Compound Shouwu Jiangzhi Granule regulates triacylglyceride synthesis to alleviate hepatic lipid accumulation

• Published in: Phytomedicine (Stuttgart) 2024-07, Vol.129, p.155691-155691, Article 155691
• Main Authors: Qian, Fei, Ouyang, Bingchen, Cai, Zuhuan, Zhu, Dan, Yu, Simiao, Zhao, Jingcheng, Wei, Naijie, Wang, Guangji, Wang, Lin, Zhang, Jingwei
• Format: Article
• Language: English
• Subjects: Animals; Compound Shouwu Jiangzhi Granule; Diet, High-Fat; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Female; Humans; Lipid Metabolism - drug effects; Lipidomics; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Middle Aged; Network pharmacological; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Nonalcoholic fatty liver disease; Retrospective Studies; Triacylglyceride synthesis; Triglycerides - blood; Triglycerides - metabolism
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2024.155691

•Compound Shouwu Jiangzhi Granule (CSJG) attenuated NAFLD in both patients and mice.•CSJG moderately regulated FFAs synthesis predicted by network pharmacology.•CSJG significantly regulated TAGs synthesis so as to lower the level of TAGs in the liver. Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with few therapeutic options currently available. Traditional Chinese medicine has been used for thousands of years and exhibited remarkable advantages against such complicated disease for its “multi-component, multi-target and multi-pathway” characteristics. Compound Shouwu Jiangzhi Granule (CSJG) is a clinical empirical prescription for the treatment of NAFLD, but its pharmacological mechanism remains unknown. The clinical efficacy of CSJG was retrospectively analyzed in NAFLD patients by comparing blood biomarkers levels and liver MR images before and after CSJG treatment. Then, high-fat/high-fructose (HFHF) diet-induced NAFLD mice were used to further confirm CSJG's effect against hepatic lipid accumulation through hepatic lipid determination and histopathological staining of liver samples. Next, the ingredients of CSJG were determined, and network pharmacology analysis was performed to predict potential targets of CSJG, followed by quantitative PCR (qPCR) and western blotting for verification. Then, lipidomics study was carried out to further explore the anti-NAFLD mechanism of CSJG from the perspective of triacylglyceride (TAG) synthesis but not free fatty acid (FFA) synthesis. The enzymes involved in this process were assayed by qPCR and western blotting. The potential interactions between the key enzymes of TAG synthesis and the active ingredients of CSJG were analyzed by molecular docking. CSJG attenuated blood lipid levels and hepatic fat accumulation in both NAFLD patients and mice. Although network pharmacology analysis revealed the FFA synthesis pathway, CSJG only slightly affected it. Through lipidomics analysis, GSJG was found to significantly block the synthesis of diglycerides (DAGs) and TAGs in the liver, with decreased DGAT2 and increased PLD1 protein expression, which diverted DAGs from the synthesis of TAGs to the production of PEs, PCs and PAs and thus lowed TAGs level. Molecular docking suggested that rhein, luteolin and liquiritigenin from CSJG might be involved in this regulation. Clinical and experimental evidence demonstrated that CSJG is a promising agent for the treatment of NAFLD. CSJG regulated TAGs synth