Department of General Surgery, Dafeng People's Hospital, Yancheng, Jiangsu, China.
Department of Gastroenterology, Dafeng People's Hospital, Yancheng, Jiangsu, China.
Chem Biol Drug Des. 2024 Apr;103(4):e14519. doi: 10.1111/cbdd.14519.
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.
山奈酚(KPR)是一种存在于多种植物和食物中的类黄酮化合物,因其具有抗炎、抗氧化和抗癌特性而受到关注。在初步研究中,KPR 可以调节几种与炎症相关的信号通路,使其成为治疗胆囊炎的候选药物。本研究旨在探讨 KPR 对脂多糖(LPS)诱导的人胆囊上皮细胞(HGBECs)的作用及其机制。为了评估 KPR 对 HGBECs 的影响,将 HGBECs 分为对照组、KPR 组、LPS 组、LPS+KPR 组和 LPS+UDCA 组。通过 MTT 检测和乳酸脱氢酶(LDH)检测分别评估细胞活力和细胞毒性,检测 KPR 浓度(10-200 μM)。用 LPS 诱导 HGBECs 产生炎症反应,建立体外胆囊炎模型。采用 ELISA 检测关键炎症标志物(IL-1β、IL-6 和 TNF-α)水平,用特异性抗体通过 Western blot 检测 MAPK/NF-κB 信号通路的调节,检测通路成分(p-IκBα、IκBα、p-p65、p65、p-JNK、JNK、p-ERK、ERK、p-p38 和 p38)。50 μM KPR 对 HGBECs 的细胞活力和 LDH 水平没有显著影响,因此选择其作为最佳 KPR 干预浓度。KPR 增加了 LPS 诱导的 HGBECs 的活力。此外,KPR 抑制了 LPS 诱导的 HGBECs 中炎症因子水平(IL-1β、IL-6 和 TNF-α)和蛋白表达(iNOS 和 COX-2)。此外,KPR 逆转了 LPS 诱导的 p-IκBα/IκBα、p-p65/p65、p-JNK/JNK、p-ERK/ERK 和 p-p38/p38 比值的升高。KPR 可减轻 LPS 诱导的 HGBECs 中的炎症反应,可能是通过抑制 MAPK/NF-κB 信号通路。