Berberine in combination with evodiamine ameliorates gastroesophageal reflux disease through TAS2R38/TRPV1-mediated regulation of MAPK/NF-κB signaling pathways and macrophage polarization

作者：Guoliang Cui, Manli Wang, Xiaofeng Li, Can Wang, Kinyu Shon, Zhiting Liu, Ren Lang, Xiaoxian Yang, Xiaoman Li, Yuanyuan Wu, Zhiguang Sun · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.156251 · 被引用次数：21 · 研究领域：Biochemical Analysis and Sensing Techniques、Gastrointestinal motility and disorders、Berberine and alkaloids research

BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic condition of the digestive tract with limited therapeutic options. Bitter taste receptors (TAS2Rs) and transient receptor potential vanilloid-1 (TRPV1) are implicated in modulating inflammatory responses. Berberine (BBR) and evodiamine (EVO) are known to activate TAS2Rs and TRPV1, respectively. However, whether BBR and EVO can ameliorate GERD by targeting TAS2Rs and TRPV1 remains uncertain. PURPOSE: This study aims to determine whether BBR and EVO mitigate esophageal injury by targeting TAS2R38 and TRPV1 and to elucidate their underlying molecular mechanisms. METHODS: mobilization assays. Finally, in vivo validation was conducted using U73122 to inhibit TAS2Rs and resiniferatoxin (RTX) to ablate TRPV1. RESULTS: BBR and EVO treatments significantly improved esophageal pathology in GERD rats and reduced BA-induced inflammation in HEECs. Additionally, BBR and EVO suppressed proinflammatory factors expression, upregulated barrier proteins such as E-cadherin and claudin-1, and inhibited the phosphorylation of p65, JNK, and ERK in the MAPK/NF-κB signaling pathways in both in vivo and in vitro models. Furthermore, BBR and EVO, whether individually or in combination, reduced dilated intercellular spaces (DIS), increased desmosome numbers, and modulated macrophage polarization in GERD rats. Knockdown of TAS2R38 and TRPV1 in HEECs notably diminished the stimulatory effects of BBR and EVO. Moreover, the regulation of barrie...