J Ethnopharmacol [journal]
- Apoptotic activities of cardenolide glycosides from Asclepias subulata. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 18.
Asclepias subulata Decne. (Apocynaceae) is a shrub occurring in Sonora-Arizona desert. The ethnic groups of Sonora, Mexico, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer.To determine the cell death pathways that the cardenolide glycosides with antiproliferative activity found in the methanol extract of A. subulata are able to activate.The effect of cardenolide glycosides isolated of A. subulata on induction of apoptosis in cancer cells was evaluated through the measuring of several key events of apoptosis. A549 cells were treated for 12h with doses of 3.0, 0.2, 3.0 and 1.0µM of 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, respectively. Apoptotic and necrotic cell levels were measured by double staining with annexin V-FITC/PI. Mitochondrial membrane depolarization was examined through JC-1 staining. Apoptosis cell death and the apoptosis pathways activated by cardenolide glycosides isolated of A. subulata were further characterized by the measurement of caspase-3, caspase-8 and caspase-9 activity.Apoptotic assays showed that the four cardenolide glycosides isolated of A. subulata induced apoptosis in A549 cells, which was evidencing by phosphatidylserine externalization in 18.2, 17.0, 23.9 and 22.0% for 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, respectively, compared with 4.6% of control cells. Cell death was also associated with a decrease in mitochondrial membrane potential, which was more than 75% in the treated cultures respect to control. The activation of caspase-3 was observed in all cardenolide glycosides-treated cancer cells indicating the caspase-dependent apoptosis of A549 cells. Extrinsic and intrinsic apoptosis pathways were activated by cardenolide glycosides treatment at the doses tested.In this study was found that cardenolide glycosides, 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, isolated from A. subulata induced the cell death trough caspase-dependent apoptosis, which was activated, preferably, by extrinsic pathway.
- Anti-inflammatory and associated analgesic activities of HPLC standardized alcoholic extract of known ayurvedic plant Schleichera oleosa. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 17.
Schleichera oleosa (Lour.) Oken. commonly known as 'Koshamra' in Ayurveda is a tropical tree readily found in Asia and is used to treat pain and rheumatism, as traditional medicine in different parts of India. However, scientific evidences to justify these claims are lacking. Considering the traditional use of S.oleosa and the lack of information about its pharmacological properties, we investigated the anti-inflammatory and analgesic effect of the alcoholic extract of S.oleosa (SE) against different animal models in rodents.The anti-inflammatory activity was evaluated against carrageenan induced paw edema and TPA (12-O-tetradecanoylphorbol-13-acetate) induced ear edema. To assess the mechanism of anti-inflammatory action the extract was tested against different phlogistic agents like histamine, serotonin, bradykinin and, prostaglandin E2. The analgesic activity was assessed against formalin induced pain.The ethanolic extract of S. oleosa bark, did not exhibited any signs of toxicity up to a dose of 2000mg/kg. The extract significantly inhibited increase in paw edema and ear edema. A percent reduction of 60.84% was found against carrageenan induced paw edema by 400mg/kg dose of SE. The extract was effective against edema induced by serotonin, histamine and PGE2. In formalin test the extract inhibited both the neurogenic 1(st) and mainly the inflammatory 2(nd) phase. Significant reduction in tissue levels of inflammatory mediators was also observed (p<0.05 for NO and p<0.01 for MDA). The extract showed presence of potent analgesic and anti-inflammatory compounds lupeol, lupeol acetate, betulin and betulinic acid on HPLC analysis which can be held responsible for its studied biological activity.The results suggest that SE is effective in inflammatory processes and targets multiple mediators of inflammation. Its action is markedly influenced by the inhibition of neutrophil migration, anti-oxidant action and reduction in inflamed tissue.
- Management of Parkinson's disease in Ayurveda: Medicinal plants and adjuvant measures. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 17.
Medicinal plants like Mucuna pruriens, Withania somnifera have been used in traditional Ayurvedic medicine to manage neurodegenerative diseases like Parkinson's disease.The aim of this review is to share the role of Ayurveda's insights, traditional usage and contemporary investigations for translational, integrative applications to manage Parkinson's Disease.High impact journals for Parkinson's diseases, traditional textbooks from Ayurveda as well as relevant clinical and para clinical studies with botanicals are selectively incorporated to evolve the aforesaid translational application.Parkinson's disease (PD) is a complex multi-system, neurodegenerative disease. Though predominantly perceived as a motor disease, it also has debilitating non- motor features, which are frequently missed and not treated. Major treatment goals are to increase striatal dopamine levels with precursor-substitution and/or reduce its breakdown. As the disease progresses, a steady increase in the dose of levodopa is inevitable. However, higher doses cause motor complications of dyskinesia and dystonia and compromise medical treatment. ROLE OF MUCUNA PRURIENS L.Ayurveda offers a natural source of levodopa - the seeds of Mucuna pruriens L.(DC) - which have a long standing safe use in the condition. Its clinical studies have shown pharmacokinetic profile distinct from synthetic levodopa, which is likely to reduce the untoward motor complications. Additionally, its seed extracts have shown neuroprotective benefits which are unrelated to levodopa. AYURVEDIC REGIMENS AND MEDICINAL PLANTS FOR NEUROPROTECTIVE AND SYMPTOMATIC BENEFITS: Other regimens (Panchakarma) and medicinal plants used in Ayurveda have been subjected to exploratory studies with promising early results in the condition. The debilitating non motor symptoms in patients have shown response with one of the regimens - medicated oil enema (basti). Effects of two medicinal plants Withania somnifera(L.)Dunal and Curcuma longa Linn in Parkinson's Disease related models have been discussed in detail. We have also shared a shortlist of medicinal plants most likely to be useful in management of specific features of the disease such as cognitive decline, mood disorders, risk of osteoporosis amongst others.Ayurveda with its medicinal plants and treatment approaches, can strengthen the therapeutic armamentarium of PD to improve clinical outcomes, if these leads are systematically further investigated by well-designed longer term studies.
- Government Policies and Initiatives for Development of Ayurveda. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 16.
Ayurveda (Sanskrit: Ayus - life + Veda - knowledge) means the "True knowledge of life". Ayurveda deals with a complete self-sustainable system of medicine. The Government of India through its Ministry of AYUSH is responsible for policy formulation, development and implementation of programs for the growth, development and propagation of Ayurveda.This review aimed to highlight the various aspects of government policies and initiatives for development of Ayurveda.We critically reviewed various books, annual reports, policy documents and various ancient Ayurvedic literatures. Besides the websites of Ministry of AYUSH, National Medicinal Plant Board, Central Council for Research on Ayurvedic Sciences (CCRAS) and AYUSH research portal have been searched and data was recorded.The vision of the ministry is to position AYUSH systems as the preferred systems of living and practice for attaining healthy nation. The ministry has identified its mission in terms of seven broad thematic functional areas of AYUSH activities. These are information, education and communication; drug administration, human resource development, medicinal plants, research and development, international collaborations, AYUSH services. Different programs have been taken up towards increasing visibility, acceptability and usage of Ayurveda vis-a vis its integration in the health system. Strategies to globalize and promote Ayurveda are being taken up through AYUSH clusters focusing its safety-efficacy-quality aspects and rational use of Ayurveda CONCLUSION: The government policies are taking firm steps towards promotion and development of Ayurveda. Research and development towards validation of Ayurveda is being projected as the thrust area.
- Functional aspects of the use of plants and animals in local medical systems and their implications for resilience. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 15.
This study sought to understand the role of plants and animals in traditional medical systems and evaluate the capacity of these systems to absorb impacts and maintain their identity by determining the existence of functional substitutes.Ethnobiological data were collected through semi-structured interviews and free lists at a rural community in the semiarid region of northeastern Brazil. The data were subjected to the utilitarian redundancy model and analyzed by tests of proportion and variance.We found that most of the therapeutic targets treated with animal-based remedies were also treatable by plant-based remedies; these targets were perceived as very usual, although they were not considered dangerous. Furthermore, people considered the plants and animals to be equally effective at curing overlapping therapeutic targets, but the plant remedies were used more frequently. The findings show that local knowledge about medicinal plants and animals follows similar patterns regarding the utilitarian redundancy, with high functional overlap among these features. However, the ease of access to the medicinal resource influences the choice of treatment, leading to an increased preference for plants over animals. In addition, we suggest that during the cultural evolution process, people concentrated their efforts on experimenting with different resources for the treatment of diseases that were very frequent locally, even if not very severe, which contributed to the resilience of the local medical system.Furthermore, we infer that plants may effectively perform the function of healing, whereas animals act as reserves of resilience for the system, maintaining system function in the face of disturbances that may affect the availability of plant species.
- Kai-Xin-San, a traditional Chinese medicine formula, induces neuronal differentiation of cultured PC12 Cells: modulating neurotransmitter regulation enzymes and potentiating NGF inducing neurite outgrowth. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 12.
Kai-Xin-San, an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for major depression disorders for thousands of years. However, its molecular mechanism has not clearly been investigated.We aimed to reveal the action mechanism of KXS on anti-depression on inducing neuronal differentiation on PC12 cells.A chemically standardized water extract of KXS was applied onto cultured PC12 cells in determining its effect on neurotransmitter regulation enzymes and neurite outgrowth.Single KXS treatment showed obvious changes in the expression of neurofilament and neurotransmitter regulation enzymes, which in parallel to treatment of nerve growth factor (NGF). Although KXS by itself did not show significant inductive effect on neurite outgrowth of PC12 cells, KXS could potentiate the NGF induced neurite outgrowth. Among the three ratios, K-652 showed the most powerful effect and cAMP-dependent pathway might play the major role.KXS might exert the anti-depressant-like action of be inducing neuronal differentiation, which supported the clinically usage of this decoction.
- Ginkgoghrelins, unique acylated flavonoid diglycosides in Folium Ginkgo, stimulate growth hormone secretion via activation of the ghrelin receptor. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 11.
Folium Ginkgo, the dried leaf of Ginkgo biloba L. is a traditional Chinese medicine listed in the Pharmacopoeia of the People's Republic of China with several therapeutic effects, including prevention of aging. It is used as herbal medicine for the treatment of several aging-related diseases. The therapeutic effects of Folium Ginkgo on aging-related diseases are suspected to be similar to the anti-aging effects of growth hormone release induced by ghrelin.Candidate components responsible for the anti-aging effects via the ghrelin receptor-activated pathway were searched from the known compounds found in Folium Ginkgo. Two acylated flavonoid diglycosides, tentatively named ginkgoghrelins in this study, were selected and isolated from the methanol extract of Folium Ginkgo, and their chemical structures were confirmed by spectroscopic analysis. These two compounds were examined for their capability of stimulating growth hormone release of rat primary anterior pituitary cells via activation of the ghrelin receptor. The major metabolites of ginkgoghrelins in rat bile were detected after intravenous injection and structurally analyzed by mass spectroscopy. Molecular modeling of ginkgoghrelins docking to the ghrelin receptor was exhibited to explore the possible interaction within the binding pocket.Similar to growth hormone-releasing hormone-6 (GHRP-6), a synthetic analog of ghrelin, ginkgoghrelins were demonstrated to stimulate growth hormone secretion of rat primary anterior pituitary cells in a dose dependent manner, and the stimulation was inhibited by [d-Arg(1), d-Phe(5), d-Trp(7,9), Leu(11)]-substance P, an inverse agonist of the ghrelin receptor. Putative metabolites of ginkgoghrelins via glucuronidation and methylation were detected in bile of rats after intravenous injection. Molecular modeling and docking showed that ginkgoghrelins as well as GHRP-6 could fit in and adequately interact with the binding pocket of the ghrelin receptor.The results suggest that ginkgoghrelins are putative components partly accounting for the anti-aging effects of Folium Ginkgo possibly via activation of the ghrelin receptor, and possess great potential to be developed as non-peptidyl analogs of ghrelin.
- Investigation of anti-asthmatic potential of Kanakasava in ovalbumin-induced bronchial asthma and airway inflammation in rats. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 5.
Kanakasava is an Indian traditional Ayurvedic formulation containing Datura (Datura metel), Vasaca (Adhatoda vasica), Dhataki (Woodfordia fruticosa) and Grape (Vitis vinifera) extracts as major constituents and used to treat pulmonary diseases including coughing, breathing difficulty and asthma. The present study was designed to assess the safety and therapeutic efficacy of Kanakasava against ovalbumin-induced bronchial asthma and related airway inflammation in rats due to lack of evidence based therapeutic efficacy data.Male wistar rats were sensitized with allergen (ovalbumin, 40mg/rat+aluminum hydroxide, 2.0mg/rat) and treated orally with standard dexamethasone (2.5mg/kg, b.w.) or Kanakasava (1.23 and 2.46ml/kg, b.w.) from day 1 to day 28. Inflammatory markers, including cell counts and cytokines such as interleukins (IL-4, IL-5, IL-1β), tumor necrosis factor (TNF-α), leukotriene (LTD-4), immunoglobulin (IgE), nitric oxide and nitrite levels in both blood and broncheo alveolar lavaged fluid (BALF) were analyzed. Abdominal mesentery was studied histologically for mast cell degranulation, whereas lung functions were investigated by spirometer. Method was also developed to quantify gallic acid and ethyl gallate content in Kanakasava by HPTLC for its quality control.None of the rats exhibited mortality and Kanakasava was found to be safe at the tested doses. Treatment with Kanakasava significantly (P<0.01) reversed elevated levels of IgE, cytokines, nitrites and influx of eosinophils and neutrophils in blood and BALF. These findings were further supported by the significant improvement in lung functions (P<0.01) and suppression (P<0.01) of degranulation of mast cells. The content of gallic acid and ethyl gallate in Kanakasava was found to be 1.94% and 0.98%, respectively.These findings demonstrated the preventive effect of Kanakasava in allergen induced model of asthma providing scientific basis for its traditional use in Ayurveda, since long time.
- The effects of Qi Teng Xiao Zhuo granules, traditional Chinese medicine, on the expression of genes in chronic glomerulonephritis rats. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 3.
Chronic glomerulonephritis (CGN) is a primary glomerular disease that is related to immune-mediated inflammatory diseases. Qi Teng Xiao Zhuo granules have been proposed as a prescription of traditional Chinese medicine for treatment of CGN, but the comprehensive molecular mechanism underlying this therapeutic effect is not clear to date. The aim of this study was to evaluate and analyze the possible roles and molecular mechanisms of Qi Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats.For gene expression analysis, four samples of glomerular tissue from rats in the Qi Teng Xiao Zhuo granule group and four samples each from the adriamycin treated and control groups were hybridized with Agilent Rat 4 × 44K whole genome microarrays. KEGG and Gene Ontology (GO) analyses and LIMMA, String and Cytoscape software were used to analyze the functional microarray data and screen differentially expressed genes. Hub genes were identified using Pathway Studio software. Real-time PCR was performed to verify the selected genes.Microarray gene expression analysis showed that Pnoc, Cacfd1, Fos, Igll1, Lcn2, and Syk were among the most downregulated genes in the Qi Teng Xiao Zhuo granule group compared with the adriamycin treated group, whereas Cyp2c7, Hsd3b6, Acsm5, and Ugt2b15 were significantly upregulated. Functional analysis demonstrated that metabolism of xenobiotics by cytochrome P450, the B cell receptor signaling pathway, and cytokine-cytokine receptor interaction pathways were significantly downregulated in the Qi Teng Xiao Zhuo granule group and that GO terms related to positive regulation of immune response, immune response-activating signal transduction, cell differentiation, cell cycle, proliferation, and adhesion were significantly affected. Fos and Syk were considered to be potential hub genes.In the adriamycin-induced CGN rat model, comprehensive molecular mechanisms were involved with complex gene expression alterations containing many altered pathways and GO terms. However, how Qi Teng Xiao Zhuo granules regulate these events warrants further investigation.
- Identificationof UQCRB as an Oxymatrine Recognizing Protein Using a T7Phage Display Screen. [JOURNAL ARTICLE]
- J Ethnopharmacol 2016 Aug 3.
Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China.We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands.A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR).A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p<0.05 or p<0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and Glu91. The binding affinity constant (Kb) from SPR was 4.2mM. The Kb from ITC experiment was 3.9mM and stoichiometry was fixed as 1, which fit very well with the result of SPR. The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157kcal/mol and △G was less than zero.In this study, using the T7 phage display system, we have identified UQCRB as a direct binding protein of oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that UQCRB is a potential target of oxymatrine in treating CHB. These results provide new understanding into the mechanism of oxymatrine and insights into the strategy on the treatment of CHB.