Shouhui Tongbian Capsule ameliorates obesity by enhancing energy consumption and promoting lipolysis via cAMP-PKA pathway.

Background: The prevalence of obesity and its associated diseases has sharply increased, becoming a global health issue. White adipose tissue (WAT), responsible for lipid storage via hyperplasia and hypertrophy, and brown adipose tissue (BAT), which facilitates energy dissipation, have increasingly been recognized as critical regulators of weight loss. Shouhui Tongbian Capsule (SHTB) has traditionally been used for detoxification, weight loss, and lipid reduction, and clinical evidence supports its use for relieving constipation. In traditional Chinese medicine (TCM), "dissipating turbidity" is seen as a shared approach to treating both constipation and obesity. Our evidence suggests that SHTB improves obesity and metabolic disorders, but the underlying mechanisms remain unclear.

Objective: This study aimed to evaluate the pharmacological effects of SHTB on obesity and to explore the underlying mechanisms involved.

Methods: Obese mice induced by a high-fat diet were treated with SHTB, and effects on body weight, adipose tissue, and metabolism were assessed. Active ingredients were identified through UPLC-MS, while metabolomics and RNA sequencing were performed to explore the mechanisms of SHTB in obesity, and molecular biology techniques validated its effects on energy consumption and lipolysis in adipose tissue. Finally, rescue experiments in vivo and in vitro confirmed the proposed mechanisms.

Results: SHTB significantly reduced body weight, body fat percentage, and WAT mass while increasing BAT weight, and enhancing energy expenditure. Metabolomics and RNA sequencing indicated activation of the G-protein coupled receptor signaling and cAMP-PKA pathway, leading to increased lipolysis in WAT and enhanced thermogenesis in BAT. H89, a PKA agonist, counteracted these effects, supporting the involvement of cAMP-PKA signaling.

Conclusions: SHTB may prevent obesity by promoting lipolysis and enhancing BAT thermogenesis via the cAMP-PKA pathway, offering a potential therapeutic approach for obesity management.