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

Abstract

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 JinQi-JiangTang 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 KKAy mice 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 KKAy mice. 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 (IκB α), 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 KKAy mice. 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.

UPLC-Q/TOF-MS-Based Serum Metabolomics Reveals Hypoglycemic Effects of Rehmannia glutinosa, Coptis chinensis and Their Combination on High-Fat-Diet-Induced Diabetes in KK-Ay Mice

“…Although it was observed that water extract of raw RG radix could greatly increase the weight of high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice [28]; however, the body weight of all the groups in our study increased with the experimental time and showed no significant difference among the medication groups and the model control group (Figure 1A). This result was also found in the study [29] using KK-Ay mice with the spontaneous obesity diabetic symptom. The normal control mice fed normal diet had the steady FBG levels during the experiment, ranging on average from 5.40 ± 0.76 mmol/L (at Week 0) to 7.61 ± 0.86 mmol/L (at Week 5).…”

“…The KK-Ay mice with both FBG values >7.9 mmol /L were used as diabetic models in the latter administration experiments and randomly divided into five groups containing 7 to 10 mice each. Four groups of diabetic KK-Ay mice were dosed daily by gavage with MET (200 mg/kg), RG, CC, and RG/CC (10 g/kg each) [29], respectively. Simultaneously, another fifth KK-Ay mice group (diabetic model control, abbreviated as M) and C57BL/6 J mice (normal control, abbreviated as C) were given just with the same volume of normal saline.…”

A Novel Antidiabetic Monomers Combination Alleviates Insulin Resistance Through Bacteria-Cometabolism-Inflammation Responses

“…Traditional Chinese medicine (TCM) has a long history of use for the prevention and treatment of diabetes. Recently, much evidence-based medical data has confirmed the curative effect of TCM on diabetes and associated complications (Liu Q. et al, 2017;Gao et al, 2018;Nie et al, 2019;Xiang et al, 2019). TCM Herbal formulations are guided by the principles of compatibility and of "monarch, minister, assistant, and guide, " which are applied when deciding which combination of herbs will achieve the desired effect in treating the disease (Ma et al, 2019).…”

JinQi Jiangtang Tablet Regulates Gut Microbiota and Improve Insulin Sensitivity in Type 2 Diabetes Mice

“…The researches of JQJT tablets about the active ingredients [11] and quality stability [12] showed that the major biologically active fractions of JQJT tablets are from three herbal components of Coptis chinensis (the total alkaloid fraction of C. chinensis ), Astragalus membranaceus (the saponins, polysaccharides, and astragalosides of A. membranaceus ), and Lonicera japonica (the polyphenolic acid of L. japonica ). These ingredients effectively regulate blood glucose metabolism and related inflammatory responses [13]. Previous studies have indicated that these effective components (berberine, Astragalus polysaccharide and astragaloside, chlorogenic acid) have effects on the regulation of gut microbiota [14–16] and protection of intestinal barrier function [17–19], since gut microbiota regulation is important to improve the host low-grade inflammation and insulin resistance.…”