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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  [1579 journals]
  • Acute cardiovascular effects of bitter orange extract (p‐synephrine)
           consumed alone and in combination with caffeine in human subjects: A
           placebo‐controlled, double‐blind study
    • Abstract: The purpose was to examine cardiovascular responses to supplementation with p‐synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects were given (in double‐blind manner) either 103 mg of p‐synephrine (S), 233 mg of caffeine +104 mg of p‐synephrine (LC + S), 240 mg of caffeine (LC), 337 mg of caffeine +46 mg of p‐synephrine (HC + S), 325 mg of caffeine (HC), or a placebo. The subjects sat quietly for 3 hr while heart rate (HR) and blood pressure were measured. Only HC + S and HC significantly increased mean systolic blood pressure (SBP) during the second hour and tended to increase mean SBP during the third hour. Mean diastolic blood pressure in S was significantly lower than the other trials during the first and second hours, and mean arterial pressure was significantly lower in S compared to the LC, LC + S, HC, and HC + S trials. No differences were observed in HR. Consumption of p‐synephrine may acutely reduce diastolic blood pressure and mean arterial pressure and not affect SBP or HR during quiet sitting. The addition of p‐synephrine to caffeine did not augment SBP or HR indicating that consumption of up to 104 mg of p‐synephrine does not induce cardiovascular stress during quiet sitting.
  • Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal
           applications, animal models, and possible mechanism of actions
    • Abstract: Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol‐induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta‐1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.
  • Pharmacological and chemical features of Nepeta L. genus: Its importance
           as a therapeutic agent
    • Abstract: Medicinal plants have always had great value for the human population due to their valuable constituents and potential bioactivities. The objective of this review is to present an updated overview of an important medicinal plant genus Nepeta L., from the family Lamiaceae, revealing its traditional utilization, biological activity, phytoconstituents, and mechanisms of action. For this purpose, a literature survey was carried out by using SciFinder, ScienceDirect, Scopus, PubMed, and Web of Science followed by a revision of the bibliographies of the related articles. We have described and analyzed the role of plants in drug discovery and the importance of Nepeta species. Information on the utilization purposes of Nepeta species in folk medicine has been emphasized, and scientific studies on the biological effects and secondary metabolites are addressed. Nepeta species are characterized by terpenoid‐type compounds and phenolic constituents, which exert several activities such as an antimicrobial, repellent against major pathogen vector mosquitoes, insecticide, larvicide against Anopheles stephensi, cytotoxic anticarcinogen, antioxidant, anticonvulsant, analgesic, anti‐inflammatory agent, and antidepressant, revealing its importance in medicinal and agricultural fields. On the basis of numerous studies, the Nepeta genus demonstrates remarkable therapeutic effects against various diseases. However, clinical studies are warranted to confirm preclinical findings.
  • Effects of Rubiadin isolated from Prismatomeris connata on
           anti‐hepatitis B virus activity in vitro
    • Abstract: Prismatomeris connata was a kind of Rubiaceae plant for treatment of hepatitis, hepatic fibrosis and silicosis. Whereas, the effective components of Prismatomeris connata remains unexplored. The aim of this study was to investigate the inhibitory effects and mechanisms of Rubiadin isolated from Prismatomeris connata against HBV using HepG2.2.15 cells. The levels of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg) in the supernatants or cytoplasm were examined using by enzyme‐linked immunosorbent assay. HBV DNA was qualified q‐PCR. Rubiadin was isolated by silica gel column. The structure of the compound was elucidated by HPLC, FT‐IR, 1H‐NMR, 13C‐NMR and identified as 1,3‐Dihydroxy‐2‐methyl‐9, 10‐anthraquinone. Rubiadin significantly decreased HBeAg,HBcAg secretion level and inhibit HBV DNA replication. Rubiadin inhibits the proliferation of the cells and HBx protein expression in a dose‐dependent manner. The intracellular calcium concentration was significantly reduced. These results demonstrated that Rubiadin could inhibit HepG2.2.15 cells proliferation, reduce the level of HBx expression, and intracellular free calcium, which might become a novel anti‐HBV drug candidate.
  • Epoxyazadiradione Purified from the Azadirachta indica Seed Induced
           Mitochondrial Apoptosis and Inhibition of NFκB Nuclear Translocation in
           Human Cervical Cancer Cells
    • Abstract: Epoxyazadiradione (EAD) is an important limonoid present in Neem (Azadirachta indica) plant. In the present study, we have purified EAD from Neem seed and studied its anticancer potential in human cervical cancer (HeLa) cells. Cell proliferation inhibition studies indicated that the GI50 value of EAD is 7.5 ± 0.0092 μM in HeLa cells, whereas up to 50 μM concentrations EAD did not affect the growth of normal H9C2 cells. The control drug cisplatin inhibited the growth of both HeLa and H9C2 cells with a GI50 value of 2.92 ± 1.192 and 4.22 ± 1.568 μM, respectively. Nuclear DNA fragmentation, cell membrane blebbing, phosphatidylserine translocation, upregulation of Bax, caspase 3 activity and poly (ADP ribose) polymerase cleavage and downregulation of BCl2 in HeLa cells on treatment with EAD indicated the apoptotic cell death. Increase in caspase 9 activity and release of active cytochrome c to the cytoplasm on treatment with EAD confirmed that the apoptosis was mediated through the mitochondrial pathway. Epoxyazadiradione also inhibited the nuclear translocation of nuclear factor κB in HeLa cells. Thus, our studies demonstrated EAD as a potent and safe chemotherapeutic agent when compared with the standard drug cisplatin that is toxic to both cancer and normal cells equally. Copyright © 2017 John Wiley & Sons, Ltd.
  • A comparative study on the effect of promoting the osteogenic function of
           osteoblasts using isoflavones from Radix Astragalus
    • Abstract: Radix Astragalus has been shown to exert beneficial effects regarding the prevention postmenopausal osteoporosis. However, its mechanism of action remains to be investigated. Calycosin, formononetin, and calycosin‐7‐O‐β‐d‐glucoside are the main isoflavone constituents of Astragalus. In this study, the abilities of these 3 compounds to promote osteogenic function of osteoblasts were compared, and the structure–activity relationships of these osteotrophic isoflavones were determined. Calycosin exhibited a greater effect than formononetin and calycosin‐7‐O‐β‐d‐glucoside regarding improvements in osteogenic function of osteoblasts, as demonstrated by cell proliferation, alkaline phosphatase activity, collagen I and osteocalcin secretion, and the number and area of mineralized bone nodules. This suggests that calycosin may be better than formononetin and calycosin‐7‐O‐β‐d‐glucoside at preserving bone mass. In addition, calycosin, formononetin, and calycosin‐7‐O‐β‐d‐glucoside stimulate the expression of bone morphogenetic protein 2 and runt‐related transcription factor 2 proteins, which indicates that all 3 agents may promote the osteogenesis of osteoblasts via regulation of bone morphogenetic protein 2 expression. In conclusion, calycosin may be the best candidate, with higher osteogenic activity than formononetin and calycosin‐7‐O‐β‐d‐glucoside. The higher osteogenic activity of calycosin could be attributable to the superiority of its chemical structure (a hydroxyl group at position C3 of Ring B and no glucosyl group).
  • Chelidonine inhibits TNF‐α‐induced inflammation by suppressing the
           NF‐κB pathways in HCT116 cells
    • Abstract: Nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) is a complex that regulates several hundreds of genes, including those involved in immunity and inflammation, survival, proliferation, and the negative feedback of NF‐κB signaling. Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits antiinflammatory pharmacological properties. However, its antiinflammatory molecular mechanisms remain unclear. In this work, we explored the effect of chelidonine on TNF‐induced NF‐κB activation in HCT116 cells. We found chelidonine inhibited the phosphorylation and degradation of the inhibitor of NF‐κB alpha and nuclear translocation of RELA. Furthermore, by inhibiting the activation of NF‐κB, chelidonine downregulated target genes involved in inflammation, proliferation, and apoptosis. Chelidonine also inhibited mitogen‐activated protein kinase pathway activation by blocking c‐Jun N‐terminal kinase and p38 phosphorylation. These results suggest that chelidonine may be a potential therapeutic agent against inflammatory diseases in which inhibition of NF‐κB activity plays an important role.
  • Natural medicines for acute renal failure: A review
    • Abstract: Acute renal failure (ARF) is a life‐threating disease with high mortality percentage. Two important mechanisms of ARF are inflammation and oxidative stress. Plants are rich source of antioxidant compounds and have a strong anti‐inflammatory activity, so they may be useful for the treatment of ARF. Some herbal medicines are effective against different models of experimentally induced ARF such as cisplatin, gentamicin, glycerol, and ischemia–reperfusion injury. Some of these plants such as ginseng, black seed, ginger, garlic, grape, pomegranate, saffron, and green tea are so famous and are effective against various models of ARF. However, we found several articles examining the effectiveness of different plants for treating ARF. In the current article, we discussed plants and natural products that are effective in the treatment of ARF.
  • Current Status of Herbal Drug Standards in the Indian Pharmacopoeia
    • Abstract: The benefits of herbal drugs were well understood way back. They have been used for the promotion of health and medical purposes – in disease conditions. It is a conventional belief that herbal drugs have no side effects, are cheaper and locally available. Among Indian systems of medicines, herbs/herbal formulations are used to a larger extent. The quality control of the marketed herbs/herbal formulations is important for acquiring optimum therapeutic benefit as well as for expanding global outreach. Therefore, herbal drug standards are important. Reference standards, the Indian Pharmacopoeia Reference Substances especially the botanical reference substances and the phytochemical reference substances are required for comparison of quality of herbal drugs. The Indian Pharmacopoeia Commission has initiated the process of providing Indian Pharmacopoeia Reference Substances to the stakeholders. Therefore, this article provides an overview of the history and the status of herbal drug standards in the current and forthcoming issues of Indian Pharmacopoeia. In Indian Pharmacopeia, efforts have been made for the harmonization of standards with international counterparts wherever possible. Copyright © 2017 John Wiley & Sons, Ltd.
  • Natural Compound Licochalcone B Induced Extrinsic and Intrinsic Apoptosis
           in Human Skin Melanoma (A375) and Squamous Cell Carcinoma (A431) Cells
    • Abstract: Licochalcone B (Lico B), which is normally isolated from the roots of Glycyrrhiza inflata (Chinese Licorice), generally classified into organic compounds including retrochalcones. Potential pharmacological properties of Lico B include anti‐inflammatory, anti‐bacterial, anti‐oxidant, and anti‐cancer activities. However, its biological effects on melanoma and squamous cell carcinoma (SCC) are unknown. Based on these known facts, this study investigated the role of Lico B in apoptosis, through the extrinsic and intrinsic pathways and additional regulation of specificity protein 1 in human skin cancer cell lines. Annexin V/7‐aminoactinomycin D staining, western blot analysis, mitochondrial membrane potential assay, and an anchorage‐independent cell transformation assay demonstrated that Lico B treatment of human melanoma and SCC cells significantly inhibited cell proliferation and induced apoptotic cell death. More specifically, Lico B induced apoptosis through the regulation of specificity protein 1 and apoptosis‐related proteins including CCAAT/enhancer‐binding protein homologous protein, death receptors, and poly (ADP‐ribose) polymerase. These results indicate that Lico B has apoptotic effect on A375 and A431 skin cancer cells, suggesting the potential value of Lico B for the treatment of human melanoma and SCC. Copyright © 2017 John Wiley & Sons, Ltd.
  • Comparative Oral Absorption of Curcumin in a Natural Turmeric Matrix with
           Two Other Curcumin Formulations: An Open‐label Parallel‐arm Study
    • Abstract: Curcuminoids are the major bioactive molecules in turmeric, and poor bioavailability deters them from being the major components of many health and wellness applications. This study was conducted to assess the bioavailability of a completely natural turmeric matrix formulation (CNTMF) and compare its bioavailability with two other commercially available formulations, namely, curcumin with volatile oil (volatile oil formulation) and curcumin with phospholipids and cellulose (phospholipid formulation) in healthy human adult male subjects (15 each group) under fasting conditions. Each formulation was administrated orally as a single 500‐mg dose in capsule form, and blood samples were analyzed by liquid chromatography mass spectrometry at various time intervals up to 24 h. The ingestion of the CNTMF was very well absorbed and resulted in a mean curcuminoids plasma Cmax of 170.14 ng/mL (Tmax = 4 h) compared with 47.54 ng/mL and 69.63 ng/mL for the volatile oil (Tmax = 3 h) and phospholipid (Tmax = 2.25 h) formulations, respectively. The extent of absorption of total curcuminoids in the blood for the CNTMF was 6× greater than volatile oil formulation and 5× greater than phospholipids formulation. The results of this study indicate that curcumin in a natural turmeric matrix exhibited greater bioavailability than the two comparator products. Copyright © 2017 John Wiley & Sons, Ltd.
  • The yerba mate intake has a neutral effect on bone: A case–control study
           in postmenopausal women
    • Abstract: Nutritional factors have been associated with osteoporosis and fractures. The intake of coffee may increase the risk of fracture whereas the intake of black and green tea is associated with its reduction. Recently, consumption of yerba mate was associated with increased bone mineral density in postmenopausal women. Nonetheless, its influence on fracture is not known. The aim of this study was to evaluate the effect of yerba mate tea intake on fractures, bone markers, calcium homeostasis, and oxidative stress in postmenopausal women. A case–control study was carried out in South Brazil, 46 women with fractures and 49 controls completed the study. There was no significant difference between the frequency of fractures in women who drank mate tea and women who did not (48.3% vs. 48.5%, p = .99). Moreover, there was no significant difference concerning the serum levels of total calcium, phosphorus, PTH, vitamin D, P1NP, and CTX in the subjects with the history of yerba mate use when compared to controls. Higher serum levels of NOx were found in women who drank the yerba mate infusion. In conclusion, the yerba mate intake is not associated with fracture, and it appears to have a neutral effect on the bone metabolism.
  • Protective effect of cinnamic acid in endotoxin‐poisoned mice
    • Abstract: In this work, we aimed to evaluate the protective effect of cinnamic acid (CD) on lipopolysaccharide (LPS; Escherichia coli 055:B5)‐induced endotoxin‐poisoned mice and clarify the underlying mechanisms. The mice were administrated CD 5 d before 15 mg/kg LPS challenge. 12 hr later, thymus was separated for determination of thymus indexes. Lung and spleen tissues were collected for histologic examination and the wet/dry weight ratio of lung was calculated, and serum was acquired for tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐18, and IL‐1β measurement. Moreover, the expression of NOD‐like receptor (NLR) family, pyrin domain‐containing 3 (NLRP3) inflammasome was determined in lung. CD increased the thymus indexes and decreased lung wet/dry weight ratio. In addition, CD improved the lung and spleen histopathological changes induced by LPS and decreased the number of neutrophils in lung tissues. CD also inhibited the pro‐inflammatory cytokines (TNF‐α, IL‐18, and IL‐1β) production in serum. Furthermore, CD suppressed the LPS‐induced NLRP3, Caspase‐1, and IL‐1β mRNA expression in lung, as well as the expression of NLRP3 and Caspase‐1 (p20) protein. CD may have protective effects in endotoxin‐poisoned mice via inhibiting the activation of NLRP3 inflammasome, and can be considered as a potential therapeutic candidate for diseases involved in endotoxin poisoning such as sepsis.
  • The effect of Rosa (L. Rosa canina) on the incidence of urinary tract
           infection in the puerperium: A randomized placebo‐controlled trial
    • Abstract: Urinary tract infection (UTI) is an infection that can occur in any area of the urinary tract which is characterized by a positive urine culture (U/C). The risk of UTI following cesarean section (CS) increases due to procedures such as catheterization. In vitro studies have demonstrated the effect of Rosa canina fruit in preventing Escherichia coli growth. This study was conducted to determine the effect of R. canina fruit in preventing the incidence of UTI in women following CS. This triple‐blind randomized clinical trial was conducted in 2016 on 400 women following CS with negative U/C in Alzahra and Taleghani educational hospitals in the city of Tabriz‐Iran. Participants were assigned into two groups of 200 women using block randomization. Each group received a twice daily dose of 500 mg capsules containing R. canina or placebo from the second day after CS for 20 days. Women were assessed by U/C on the 7th–10th and 20th days following CS. UTI was significantly lower in the intervention group compared with the control in the follow‐ups conducted on the 7th–10th days (odds ratio = 0.22; confidence interval 95% [0.07, 0.67]; p = .006) and 20th day (odds ratio = 0.32; confidence interval 95% [0.14, 0.75]; p = .008). But the incidence of cystitis in the two groups was not statistically significant (p > .05). R. canina fruit capsules were able to reduce the incidence of UTI after CS. Thus, it is likely that administration of this medication can promote maternal health following CS.
  • Bio‐prospecting endemic Mascarene Aloes for potential
    • Abstract: The Mascarene Aloes are used in the traditional pharmacopoeia against various ailments including cutaneous diseases and as antispasmodics. Scientific evidence to support these claims is non‐existent and mainly based on the scientific repute of A. vera. The antioxidant profile of methanolic leaf extracts of A. purpurea Lam., A. tormentorii (Marais) L. E. Newton & G. D. Rowley, A. lomatophylloides Balf. f., A. macra Haw. and A. vera (L.) Burm. f. was studied using the total antioxidant capacity, copper equivalent and superoxide dismutase assays. In vitro cytotoxicity was evaluated on CAD (Cath.‐a‐differentiated) neuronal cells by the methyl tetrazolium assay, and the neuroprotective profile was assessed using hydrogen peroxide‐induced neurotoxicity with the CAD cells. The aloin and vitexin content were determined by high‐performance liquid chromatography with diode‐array detection. A. purpurea had the highest aloin content (546.6 nmol/g), while A. tormentorii had the highest vitexin content (67.3 nmol/g). A. macra (concentration
  • Safranal Inhibits HeLa Cell Viability by Perturbing the Reassembly
           Potential of Microtubules
    • Abstract: Saffron, a spice from Crocus sativus, has been known for its health benefits and medicinal properties. Safranal is a component of saffron and is known for its antioxidant and anticancer properties. In this study, we elucidated a possible tubulin‐targeted antiproliferative mechanism of action of safranal. In vitro, the compound perturbed secondary structure of tubulin without altering net microtubule polymer mass. It inhibited HeLa cell viability in a concentration‐dependent manner, with minimal damage to cellular microtubules. However, it strongly inhibited recovery of microtubule network after cold‐induced disassembly, indicating its ability to interfere with the nucleation potential of tubulin. Further, as the acetylation pattern of the safranal‐treated microtubules revealed, unlike many tubulin‐targeted agents, the compound did not appear to induce persistent stabilization of microtubules. Our data shows an unusual, tubulin‐targeted antiproliferative mechanism of safranal. Copyright © 2017 John Wiley & Sons, Ltd.
  • Dose–Response Effects of p‐Synephrine on Fat Oxidation Rate During
           Exercise of Increasing Intensity
    • Abstract: The aim of this investigation was to determine the effects different doses of p‐synephrine on maximal fat oxidation during exercise. Seventeen healthy subjects volunteered to participate in a double‐blind and randomised experimental design composed of four identical experimental trials. On four trials separated by 72 h, participants ingested a placebo or 1, 2 or 3 mg/kg of p‐synephrine. After resting for 60 min to allow substance absorption, participants performed an exercise test of increasing intensity on a cycle ergometer while gas exchange was measured continuously. None of the doses of p‐synephrine affected energy expenditure or heart rates during the test. The highest rate of fat oxidation with the placebo (0.35 ± 0.05 g/min) was reached at 38.0 ± 1.9% of VO2max. The ingestion of 1 mg/kg increased maximal fat oxidation to 0.47 ± 0.11 g/min (p = 0.01) but did not change the intensity at which it was obtained (42.0 ± 9.4% of VO2max). The ingestion of 2 and 3 mg/kg of p‐synephrine increased maximal fat oxidation to 0.55 ± 0.14 g/min (p 
  • Oxyresveratrol, a Stilbene Compound from Morus alba L. Twig Extract Active
           Against Trichophyton rubrum
    • Abstract: Morus alba L. (mulberry) twig is known to have an inhibitory effect on pathogens in traditional Chinese medicine. In the present study, the dermophytic fungus, Trichophyton rubrum, was used to evaluate the inhibitory effect of total M. alba twig extract and extracts obtained using solvents with different polarities by the method of 96‐well MTT colorimetry. The main active substance was isolated and identified by tracking its activity. In addition, the inhibitory effects of active extracts and a single active substance were investigated in combination with miconazole nitrate. Our data indicated that ethyl acetate extracts of mulberry twig (TEE) exhibited a desired inhibitory activity on T. rubrum with the minimum inhibitory concentration (MIC) of 1.000 mg/mL. With activity tracking, the main substance showing antimicrobial activity was oxyresveratrol (OXY), which was isolated from TEE. Its MIC for inhibiting the growth of T. rubrum was 0.500 mg/mL. The combined use of miconazole nitrate and OXY showed a synergistic inhibitory effect, as shown by a significant decrease in the MIC of both components. Based on the OXY content in TEE, the contribution rate of OXY to the inhibitory effect of TEE on T. rubrum was 80.52%, so it was determined to be the main antimicrobial substance in M. alba twig. Copyright © 2017 John Wiley & Sons, Ltd.
  • Effects of Vernonia cinerea Compounds on Drug‐metabolizing Cytochrome
           P450s in Human Liver Microsomes
    • Abstract: Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide‐type sesquiterpene lactones, have shown an inhibition effect on the nicotine‐metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC‐MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (Ki values in competitive mode of 1.93 ± 0.05 versus 3.39 ± 0.21 μM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC50 values of 12–23 and 15–41 μM, respectively. These hirsutinolides demonstrated time‐dependent inhibition, an indication of mechanism‐based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half‐lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright © 2017 John Wiley & Sons, Ltd.
  • Inhibitory Effect of Thymoquinone on Testosterone‐Induced Benign
           Prostatic Hyperplasia in Wistar Rats
    • Abstract: This study addresses the possible protective effects of thymoquinone (TQ) against the development of experimentally‐induced benign prostatic hyperplasia (BPH) in Wistar rats. Eighteen adult male rats were divided into three groups; the negative control group (n = 6) received vehicle, and two groups received subcutaneous testosterone injection (3 mg/kg). Animals receiving testosterone were randomized to untreated BPH group (n = 6) and BPH + TQ treated group (n = 6, 50 mg/kg orally for 14 days). Histological changes and the mRNA levels of transforming growth factor‐β1 (TGF‐β1) and vascular endothelial growth factor‐A (VEGF‐A) were analyzed. Additionally, dihydrotestosterone and interleukin‐6 (IL‐6) serum levels were determined. The presented research shows significant increases in prostate weight/body weight ratio, prostate epithelial thickness, serum IL‐6 and dihydrotestosterone levels, and the prostatic expressions of TGF‐β1 and VEGF‐A in the untreated BPH rats. Histological examination of the prostate tissues in the BPH rats showed an elevated level of proliferation in the stromal area and glandular epithelia with abundant intraluminal papillary folds. However, a reduction in prostate weight/body weight ratio, epithelial hyperplasia, serum IL‐6 levels, and the expressions of TGF‐β1 and VEGF‐A were observed in the BPH + TQ treated rats compared with the untreated BPH rats. The findings support TQ as a useful natural treatment for animal BPH model. Copyright © 2017 John Wiley & Sons, Ltd.
  • Incidence of Pyrrolizidine Alkaloids in Herbal Medicines from German
           Retail Markets: Risk Assessments and Implications to Consumers
    • Abstract: The occurrence of potentially toxic pyrrolizidine alkaloids (PAs) in herbal medicines (HMs) is currently intensely being discussed in Europe. Pyrrolizidine alkaloids, particularly the 1,2‐unsaturated PAs, are undesired compounds in HMs due to their potential hepatotoxic and carcinogenic properties. In this study, 98 widely patronized HMs from six popular German retail supermarkets/drugstores, as well as from pharmacies, were analyzed by high‐performance liquid chromatography–electrospray ionization–tandem mass spectrometry for the presence of PAs. The results showed that about 63% of the HMs were PA positive, whereas the average PA concentration of the samples was 201 μg/kg, the highest concentration of PAs (3270 μg/kg) was attributed to a product that was purchased from the pharmacy and contained Hypericum perforatum L. (St. John's Wort) as an active ingredient. In addition, H. perforatum‐containing products were frequently contaminated with PAs from Echium spp., while both Cynara cardunculus L. products and fixed‐combination products of Gentiana lutea L., Rumex acetosa L., Verbena officinalis L., Sambucus nigra L., and Primula veris L. products were commonly contaminated with PAs of Senecio spp. The study showed that H. perforatum, C. cardunculus, Urtica dioica L., and fixed‐combination products were frequently contaminated with PA levels above the recommended values of both the German and European Medicines Agencies. Copyright © 2017 John Wiley & Sons, Ltd.
  • Aqueous Extracts of Wild Mushrooms Show Antimicrobial and Antiadhesion
           Activities against Bacteria and Fungi
    • Abstract: Mushrooms represent promising sources of novel bioactive compounds and can be applied as innovative strategies to control microbial contamination and infection via the food chain. We characterized aqueous extracts from 21 wild basidiomycete mushrooms and the cultivated oyster mushroom, Pleurotus ostreatus, as putative sources of antimicrobial and antiadhesive compounds. Broth microdilutions and adhesion to a polystyrene surface were evaluated on Gram‐positive and Gram‐negative bacteria and on fungi. The aqueous extracts tested showed antimicrobial and antiadhesive activities against these microorganisms. Biochemical analyses of the P. ostreatus extract indicated the involvement of several compounds with different molecular masses. Copyright © 2017 John Wiley & Sons, Ltd.
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  • Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake
           by Brain Microvascular Endothelial Cells
    • Abstract: We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound 3H‐propranolol and 14C‐warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1–1000 μM) increased the free fraction (fu) of both albumin and alpha‐acid glycoprotein bound drugs in a concentration‐dependent manner (p 
  • Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated
           into a Lipid‐Based Solid Dispersion to Improve Rat Sperm Count
    • Abstract: Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)‐Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P‐glycoprotein (P‐gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid‐based solid dispersion (TAF2‐SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2‐SD‐treated rats showed significantly twofold (p 
  • A Critical Review on Phytochemistry, Pharmacology of Viola odorata L. and
           Related Multipotential Products in Traditional Persian Medicine
    • Abstract: Common violet (Viola odorata L., Violaceae) has shown various medical applications. Current study aimed to compile a review over chemical composition and medicinal properties of this plant in modern phytotherapy and its related multipotential products from traditional Persian medicine (TPM). Medicinal applications of V. odorata and respective products were derived from credible pharmaceutical textbooks of TPM (10th–18th century AD). In parallel, electronic databases including PubMed, Scopus, and ScienceDirect were explored for targeted purposes. Management of cough, fever, common cold, headache, insomnia, epilepsy, constipation, palpitation, dyspnea, dysuria, and skin diseases is of most applications of V. odorata, reported in TPM. On the other side, this herb plant has exerted antiinflammatory, analgesic, antioxidant, diuretic, antihypertensive, and antibacterial activities in modern phytotherapy. Violet TPM therapeutic preparations are including violet oil in the form of nasal or topical application for neurologic and skin disorders as well as pill, decoction, sweet syrup, and confection or semisolid oral preparations for skin, respiratory, gastrointestinal, and urinary ailments. Flavonoids, saponins, and alkaloids are responsible for pharmacological activities. Some medical applications of V. odorata in TPM have been proven by recent studies. However, more studies are needed to confirm these medicinal properties. Copyright © 2017 John Wiley & Sons, Ltd.
  • Scopoletin Supplementation Ameliorates Steatosis and Inflammation in
           Diabetic Mice
    • Abstract: Scopoletin is a bioactive component in many edible plants and fruits. This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high‐fat diet fed type 1 diabetic mice by comparison with metformin. Scopoletin (0.01%, w/w) or metformin (0.5%, w/w) was provided with a high‐fat diet to streptozotocin‐induced diabetic mice for 11 weeks. Both scopoletin and metformin lowered blood glucose and HbA1c, serum ALT, TNF‐α and IL‐6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group. Scopoletin or metformin down‐regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up‐regulated Cyp7a1 gene. Hepatic PPARγ and DGAT2 protein levels were also down‐regulated in scopoletin or metformin group compared with the control group. Scopoletin or metformin also inhibited hepatic fatty acid synthase and phosphatidate phosphohydrolase activities. These results suggest that scopoletin protects against diabetes‐induced steatosis and inflammation by inhibiting lipid biosynthesis and TLR4‐MyD88 pathways. Copyright © 2017 John Wiley & Sons, Ltd.
  • Anti‐Obesity Activity of Saringosterol Isolated from Sargassum muticum
           (Yendo) Fensholt Extract in 3T3‐L1 Cells
    • Abstract: Saringosterol, a steroid isolated from Sargassum muticum, a brown edible alga widely distributed on the seashores of southern and eastern Korea, has been shown to exhibit anti‐obesity effect. In this study, we investigated the anti‐obesity activity of saringosterol through various experiments. The inhibitory effect of saringosterol on adipogenesis was evaluated via Oil Red O staining in 3T3‐L1 preadipocytes. After confirming that saringosterol is not cytotoxic to these cells by using the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay, the effect of saringosterol on the expression of various adipogenesis‐related genes was analyzed via quantitative real‐time polymerase chain reaction and western blotting. We demonstrated that saringosterol dose dependently inhibited adipocyte differentiation and expression of adipogenic marker genes such as adipocyte fatty acid‐binding protein, adiponectin, resistin, and fatty acid synthase in 3T3‐L1 cells. In addition, saringosterol significantly inhibited the mRNA and protein expression of peroxisome proliferator‐activated receptor γ and CCAAT enhancer‐binding protein α in 3T3‐L1 cells. Collectively, these findings indicate that saringosterol isolated from S. muticum exhibits anti‐obesity effect by inhibiting the expression of adipogenic transcription factors and marker genes and that it may be developed as a drug to suppress adipogenesis. Copyright © 2017 John Wiley & Sons, Ltd.
  • Chebulinic Acid Isolated From the Fruits of Terminalia chebula
           Specifically Induces Apoptosis in Acute Myeloid Leukemia Cells
    • Abstract: Chebulinic acid, an ellagitannin found in the fruits of Terminalia chebula, has been extensively used in traditional Indian system of medicine. It has shown to have various biological activities including antitumor activity. The present study aims to investigate the cytotoxic potential of chebulinic acid in human myeloid leukemia cells. Interestingly, chebulinic acid caused apoptosis of acute promyelocytic leukemia HL‐60 and NB4 cells but not K562 cells. In vitro antitumor effects of chebulinic acid were investigated by using various acute myeloid leukemia cell lines. Chebulinic acid treatment to HL‐60 and NB4 cells induced caspase activation, cleavage of poly(ADP‐ribose) polymerase, DNA fragmentation, chromatin condensation, and changes in the mitochondrial membrane permeability. Additionally, inhibition of caspase activation drastically reduced the chebulinic acid‐induced apoptosis of acute promyelocytic leukemia cells. Our data also demonstrate that chebulinic acid‐induced apoptosis in HL‐60 and NB4 cells involves activation of extracellular signal‐regulated kinases, which, when inhibited with ERK inhibitor PD98059, mitigates the chebulinic acid‐induced apoptosis. Taken together, our findings exhibit the selective potentiation of chebulinic acid‐induced apoptosis in acute promyelocytic leukemia cells. Copyright © 2017 John Wiley & Sons, Ltd.
  • Cardioprotective Effects of Pomegranate (Punica granatum) Juice in
           Patients with Ischemic Heart Disease
    • Abstract: Ischemic heart disease is the leading cause of mortality worldwide. The purpose of this study was to evaluate the cardioprotective effects of pomegranate juice in patients with ischemic heart disease. One hundred patients, diagnosed with unstable angina or myocardial infarction, were randomly assigned to the test and the control groups (n = 50, each). During 5 days of hospitalization, in addition to the conventional medical therapies, the test groups received 220 mL pomegranate juice, daily. During the hospitalization period, the blood pressure, heart rate, as well as the intensity, occurrence, and duration of the angina were evaluated on a regular basis. At the end of the hospitalization period, the serum levels of malondialdehyde, interleukin‐6, and tumor necrosis factor alpha were measured in all patients. The levels of serum troponin and high‐sensitive C‐reactive protein levels were also assayed in patients diagnosed with myocardial infarction. Pomegranate juice caused significant reductions in the intensity, occurrence, and duration of angina pectoris in patients with unstable angina. Consistently, the test patients had significantly lower levels of serum troponin and malondialdehyde. Other studied parameters did not change significantly. The results of this study suggest protective effects of pomegranate juice against myocardial ischemia and reperfusion injury. Copyright © 2017 John Wiley & Sons, Ltd.
  • The Use of Traditional Herbal Medicines Amongst South Asian Diasporic
           Communities in the UK
    • Abstract: Migrant South Asian communities in the UK have brought with them their own traditional forms of medicine, yet little is known about their current use of herbal medicines (HMs) in the UK. The aim of the study was to explore the origins, use and transmission of knowledge of traditional HMs used by diasporic South Asian communities in the UK. A researcher‐administered questionnaire was used for data collection (n = 192). An opportunity sampling technique was used to recruit participants across several locations in Birmingham and Leicester. Two thirds of participants (n = 126) stated they used HMs to maintain their health and to treat various health conditions such as digestive problems, skin conditions and diabetes. Almost 2000 actively used HMs were documented including 123 plant species that were identified. Participants imported HMs from abroad as well as sourcing them locally and even growing some of their own plants. Up to 82% (n = 87) of participants who took prescription medicines did not tell their healthcare professionals about any HMs they consumed; this raises concerns about people's knowledge of herb–drug interactions, compliance and effect on prescribed medicine regimens. Similar studies to explore the use of HMs by other ethnic groups are imperative to help optimise pharmaceutical care of patients. Copyright © 2017 John Wiley & Sons, Ltd.
  • Potential Role of Curcumin Against Biofilm‐Producing Organisms on
           the Skin: A Review
    • Abstract: Turmeric root (Curcuma longa) is predominantly used as a spice, but has also long been known to possess antimicrobial, analgesic, antiinflammatory, and anticancer properties. One predominant group of active compounds in turmeric are curcuminoids, namely bright yellow‐pigmented curcumin. While modern science has yet to fully investigate the therapeutic claims of turmeric and its derivatives, results have proven promising in decreasing pain and inflammation in arthritis, improving insulin sensitivity in diabetes, and even curing a variety of infections. The purpose of this review is to discuss the potential for curcumin as an agent against microbial infections, with a special focus on the skin and in the development of bacterial biofilms. Curcumin has demonstrated bactericidal efficacy against a variety of infections when administered with antibiotics in several clinical studies, with consistent antimicrobial activity demonstrated in vitro, as well as in urinary tract infections, gingival infections, and chronic wound infections. Hypothesized mechanisms of action include curcumin's ability to perturb bacterial membranes, disturb protofillament assembly, and even impair bacterial virulence factors. Further investigation is needed to fully understand which organisms are most susceptible to the effects of curcumin and how curcumin can be implemented in dermatology to treat skin conditions such as chronic wounds and acne vulgaris. Copyright © 2017 John Wiley & Sons, Ltd.
  • Curcuminoids Lower Plasma Leptin Concentrations: A Meta‐analysis
    • Abstract: Curcumin is a naturally occurring polyphenol that has been suggested to improve several metabolic diseases. Leptin is an adipokine involved in metabolic status and appetite, with marked crosstalk with other systems. Available data suggest that curcumin may affect leptin levels; therefore, this meta‐analysis was performed to evaluate this. A systematic review and meta‐analysis were undertaken on all randomized controlled trials of curcumin studies that included the measurement of leptin. The search included PubMed‐Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases. Quantitative data synthesis was performed by using a random‐effects model, with standardized mean difference and 95% confidence interval as summary statistics. A funnel plot, Begg's rank correlation, and Egger's weighted regression tests assessed the presence of publication bias. Four eligible articles comprising five treatment arms were selected for the meta‐analysis. Meta‐analysis showed a significant decrease in plasma leptin concentrations following curcumin treatment (standardized mean difference: −0.69, 95% confidence interval: −1.16, −0.23, p = 0.003; I2 = 76.53%). There was no evidence of publication bias. This meta‐analysis showed that curcumin supplementation is associated with a decrease in leptin levels that may be regarded as a potential mechanism for the metabolic effects of curcumin. Copyright © 2017 John Wiley & Sons, Ltd.
  • Oral herbal medicines marketed in Brazil for the treatment of
           osteoarthritis: A systematic review and meta‐analysis
    • Abstract: Herbal medications are commonly used to manage symptoms associated with osteoarthritis (OA). This systematic review evaluated the effectiveness and safety of oral medications used in Brazil for the treatment of OA. Randomized clinical trials involving adults with OA treated by a herbal medicine or a control group were eligible. The primary outcomes measured were pain, physical function, swelling, stiffness and quality of life; and the secondary outcomes were adverse events, activity limitations and treatment satisfaction. Sixteen studies were included (n = 1,741 patients) in the systematic review and nine studies in the meta‐analysis, representing 6 of the 13 herbal medicines studied: Boswellia serrata (n = 2), Curcuma longa (n = 3), Harpagophytum procumbens (n = 1), Salix daphnoides (n = 3), Uncaria guianensis (n = 2) and Zingiber officinale (n = 5). B. serrata was more effective than both placebo and valdecoxib for improvement of pain and physical function. No difference was observed for H. procumbens, C. longa and U. guianensis compared with control. Z. officinale showed improvement of pain over placebo. The evidence was insufficient to support the effective and safe use of these herbal medicines, because the quality of evidence of studies was low. This study guides managers of the Brazilian public health system and prescribers in decision‐making regarding the use of these herbal medicines for OA. Copyright © 2017 John Wiley & Sons, Ltd.
  • Emerging Importance of Phytochemicals in Regulation of Stem Cells Fate via
           Signaling Pathways
    • Abstract: To reach ideal therapeutic potential of stem cells for regenerative medicine purposes, it is essential to retain their self-renewal and differentiation capacities. Currently, biological factors are extensively used for stemness maintaining and differentiation induction of stem cells. However, low stability, high cost, complicated production process, and risks associated with viral/endotoxin infection hamper the widespread use of biological factors in the stem cell biology. Moreover, regarding the modulation of several signaling cascades, which lead to a distinct fate, phytochemicals are preferable in the stem cells biology because of their efficiency. Considering the issues related to the application of biological factors and potential advantages of phytochemicals in stem cell engineering, there is a considerable increasing trend in studies associated with the application of novel alternative molecules in the stem cell biology. In support of this statement, we aimed to highlight the various effects of phytochemicals on signaling cascades involved in commitment of stem cells. Hence, in this review, the current trends in the phytochemicals-based modulation of stem cell fate have been addressed. Copyright © 2017 John Wiley & Sons, Ltd.
  • Stability of an Aqueous Extract of Larrea divaricata Cav. during a
           Simulated Digestion Process
    • Abstract: Larrea divaricata Cav. (Zygophyllaceae) is a South American plant widely distributed in Argentina that is used in folk medicine to treat inflammatory diseases. The aqueous extract is known to have well-documented biological activities such as antitumour, immunomodulatory, antimicrobial, antiinflammatory and antioxidant. However, its stability in gastrointestinal fluids is unknown. The latter is an important factor to assure the bioavailability of plant extracts intended to be administered via the oral route. The aim of this work was to study the stability of a lyophilized aqueous extract of L. divaricata compressed as a pill. To this end, the main polyphenol compound found in the extract, that is, the nordihydroguaiaretic acid, the total polyphenols and flavonoids content and the antioxidant activity such as diphenylpicrylhydrazyl scavenger activity and reducing power were assayed after subjecting the extract to different incubation times in simulated digestive fluids. The HPLC and spectroscopic methods were employed. Although the levels of polyphenols and flavonoids decreased upon incubation in gastric and intestinal fluids, the extract maintained its antioxidant activity related to the presence of nordihydroguaiaretic acid. These results are promising and encourage the potential use of the extract by the oral route as a supplement or phytomedicine with antioxidant activity. Copyright © 2017 John Wiley & Sons, Ltd.
  • Anticancer Effects of a Korean Herbal Medicine Formula (H9) via AMPK and
           HER2-PI3K/Akt Signaling in Breast Cancer Cells
    • Abstract: An H9 is a formula of nine medicinal herbs derived from Osuyubujaijung-tang, a traditional Korean prescription for Soeumin constitution. In our previous study, H9 showed anticancer effects against breast cancer and non-small-cell lung cancer. However, the underlying mechanisms of these effects have not yet been elucidated. In this study, we investigated the effects of H9, both alone and in combination with trastuzumab, on breast cancer cells and sought to elucidate the mechanisms involved. H9 suppressed the proliferation of human breast cancer cells, induced arrest of the cell cycle at the G0/G1 phase, and caused mitochondrial dysfunction and apoptosis. In addition, H9 induced the activation of AMPK and inhibited the HER2-PI3K/Akt signaling pathway. Furthermore, H9 attenuated hypoxia-induced HIF-1α and VEGF, resulting in decreased migration and invasion of breast cancer cells. Compared with treatment with either drug alone, co-treatment with H9 and trastuzumab significantly inhibited the growth of BT-474 cells through induction of apoptosis. These results suggest that H9 should be considered as a potent anticancer agent that targets the HER2-PI3K/Akt pathway, and the combination of H9 with trastuzumab should be considered as a new therapeutic regimen for treating breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.
  • Supplementation with a Polyphenol-Rich Extract, TensLess®, Attenuates
           Delayed Onset Muscle Soreness and Improves Muscle Recovery from Damages
           After Eccentric Exercise
    • Abstract: High-intensity exercises are known to provoke delayed onset muscle soreness (DOMS). Delayed onset muscle soreness typically occurs within the first 24 h, peaks between 24 and 72 h, and can last as long as 5–7 days post-exercise. Delayed onset muscle soreness is a multifactorial process involving both mechanical and biochemical components, associated with clinical features that may limit range of motion, and athletes seek for effective recovery strategies to optimize future training sessions. TensLess® is a food supplement developed to help manage post-exercise recovery. The supplement has been investigated on 13 recreationally active athletes of both sex, during a randomized, double-blind, and crossover clinical investigation, including a 3-week washout period. The clinical investigation was based on the study of TensLess® effects for DOMS management and on the reduction of associated muscle damages following an eccentric exercise protocol. Supplementation with TensLess® induced significant decrease in DOMS perception (−33%; p = 0.008) as of the first 24 h; this was significantly correlated with a lowered release of muscle damage-associated biomarkers, namely myoglobin, creatinine, and creatine kinase, for the whole length of the recovery period. Taken together, these positive results clearly indicate that post-exercise supplementation with TensLess® may preserve myocytes and reduce soreness following eccentric exercise-induced damages, and, accordingly, significantly shorten muscle recovery. Copyright © 2017 John Wiley & Sons, Ltd.
  • Identification of a Triterpenoid as a Novel PPARγ Activator Derived
           from Formosan Plants
    • Abstract: Peroxisome proliferator-activated receptor γ (PPARγ), one of the transcription factors that regulate lipid metabolism and energy use in tumor cells, is a viable target for cancer therapy. In our search for potential PPARγ activator, extracts from five Formosan plants were tested. Among them, Momordica charantia L. showed the highest ability to activate PPARγ, which led us to identify its potential constituents. Among the seven compounds isolated from M. charantia, a triterpenoid, 5β,19-epoxy-19-methoxycucurbita-6,23-dien-3β,25-diol (compound 1), was identified as a PPARγ activator with an IC50 of 10 μM in breast cancer MCF-7 cells. Flow cytometric analysis indicated that compound 1 induced G1 cell cycle arrest which might be attributable to the modulation of phosphorylation and expression of numerous key signaling effectors, including cyclin D1, CDK6, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 1, leading to increased histone H3 acetylation. Taken together, these findings suggest that compound 1 may have therapeutic applications in cancer treatment through PPARγ activation. Copyright © 2017 John Wiley & Sons, Ltd.
  • Evaluating Efficacy and Safety of Combination Medication of Atorvastatin
           and a Herbal Formula Containing Salvia miltiorrhiza and Pueraria lobata on
    • Abstract: Despite being a potent hypolipidemic drug, atorvastatin (AS) possesses certain adverse effects. Using AS and an herbal formula (Danshen and Gegen, DG) in combination may achieve potentiated hypolipidemic effects and also reduce its adverse effects. Hence, this study aimed to investigate the efficacy and safety of an AS and DG combination on high-fat diet-induced hyperlipidemia. Treatment outcomes were assessed by measuring parameters including body weight, adipose tissue, liver, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterol. Measurements of adverse effects were achieved by determining aspartate aminotransferase (AST), alanine transaminase (ALT), and creatine kinase (CK). Danshen and Gegen, as well as AS alone, reduced body weight, adipose tissue, liver weight, liver fat vacuoles, total liver lipids, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in high-fat diet-fed mice but increased AST, ALT, and CK. A combination of AS and DG was able to enhance reduced effects on the aforementioned parameters in relation to hyperlipidemia over AS or DG alone. It also reduced the elevation of AST, ALT, and CK induced than by AS or DG alone. Results demonstrated that an AS and DG combination resulted in stronger hypolipidemic effects than with AS or DG alone. Additionally, DG might attenuate adverse effects of AS on the liver and skeletal muscle. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pharmacological Evaluation of Gut Modulatory and Bronchodilator Activities
           of Achyranthes aspera Linn.
    • Abstract: Achyranthes aspera L. is traditionally used to relieve constipation, diarrhea, and asthma. Its crude extract (Aa.Cr) was evaluated through in vivo and ex vivo experiments to rationalize these medicinal uses of A. aspera and to provide their scientific basis. Aa.Cr, at 3 and 10 mg/kg, increased fecal output, similar to castor oil, whereas at 30, 100, 300, and 700 mg/kg, it protected against castor oil-induced diarrhea in mice when administered orally. Aa.Cr caused spasmogenic effect on rabbit jejunum and guinea pig ileum preparations, which was partially inhibited by atropine while completely blocked by cyproheptadine preincubation. Aa.Cr also relaxed high K+ (80 mM)-induced contraction in rabbit jejunum. Aa.Cr inhibited CCh (100 μg/kg)-induced bronchospasm in rats, similar to aminophylline. Like dicyclomine, Aa.Cr relaxed high K+ and CCh (1 μM)-induced contractions in guinea pig trachea and caused rightwards parallel shift of CCh concentration–response curves at the lower concentrations followed by non-parallel shift at the higher concentrations. On activity-directed fractionation, spasmogenic and spasmolytic activities of Aa.Cr were concentrated in aqueous and organic fraction, respectively. This study suggests the presence of dose-specific laxative and antidiarrheal effects in A. aspera, possibly mediated through cyproheptadine-sensitive receptors and dual cholinergic and calcium channel blockade, respectively. The latter combination is also a suggested mechanism underlying its bronchodilator effect. Copyright © 2017 John Wiley & Sons, Ltd.
  • Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with
           Ameliorative Effect in Alloxan-Induced Diabetic Rats
    • Abstract: Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan-induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes-induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose-lowering action is partly a consequence of ATP-sensitive K+ channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd.
  • The Effects of Curcumin and Curcumin–Phospholipid Complex on the Serum
           Pro-oxidant–Antioxidant Balance in Subjects with Metabolic Syndrome
    • Abstract: Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant–antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p 
  • The Beneficial Effect of Anthocyanidin-Rich Vitis vinifera L. Grape Skin
           Extract on Metabolic Changes Induced by High-Fat Diet in Mice Involves
           Antiinflammatory and Antioxidant Actions
    • Abstract: We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF-fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd.Consumption of Vitis vinifera L. grape skin (GSE)-derived polyphenols protected against obesity, dyslipidemia, and insulin resistance in high-fat-fed mice. The beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins, pAMPK/AMPK ratio, and GLUT4 expression in the skeletal muscle and adipose tissue. The prevention of obesity and related metabolic disorders by GSE may also be attributed to its antioxidant and anti-inflammatory actions.
  • Immunomodulatory Activity of the Glycoprotein Isolated from the Chinese
           Yam (Dioscorea opposita Thunb)
    • Abstract: The yam (Dioscorea opposita Thunb) is a well-known edible food and widely used as the traditional Chinese medicine. The present investigation was designed to evaluate the immunomodulatory activity of glycoprotein (DOT) from yam and explore its possible molecular mechanisms. Results showed that the DOT could improve the cell immunity, humoral immunity and phagocytic system function of the normal mice. The DOT could also increase the production of TNF-α, interleukin-6 and nitric oxide and enhance the pinocytosis function of macrophages. Furthermore, the DOT increased phosphor-p38, JNK, ERK1/2 and nuclear factor kappa B (NF-κB) p65 protein expression in peritoneal macrophages. Taken together, our data suggest that DOT could be used as a potential immunostimulant and exert its immunomodulatory activity via mitogen-activated protein kinases and NF-κB signal pathways. Copyright © 2017 John Wiley & Sons, Ltd.
  • Chemical Composition and Antioxidant, Antinociceptive, and
           Anti-inflammatory Activities of Four Amazonian Byrsonima Species
    • Abstract: Species of the Byrsonima genus are widely used in Brazil, especially for the treatment of gastrointestinal disorders. However, species from the Amazonian region are still poorly studied. Thus, we studied the antioxidant, antinociceptive, and anti-inflammatory activities of for Amazonian species, Byrsonima crispa, Byrsonima duckeana, Byrsonima garcibarrigae, and Byrsonima incarnata. Phenolic composition was determined by chemical and chromatographic methods. The aqueous extracts were evaluated in DPPH•, ABTS+•, and superoxide (O2•−) tests, LPS-activated macrophage assay, and formalin test. All species contained a high phenolic and flavonoid content. We identified 15 phenolic compounds, including phenolic acids, hydroxycinnamic acids, flavonoids, and catechins. The extracts showed high antioxidant activity and were more active than quercetin at inhibiting nitric oxide release in the LPS-activated macrophage assay. B. duckeana and B. garcibarrigae showed higher in vivo antinociceptive and anti-inflammatory activities. B. garcibarrigae presented significant effect on the early phase of the formalin test, pointing to an antinociceptive mechanism distinct from traditional anti-inflammatory medicines. In conclusion, the pharmacological potential of these species is closely related to their flavonoid-rich chemical composition, which seems to act through antioxidant mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.
  • Comparative Study of Different Acorus Species in Potentiating Neuronal
           Differentiation in Cultured PC12 Cells
    • Abstract: Acori Tatarinowii Rhizoma (ATR), the rhizome of Acorus tatarinowii Schott, is a common traditional Chinese medicine being used clinically for mental disorder. However, other Acorus species herbs are all having the same Chinese name ‘Chang Pu’, making the confusion in herbal market. Acori Graminei Rhizoma (AGR) and Acori Calami Rhizoma (ACR) are common adulterants of ATR. Here, we aim to provide a comparative analysis between ATR, AGR, and ACR in potentiating neuronal differentiation. Volatile oil, derived from Acorus species, was applied onto cultured PC12 cells, and various parameters were determined: (i) transcriptional activation of neurofilament promoters was determined by the promoter-driven luciferase activity assay; (ii) the neurite outgrowth of PC12 cells was captured and measured; and (iii) the neurofilament expression and its underlying mechanism were analyzed by western blotting. The co-treatment of ATR, AGR, or ACR volatile oil with low concentration of nerve growth factor (NGF) could potentiate the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitor H89 in cultures blocked the induction of neurofilament. Among these three Acorus species, ATR volatile oil showed the highest NGF-induced induction in neurite outgrowth and neurofilament expression, as compared with that of AGR and ACR. Copyright © 2017 John Wiley & Sons, Ltd.
  • Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review
    • Abstract: Licorice (Glycyrrhiza glabra) has been considered as an herbal drug since ancient time. Nowadays, it is a well-known spice that possesses worth pharmacological effects. However, some relevant articles have revealed negative impacts of licorice in health. By considering the great wishes in using herbal medicine, it is important to show adverse effects of herbal medicine in health. At present, there are misunderstandings toward the safety of herbal medicines. Herein, we gathered scientific research projects on the toxicity effects of licorice and glycyrrhizin to highlight their safety. In this regards, we categorized our findings about the toxicity effects of licorice and glycyrrhizin in acute, sub-acute, sub-chronic, and chronic states. Besides, we discussed on the cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity of licorice and glycyrrhizin as well as their developmental toxicity. This review disclosed that G. glabra and glycyrrhizin salts are moderately toxic. They need to be used with caution during pregnancy. G. glabra and glycyrrhizin possess selective cytotoxic effects on cancerous cells. The most important side effects of licorice and glycyrrhizin are hypertension and hypokalemic-induced secondary disorders. Licorice side effects are increased by hypokalemia, prolonged gastrointestinal transient time, decreased type 2 11-beta-hydroxysteroid dehydrogenase activities, hypertension, anorexia nervosa, old age, and female sex. Copyright © 2017 John Wiley & Sons, Ltd.
  • Pycnogenol Cytotoxicity in Pancreatic INS-1E β cells Induced by
           Calcium Dysregulation
    • Abstract: Natural standardized flavonoid extract from the bark of Pinus pinaster, Pycnogenol (Pyc), was recently found to decrease intensively the activity of sarcoplasmic reticulum Ca2+-ATPase of rabbit skeletal muscle (SERCA1). On the basis of this inhibitory effect in a cell-free system and similarities of SERCA1 to its other isoforms, proapoptotic properties of Pyc may be expected in cellular systems. Pycnogenol (40–100 μg/mL) induced a concentration-dependent decrease of the viability of pancreatic INS-1E β cells associated with induction of apoptosis. In addition, intracellular Ca2+ level increase was found along with reduction of protein expression level of SERCA2b and impairment of insulin secretion by β cells. These facts indicate that Pyc may induce apoptosis by impairment of calcium homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.
  • The In Vitro and In Vivo Antiangiogenic Effects of Flavokawain B
    • Abstract: Angiogenesis is implicated in the development of a variety of pathological processes, most commonly cancer. It is essential for tumor growth and metastasis, making it an important cancer therapeutic target. Naturally occurring substances have led to the discovery of anticancer agents. Flavokawain B (FKB), a chalcone isolated from the root extracts of kava-kava plant, inhibits proliferation and causes apoptosis in vitro and in vivo of various cancer cell lines. The antimetastatic potential of FKB has also been suggested. In our study, we confirm the antiangiogenic action of FKB in vitro and, for the first time, demonstrate its strong antiangiogenic activity in vivo, using a zebrafish model. Our data show that FKB inhibits human brain endothelial cell (HUVEC) migration and tube formation even at very low and non-toxic concentrations. Moreover, FKB blocks angiogenesis process in zebrafish, with a dramatic reduction of subintestinal vein formation in a dose-dependent manner. Flavokawain B at the concentration of 2.5 μg/mL did not exhibit any toxic effects in zebrafish larvae and caused a markedly or complete obliteration of subintestinal vein formation. Our findings along with previously published data confirm that FKB may form the basis for creating an additional tool in the treatment of cancer and other neovascularization-related diseases. Copyright © 2017 John Wiley & Sons, Ltd.
  • In vitro Study of Five Herbs Used Against Microbial Infections in Burundi
    • Abstract: The emergence of antimicrobial resistant infectious diseases remains a major threat to worldwide public health, in developed and in developing countries. Therefore, new antimicrobial agents acting by new mechanisms of action are urgently needed. As plants used in traditional medicine may help to overcome these problems, Justicia subsessilis, Platostoma rotundifolium, Pavetta ternifolia, Stomatanthes africanus, and Virectaria major (plants highly cited to be used against microbial infections in traditional Burundian medicine) were studied to assess their traditional use efficacy. We conducted a preliminary phytochemical screening of the extracts, as well as their direct and indirect (effect on antibiotic resistance) antibacterial activity on four bacterial strains (Staphylococcus sp. and Escherichia coli) by broth microdilution methods. All five medicinal plants investigated in this work were found to have direct antibacterial activity against all tested bacterial strains (minimum inhibitory concentration = 62.5–1000 μg/mL) that may support the use of these species in traditional Burundian medicine. Extracts (with no direct antibacterial activity), tested at 200 μg/mL, decreased the MIC values of β-lactams and aminoglycoside antibiotics by a factor of 2 to 64-fold. These interactions between plant extracts and antibiotics could open an avenue of research against antibiotic resistance. Copyright © 2017 John Wiley & Sons, Ltd.
  • In vitro Antitubercular Activity of 3-Deoxysappanchalcone Isolated From
           the Heartwood of Caesalpinia sappan Linn.
    • Abstract: Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic. New drugs are urgently needed to combat the growing threat of antimicrobial resistance. To achieve this goal, we screened approximately 500 species of medicinal plant methanol extracts and their solvent partitioned fractions for potential inhibitors of Mycobacterium tuberculosis growth. Using microdilution screening, the ethyl acetate solvent partitioned fraction from the heartwood of Caesalpinia sappan exhibited strong antitubercular activity. We isolated the active compound and identified it as 3-deoxysappanchalcone. The extracted 3-deoxysappanchalcone possessed activity against both drug-susceptible and drug-resistant strains of M. tuberculosis at MIC50s of 3.125–12.5 μg/mL in culture broth and MIC50s of 6.25–12.5 μg/mL inside macrophages and pneumocytes. 3-Deoxysappanchalcone was also found to act in partial synergy with streptomycin/ethambutol against M. tuberculosis H37Rv. 3-Deoxysappanchalcone had no cytotoxicity against the A549 cell line up to a concentration of 100 μg/mL (selectivity index > 8–32). Further studies are warranted to establish the in vivo effect and therapeutic potential of 3-deoxysappanchalcone. Copyright © 2017 John Wiley & Sons, Ltd.
  • Apoptotic Effect of Astragalin in Melanoma Skin Cancers via Activation of
           Caspases and Inhibition of Sry-related HMg-Box Gene 10
    • Abstract: Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner. Also, Astragalin significantly increased the number of TdT-mediated dUTP nick end labeling positive cells and sub-G1 population as a feature of apoptosis in A375P and SK-MEL-2 cells compared with untreated control. Consistently, western blotting revealed that Astragalin activated caspase 9/3 and Bax, cleaved poly (ADP-ribose) polymerase, and attenuated the expression of cyclin D1, Mcl-1, and Sry-related HMg-Box gene 10 (SOX10) in A375P and SK-MEL-2 cells. Of note, ectopic expression of SOX10 reduced the apoptotic ability of Astragalin to inhibit proliferation, cleave poly (ADP-ribose) polymerase, and caspase 3 in A375P and SK-MEL-2 melanoma cells. Overall, our findings provide evidence that Astragalin induces apoptosis in A375P and SK-MEL-2 melanoma cells via activation of caspase9/3 and inhibition of SOX10 signaling. Copyright © 2017 John Wiley & Sons, Ltd.
  • The Phytochemistry and Pharmacology of Butia sp.: A Systematic Review and
           an Overview of the Technological Monitoring Process
    • Abstract: The Butia sp. are native South America trees, whose fruits are consumed in natura and have significant biological properties; however, trees of this genus plant are in danger of extinction. A systematic review of the literature and a technological overview were carried out to summarize the available evidence on the therapeutic uses and the phytochemical compounds of Butia sp. The following electronic databases were researched: MedLine (PubMed), Web of Science, Scopus, Scielo, and the gray literature. Furthermore, the online system such as the US Patent and Trademark Office, Espacenet, National Institute of Industrial Property, and Google Patents were accessed to obtain patent data. The inclusion criteria were articles that describe either the therapeutic uses of Butia sp. (antimicrobial activity, antioxidant activity, anti-inflammatory activity, antineoplastic activity) or studies describing phytochemical compounds of Butia sp. A limited amount of manual search was also undertaken. Reference lists were scanned to identify other relevant studies, and requests for unpublished data were conducted to people working in the field. Among 12 papers and 14 patents, 9 complete texts of scientific articles and 1 patent were scrutinised by two reviewers. We concluded that Butia has shown some antioxidant, anti-inflammatory, and antimicrobial activity, and its use could have important implications for future therapeutic uses. Although there is evidence of pharmacological potential from in vitro studies, clinical studies must be conducted to confirm the effectiveness of Butia sp. The evidence of its therapeutic uses has not been extensively studied yet, and the available evidence still needs further confirmation. Copyright © 2017 John Wiley & Sons, Ltd.
  • Acylated Iridoids and Rhamnopyranoses from Premna odorata (Lamiaceae) as
           Novel Mesenchymal–Epithelial Transition Factor Receptor Inhibitors for
           the Control of Breast Cancer
    • Abstract: Phytochemical investigation of Premna odorata Blanco, Lamiaceae, leaves afforded three new acylated iridoid glycosides 1–3 and two new acylated rhamnopyranoses 9 and 10, in addition to ten known compounds. The structures of the new compounds were confirmed using extensive 1D and 2D NMR analysis. Molecular modeling study suggested the potential of the acylated rhamnopyranoses to bind at the c-Met kinase domain. Cell-free Z′-LYTE™ assay testing revealed the good c-Met phosphorylation inhibitory activity of 9, followed by 8, and 10, with IC50 values of 2.5, 6.9, and 12.7 μM, respectively. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay testing against the human c-Met expressing highly invasive MDA-MB-231 suggested compound 9 as the most active with IC50 value of 13.3 μM. Testing of compound 9 against multiple phenotypic breast cancer cell lines including MCF-7, BT-474 cells, and MDA-MB-468 proved enhanced activity against the highly c-Met expressing triple-negative breast cancer cell lines. Acylated rhamnopyranoses are potential novel c-Met inhibitors appropriate for future optimizations to control c-Met-dependent breast malignancies. Copyright © 2017 John Wiley & Sons, Ltd.
  • Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid
           Peroxidation in Type 2 Diabetes: A Randomized Double-Blind
           Placebo-Controlled Clinical Trial
    • Abstract: This study aimed to examine the effects of hesperidin supplement on the glycemic parameters, oxidative DNA damage, and lipid peroxidation in patients with type 2 diabetes. Sixty-four patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on glycemic parameters, total antioxidant capacity (TAC), 8-hydroxydeoxyguanosine (8-OHDG), and malondialdehyde (MDA) were collected at the baseline and at the end of the study. In hesperidin group, TAC increased (0.74 ± 0.16 vs. 0.82 ± 0.18), while serum froctoseamin (5.79 ± 5.86 vs. 5.01 ± 4.95; p = 0.001), 8-OHDG (14.32 ± 6.4 vs. 11.00 ± 7.0; p = 0.000), and MDA (5.78 ± 1.76 vs. 4.60 ± 0.75; p = 0.000) decreased in comparison with the baseline values. There was a significant difference in percent change of TAC (13.35 ± 19.21 vs. 3.13 ± 10.02; p = 0.043), froctoseamin (−10.10 ± 16.84 vs. 4.27 ± 34.646), 8-OHDG (−25.11 ± 28.23 vs. 8.69 ± 35.41; p = 0.000), and MDA (−16.46 ± 18.04 vs. −1.82 ± 22.63; p = 0.007) between hesperidin and control groups following intervention in adjusted models. These results suggest that hesperidin may improve TAC and alleviate serum froctoseamin, 8-OHDG, and MDA levels in type 2 diabetes. Copyright © 2017 John Wiley & Sons, Ltd.
  • 4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses
           Inflammatory Responses Through TRPV1 Activation
    • Abstract: Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca2+ levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC50 = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd.
  • Plants of the Melaleuca Genus as Antimicrobial Agents: From Farm to
    • Abstract: Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad-spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80–90% several monoterpenes (terpinen-4-ol, α-terpinene, 1,8-cineol, p-cymene, α-terpineol, α-pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8-cineol, terpinen-4-ol and methyl eugenol play the key role in mediating this oil's antimicrobial activity. Copyright © 2017 John Wiley & Sons, Ltd.
  • The Preparation of Hyaluronic Acid Nanoparticles from Aspicilia lichens
           Using Bifido Bacteria for Help in the Treatment of Diabetes in Rats In
    • Abstract: Many common herbs and spices are claimed to have blood sugar lowering properties that make them useful for people with or at high risk of diabetes. The main of compounds of kiwifruit (Actinidia deliciosa), rhubarb (Rheum ribes), membrane inner of egg shell, wool of sheep, human fingernail (unguis), hyaluronic acid produced by the Bifidobacterium, and usnic acid of Aspicilia lichen were extracted by different methods. All compounds of the extract were divided into five groups. We used variables such as pH, different compounds, concentration, number of injections, and blood glucose monitoring in different situations. Our study, extracts changed to nanoform. The extract compounds and nanoparticles were analyzed by gas chromatography mass spectroscopy, Fourier transform infrared spectroscopy, hydrogen-1 nuclear magnetic resonance, and scanning electron microscope. The average size of the nanoparticles was found to be 55 nm. Five groups of nanoparticles were injected into rats, and they reduced their blood glucose levels significantly (statistical significance was declared at p 
  • Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast
           Cancer Cells
    • Abstract: Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p 
  • Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium
           (Bitter Orange) Extract and p-Synephrine
    • Abstract: Citrus aurantium L. (bitter orange) extracts that contain p-synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p-synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter orange extracts and p-synephrine. Numerous studies have been conducted with respect to p-synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. Approximately 30 human studies indicate that p-synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Mechanistic studies suggest that p-synephrine exerts its effects through multiple actions, which are discussed. Because p-synephrine exhibits greater adrenergic receptor binding in rodents than humans, data from animals cannot be directly extrapolated to humans. This review, as well as several other assessments published in recent years, has concluded that bitter orange extract and p-synephrine are safe for use in dietary supplements and foods at the commonly used doses. Copyright © 2017 The
      Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
  • Influence of Prostanoids in the Diuretic and Natriuretic Effects of
           Extracts and Kaempferitrin from Bauhinia forficata Link Leaves in Rats
    • Abstract: Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis, no scientific investigation has focused on demonstrating its efficacy in preclinical trials. For that, normotensive male Wistar and spontaneously hypertensive rats were used to test the effect of extracts and kaempferitrin obtained from Bauhinia forficata leaves in the experimental model of diuresis. Cumulative urine volume, Na+ and K+ excretion, calcium, creatinine, prostaglandin E2, pH, density, and conductivity were measured at the end of the experiment (after 8 or 24 h). The treatment with aqueous infusion, methanolic extract, trichloromethane, or ethyl acetate–butanolic fractions significantly increase urinary volume and electrolytes levels when orally given to rats, without altering the pH or density parameters. Kaempferitrin induced diuretic, natriuretic, but not kaliuretic effects in both normotensive and hypertensive rats. In addition, kaempferitrin enhanced urinary creatinine and prostaglandin E2 excretion, without modifying calcium levels. Kaempferitrin-induced diuresis was unaffected by previous treatment with a nonselective inhibitor of nitric oxide synthase and neither with a nonselective muscarinic receptor antagonist. On the other hand, a cyclooxygenase inhibitor was able to decrease its effect when compared with vehicle-treated rats, suggesting that the diuretic and natriuretic properties from kaempferitrin are associated with endogenous prostanoids generation. Copyright © 2017 John Wiley & Sons, Ltd.
  • Antiproliferative Activity of Phenylpropanoids Isolated from Lagotis
           brevituba Maxim
    • Abstract: The aim of the present study was to evaluate the antiproliferative effect of phenylpropanoids isolated from the n-BuOH-soluble fraction of an ethanolic extract of Lagotis brevituba Maxim. The phenylpropanoids were identified as echinacoside, lagotioside, glucopyranosyl(1–6)martynoside, plantamoside, and verbascoside. Three of the compounds, lagotioside, glucopyranosyl(1–6)martynoside, and plantamoside, were isolated from L. brevituba for the first time. The antiproliferative activity of the isolates was evaluated in human gastric carcinoma (MGC-803), human colorectal carcinoma (HCT116), human hepatocellar carcinoma (HepG2), and human lung cancer (HCT116) cells using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Plantamoside showed promising activity against MGC-803 cells, with a half maximal inhibitory concentration value of 37.09 μM. The mechanism of the pro-apoptosis effect of plantamoside was then evaluated in MGC-803 cells. Changes in cell morphology, including disorganization of the architecture of actin microfilaments and formation of apoptotic bodies, together with cell cycle arrest in G2/M phases, were observed after treatment of plantamoside. The antiproliferative and pro-apoptotic effects were associated with a decrease in the ratio of Bcl-2/Bax and reduced mitochondrial membrane potential, which was accompanied by the release of reactive oxygen species and Ca2+ into the cytoplasm. Taken together, the results indicated that plantamoside promotes apoptosis via a mitochondria-dependent mechanism. Copyright © 2017 John Wiley & Sons, Ltd.
  • Anticandidal Activity of Extracts and a Novel Compound, Amnomopin,
           Isolated From Petriella setifera
    • Abstract: A novel triterpenoidal compound named ‘amnomopin’ (3β-diglucoside-5,12-28-oic acid), which is named IUPAC as 3-O-(2′ ➔ 1″diglucoside)1,2,3,4,4a,5,6,6a,6b,7,9,10,11,12,12a,12b,13,14b-octadecahydro-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethylpicene-4a-carboxylic acid, was isolated from the extract Petriella setifera. The total alcoholic extract of P. setifera showed a great activity against clinically isolated Candida species, including Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida inconspicua, Candida kefyr, Candida krusei, Candida norvegensis, Candida parapsilosis and Candida tropicalis. Also, the new compound amnomopin was active against all the investigated Candida species. The highest anticandidal activity of P. setifera extract was obtained against C. kefyr (22.6 ± 1.5 mm), C. albicans and C. norvegensis (21.3 ± 0.63 mm) and C. krusei (20.6 ± 1.5 mm). Moreover, the minimum inhibitory concentrations of both the total extract and the isolated compound were low. The minimum inhibitory concentration of the compound isolated from P. setifera was 0.49 μg/mL against C. kefyr, 0.98 μg/mL against C. albicans and C. norvegensis and 1.95 μg/mL against C. krusei. The oral dosing of the extract and the isolated compound did not show any significant effect on the activity of alanine aminotransferase, aspirate aminotransferase and the levels of blood urea and serum creatinine. Copyright © 2017 John Wiley & Sons, Ltd.
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