Synergistic potential of Berberine and Wogonin improved adipose inflammation and insulin resistance associated with obesity through HIF-α axis

作者：Zihan Zhou, Mingsu Wang, Xiaoyu Zhang, Yinyue Xu, Ping Li, Zu‐Guo Zheng, Hua Yang · 发表于：Chinese Medicine · 年份：2025 · DOI：10.1186/s13020-025-01223-w · 被引用次数：7 · 研究领域：Berberine and alkaloids research、Flavonoids in Medical Research、Metabolomics and Mass Spectrometry Studies

BACKGROUND: Obesity-induced adipose hypoxia activates the hypoxia-inducible factor alpha (HIF-α) axis, where HIF-1α and HIF-2α exhibit functional antagonism: HIF-1α exacerbates insulin resistance (IR) and inflammation, whereas HIF-2α counteracts these effects. This dichotomy suggests dual targeting (inhibiting HIF-1α/activating HIF-2α) could synergistically ameliorate obesity-associated IR. Coptidis Rhizoma and Scutellariae Radix, a classic traditional Chinese medicine (TCM) pair for damp-heat obesity-demonstrate efficacy, but their synergistic components and mechanistic basis remain unclear. Therefore, this study aims to identify active ingredients through the dual targeting strategy and subsequently validate their therapeutic efficacy. METHODS: Based on the dual-targeting strategy, potential active ingredients were identified using a specifically designed dual-luciferase reporter system that simultaneously inhibits HIF-1α and activates HIF-2α. The optimal synergistic ratio was determined by applying the Loewe model. In vitro anti-inflammatory efficacy was evaluated in macrophages stimulated with palmitic acid or lipopolysaccharide. In vivo effects were assessed in a high-fat diet-induced obese mouse. Insulin sensitivity was determined by measuring fasting blood glucose levels and performing oral glucose tolerance test and insulin tolerance tests. Tissues were analysed for lipid metabolism and inflammatory markers via immunohistochemistry, quantitative real-time PCR, and enz...