Antioxidant, anti-inflammatory and antiseptic molecular actions of gedunin against lipopolysaccharide-induced sepsis in experimental rats.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Advances in Clinical and Experimental Medicine Pub Date : 2024-07-01 DOI:10.17219/acem/171537

Liyun Fang, Mao Zheng, Fengying He

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Abstract

Background: Sepsis is a life-threatening organ dysfunction without effective therapeutic options. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce sepsis. It is associated with oxidative stress, inflammation and multiple organ failure. Gedunin (GN) is a tetranortriterpenoid isolated from the Meliaceae family. Gedunin possesses numerous pharmacological properties, including antibacterial, anti-inflammatory, antiallergic, and anticancer activities. However, the molecular anti-inflammatory mechanism of GN in sepsis has not been established.

Objectives: The aim of the study was to explore the antioxidant and anti-inflammatory molecular actions underlying the antiseptic activity of GN in an LPS-induced rat model.

Material and methods: Rats were randomized into 4 sets: group 1 (control) was given 1 mL of dimethyl sulfoxide (DMSO) by gavage, group 2 rats were treated with LPS (100 μg/kg body weight (BW), intraperitoneally (ip.)), group 3 rats were given LPS (100 μg/kg BW, ip.)+GN (50 mg/kg BW in DMSO), and rats in the group 4 were given GN (50 mg/kg BW in DMSO) alone. We studied hepatic markers, inflammatory cytokines and antioxidants using specific biochemical kits and analyzed their statistical significance. Histopathology of liver, lungs and kidney tissues was also explored. The mRNA levels and conducted protein investigations were performed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, respectively.

Results: Our findings revealed that GN significantly (p < 0.05) inhibited oxidative stress, lipid peroxides, toxic markers, pro-inflammatory cytokines, and histological changes, thereby preventing multi-organ impairment. Additionally, GN attenuated the HMGβ1/NLRP3/NF-κB signaling pathway and prevented the degradation of Iκβα.

Conclusions: Gedunin is a promising natural antiseptic agent for LPS-induced sepsis in rats.

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格杜宁对脂多糖诱导的实验性大鼠败血症的抗氧化、抗炎和抗菌分子作用。

背景：脓毒症是一种危及生命的器官功能障碍，没有有效的治疗选择。脂多糖（LPS）是一种细菌内毒素，已知可诱导败血症。它与氧化应激、炎症和多器官衰竭有关。格杜宁（GN）是从木犀科植物中分离得到的一种四去甲三萜类化合物。格杜宁具有许多药理特性，包括抗菌、抗炎、抗过敏和抗癌活性。然而，GN在败血症中的分子抗炎机制尚未建立。目的：本研究的目的是探索GN在LPS诱导的大鼠模型中具有抗菌活性的抗氧化和抗炎分子作用。材料和方法：将大鼠随机分为4组：第一组（对照组）灌胃给予二甲基亚砜（DMSO）1mL，第二组大鼠用LPS（100μg/kg体重，腹腔注射），第三组大鼠给予LPS（100µg/kg体重，ip）+GN（50mg/kg体重，在DMSO中），第四组大鼠单独给予GN（50mmg/kg体重，在二甲基亚亚砜中）。我们使用特定的生化试剂盒研究了肝脏标志物、炎性细胞因子和抗氧化剂，并分析了它们的统计学意义。还对肝、肺和肾组织的组织病理学进行了探讨。分别使用实时定量逆转录聚合酶链式反应（qRT-PCR）和蛋白质印迹进行mRNA水平和蛋白质研究。结果：我们的研究结果显示，GN显著（p<0.05）抑制氧化应激、脂质过氧化物、毒性标志物、促炎细胞因子和组织学变化，从而预防多器官损伤。此外，GN减弱了HMGβ1/NLRP3/NF-κB信号通路，并阻止了Iκβα的降解。结论：格杜宁是一种很有前景的治疗LPS诱导的大鼠败血症的天然抗菌剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.70

自引率

4.80%

发文量

153

审稿时长

6-12 weeks

期刊介绍： Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.