Wu Zhizhongbin, Yang Wei, Wu Tianyue, Liu Yulin, Pu Yu, Hu Weiqing, Jiang Yunbin, Zhang Jifen, Zhu Huifeng, Li Xuegang, Feng Shan
Department of Traditional Chinese Medicine, College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University, Chongqing 400715, China.
Phytomedicine. 2025 Jan;136:156292. doi: 10.1016/j.phymed.2024.156292. Epub 2024 Nov 26.
Coptidis Rhizoma, a classic bitter traditional Chinese medicine, can lead to digestive dysfunction when long-term use according to traditional experience. Bitter taste receptors have been found to regulate gastrointestinal smooth muscle contraction. Coptidis Rhizoma alkaloids are potential agonists for bitter taste receptors, but whether they can induce gastrointestinal dysfunction via bitter taste receptors is not clear.
The purpose of this study is to elucidate whether long-term Coptidis Rhizoma decoction/berberine intake can affect gastrointestinal function via bitter taste receptors.
Firstly, mice were orally administered Coptidis Rhizoma decoction (or berberine) for 8 weeks, then their appetite, gastrointestinal emptying function, colon barrier function, and gut microbiota homeostasis were evaluated. Subsequently, isolated intestine, molecular docking, calcium release, and immunofluorescence co-localization experiments were applied to explore the mechanism of Coptidis Rhizoma decoction (or berberine) inhibition effects on gastrointestinal motility. Finally, transmembrane resistance, scratch assay, tight junction and cytoskeletal protein immunofluorescence staining were conducted to verify that the bitter taste receptor is the target for Coptidis Rhizoma decoction (or berberine) to damage the colon barrier function.
Long-term Coptidis Rhizoma decoction (or berberine) intake can reduce appetite, inhibit gastrointestinal contractions, disrupt bacterial balance and colon barrier function in mice. Further mechanistic studies have shown that the alkaloids of Coptidis Rhizoma are agonists for bitter taste receptors, which can promote α-gustducin binding to CHRM3 by activating bitter taste receptors, finally inhibiting gastrointestinal smooth muscle contraction. In addition, Coptidis Rhizoma decoction (or berberine) can activate bitter taste receptors and its downstream pathways PKCβ/RhoA/ROCK1/MLC-2, reshape skeletal proteins, downregulate tight junction protein expression, and ultimately disrupt colon barrier function.
Long term Coptidis Rhizoma intake induce gastrointestinal emptying inhibition and colon barrier weaken via bitter taste receptor activation in mice.
黄连是一种典型的苦味传统中药，根据传统经验，长期使用会导致消化功能障碍。现已发现苦味受体可调节胃肠道平滑肌收缩。黄连生物碱是苦味受体的潜在激动剂，但它们是否能通过苦味受体诱导胃肠功能障碍尚不清楚。
本研究旨在阐明长期服用黄连汤剂/黄连素是否能通过苦味受体影响胃肠功能。
首先，给小鼠口服黄连汤剂（或黄连素）8周，然后评估其食欲、胃肠排空功能、结肠屏障功能和肠道微生物群稳态。随后，进行离体肠实验、分子对接、钙释放和免疫荧光共定位实验，以探讨黄连汤剂（或黄连素）对胃肠动力抑制作用的机制。最后，进行跨膜电阻、划痕实验、紧密连接和细胞骨架蛋白免疫荧光染色，以验证苦味受体是黄连汤剂（或黄连素）破坏结肠屏障功能的靶点。
长期摄入黄连汤剂（或黄连素）可降低小鼠食欲，抑制胃肠收缩，破坏细菌平衡和结肠屏障功能。进一步的机制研究表明，黄连生物碱是苦味受体的激动剂，可通过激活苦味受体促进α - 味导素与毒蕈碱型乙酰胆碱受体M3结合，最终抑制胃肠平滑肌收缩。此外，黄连汤剂（或黄连素）可激活苦味受体及其下游通路蛋白激酶Cβ/ RhoA/ROCK1/肌球蛋白轻链 - 2，重塑骨架蛋白，下调紧密连接蛋白表达，最终破坏结肠屏障功能。
长期摄入黄连可通过激活小鼠苦味受体诱导胃肠排空抑制和结肠屏障减弱。
