Tsumura Kampo Research Laboratories, Kampo Research and Development Division, Tsumura & Co, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
J Nat Med. 2021 Jun;75(3):717-725. doi: 10.1007/s11418-021-01515-z. Epub 2021 Apr 20.
Transient receptor potential (TRP) channels are non-selective cation channels that are implicated in analgesia, bowel motility, wound healing, thermoregulation, vasodilation and voiding dysfunction. Many natural products have been reported to affect the activity of TRP channels. We hypothesize that numerous traditional herbal medicines (THMs) might exert their pharmacological activity through modulating the activity of TRP channels. The present study aimed to evaluate the effects of flavonoid aglycones and their glycosides, which are the main components of many THMs, on the TRP channel subtypes. A Ca influx assay was performed using recombinant human TRPA1, TRPV1, TRPV4 and TRPM8 cell lines. Our findings showed that flavonoid aglycones and glycycoumarin activated TRPA1. In particular, isoflavone and chalcone compounds displayed potent TRPA1 agonistic activity. Furthermore, flavone aglycones showed concomitant potent TRPM8 inhibiting activity. Indeed, flavone, isoflavone aglycones, non-prenylated chalcones and glycycoumarin were found to be TRPM8 inhibitors. Hence, flavonoid aglycones metabolized by lactase-phlorizin hydrolase and β-glucosidase in the small intestine or gut microbiota of the large intestine could generate TRPA1 agonists and TRPM8 antagonists.
瞬时受体电位 (TRP) 通道是非选择性阳离子通道，与镇痛、肠道蠕动、伤口愈合、体温调节、血管扩张和排尿功能障碍有关。许多天然产物已被报道影响 TRP 通道的活性。我们假设许多传统草药 (THM) 可能通过调节 TRP 通道的活性发挥其药理活性。本研究旨在评估黄酮苷元和其糖苷，这是许多 THM 的主要成分，对 TRP 通道亚型的影响。使用重组人 TRPA1、TRPV1、TRPV4 和 TRPM8 细胞系进行 Ca 内流测定。我们的研究结果表明，黄酮苷元和糖苷激活了 TRPA1。特别是异黄酮和查尔酮化合物显示出强烈的 TRPA1 激动活性。此外，黄酮苷元显示出同时强烈的 TRPM8 抑制活性。事实上，发现黄酮、异黄酮苷元、非prenylated 查尔酮和糖苷是 TRPM8 抑制剂。因此，在小肠中由乳糖酶-根皮苷水解酶和 β-葡萄糖苷酶代谢或在大肠中的肠道微生物群中代谢的黄酮苷元可以产生 TRPA1 激动剂和 TRPM8 拮抗剂。
