Effects of Zuogui Jiangtang Qingzhi Formula on the cGAS/STING/TBK1 signaling pathway in mice with type 2 diabetes mellitus combined with non-alcoholic fatty liver disease
10.3969/j.issn.1006-2157.2025.03.010
- VernacularTitle:左归降糖清脂方对2型糖尿病合并非酒精性脂肪性肝病小鼠cGAS/STING/TBK1信号通路的影响
- Author:
Yangyang GOU
1
;
Jiahui MA
1
;
Cong CHEN
1
Author Information
1. School of Basic Medicine, Guizhou University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
type 2 diabetes mellitus;
non-alcoholic fatty liver disease;
Zuogui Jiangtang Qingzhi Formula;
cyclic GMP-AMP synthase/stimulator of interferon genes/TANK-binding kinase 1 signaling pathway;
mice
- From:
Journal of Beijing University of Traditional Chinese Medicine
2025;48(3):370-378
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate how Zuogui Jiangtang Qingzhi Formula (ZGJTQZF), a traditional Chinese medicine compound for lowering blood glucose levels and clearing lipids based on Zuogui Pill, regulates the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) signaling pathway to improve type 2 diabetes mellitus combined with non-alcoholic fatty liver disease.
Methods:According to fasting blood glucose (FBG) levels, body weight, and sex, 40 MKR mice, with half being male and the other half female, were randomly divided into four groups: blank, model, ZGJTQZF (29.6 g/kg), metformin + simvastatin ([65.0+ 2.6] mg/kg), 10 mice per group, and a normal group consisting of 10 age-matched FVB mice. Mice in all groups, except in the normal and blank groups, were fed a high-fat diet for 8 weeks to induce the disease model. Each group received daily gavage of the respective treatments for 8 weeks after successful modeling. Various parameters were measured, including FBG, liver function (alanine aminotransferase [ALT] and aspartate transaminase [AST]), and blood lipids (triglyceride [TG] and total cholesterol [TC]). Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using enzyme-linked immunosorbent assays. Histological liver changes were examined using transmission electron and optical microscope. cGAS, STING, and TBK1 protein and mRNA expression levels in liver tissues were detected using Western blotting and real-time PCR, respectively.
Results:Compared with the normal group, the model group exhibited significant fat accumulation in hepatocytes and liver damage. Additionally, FBG, ALT, AST, serum TNF-α, IL-6, cGAS, STING and TBK1 expression levels in liver tissues were significantly elevated (P<0.05). Treatment with ZGJTQZF and metformin + simvastatin significantly improved FBG, ALT, AST, TG, TC, TNF-α, and IL-6 (P<0.01). Histologically, hepatic steatosis was notably alleviated. Expression of protein and mRNA of cGAS, STING, and TBK1 in liver tissues was significantly reduced (P<0.05).
Conclusion:ZGJTQZF improves lipid and glucose metabolism, mitigates liver injury, and reduces inflammatory markers in MKR mice. These effects may be mediated through the regulation of the cGAS/STING/TBK1 signaling pathway.
- Full text:2025052116164144287Effects of Zuogui Jiangtang Qingzhi Formula on the cGAS_STING_TBK1 signaling pathway in mice with type 2 diabetes mellitus combined with non-alcoholic fatty liver disease.pdf
