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南非钩麻素 5,4'-二羟基-6,8-二甲氧基 7-O-鼠李糖苷黄酮对脂多糖诱导的小鼠肠道损伤的保护作用。

Protective effect of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone from Indigofera aspalathoides Vahl on lipopolysaccharide-induced intestinal injury in mice.

机构信息

Department of Biological Sciences, College of Science, King Faisal University, Al-Hofuf, Al-Ahsa, Saudi Arabia.

Department of Biochemistry, Centre of Molecular Medicine and Diagnostics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India.

出版信息

Inflammopharmacology. 2024 Oct;32(5):3537-3551. doi: 10.1007/s10787-024-01530-y. Epub 2024 Aug 1.

Abstract

Intestinal inflammation is one of the main health challenges affecting the quality of life of millions of people worldwide. Accumulating evidence introduces several flavonoids with multifaceted therapeutic properties in inflammatory diseases including intestinal inflammation. Herein, we examined potential anti-inflammatory properties of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone (DDR) flavone derived from Indigofera aspalathoides Vahl (I. aspalathoides Vahl) on lipopolysaccharide (LPS)-induced intestinal inflammation and injury in mice. Oral DDR treatment decreased serum levels of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β. It reduced oxidative stress through augmenting the activities of catalase (CAT) and superoxide dismutase (SOD) and reducing the level of malondialdehyde (MDA) in the duodenum and colon tissues. Moreover, DDR enhanced the activities of digestive enzymes including trypsin, pancreatic lipase, and amylase, and increased the production of short-chain fatty acids (SCFAs) by colon microbiota. Histopathological investigation of duodenum and colon revealed that DDR inhibited inflammatory infiltration and largely restored mucosal architecture and protected lining integrity. Importantly, DDR suppressed activation of nuclear factor-κB (NF-κB) signaling pathway through reduced expression of Toll-like receptor 4 (TLR4) and expression and phosphorylation of P65. The current study identified DDR as anti-inflammatory flavonoid capable of ameliorating LPS-induced intestinal inflammation through suppression of NF-κB signaling.

摘要

肠道炎症是影响全球数百万人生活质量的主要健康挑战之一。越来越多的证据表明,多种类黄酮在包括肠道炎症在内的炎症性疾病中具有多方面的治疗特性。在此,我们研究了源自蓝靛果(I. aspalathoides Vahl)的 5,4'-二羟基-6,8-二甲氧基 7-O-鼠李糖苷黄酮(DDR)对脂多糖(LPS)诱导的小鼠肠道炎症和损伤的潜在抗炎特性。口服 DDR 治疗可降低血清中促炎细胞因子 TNF-α、IL-6 和 IL-1β 的水平。它通过增强过氧化氢酶 (CAT) 和超氧化物歧化酶 (SOD) 的活性以及降低十二指肠和结肠组织中丙二醛 (MDA) 的水平来减轻氧化应激。此外,DDR 增强了包括胰蛋白酶、胰脂肪酶和淀粉酶在内的消化酶的活性,并增加了结肠微生物群产生的短链脂肪酸 (SCFA)。对十二指肠和结肠的组织学研究表明,DDR 抑制了炎症浸润,并在很大程度上恢复了黏膜结构并保护了衬里的完整性。重要的是,DDR 通过降低 Toll 样受体 4 (TLR4) 的表达以及 P65 的表达和磷酸化,抑制了核因子-κB (NF-κB) 信号通路的激活。本研究确定 DDR 是一种抗炎类黄酮,可通过抑制 NF-κB 信号通路来改善 LPS 诱导的肠道炎症。

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