Jinlida Granules Reduce Obesity in db/db Mice by Activating Beige Adipocytes

Abstract

Recent studies indicate existence of beige adipocytes in adults. Upon activation, beige adipocytes burn energy for thermogenesis and contribute to regulation of energy balance. In this study, we have analyzed whether Jinlida granules (JLD) could activate beige adipocytes. JLD suspended in 0.5% carboxymethyl cellulose (CMC) was gavage fed to db/db mice at a daily dose of 3.8 g/kg. After 10 weeks, body weight, biochemical, and histological analyses were performed. In situ hybridization, immunofluorescence, and western blotting were conducted to test beige adipocyte activation in mice. X9 cells were induced with induction medium and maintenance medium containing 400 μg/mL of JLD. After completion of induction, cells were analyzed by Nile red staining, time polymerase chain reaction (PCR), western blotting, and immunofluorescence to understand the effect of JLD on the activation of beige adipocytes. A molecular docking method was used to preliminarily identify compounds in JLD, which hold the potential activation effect on uncoupling protein 1 (UCP1). JLD treatment significantly improved obesity in db/db mice. Biochemical results showed that JLD reduced blood glucose (GLU), triglyceride (TG), and low-density lipoprotein cholesterol (LDL) levels as well as liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in mice. Hematoxylin and eosin staining (H&E) showed that JLD reduced hepatocyte ballooning changes in the liver. Immunofluorescence showed that JLD increased the expression of the thermogenic protein, UCP1, in the beige adipose tissue of mice. JLD also increased the expression of UCP1 and inhibited the expression of miR-27a in X9 cells. Molecular docking results showed that epmedin B, epmedin C, icariin, puerarin, and salvianolic acid B had potential activation effects on UCP1. The results suggest that JLD may activate beige adipocytes by inhibiting miR-27a expression, thereby promoting thermogenesis in beige adipocytes. This study provides a new pharmacological basis for the clinical use of JLD.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities

“…Approved by the Chinese National Medical Products Administration in 2005 for treating type 2 diabetes, JLD has demonstrated potential in alleviating insulin resistance, lowering blood glucose level and glycated hemoglobin (HbA 1c ), and even reversing IGT. 11 , 12 , 13 , 14 Further foundational research underscores the comprehensive benefits of JLD, including reports of decreased weight and waist circumference in mice, 15 along with significant improvements in high-fat diet–induced obesity and fat accumulation. 15 Importantly, JLD promotes glucose and lipid homeostasis, ameliorates hepatic steatosis and inflammation, and significantly activates brown adipose tissue thermogenesis in high-fat diet–induced obese mice, enhancing mitochondrial biogenesis and fatty acid oxidation metabolism.…”

“… 11 , 12 , 13 , 14 Further foundational research underscores the comprehensive benefits of JLD, including reports of decreased weight and waist circumference in mice, 15 along with significant improvements in high-fat diet–induced obesity and fat accumulation. 15 Importantly, JLD promotes glucose and lipid homeostasis, ameliorates hepatic steatosis and inflammation, and significantly activates brown adipose tissue thermogenesis in high-fat diet–induced obese mice, enhancing mitochondrial biogenesis and fatty acid oxidation metabolism. 16 Additionally, JLD significantly reduces insulin resistance in high-fat diet–fed rats, thereby improving hyperglycemia, hyperinsulinemia, and hyperlipidemia.…”

Jinlida granules combined with metformin improved the standard-reaching rate of blood glucose and clinical symptoms of patients with type 2 diabetes: secondary analysis of a randomized controlled trial

“…Furthermore, meta-analysis and systematic reviews of Jinlida granules showed significant reductions in fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), and HbA1c ( 12 , 13 ). Animal experiments show that Jinlida granules could promote the thermogenesis of brown and beige adipocytes by enhancing the mitochondrial function and inhibiting the expression of miR-27a, thereby improving the metabolism of glucose and lipids ( 14 , 15 ). Jinlida granules could also reduce insulin resistance in rats fed with high fat by regulating phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) ( 16 ).…”

Effect of Jinlida granule on glycolipid metabolism, oxidative stress, and inflammatory factors in type 2 diabetes mellitus patients with non alcoholic fatty liver disease

“…It functions in fortifying the spleen and boosting Qi, removing blood stasis and eliminating dampness, as well as increasing blood flow to the liver and rectifying Qi. It also plays a role in controlling blood glucose in T2DM and treating T2DM-related metabolic fatty liver and peripheral neuropathy in T2DM [3]. This study analyzes the efficacy of Jinlida granules in treating T2DM with NAFLD, and the effect of Jinlida granules on the levels of oxidative stress and inflammatory factors in affected patients.…”