AIM OF THE STUDY: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach.
MATERIALS AND METHODS: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model.
RESULTS: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70% ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract.
CONCLUSIONS: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote.
AIM OF THIS REVIEW: In this article, we have reviewed the literature on the phytochemicals of several Tinospora species, which have shown strong immunomodulatory effects and critically analyzed the reports to provide perspectives and instructions for future research for the plants as a potential source of new immunomodulators for use as medicinal agents or dietary supplements.
MATERIALS AND METHODS: Electronic search on worldwide accepted scientific databases (Google Scholar, Science Direct, SciFinder, Web of Science, PubMed, Wiley Online Library, ACS Publications Today) was performed to compile the relevant information. Some information was obtained from books, database on medicinal plants used in Ayurveda, MSc dissertations and herbal classics books written in various languages.
RESULTS: T. cordifolia, T. crispa, T. sinensis, T. smilacina, T. bakis, and T. sagittata have been reported to possess significant immunomodulatory effects. For a few decades, initiatives in molecular research on the effects of these species on the immune system have been carried out. However, most of the biological and pharmacological studies were carried out using the crude extracts of plants. The bioactive compounds contributing to the bioactivities have not been properly identified, and mechanistic studies to understand the immunomodulatory effects of the plants are limited by many considerations with regard to design, conduct, and interpretation.
CONCLUSION: The plant extracts and their active constituents should be subjected to more detail mechanistic studies, in vivo investigations in various animal models including pharmacokinetic and bioavailability studies, and elaborate toxicity study before submission to clinical trials.
METHODOLOGY/PRINCIPAL FINDINGS: The in vitro study demonstrated that T. indica fruit pulp had significant amount of phenolic (244.9 ± 10.1 mg GAE/extract) and flavonoid (93.9 ± 2.6 mg RE/g extract) content and possessed antioxidant activities. In the in vivo study, hamsters fed with high-cholesterol diet for ten weeks showed elevated serum triglyceride, total cholesterol, HDL-C and LDL-C levels. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters significantly lowered serum triglyceride, total cholesterol and LDL-C levels but had no effect on the HDL-C level. The lipid-lowering effect was accompanied with significant increase in the expression of Apo A1, Abcg5 and LDL receptor genes and significant decrease in the expression of HMG-CoA reductase and Mtp genes. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters also protected against oxidative damage by increasing hepatic antioxidant enzymes, antioxidant activities and preventing hepatic lipid peroxidation.
CONCLUSION/SIGNIFICANCE: It is postulated that tamarind fruit pulp exerts its hypocholesterolaemic effect by increasing cholesterol efflux, enhancing LDL-C uptake and clearance, suppressing triglyceride accumulation and inhibiting cholesterol biosynthesis. T. indica fruit pulp has potential antioxidative effects and is potentially protective against diet-induced hypercholesterolaemia.