Tian Rui, Wang Wen-Xiao, Bai Ya-Ya, Tang Yu-Ping, Zhang Qiao, Yue Shi-Jun
Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi'an, China.
International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, China.
Front Pharmacol. 2024 Nov 18;15:1492047. doi: 10.3389/fphar.2024.1492047. eCollection 2024.
Coptis deltoidea C.Y. Cheng et Hsiao (CD), commonly used in the treatment of heat-toxin congestion and excessiveness. However, CD needs to be processed with wine for alleviating the bitter and cold of CD, meanwhile, reducing the gastrointestinal damage. The research assessed the discrepant effects of CD on gastrointestinal system before and after processing with wine, and explore the potential mechanisms.
The ingredients in CD and CD processed with wine (PCD) were performed on Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC-MS). The mice were treated with CD and PCD once a day for 6 weeks (0.65 and 2.6 g/kg, i.g.). The pathological changes of gastrointestinal tract were evaluated, and the serum inflammatory factors and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) RelA (p65) protein of tissues were determined. The short chain fatty acids (SCFAs) of feces were analyzed by UPLC-MS, the gut microbiota (GM) changes were performed on 16 S rRNA sequencing.
Ingredients analysis declared that the alkaloids, flavonoids, phenylpropanoid compounds were the main metabolites in CD and PCD. CD reduced body weight and food intake, and the effect of CD on fecal water content increased first and then decreased with the prolongation of administration time, while its effect on intestinal transport time was exactly the opposite, reduced the SCFAs contents of feces. CD caused different degree of damage to the gastrointestinal tract, and the effect on the small intestine and colon was more obvious, which increased the expression of NF-κB p65 and elevated the inflammatory factors levels. PCD were weaker than that of CD. In addition, CD and PCD can change the composition of GM, and reduced the levels of , , , and , increased the levels of , , , and at the genus level. However, PCD induced a milder effect of GM dysregulation than that of CD.
CD can cause damage to the gastrointestinal tract, which may be related to the GM disorders, SCFAs changes-mediated by GM, abnormal NF-κB p65 expression and increased inflammatory factors levels, interestingly, PCD had a lower effect than CD, which may be related to the differences in the types and contents of ingredients in CD after processing. And this study provided data support for the mechanism of processing with wine to alleviate "bitter-cold injury the stomach" of CD.
三角叶黄连(Coptis deltoidea C.Y. Cheng et Hsiao, CD)常用于治疗热毒壅盛。然而,黄连需酒制以减轻其苦寒之性,同时减少对胃肠道的损伤。本研究评估了黄连酒制前后对胃肠道系统的不同影响,并探讨其潜在机制。
采用超高效液相色谱-质谱联用(UPLC-MS)对黄连及酒黄连(PCD)中的成分进行分析。将小鼠每日灌胃给予黄连和酒黄连一次,持续6周(0.65和2.6 g/kg,灌胃)。评估胃肠道的病理变化,测定血清炎症因子及组织中核因子κB(NF-κB)RelA(p65)蛋白水平。采用UPLC-MS分析粪便中的短链脂肪酸(SCFAs),通过16S rRNA测序检测肠道微生物群(GM)的变化。
成分分析表明,生物碱、黄酮类、苯丙素类化合物是黄连及酒黄连中的主要代谢产物。黄连降低体重和食物摄入量,其对粪便含水量的影响随给药时间延长先升高后降低,而对肠道转运时间的影响则相反,降低了粪便中SCFAs含量。黄连对胃肠道造成不同程度损伤,对小肠和结肠的影响更明显,增加了NF-κB p65的表达并升高炎症因子水平。酒黄连的作用较黄连弱。此外,黄连和酒黄连均可改变GM的组成,在属水平上降低了[具体菌属1]、[具体菌属2]、[具体菌属3]和[具体菌属4]的水平,增加了[具体菌属5]、[具体菌属6]、[具体菌属7]和[具体菌属8]的水平。然而,酒黄连诱导的GM失调作用比黄连轻。
黄连可导致胃肠道损伤,这可能与GM紊乱、GM介导的SCFAs变化、NF-κB p65异常表达及炎症因子水平升高有关,有趣的是,酒黄连的作用比黄连弱,这可能与黄连酒制后成分种类和含量的差异有关。本研究为酒制减轻黄连“苦寒伤胃”的机制提供了数据支持。