Kim Hyun Ju, La Jun-Ho, Kim Hee Man, Yang Il-Suk, Sung Tae Sik
Department of Veterinary Physiology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA.
Exp Ther Med. 2019 Jun;17(6):4748-4756. doi: 10.3892/etm.2019.7469. Epub 2019 Apr 5.
() has been used to manage diarrhea, and its anti-inflammatory effects are responsible for anti-diarrheal effects. However, there are no data concerning its direct effect on colonic motility. Therefore, the effects of the major components of (baicalin, baicalein and wogonin) on colonic motility were investigated. A segment of the distal colon of rats was placed in Krebs solution to monitor spontaneous giant contractions (GCs). Changes in GCs were recorded after applying baicalin, baicalein or wogonin. After pretreatment with N-nitro-L-arginine methyl ester hydrochloride (L-NAME), 1H-(1,2,4)-oxadiazolo (4,2-a) quinoxalin-1-one (ODQ), tetradotoxin, w-conotoxin, apamin, and iberiotoxin, changes in GCs by wogonin were recorded and analyzed. The segment of the distal colon showed spontaneous GCs at a mean amplitude of 3.7±0.3 g with a frequency of 0.8±0.1/min. Baicalin, baicalein, and wogonin reduced both the amplitude and the frequency of GCs in a dose-dependent manner. Wogonin had the most potent inhibitory effect on GCs (IC was 14.6 µM in amplitude and 14.2 µM in frequency). Wogonin-induced GC reduction was not significantly affected by the inhibition of nitric oxide/cGMP pathways with L-NAME and ODQ. Blocking the enteric neurotransmission with tetradotoxin and ω-conotoxin was ineffective on the wogonin-induced reduction of GCs. Ca-activated K (K) channel blockers (apamin and iberiotoxin) significantly attenuated the inhibitory effects of wogonin on GCs (P<0.01). Wogonin was effective in inhibiting colonic motility, probably through the opening of K channels located in the smooth muscle apparatus. These findings suggest that wogonin may be a candidate drug for the management of dysmotility-related diarrhea.
()已被用于治疗腹泻,其抗炎作用是止泻作用的原因。然而,尚无关于其对结肠动力直接作用的数据。因此,研究了(黄芩苷、黄芩素和汉黄芩素)主要成分对结肠动力的影响。将大鼠远端结肠段置于 Krebs 溶液中以监测自发性巨收缩(GCs)。应用黄芩苷、黄芩素或汉黄芩素后记录 GCs 的变化。在用盐酸 N-硝基-L-精氨酸甲酯(L-NAME)、1H-(1,2,4)-恶二唑并(4,2-a)喹喔啉-1-酮(ODQ)、河豚毒素、ω-芋螺毒素、蜂毒明肽和iberiotoxin 预处理后,记录并分析汉黄芩素引起的 GCs 变化。远端结肠段显示出自发性 GCs,平均振幅为 3.7±0.3 g,频率为 0.8±0.1/min。黄芩苷、黄芩素和汉黄芩素以剂量依赖性方式降低了 GCs 的振幅和频率。汉黄芩素对 GCs 具有最有效的抑制作用(振幅的 IC 为 14.6 µM,频率的 IC 为 14.2 µM)。L-NAME 和 ODQ 对一氧化氮/cGMP 途径的抑制对汉黄芩素诱导的 GC 减少没有显著影响。用河豚毒素和ω-芋螺毒素阻断肠神经传递对汉黄芩素诱导的 GCs 减少无效。钙激活钾(K)通道阻滞剂(蜂毒明肽和iberiotoxin)显著减弱了汉黄芩素对 GCs 的抑制作用(P<0.01)。汉黄芩素可能通过打开位于平滑肌装置中的 K 通道有效抑制结肠动力。这些发现表明汉黄芩素可能是治疗动力障碍相关腹泻的候选药物。