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Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti‐inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)‐induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10–200 μM) were tested. LPS‐induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL‐1β, IL‐6, and TNF‐α) levels were quantified using ELISA, The modulation of the MAPK/NF‐κB signaling pathway was measured by western blot using specific antibodies against pathway components (p‐IκBα, IκBα, p‐p65, p65, p‐JNK, JNK, p‐ERK, ERK, p‐p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 μM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS‐induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL‐1β, IL‐6, and TNF‐α) and protein expression (iNOS and COX‐2) in LPS‐induced HGBECs. Furthermore, KPR reversed LPS‐induced elevation of p‐IκBα/IκBα, p‐p65/p65, p‐JNK/JNK, p‐ERK/ERK, and p‐p38/p38 ratios. KPR attenuates the LPS‐induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF‐κB signaling. [ABSTRACT FROM AUTHOR]

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor-mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gαt proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gαt released by Tas2R activation complexes with AChR and blocks the Gαq cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gαq-associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD. [ABSTRACT FROM AUTHOR]