Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-R in vitro and in diabetic KKAy mice

Refined-JQ（JQ-R） is a mixture of refined extracts from Coptis chinensis（Ranunculaceae）,Astragalus membranaceus（Leguminosae） and Lonicera japonica（Caprifoliaceae）, the three major herbs of Jin Qi-Jiang Tang tablet, a traditional Chinese medicine（TCM） formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKAymice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid（PA） was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKAymice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase（SOD） and decreased malondialdehyde（MDA） as well as inducible nitric oxide synthase（iNOS） levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B（NF-κB p65）, inhibitor of NF-κB（IκBα）, c-Jun N-terminal kinase（JNK1/2） and extracellular-signal-regulated kinases（ERK1/2） were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKAymice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.