antagonist of opioid receptors), significantly blocked morin attenuation of behavioral hypersensitivities. Taken together, these results suggest that morin suppresses astrocyte activation and neuro-inflammation induced by bone cancer pain and its antinociceptive effects on bone cancer pain may be associated with activation of CB2 receptors in the spinal cord. Copyright © 2017 John Wiley & Sons, Ltd.
  • Phytoestrogen-Rich Natural Preparation for Treatment of Climacteric
           Syndrome and Atherosclerosis Prevention in Perimenopausal Women
    • Abstract: The present study evaluated the risks and benefits of phytoestrogen treatment in healthy perimenopausal women in relation to the dynamics of climacteric syndrome and progression of atherosclerosis. Study participants were treated with placebo or phytoestrogen-rich natural preparation Karinat based on grape (Vitis vinifera) seeds, green tea (Camellia sinensis) leaves, hop (Hunulus lupulus) cone powder and garlic (Allium sativum) powder. The dynamics of climacteric syndrome was evaluated by Kupperman Index and Utian Quality of Life Scale. Atherosclerosis progression was evaluated by measuring carotid intima-media thickness. Significant changes of climacteric syndrome's severity in both Karinat and placebo groups (p = 0.005 and p = 0.001) were obtained after 24 months of follow-up. Detailed analysis of Kupperman Index suggested that Karinat possessed a significant effect on nervousness (p = 0.010), weakness (p = 0.020) and formication (p = 0.010). A significant improvement of medical (p = 0.070) and emotional (p = 0.060) components of Kupperman Index and Utian Quality of Life Scale was also observed in Karinat group. However, difference in carotid intima-media thickness between the two groups was not statistically significant at follow-up. A slight positive effect of phytoestrogens on climacteric syndrome manifestations was demonstrated in this study. Karinat can be used for alleviation of climacteric syndrome and cardiovascular disease prevention in perimenopausal women. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway
           Activation and Epithelial–Mesenchymal Transition In Vivo
    • Abstract: Tobacco smoke is a major risk factor for hepatic cancer. Epithelial–mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein-1 (AP-1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke-induced activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke-triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke-associated hepatic cancer. Copyright © 2017 John Wiley & Sons, Ltd.
  • A Randomized, Double-blind, Placebo-controlled Clinical Trial Examining
           the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease
           Activity and Quality of Life
    • Abstract: Antiinflammatory and immunomodulatory benefit of green tea (Camellia sinensis) in autoimmune disease has been proven in recent studies. The objective of this study was to assess the effects of green tea on disease activity and quality of life in systemic lupus erythematosus patients. A randomized controlled trial on subjects with lupus was conducted, and 68 patients in the age range of 39.1 ± 10.3 years and body mass index of 25.7 ± 5.21 kg/m2 completed the 12-week study. Patients were randomly divided into two groups of intervention (1000 mg green tea extract, two capsules/day) and control (1000 mg of starch, two capsules/day). Main outcome measure, systemic lupus erythematosus disease activity, was assessed by the systemic lupus erythematosus disease activity index at the first and after 3 months of intervention. In addition, patient's quality of life was evaluated by short form of quality-of-life questionnaire at baseline and after 3 months. Green tea extract supplementation significantly reduced disease activity in lupus patients (p 
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  • Cytotoxic Properties of the Stem Bark of Citrus reticulata Blanco
    • Abstract: The bioassay-guided fractionation of the n-hexane extract of Citrus reticulata Blanco (Rutaceae) stem bark yielded scoparone (1), xanthyletin (2), lupeol (3), β-amyrin (4), stigmasterol (5), β-sitosterol (6) and palmitic acid. The structures of these compounds were determined by comprehensive spectroscopic analyses, i.e., 1D and 2D NMR and EI-MS, and by comparison with the reported data. Extracts, fractions and isolated compounds 1–6 were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) assay against three human cancer cell lines, i.e., human lung adenocarcinoma cell line A549, human breast adenocarcinoma cell line MCF7 and human Caucasian prostate adenocarcinoma cell line PC3. Significant activity of the n-hexane and the dichloromethane extracts was observed against the breast cancer cell line MCF7 with IC50s of 45.6 and 54.7 μg/mL, respectively. Moreover, the 70% ethyl acetate in n-hexane chromatographic fraction showed significant activity displaying IC50 values of 53.0, 52.4 and 49.1 μg/mL against the cancer cell lines A549, MCF7 and PC3, respectively. Encouragingly, an IC50 of 510.0 μg/mL against the human normal prostate cell line PNT2 indicated very low toxicity and hence favourable selectivity indices for the 70% ethyl acetate in n-hexane fraction in the range of 9.6–10.4 towards cell lines A549, MCF7 and PC3. Because compounds isolated from the above fraction only delivered IC50 values in the range of 18.2–96.3, 9.2–34.1 and 7.5–97.2 μg/mL against A549, MCF7 and PC3 cell lines, respectively, synergistic action between compounds is suggested. Bioassay results valorize the anticancer effectivity of the stem bark of this plant in Cameroonian pharmacopoeia. Copyright © 2017 John Wiley & Sons, Ltd.
  • Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced
           by Alcohol Withdrawal in Rats
    • Abstract: Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd.
  • Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their
           Derivatives: A Systematic Review
    • Abstract: Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/ in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacological and Toxicological Effects of Catha edulis F. (Khat)
    • Abstract: Khat chewing is deeply rooted in the culture and tradition of communities in khat belt countries, and its consumption is spread to other countries through the suitcase trade. The aim of this article is to review current knowledge on the chemistry, social, pharmacology and toxicology of khat and its use. Khat produces effect invariably in every system, which is harmful or beneficial in some instances. Harmful effects are observed in heavy users, although firm evidence is lacking. Chewing khat acutely elicits states of euphoria, which is followed by low mood. Khat contains alkaloids with psychostimulant properties, but the effect cannot be totally explained by these alkaloids. It is also not clear whether the effect produced in some organs like liver could be attributed to khat or pesticides sprayed during farming. Although the evidence indicates that khat has adverse effects in most organs, our understanding of the complex interaction between use and effect is incomplete, and causal relationships have not yet been described. Moreover, khat has positioned itself well in the social, economic and political arena. Thus, a multidisciplinary research is required to understand the different dimensions and come up with ways that maximize the benefit while minimizing the risk. Copyright © 2017 John Wiley & Sons, Ltd.
  • Elucidation of Compatibility Interactions of Traditional Chinese
           Medicines: In Vitro Absorptions Across Caco-2 Monolayer of Coptidis
           Rhizoma and Euodiae Fructus in Zuojin and Fanzuojin Formulas as A Case
    • Abstract: Traditional Chinese medicines are often combined as formulae and interact with each other. As for Coptidis Rhizoma (CR) and Euodiae Fructus (EF), the most classical compatibilities were Zuojin (ZJF) and Fanzuojin formulas (FZJF) with reverse mixture ratios and opposite effects. To compare in vitro absorption interactions between CR and EF, bidirectional transports across Caco-2 cell monolayer of extracts of two formulas and equivalent single herbs were studied. Eighteen alkaloids from CR and EF were determined by liquid chromatography coupled to tandem mass spectrometry. Parameter apparent permeability coefficient (Papp) and efflux rate (ER) values showed that most alkaloids were well or moderately absorbed and six quaternary protoberberine alkaloids from CR had obvious efflux. ZJF compatibilities reduced both Papp BLAP and ER values of three indole alkaloids, and increased ER values of two quinolone alkaloids from EF. FZJF compatibilities obviously affected the bidirectional Papp values of CR alkaloids, weakened ERs of five protoberberines from CR and enlarged ERs of two quinolones from EF. Conclusions were drawn that different compatibility ratios of CR and EF led to different interactions on the in vitro absorption of alkaloids. The results may provide a good reference for interaction studies on the compatibilities of traditional Chinese medicines. Copyright © 2017 John Wiley & Sons, Ltd.
  • Wheatgrass-Derived Polysaccharide Has Antiinflammatory, Anti-Oxidative and
           Anti-Apoptotic Effects on LPS-Induced Hepatic Injury in Mice
    • Abstract: Hepatic injury occurs frequently during sepsis, and polysaccharides isolated from plants have been reported to have antiinflammatory and antioxidant effects in various models. However, the effect of wheatgrass-derived polysaccharide (WGP) has not been previously studied. In the present study, we investigated the effect of WGP on lipopolysaccharide (LPS)-induced hepatic injury in mice. Mice were pre-treated with WGP (100 or 200 mg/kg daily for 2 days) and then challenged with LPS (1 mg/kg, intraperitoneal), and sacrificed after 12 h. Wheatgrass-derived polysaccharide decreased serum aminotransferase levels and histological changes as compared with LPS-challenged mice. Wheatgrass-derived polysaccharide also significantly inhibited LPS-induced pro-inflammatory cytokine up-regulation and improved the oxidative status of liver tissues. Furthermore, these effects were found to be mediated by the suppression of the transcriptional activity of nuclear factor-kappa B (NF-κB), due to inhibitions of transforming growth factor beta (TGF-β)-activated kinase (TAK)-1 phosphorylation and inhibition of kappa B (IκB)-α degradation. In addition, WGP inhibited the activations of mitogen-activated protein kinases (MAPKs). Wheatgrass-derived polysaccharide also attenuated hepatic cell death by modulating caspase-3 and apoptosis associated mitochondrial proteins, such as, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). Taken together, WGP possesses antiinflammatory, anti-oxidant and anti-apoptotic activity and ameliorates LPS-induced liver injury in mice. Copyright © 2017 John Wiley & Sons, Ltd.
  • Chemical Composition and Immuno-Modulatory Effects of Urtica dioica L.
           (Stinging Nettle) Extracts
    • Abstract: The purpose of this work was to determine the chemical profile of stinging nettle and to provide an insight into the mechanisms by which it ameliorates the immune response. Qualitative and quantitative liquid chromatography tandem mass spectrometry analyses indicated that phenolic acids (5-O-caffeoylquinic acid as dominant) and flavonol glycosides (rutin, isoquercitrin, and kaempferol 3-O-glucoside) are present in the aerial parts, while lignans (secoisolariciresinol, 9,9′-bisacetyl-neo-olivil and their glucosides) were detected in the root. Herb and root extracts expressed selective inhibition toward cyclooxygenase and lipoxygenase branches in human platelets: root extracts were better at inhibiting thromboxane production, while herb extracts were more specific toward inhibition of 12-lipoxygenase pathway. Stinging nettle extracts mildly increased monocyte chemoattractant protein-1 and growth-related oncogene release from nonstimulated intestinal epithelial cells, stimulating MyD88/NF-κB/p38 signaling, hence preserving the epithelial integrity and enhancing intestinal steady-state defense. Additionally, root extract reduced lipopolysaccharide-induced monocyte chemoattractant protein-1/growth-related oncogene secretion and cyclooxygenase-2 expression in intestinal epithelial cells, thus showing the potential protective effect against tissue damage caused by inflammation processes. These observations suggest that stinging nettle is an interesting candidate for the development of phytopharmaceuticals or dietary supplements for cotreatment of various inflammatory diseases, particularly inflammatory bowel diseases. Copyright © 2017 John Wiley & Sons, Ltd.
  • Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib
           through Abrogation of CREB and c-Jun Activation in Renal Cell Carcinoma
    • Abstract: Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase-3; caused poly(ADP-ribose) polymerase cleavage; abrogated the expression of B-cell lymphoma 2, B-cell lymphoma extra large, survivin, inhibitors of apoptosis proteins-1/2, cyclooxygenase-2, cyclin D1, matrix metallopeptidase-9, and vascular endothelial growth factor; and upregulated pro-apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element-binding protein and c-Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.
  • Supplementation with Herbal Extracts to Promote Behavioral and
           Neuroprotective Effects in Experimental Models of Parkinson's Disease: A
           Systematic Review
    • Abstract: Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti-apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antifungal Activity of Gallic Acid In Vitro and In Vivo
    • Abstract: Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.
  • One Plant, Many Uses: A Review of the Pharmacological Applications of
           Morinda citrifolia
    • Abstract: Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.
  • Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly
           Through Regulation of the TLR4/MAPK/NF-κB Axis via AMPK Activation
    • Abstract: Acute lung injury (ALI) often leads to high mortality, and there is as yet no effective drug treatment. The present study aimed to investigate protective effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1, 10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose-dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1β, IL-6, TNF-α and HMGB1) release and higher MPO activity in lung tissues induced by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not only increased the phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also inhibited the activation of MAPKs and nuclear factor κB (NF-κB) signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down-regulating TLR4/MAPK/NF-κB signalling pathways. Copyright © 2017 John Wiley & Sons, Ltd.
  • Phytochemistry and Pharmacology of Phyllanthus niruri L.: A Review
    • Abstract: Phyllanthus niruri, a typical member of family Euphorbiaceae, is a small annual herb found throughout the tropical and subtropical regions of both hemispheres. The genus Phyllanthus has been used in traditional medicine for its wide range of pharmacological activities like antimicrobial, antioxidant, anticancer, antiinflammatory, antiplasmodial, antiviral, diuretic and hepatoprotective. This review summarizes the information about morphological, biochemical, ethanobotanical, pharmacological, biological and toxicological activities with special emphasis on mechanism of anticancer activity of P. niruri. Gaps in previous studies such as taxonomic inconsistency of P. niruri, novel phytochemicals and their therapeutic properties, especially mechanisms of anticancerous activity and market products available, have been looked into and addressed. Scientific information related to 83 phytochemicals (including many novel compounds detected recently by the authors) has been provided in a very comprehensive manner. Copyright © 2017 John Wiley & Sons, Ltd.
  • Glycyrrhetinic Acid Accelerates the Clearance of Triptolide through P-gp
           In Vitro
    • Abstract: Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process. An ultra performance liquid chromatography–electrospray ionization–mass spectrometry (UPLC-ESI-MS) analytical method was established to determine the intracellular concentration of TP. In order to study the role of efflux transporters of P-gp and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results showed that GA could enhance the elimination of TP and reduce the TP accumulation in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration of TP; in addition, GA co-incubation with verapamil significantly increased the TP cellular concentration compared with the control group. In conclusion, GA could reduce the accumulation of TP in HK-2 cells, which was related to P-gp. This is probably one of the mechanisms that TP combined with GA to detoxify its toxicity. Copyright © 2017 John Wiley & Sons, Ltd.
  • Inhibition of Prion Propagation by 3,4-Dimethoxycinnamic Acid
    • Abstract: Neurodegenerative diseases are associated with accumulation of amyloid-type protein misfolding products. Prion protein (PrP) is known for its ability to aggregate into soluble oligomers that in turn associate into amyloid fibrils. Preventing the formation of these infective and neurotoxic entities represents a viable strategy to control prion diseases. Numerous attempts to find dietary compounds with anti-prion properties have been made; however, the most promising agent found so far was curcumin, which is poorly soluble and merely bioavailable. In the present work, we identify 3,4-dimethoxycinnamic acid (DMCA) which is a bioavailable coffee component as a perspective anti-prion compound. 3,4-Dimethoxycinnamic acid was found to bind potently to prion protein with a Kd of 405 nM. An in vitro study of DMCA effect on PrP oligomerization and fibrillization was undertaken using isothermal titration calorimetry (ITC), dynamic light scattering (DLS) and circular dichroism (CD) methodologies. We demonstrated that DMCA affects PrP oligomer formation reducing the oligomer content by 30–40%, and enhancing SH-SY5Y cell viability treated with prion oligomers. Molecular docking studies allowed to suggest a site where DMCA is able to bind stabilizing PrP tertiary structure. We suggest that DMCA is a perspective dietary compound for prophylaxis of neurodegenerative diseases that needs further research. Copyright © 2017 John Wiley & Sons, Ltd.
  • Evaluation of Benefit and Tolerability of IQP-CL-101 (Xanthofen) in the
           Symptomatic Improvement of Irritable Bowel Syndrome: A Double-Blinded,
           Randomised, Placebo-Controlled Clinical Trial
    • Abstract: Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown aetiology. There is currently no known cure, and pharmacological interventions are usually targeting symptomatic relief, where natural and herbal remedies also play a role. This study aimed to evaluate the benefit and tolerability of IQP-CL-101 in symptomatic IBS relief. A double-blinded, randomised, placebo-controlled trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME-III criteria for IBS were randomised into two groups, given either two IQP-CL-101 softgels or matching placebo twice daily before main meals. The primary endpoint was the difference in change of IBS Symptom Severity Score (IBS-SSS) after an 8-week intake of IQP-CL-101 compared to placebo. After 8 weeks, subjects on IQP-CL-101 showed a significant reduction in IBS-SSS (113.0 ± 64.9-point reduction) compared to subjects on placebo (38.7 ± 64.5-point reduction) (p 
  • Neuroprotective Natural Products for the Treatment of Parkinson's Disease
           by Targeting the Autophagy–Lysosome Pathway: A Systematic Review
    • Abstract: The autophagy–lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.
  • Nepetoidin B, a Natural Product, Inhibits LPS-stimulated Nitric Oxide
           Production via Modulation of iNOS Mediated by NF-κB/MKP-5 Pathways
    • Abstract: Previous reports showed that nepetoidin B (NTB), a natural product isolated from many herbs, has anti-fungal and anti-bacterial effects. In this study, the antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was determined by MTT assay. The nitric oxide (NO) production was detected by Griess assay. The TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay kits. Protein expressions were tested by western blotting. The transcription activity of inducible nitric oxide synthase (iNOS) was detected by luciferase assay. Immunofluorescence assay was used to observe the visualization of NF-κB/p65 nuclear translocation. NTB and LPS showed no obvious cytotoxic effect on RAW 264.7 cells. NTB remarkably inhibited LPS-induced NO and TNF-α secretion in a concentration-dependent manner while showed no significant effect on IL-6 secretion. NTB inhibited LPS-induced iNOS protein expression and transcription activity without affecting cyclooxygenase-2. Furthermore, NTB suppressed LPS-stimulated NF-κB/p65 phosphorylation and nuclear translocation. In addition, NTB significantly inhibited LPS-induced phosphorylation of JNK1/2 and p38MAPK without affecting ERK1/2. LPS-induced inhibition of mitogen-activated protein kinase phosphatase-5 (MKP-5) was completely reversed by NTB. In conclusion, these results suggested that NTB inhibited LPS-stimulated NO production possibly via modulation of iNOS mediated by MKP-5/NF-κB pathways in RAW 264.7 cells. Copyright © 2017 John Wiley & Sons, Ltd.
  • Polyphenols and Their Role in Obesity Management: A Systematic Review of
           Randomized Clinical Trials
    • Abstract: Polyphenols have been suggested to reduce body weight and modify body composition through different mechanisms. These effects have been extensively studied in animals and in vitro and to a lesser extent in humans. The aim of this review is to consider the association between polyphenols and body weight status by focusing on human intervention studies. We conducted a systematic literature search in MEDLINE (via EBSCOhost), ProQuest CENTRAL, and Cochrane CENTRAL without time restrictions. Randomized controlled trials assessing the effect of polyphenols on weight and/or body composition in the overweight and/or obese population were included. Nineteen studies met our inclusion criteria. Results suggest that further research is required before supporting a potential role of polyphenols in reducing weight in overweight and obese individuals (nine studies showed a significant decrease in weight by a mean of 1.47 ± 0.58 kg). Nevertheless, several studies indicated that polyphenols might be effective in preventing small increases in weight during periods of overfeeding rather than reducing weight as such. The outcomes noted do not yet support polyphenol supplementation as a complementary approach in weight loss diets. Further larger trials with a duration of 12 months or more are needed to elucidate the effect of polyphenols on body weight status. Copyright © 2017 John Wiley & Sons, Ltd.
  • Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the
           Trigeminovascular System
    • Abstract: Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus. As a result, baicalin administration (0.22 mm/kg) alleviated pain responses of migraine rats. It profoundly decreased NO and calcitonin gene-related peptide levels, increased ET levels, and rebuilt the NO/ET balance in migraine rats. Besides, baicalin pretreatment significantly reduced the number, the stained area size, and integrated optical density value of C-fos positive cells. In brief, this paper supports the possibility of baicalin as a potential migraine pharmacotherapy. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf
           Extract. Part I – Preclinical Studies
    • Abstract: One of the Brazilians medicinal plants most cited in ethnopharmacological surveys for the treatment of ulcers and gastric diseases was evaluated for its efficacy and toxicity. Maytenus ilicifolia leaf extract (MIE) was acutely and chronically (180 days) administered to rats, mice, and dogs. Acute tests were antiulcer effect and toxicological trials (observational pharmacological screening, LD50, motor coordination, sleeping time and motor activity). Chronic tests were the following: weight gain/loss and behavioral parameters in rats and mice; estrus cycle, effects on fertility, and teratogenic studies in rats and mutagenic features in mice, in addition to the Ames and micronucleus test. The following parameters were assessed in dogs: weight gain/loss, general physical conditions, water/food consumption, and anatomopathological examination of the organs subsequent to the 180-day treatment. The results showed a clear antiulcer activity for MIE from 70 mg/kg and an absence of toxicological effects in the three animal species, even if given in high doses or over a long period. The present results confirm the antiulcer property and absence of toxicological effects in three animal species of MIE, which is in line with its current popular medicinal use. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf
           Extract Part II—Clinical Study (Phase I)
    • Abstract: Maytenus ilicifolia is a plant widely used in South American folk medicine as an effective anti-dyspeptic agent, and the aim of this study was to evaluate their clinical and toxicological effects in healthy volunteers in order to establish its maximum safe dose. We selected 24 volunteers (12 women and 12 men) between 20 and 40 years of age and put them through clinical/laboratory screening and testing to ascertain their psychomotor functions (simple visual reaction, speed and accuracy, finger tapping tests). M. ilicifolia tablets were administered in increasing weekly dosages, from an initial dose of 100 mg to a final dose of 2000 mg. The volunteers' clinical and biochemical profiles and psychomotor functions were evaluated weekly, and they also completed a questionnaire about any adverse reactions. All subjects completed the study without significant changes in the evaluated parameters. The most cited adverse reactions were xerostomia (dry mouth syndrome) (16.7%) and polyuria (20.8%), with reversal of these symptoms without any intervention during the study. The clinical Phase I study showed that the administration of up to 2000 mg of the extract was well tolerated, with few changes in biochemical, hematological or psychomotor function parameters, and no significant adverse reactions. Copyright © 2017 John Wiley & Sons, Ltd.
  • C-Glycosyl Flavonoids from Beta vulgaris Cicla and Betalains from Beta
           vulgaris rubra: Antioxidant, Anticancer and Antiinflammatory
           Activities—A Review
    • Abstract: The green beet (Beta vulgaris var. cicla L.) and red beetroot (B. vulgaris var. rubra L.) contain phytochemicals that have beneficial effects on human health. Specifically, the green beet contains apigenin, vitexin, vitexin-2-O-xyloside and vitexin-2-O-rhamnoside, while the red beetroot is a source of betaxanthins and betacyanins. These phytochemicals show considerable antioxidant activity, as well as antiinflammatory and antiproliferative activities. Vitexin-2-O-xyloside, in combination with betaxanthins and betacyanins, exerts antiproliferative activity in breast, liver, colon and bladder cancer cell lines, through the induction of both intrinsic and extrinsic apoptotic pathways. A significant body of evidence also points to the role of these phytochemicals in the downregulation of the pro-survival genes, baculoviral inhibitor of apoptosis repeat-containing 5 and catenin beta-1, as well as the genes controlling angiogenesis, hypoxia inducible factor 1A and vascular endothelial growth factor A. The multi-target action of these phytochemicals enhances their anticancer activity. Vitexin-2-O-xyloside, betaxanthins and betacyanins can be used in combination with conventional anticancer drugs to reduce their toxicity and overcome the multidrug resistance of cancer cells. In this review, we describe the molecular mechanisms that enable these dietary phytochemicals to block the proliferation of tumor cells and inhibit their pro-survival pathways. Copyright © 2017 John Wiley & Sons, Ltd.
  • Optimization of Aqueous Extraction and Biological Activity of
           Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model
    • Abstract: Harpagophytum procumbens has a long story of use for the treatment of inflammatory diseases. Considering both the antiinflammatory effects of H. procumbens in multiple tissues and the stability of harpagoside in artificial intestinal fluid, the aim of the present study was to explore the possible protective role of a microwave-assisted aqueous Harpagophytum extract (1–1000 μg/mL) on mouse myoblast C2C12 and human colorectal adenocarcinoma HCT116 cell lines, and isolated rat colon specimens challenged with lipopolysaccharide (LPS), a validated ex vivo model of acute ulcerative colitis. In this context, we evaluated the effects on C2C12 and HCT116 viability, and on LPS-induced production of serotonin (5-HT), tumor necrosis factor (TNF)-α, prostaglandin (PG)E2 and 8-iso-prostaglandin (8-iso-PG)F2α. Harpagophytum extract was well tolerated by C2C12 cells, while reduced HCT116 colon cancer cell viability. On the other hand, Harpagophytum extract reduced H2O2-induced (1 mM) reactive oxygen species (ROS) production, in both cell lines, and inhibited LPS-induced colon production of PGE2, 8-iso-PGF2α, 5-HT and TNFα. Concluding, we demonstrated the efficacy of a microwave-assisted Harpagophytum aqueous extract in modulating the inflammatory, oxidative stress and immune response in an experimental model of inflammatory bowel diseases (IBD), thus suggesting a rational use of Harpagophytum in the management and prevention of ulcerative colitis in humans. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antiinflammatory Activity of Cinnamon (Cinnamomum zeylanicum) Bark
           Essential Oil in a Human Skin Disease Model
    • Abstract: The effect of cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) on human skin cells has not been elucidated. Therefore, we investigated the activity of a commercially available CBEO in a validated human dermal fibroblast system, a model of chronic inflammation and fibrosis. We first evaluated the impact of CBEO on 17 protein biomarkers that play critical roles in inflammation and tissue remodeling. The impact of CBEO on genome-wide gene expression was also evaluated. CBEO showed strong anti-proliferative effects on skin cells and significantly inhibited the production of several inflammatory biomarkers, including vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interferon gamma-induced protein 10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by gamma interferon. In addition, CBEO significantly inhibited the production of several tissue remodeling molecules, including epidermal growth factor receptor, matrix metalloproteinase-1, and plasminogen activator inhibitor-1. Macrophage colony-stimulating factor, which is an immunomodulatory protein molecule, was also significantly inhibited by CBEO. Furthermore, CBEO significantly modulated global gene expression and altered signaling pathways, many of which are important in inflammation, tissue remodeling, and cancer biology. The study shows that CBEO is a promising antiinflammatory agent; however, further research is required to clarify its clinical efficacy. © 2017 The
      Authors . Phytotherapy Research published by John Wiley & Sons Ltd.
  • Aloe-emodin Induces Apoptosis in Human Liver HL-7702 Cells through Fas
           Death Pathway and the Mitochondrial Pathway by Generating Reactive Oxygen
    • Abstract: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe-emodin on human normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin decreased the viability of HL-7702 cells in a dose-dependent and time-dependent manner. Aloe-emodin induced S and G2/M phase cell cycle arrest in HL-7702 cells. This apoptosis was further investigated by flow cytometry and nuclear morphological changes by DAPI staining, respectively. Moreover, aloe-emodin provoked the production of intracellular reactive oxygen species and the depolarization of mitochondrial membrane potential (MMP). Further studies by western blot indicated that aloe-emodin dose-dependently up-regulated the levels of Fas, p53, p21, Bax/Bcl-2 ratio, and cleaved caspase-3, -8, -9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). Taken together, these results suggest that aloe-emodin inhibits cell proliferation of HL-7702 cells and induces cell cycle arrest and caspase-dependent apoptosis via both Fas death pathway and the mitochondrial pathway by generating reactive oxygen species, indicating that aloe-emodin should be taken into account in the risk assessment for human exposure. Copyright © 2017 John Wiley & Sons, Ltd.
  • The effects of chosen plant extracts and compounds on mesenchymal stem
           cells—a bridge between molecular nutrition and regenerative medicine-
           concise review
    • Abstract: Mesenchymal stem cells (MSC) stand as a promising tool in regenerative medicine because of their high therapeutic potential in treatment of degenerative, metabolic and other types of diseases. The cellular therapies involving MSCs include their isolation mainly from the bone marrow, adipose tissue or umbilical cord and in vitro expansion for further autologous or allogeneic transplantation. Recent studies revealed, that bioactive compounds, naturally occurring in seaweeds, herbs, fruits and vegetables, possess the ability to modulate self-renewal and differentiation potential of adult stem cells, targeting a broad range of intracellular signal transduction pathways. Number of ongoing trials aim to find a herbal extract that may become less toxic and affordable natural therapeutic. Mesenchymal stem cells are treated with crude extracts or individual compounds to investigate its effects and mechanism on stem cells proliferation and differentiation. Deeply investigated, herbal extract which increases tissue regeneration and promotes stem cell growth may be successfully applied in the field of biomaterials. Promoting the endogenous stem cell multipotency and their differentiation potential may additionally support the regenerative processes after MSCs transplantation. The review focuses on the beneficial effects of chosen plant derived substances on MSCs proliferative activity and their osteogenic differentiation potential. Copyright © 2017 John Wiley & Sons, Ltd.
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