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α-红没药醇,一种膳食生物活性萜烯,可减轻大鼠乙酸诱导性结肠炎结肠黏膜中的氧化应激和炎症。

α-Bisabolol, a Dietary Bioactive Terpene Attenuates Oxidative Stress and Inflammation in Colonic Mucosa of Acetic Acid-Induced Colitis in Rats.

作者信息

Bastaki Salim M A, Amir Naheed, Ojha Shreesh, Adeghate Ernest

机构信息

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain P.O. Box 15551, Abu Dhabi, United Arab Emirates.

Department of Anatomy, College of Medicine and Health Sciences, UAE University, Al Ain P.O. Box 15551, Abu Dhabi, United Arab Emirates.

出版信息

Int J Mol Sci. 2025 Aug 22;26(17):8168. doi: 10.3390/ijms26178168.

Abstract

Inflammatory bowel diseases (IBDs), such as ulcerative colitis, and Crohn's disease are chronic idiopathic inflammatory diseases of the gastrointestinal system involving interaction between genetic and environmental factors mediating the occurrence of oxidative stress and inflammation. There is no permanent cure for IBD except long-term treatment or surgery (resection of the intestine), and the available agents in the long term appear unsatisfactory and elicit numerous adverse effects. To keep the disease in remission, prevent relapses and minimize adverse effects of currently used medicines, novel dietary compounds of natural origin convincingly appear to be one of the important therapeutic strategies for the pharmacological targeting of oxidative stress and inflammation. Therefore, it is imperative to investigate plant-derived dietary agents to overcome the debilitating conditions of IBD. In the present study, the effect of α-Bisabolol (BSB), a dietary bioactive monoterpene commonly found in many edible plants as well as important components of traditional medicines, was investigated in acetic acid (AA)-induced colitis model in rats. BSB was orally administered to Wistar male rats at a dose of 50 mg/kg/day either for 3 days before or 30 min after induction of IBD for 7 days through intrarectal administration of AA. The changes in body weight, macroscopic and microscopic analysis of the colon and calprotectin levels in the colon of rats from different experimental groups were observed on day 0, 2, 4, and 7. The levels of myeloperoxidase (MPO), a marker of neutrophil activation, reduced glutathione (GSH) and malondialdehyde (MDA), a marker of lipid peroxidation, and the levels of pro-inflammatory cytokines were measured. AA caused a significant reduction in body weight and induced macroscopic and microscopic ulcers, along with a significant decline of endogenous antioxidants (superoxide dismutase (SOD), catalase, and GSH), with a concomitant increase in MDA level and MPO activity. BSB significantly improved the AA-induced reduction in body weight, colonic mucosal histology, inhibited MDA formation, and restored antioxidant levels along with a reduction in MPO activity. AA also induced the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). Furthermore, AA also increased levels of calprotectin, a protein released by neutrophils under inflammatory conditions of the gastrointestinal tract. BSB treatment significantly reduced the release of calprotectin and pro-inflammatory cytokines. The findings of the present study demonstrate that BSB has the potential to improve disease activity and rescue colonic tissues from damage by inhibiting oxidative stress, lipid peroxidation and inflammation. The findings are suggestive of the benefits of BSB in IBD treatment and substantiate its usefulness in colitis management, along with its gastroprotective effects in gastric ulcer.

摘要

炎症性肠病(IBDs),如溃疡性结肠炎和克罗恩病,是胃肠道的慢性特发性炎症性疾病,涉及遗传和环境因素之间的相互作用,介导氧化应激和炎症的发生。除了长期治疗或手术(肠道切除)外,IBD没有永久性治愈方法,而长期可用的药物似乎并不理想,且会引发许多不良反应。为了使疾病缓解、预防复发并尽量减少当前所用药物的不良反应,天然来源的新型膳食化合物显然是针对氧化应激和炎症进行药理靶向治疗的重要策略之一。因此,研究植物源性膳食剂以克服IBD的衰弱状况势在必行。在本研究中,在大鼠乙酸(AA)诱导的结肠炎模型中研究了α-红没药醇(BSB)的作用,α-红没药醇是一种常见于许多可食用植物中的膳食生物活性单萜,也是传统药物的重要成分。通过直肠内给予AA诱导IBD 7天,在诱导前3天或诱导后30分钟,以50 mg/kg/天的剂量给Wistar雄性大鼠口服BSB。在第0、2、4和7天观察不同实验组大鼠的体重变化、结肠的宏观和微观分析以及结肠中钙卫蛋白水平。测量中性粒细胞活化标志物髓过氧化物酶(MPO)、还原型谷胱甘肽(GSH)和脂质过氧化标志物丙二醛(MDA)的水平以及促炎细胞因子的水平。AA导致体重显著下降,并诱导宏观和微观溃疡,同时内源性抗氧化剂(超氧化物歧化酶(SOD)、过氧化氢酶和GSH)显著下降,同时MDA水平和MPO活性增加。BSB显著改善了AA诱导的体重减轻、结肠黏膜组织学,抑制了MDA形成,并恢复了抗氧化剂水平,同时降低了MPO活性。AA还诱导促炎细胞因子如白细胞介素-1(IL-)、白细胞介素-23(IL-23)和肿瘤坏死因子-α(TNF-α)的释放。此外,AA还增加了钙卫蛋白的水平,钙卫蛋白是胃肠道炎症条件下中性粒细胞释放的一种蛋白质。BSB治疗显著降低了钙卫蛋白和促炎细胞因子的释放。本研究结果表明,BSB有潜力通过抑制氧化应激、脂质过氧化和炎症来改善疾病活动并挽救结肠组织免受损伤。这些发现提示了BSB在IBD治疗中的益处,并证实了其在结肠炎管理中的有用性,以及其在胃溃疡中的胃保护作用。

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