关键词: NLRP3 inflammasome atractylenolide I gastric ulcer indomethacin nuclear factor-κB

Mesh : Animals NLR Family, Pyrin Domain-Containing 3 Protein / metabolism genetics Indomethacin / adverse effects Stomach Ulcer / drug therapy chemically induced metabolism Rats Sesquiterpenes / pharmacology chemistry Lactones / pharmacology chemistry Inflammasomes / metabolism genetics drug effects Male Rats, Sprague-Dawley Atractylodes / chemistry Gastric Mucosa / drug effects metabolism Humans NF-kappa B / genetics metabolism immunology Tumor Necrosis Factor-alpha / genetics metabolism immunology Interleukin-1beta / genetics metabolism immunology Caspase 1 / genetics metabolism Interleukin-6 / genetics metabolism immunology Interleukin-18 / genetics metabolism

来  源:   DOI:10.1021/acs.jafc.3c08188

Abstract:
Atractylodes macrocephala Koidz, a traditional Chinese medicine, contains atractylenolide I (ATR-I), which has potential anticancer, anti-inflammatory, and immune-modulating properties. This study evaluated the therapeutic potential of ATR-I for indomethacin (IND)-induced gastric mucosal lesions and its underlying mechanisms. Noticeable improvements were observed in the histological morphology and ultrastructures of the rat gastric mucosa after ATR-I treatment. There was improved blood flow, a significant decrease in the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-18, and a marked increase in prostaglandin E2 (PGE2) expression in ATR-I-treated rats. Furthermore, there was a significant decrease in the mRNA and protein expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and nuclear factor-κB (NF-κB) in rats treated with ATR-I. The results show that ATR-I inhibits the NLRP3 inflammasome signaling pathway and effectively alleviates local inflammation, thereby improving the therapeutic outcomes against IND-induced gastric ulcers in rats.
摘要:
白术,中药,含有白术内酯I(ATR-I),具有潜在的抗癌作用,抗炎,和免疫调节特性。这项研究评估了ATR-I对吲哚美辛(IND)诱导的胃粘膜病变的治疗潜力及其潜在机制。ATR-I治疗后,大鼠胃粘膜的组织学形态和超微结构得到了显着改善。血流改善了,肿瘤坏死因子-α(TNF-α)的表达显着降低,白细胞介素-6(IL-6),IL-1β,和IL-18,并且在ATR-I处理的大鼠中前列腺素E2(PGE2)表达显着增加。此外,NOD样受体热蛋白结构域相关蛋白3(NLRP3)的mRNA和蛋白表达水平显著下降,凋亡相关斑点样蛋白(ASC),半胱氨酰天冬氨酸特异性蛋白酶-1(caspase-1),ATR-I治疗大鼠的核因子-κB(NF-κB)结果表明,ATR-I抑制NLRP3炎症小体信号通路,有效缓解局部炎症,从而改善大鼠对IND诱导的胃溃疡的治疗效果。
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