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山茱萸果中单糖基裂环烯醚萜苷对功能性胃肠疾病和胃溃疡小鼠的作用。

Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice.

机构信息

Department of Biochemical Pharmacology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan; Department of Natural Product Research Sciences, Faculty of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, Nasahara, Takatsuki, Osaka, Japan.

Department of Natural Product Research Sciences, Faculty of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, Nasahara, Takatsuki, Osaka, Japan.

出版信息

Fitoterapia. 2024 Dec;179:106249. doi: 10.1016/j.fitote.2024.106249. Epub 2024 Oct 11.

DOI:10.1016/j.fitote.2024.106249
PMID:39395697
Abstract

The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT agonist. C. officinalis extract, morroniside and 5-HT receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.

摘要

山茱萸(山茱萸科)的干燥果实被用于汉方药(如八味地黄丸和归脾丸)中,以治疗老年性骨质疏松症、糖尿病、胃弛缓、尿频以及与衰老相关的腹泻/便秘。本研究旨在探讨山茱萸果实提取物和从这些果实中分离得到的环烯醚萜苷化合物莫诺苷对 5-羟色胺(5-HT)和 1-(3-氯苯基)双胍(5-HT 受体激动剂)引起的胃排空和小肠运动减少,以及 150 或 75 mM HCl/90%乙醇(HCl-EtOH)和/或 5-HT 诱导的小鼠胃溃疡的影响。山茱萸提取物(500mg/kg)和莫诺苷(20 和 50mg/kg)抑制了 5-HT 和 5-HT 激动剂引起的胃排空减少。山茱萸提取物、莫诺苷和 5-HT 受体拮抗剂(雷莫司琼)减轻了 5-HT 诱导的腹泻。此外,莫诺苷(20 和 50mg/kg)预防了乙醇/盐酸诱导的胃溃疡和由 5-HT 引起的溃疡。莫诺苷(20 和 50mg/kg)减轻了 75mM HCl/90%EtOH 和 5-HT 处理的小鼠血浆中皮质酮、促肾上腺皮质激素释放因子(CRF)和促肾上腺皮质激素(ACTH)水平的升高。本研究结果表明,莫诺苷可能是治疗由 5-HT 引起的腹泻型肠易激综合征(如胃排空和小肠运动减少)的有效药物。本研究提示,莫诺苷在通过 5-HT 处理和/或 HCl/EtOH 刺激等应激负荷引起的下丘脑-垂体-肾上腺轴活性升高,从而调节 CRF、ACTH 和皮质酮水平方面发挥作用。

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