The Antiobesity Mechanisms of Polygonatum cyrtonema Hua Based on Network Analysis and Experimental Validation In Vivo and In Vitro

Abstract

Obesity is a chronic and complex disease that serves as a precursor to numerous chronic conditions. Its development is linked to gut microbiota and often accompanies inflammation and insulin resistance. The rhizome of Polygonatum cyrtonema Hua is commonly employed in the treatment of metabolic disorders. The mechanisms of P. cyrtonema Hua in treating obesity have not been deeply investigated. This study aimed to explore the protective effect and the possible mechanism of the water extract of P. cyrtonema Hua (PHWE) in high-fat diet–induced obesity in mice. We employed a combination of network pharmacology and molecular docking methods to predict the mechanisms of traditional Chinese medicine in treating obesity, followed by in vivo and in vitro validations. After a series of biological information analyses, 10 potential core targets were identified: AKT1, PPARG, ESR1, STAT3, SIRT1, PPARA, MMP9, FASN, mTOR, and IGF1R. The key pathways mainly include the AMPK signaling pathway, insulin signaling pathway, insulin resistance, and mTOR signaling pathway. In experiments conducted on live mice with obesity, PHWE was found to significantly reduce body weight, IL-6, and IL-1β levels in adipose tissue and improve insulin resistance. Based on the characteristics of obesity, the modulation of inflammation and insulin resistance by PHWE in obese mice may be related to gut microbiota. PHWE modulated the mTOR signaling pathway by decreasing the expression of mTOR, Raptor-mTORC1, and pS6K1 proteins while increasing the expression of pIRS1 and pAKT. PHWE could also regulate the protein expression of PPARγ and the key target FASN. These findings were further validated in in vitro experiments. Combining network pharmacology with in vivo and in vitro experiments, we investigated the potential mechanisms of PHWE in treating obesity. These findings provide an experimental foundation for the clinical utilization of P. cyrtonema Hua.