Loureirin C extracted from Dracaena cochinchinensis SC Chen prevents rotaviral diarrhea in mice by inhibiting the intestinal Ca2+-activated Cl- channels
Loureirin C extracted from Dracaena cochinchinensis SC Chen prevents rotaviral diarrhea in mice by inhibiting the intestinal Ca2+-activated Cl- channels
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DOI：
10.1016/j.jep.2023.117077
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发表时间：
2023-08-27
影响因子：
5.4
通讯作者：
Yang，Hong
中科院分区：
文献类型：
--
作者：
Guo，Si-Cheng;Yu，Bo;Yang，Hong
龙血竭（Resina Draconis，RD）是龙血树（Dracaenacochinchinensis（Lour.）S.C.陈和大多数用作止血药在传统中医。最近的研究报道RD对胃肠道疾病有治疗作用。龙血素A、B和C（LA、LB和LC）是从RD中分离的二氢查耳酮化合物。抑制Ca 2+激活的Cl−通道（CaCCs）介导的Cl−分泌可显著减少轮状病毒腹泻的液体分泌。RD用于治疗消化系统疾病，如腹泻和腹痛;然而，药理学机制仍不清楚。本研究旨在探讨RD和龙血素对肠道Cl−通道的影响及其对轮状病毒腹泻的治疗作用，旨在揭示RD治疗轮状病毒腹泻的分子基础、作用靶点和作用机制。在上皮细胞或新鲜分离的小鼠肠组织中使用短路电流实验测试电生理特性。粪便含水量，肠道水肿率，平滑肌收缩测定新生小鼠感染SA-11轮状病毒之前和之后LC treatment or adult mice.ResultsRD，LA，LB，LC抑制CaCCs介导的Cl−电流HT-29细胞和结肠上皮。LC对CaCCs的抑制作用主要在上皮细胞的顶侧，这可能部分通过影响胞浆Ca 2+水平来产生。LC显著抑制TMEM 16 A介导的Cl−电流。表征研究表明，LC抑制基底外侧K+通道活性，而不影响Na+/K+-ATP酶活性在结肠上皮。虽然LC激活上皮细胞中的囊性纤维化跨膜调节因子，但其作用在结肠上皮中不明显。结论RD及其活性化合物LC抑制肠道CaCCs活性，可能通过抑制肠道CaCCs活性介导RD抗轮状病毒的作用。
Ethnopharmacological relevanceResina Draconis (RD) is the red resin of Dracaenacochinchinensis(Lour.) S.C. Chen and most used as a hemostatic drug in traditional Chinese medicine. Recent studies have reported that RD has a therapeutic effect on gastrointestinal diseases. Loureirin A, B, and C (LA, LB, and LC) are dihydrochalcone compounds isolated from RD.Aim of the studyDehydration is the primary cause of death in rotaviral diarrhea. Inhibition of Ca2+-activated Cl−channels (CaCCs)-mediated Cl−secretion significantly reduced fluid secretion in rotaviral diarrhea. RD was used to treat digestive diseases such as diarrhea and abdominal pain; however, the pharmacological mechanism remains unclear. This study investigated the effects of RD and loureirin on intestinal Cl−channels and their therapeutic effects on rotavirus-induced diarrhea, aiming to reveal RD's molecular basis, targets, and mechanisms for treating rotaviral diarrhea.Materials and methodsCell-based fluorescence quenching assays were used to examine the effect of RD and loureirin on Cl−channels activity. Electrophysiological properties were tested using short-circuit current experiments in epithelial cells or freshly isolated mouse intestinal tissue. Fecal water content, intestinal peristalsis rate, and smooth muscle contraction were measured in neonatal mice infected with SA-11 rotavirus before and after LC treatment or adult mice.ResultsRD, LA, LB, and LC inhibited CaCCs-mediated Cl−current in HT-29 cells and colonic epithelium. The inhibitory effect of LC on CaCCs was primarily on the apical side in epithelial cells, which may be partially produced by affecting cytoplasmic Ca2+levels. LC significantly inhibited TMEM16A-mediated Cl−current. Characterization studies revealed that LC inhibited basolateral K+channel activity without affecting Na+/K+-ATPase activity in the colonic epithelium. Although LC activated the cystic fibrosis transmembrane regulator in epithelial cells, its effect was not apparent in colonic epithelium. In vivo, LC significantly reduced the fecal water content, intestinal peristalsis rate, and smooth muscle contraction of mice infected with rotavirus.ConclusionRD and its active compound LC inhibit intestinal CaCCs activity, which might mediate the anti-rotaviral diarrheal effect of RD.