Jianpi Shengqing Huazhuo Formula improves abnormal glucose and lipid metabolism in obesity by regulating mitochondrial biogenesis

Ethnopharmacological relevance: Jianpi Shengqing Huazhuo Formula (JSH) is a modified prescription based on traditional Chinese medicine theory and classic prescriptions (Buzhong Yiqi Decoction and Yuye Decoction). It has been found that JSH has a good effect on obese patients with early abnormal glucose and lipid metabolism. Therefore, this experiment was conducted to study its clinical efficacy and pharmacological effect.Aim of the study: To observe the clinical efficacy of JSH and explore the mechanism of the formula to improve glucose and lipid metabolism in obese rats.Materials and methods: 1. Clinical observation: 10 overweight/obese patients with abnormal glucose and lipid metabolism were selected to observe the indicators of serum glucose, serum lipids and liver damage of the patients before and after treatment with JSH. 2. Animal experiments: Fifty Sprague-Dawley (SD) rats were randomly divided into control group, model group, Metformin group (120 mg/kg/day), JSH-L group (5 g/kg/ day) and JSH-H group (20 g/kg/day), with 10 rats in each group.The obese SD rat model was produced by feeding 60% high-fat diet for 8 weeks, and the drug group was given prophylactic administration for 8 weeks. At the end of the experiment, body weight, abdominal fat, plasma glucose, plasma lipids, plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. The levels of interleukin-6 (IL-6), interleukin 1 beta (IL-18) and tumor necrosis factor alpha (TNF-alpha) in plasma were detected by Elisa, and the changes of malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) in plasma and liver tissue were detected by kits. The pathological changes and lipid deposition in liver were observed by HE staining and oil red O staining, and the changes in the number of mitochondria in liver cells were observed by transmission electron microscopy. RT-qPCR and Western Blot (WB) were used to detect the mitochondrial regulation-related indicators PGC-1 alpha, NRF1, TFAM, MFN2, DRP1 and apoptosis-related indicators Bcl-2, Bax, caspase 8 in liver tissue.Results: 1. Clinical observation: After one month administration, the patient's body weight, BMI, 2 h oral glucose tolerance test (2hOGTT), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) decreased significantly, and the indicators of liver damage AST and ALT also decreased significantly. 2. Animal experiments: JSH can significantly reduce body weight and abdominal fat area, improve glucose and lipid metabolism, and also reduce plasma IL-6, IL-18 and TNF-alpha content in obese rats, and improve oxidative stress; HE staining and oil red O staining also showed that JSH can alleviate liver damage and lipid deposition in the liver. Further observations of liver cell ultrastructure showed that JSH can ameliorate the reduction of liver mitochondria caused by a high-fat diet and promote the expression of indicators of mitochondrial biogenesis related to PGC-1 alpha, NRF1, and TFAM. Moreover, JSH could promote the expression of MFN2 and DRP1, decrease Bcl-2 and increase Bax in the liver.Conclusions: 1. Clinical observation: JSH can reduce body weight, serum glucose, serum lipid, and liver injury in overweight/obese patients. 2. Animal experiments: JSH regulates PGC-1 alpha/NRF1/TFAM signaling pathway promotes liver mitochondrial biogenesis, improves glucose and lipid metabolism in obese rats, and regulates mitochondrial dependent apoptosis indicators Bcl-2/Bax to reduce liver injury.