In vitro and in vivo antidiabetic effect of extracts of Melia azedarach, Zanthoxylum alatum, and Tanacetum nubigenum.

BACKGROUND: To investigate the antidiabetic effect of Himalayan Medicinal plants from India viz. Melia azedarach (Family: Meliaceae), Zanthoxylum alatum (Family: Rutaceae), Tanacetum nubigenum (Family: Asteraceae) using in-vitro as well as in-vivo approaches. METHODS: Their effects were examined on stimulation of glucose uptake by C2C12 cultured cell line, inhibitory effect on human recombinant Protein tyrosine phosphatase-1B (PTP-1B) and followed by the hypoglycaemic activity of extracts in Streptozotocin (STZ) induced diabetic rats. RESULTS: All prepared extracts had been found to enrich with polyphenolic, flavonoids, terpenoids, anthraquinones and saponins type of compounds. n-Butanol fraction of Zanthoxylum alatum showed maximum PTP-1B inhibition (61.9%) whereas ethanol extract of Tanacetum nubigenum showed strong stimulation of glucose uptake (+61.2%) in C2Cl2 myotubes. In STZ induced Sprague-Dawley rats, significant decrease in blood glucose level was observed in ethanol extract of Melia azaderach treated group as 14.8% (p < 0.01) whereas in the ethanol extract of Tanacetum nubigenum treated group, it was observed as 15.5% (p < 0.01) compare to metformin which showed 26.8% (p < 0.01) lowering of blood glucose in the same time duration of 5 h study. CONCLUSION: This study demonstrated that these plants have a significant therapeutic value in type-2-diabetes mellitus and related complications thus supporting their traditional uses in Indian traditional system of medicine.

4-Hydroxyisoleucine improves insulin resistance by promoting mitochondrial biogenesis and act through AMPK and Akt dependent pathway.

4-Hydroxyisoleucine (4-HIL) is an unusual amino acid isolated from fenugreek seeds (Trigonella foenum graecum L). Various studies have shown that it acts as an antidiabetic agent yet its mechanism of action is not clear. We therefore investigated the effect 4-HIL on the high fructose diet fed streptozotocin induced diabetic rats and L6 myotubes. 4-HIL (50 mg/kg) has improved blood lipid profile, glucose tolerance and insulin sensitivity in a diabetic rat model. It has increased the glucose uptake in L6 myotubes in AMPK-dependent manner and upregulated the expression of genes (PGC-1α, PGC-1ß, CPT 1 and CPT 2), which have role in mitochondrial biogenesis and energy metabolism in the liver, skeletal muscles as well as in L6 myotubes. Interestingly, it also increased the AMPK and Akt expression along with their phosphorylated forms in the liver and muscle tissues of treated animals. Altogether we concluded that 4-HIL acts to improve insulin resistance by promoting mitochondrial biogenesis in high fructose diet fed STZ induced diabetic rats.

Bioactivity-guided chemical analysis of Melia azedarach L. (Meliaceae), displaying antidiabetic activity.

One new Euphane-type triterpenoid 3ß-hydroxytirucalla-5, 24-dien-21-oic acid (1), and ten known compounds (2-11) were isolated from Melia azedarach L. through bioassay-guided chemical analysis. The structures of the isolated compounds were established by means of 1D and 2D NMR spectroscopic ((1)H, (13)C, DEPT, COSY, HSQC and HMBC) and MS spectral analyses. All the fractions and isolated pure compounds were evaluated for antidiabetic activity by determining their inhibitory effects on PTP-1B enzyme as well as glucose uptake stimulation in C2Cl2 myoblasts cells. Compounds 4 and 7 showed significant in vitro PTP-1B inhibitory activity with 69.2 and 66.8% inhibition at 10 µg/ml concentrations respectively.