Clinical Evidence and Potential Mechanisms of Complementary Treatment of Ling Gui Zhu Gan Formula for the Management of Serum Lipids and Obesity

OBJECTIVE: This study aims to evaluate the clinical effects of Ling Gui Zhu Gan formula (LGZG), a famous TCM formula, for the management of serum lipids and obesity and preliminarily elucidates the bioactive components and the potential mechanism. METHODS: Cluster analysis was adopted to investigate the TCM herbs and their frequency of occurrence for treating hyperlipidemia and obesity in an academic experience database of Chinese famous TCM doctors (http://www.gjmlzy.com:83). Then, relevant randomized controlled trials (RCTs) about LGZG supplementation in improving lipid levels and obesity were retrieved and analyzed. Lastly, the integration of network pharmacology, as well as greedy algorithms, which are theoretically well founded for the set cover in computer science, was exploited to identify the bioactive components of LGZG and to reveal potential mechanisms for attenuation or reversal of hyperlipidemia and obesity. RESULTS: Based on the cluster analysis of 104 cases in TCM academic experience database, four TCM herbs in LGZG showed high-use frequency for treating hyperlipidemia and obesity. Meta-analysis on 19 randomized controlled trials (RCTs) with 1716 participants indicated that LGZG supplementation significantly decreased the serum levels of total triglycerides, total cholesterol, low-density lipoprotein cholesterol, BMI, and body weight and increased high-density lipoprotein cholesterol, compared with clinical control groups. No serious adverse effect was detected in all studies. Twenty-one bioactive components of LGZG, mainly flavonoids (i.e., naringenin, kaempferol, and kumatakenin), saponins (i.e., hederagenin), and fatty acids (i.e., eicosenoic acid), had the potential benefits possibly by regulating multiple targets such as PTPN1, CYP19A1, and ESR2, as well as a few complex pathways including the TNF signaling pathway, PPAR signaling pathway, arachidonic acid metabolism, fat digestion, and absorption. CONCLUSION: The present study has proved the clinical value of LGZG as a complementary treatment for attenuation or reversal of hyperlipidemia and obesity. More high-quality clinical and experimental studies in the future are demanded to verify its effects and the precise mechanism of action.