Zuogui Jiangtang Qinggan Formula improves glucolipid metabolism in type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease by regulating FoxO1/MTP/APOB signaling pathway / 中国中药杂志

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.

Clinical Efficacy of Modified Buyang Huanwu Tang Combined with Sanrentang in Treatment of Spleen and Kidney Deficiency and Damp-heat and Blood Stasis Syndrome in Early Diabetic Nephropathy / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of modified Buyang Huanwu Tang combined with Sanrentang in treating early diabetic nephropathy(DN)with deficiency of spleen and kidney, damp-heat and blood stasis syndrome and its effect on glucose and lipid metabolism, oxidative stress and inflammatory factors, in order to explore its mechanism. Method::A total of 72 early DN atients were randomly divided into control group and treatment group, with 36 cases in each group. The control group was orally treated with losartan potassium tablets(50 mg every time, once/day), while the treatment group was treated with modified Buyang Huanwu Tang combined with Sanrentang orally in addition to the therapy of the control group(1 dose/day). Both groups were treated for 3 months. The changes in clinical efficacy and safety indicators were observed for both groups. The 24 h urine albumin excretion rate(UAER), serum creatinine(SCr), serum cystatin C(Cys C), urea nitrogen (BUN), fasting blood glucose (FBG), 2 h postprandial blood glucose (2 hPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione Peroxidase(GSH-Px), interleukin-2(IL-2), interleukin-4(IL-4), interleukin-8(IL-8), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α)of patients in two groups were observed before and after treatment. Result::The total clinical effective rate was 88.9%in therapy group, which was higher than 61.1%in control group(P<0.05). After treatment, levels of UAER, SCr, Cys C and BUN were lower in both groups(P<0.05), and the levels in treatment group were all lower than those in control group(P<0.05). Levels of FBG, 2 hPG and HbA1c were lower in both groups(P<0.05). There was no significant difference in FBG, 2 hPG and HbA1c levels between two groups after treatment. The levels of HDL-C were higher in both groups(P<0.05), and the levels in treatment group were higher than that in control group(P<0.05). The levels of TC, TG and LDL-C were lower in both groups(P<0.05), and the levels in treatment group were all lower than those in control group(P<0.05). The level of MDA was lower in both groups(P<0.05), and the level in the treatment group was lower than that in control group(P<0.05). The levels of SOD and GSH-Px were higher in both groups(P<0.05), and the levels in the treatment group were all higher than those in the control group(P<0.05). Serum levels of IL-2, IL-8 and TNF-α were lower in both groups(P<0.05), and the levels in the treatment group were lower than those in control group(P<0.05). Serum levels of IL-4 and IL-10 were higher in both groups(P<0.05), and the levels in the treatment group was higher than those in control group(P<0.05). Conclusion::Modified Buyang Huanwu Tang combined with Sanrentang is effective and safe in the treatment of early DN with spleen and kidney deficiency, damp-heat and blood stasis syndrome. They can further improve renal function and lipid metabolism, inhibit oxidative stress reaction and regulate the secretion balance of inflammatory factors in early DN patients.