{"title":"木犀草素通过 Notch 信号通路减少 NCR+ILC3 的消耗,从而改善小鼠的溃疡性结肠炎","authors":"","doi":"10.1016/S1875-5364(24)60568-6","DOIUrl":null,"url":null,"abstract":"<div><div>The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR<sup>-</sup>ILC3 but the depletion of NCR<sup>+</sup>ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR<sup>−</sup>ILC3 differentitating into NCR<sup>+</sup>ILC3 to improving the depletion of NCR<sup>+</sup>ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR<sup>+</sup>ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, <em>etc.</em>, was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR<sup>+</sup>ILC3, NCR<sup>+</sup>MNK3 and IL-22<sup>+</sup>ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol<sup>−1</sup> in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol<sup>−1</sup> and −7.7 kcal·mol<sup>−1</sup> homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR<sup>+</sup>ILC3 <em>via</em> Notch signaling, and it provides a basis for targeting NCR<sup>+</sup>ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway\",\"authors\":\"\",\"doi\":\"10.1016/S1875-5364(24)60568-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR<sup>-</sup>ILC3 but the depletion of NCR<sup>+</sup>ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR<sup>−</sup>ILC3 differentitating into NCR<sup>+</sup>ILC3 to improving the depletion of NCR<sup>+</sup>ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR<sup>+</sup>ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, <em>etc.</em>, was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR<sup>+</sup>ILC3, NCR<sup>+</sup>MNK3 and IL-22<sup>+</sup>ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol<sup>−1</sup> in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol<sup>−1</sup> and −7.7 kcal·mol<sup>−1</sup> homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR<sup>+</sup>ILC3 <em>via</em> Notch signaling, and it provides a basis for targeting NCR<sup>+</sup>ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.</div></div>\",\"PeriodicalId\":10002,\"journal\":{\"name\":\"Chinese Journal of Natural Medicines\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Journal of Natural Medicines\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1875536424605686\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Natural Medicines","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1875536424605686","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway
The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR-ILC3 but the depletion of NCR+ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR−ILC3 differentitating into NCR+ILC3 to improving the depletion of NCR+ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, etc., was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR+ILC3, NCR+MNK3 and IL-22+ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol−1 in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol−1 and −7.7 kcal·mol−1 homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR+ILC3 via Notch signaling, and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis.
期刊介绍:
The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM).
Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.