肠易激综合征的治疗效果和机制及其与 TRPV1、TRPV4 和 NaV1.5 的关系研究

IF 4.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pharmaceuticals Pub Date : 2024-09-04 DOI:10.3390/ph17091170
Na-Ri Choi, Seok-Jae Ko, Joo-Hyun Nam, Woo-Gyun Choi, Jong-Hwan Lee, Seung-Yeol Nah, Jae-Woo Park, Byung-Joo Kim
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引用次数: 0

摘要

肠易激综合征(IBS)是一种胃肠道疾病,伴随着排便习惯的改变,但没有任何特定的原因。人参皂苷是从人参中新分离出来的一种糖蛋白,是溶血磷脂酸(LPA)受体配体。为了研究人参皂苷在肠易激综合征中的疗效和作用机制,我们建立了一个由紫苏糖诱导的肠易激综合征小鼠模型。此外,我们还进行了电生理实验,以确认各种离子通道的相关性。在小鼠体内,金藤素可使结肠长度和重量恢复正常,并降低粪便评分,而食物摄入量保持不变。结肠粘膜厚度和与炎症相关的肿瘤坏死因子-α水平都因金藤素而降低,与疼痛相关的行为也有所减少。此外,与对照组小鼠的微生物群相比,经金藤素治疗的小鼠粪便微生物群中乳酸菌科和乳螺旋菌科的数量相对较多,而类杆菌科的数量较少。此外,金藤素还能抑制与内脏超敏反应有关的瞬态受体电位香草素(TRPV)1 和 TRPV4 以及与消化道功能有关的电压门控 Na+ 1.5 通道。这些结果表明,金藤素可能是治疗肠易激综合征的有效成分之一。
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Study on the Therapeutic Effects and Mechanisms of Gintonin in Irritable Bowel Syndrome and Its Relationship with TRPV1, TRPV4, and NaV1.5.

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na+ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS.

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来源期刊
Pharmaceuticals
Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍: Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.
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