β-Citronellol: a potential anti-inflammatory and gastro-protective agent-mechanistic insights into its modulatory effects on COX-II, 5-LOX, eNOS, and ICAM-1 pathways through in vitro, in vivo, in silico, and network pharmacology studies.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2024-12-01 Epub Date: 2024-09-29 DOI:10.1007/s10787-024-01569-x

Urooj Iqbal, Abdul Malik, Nabeela Tabassum Sial, Malik Hassan Mehmood, Shoaib Nawaz, Marios Papadakis, Dalia Fouad, Hayam Ateyya, Nermeen N Welson, Athanasios Alexiou, Gaber El-Saber Batiha

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Abstract

Background: The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro, in vivo assays and in silico approaches.

Methods: In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE_2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA).

Results: β-Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat's paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE₂, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100 mg/kg) increased gastric PGE_2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues.

Conclusions: The anti-inflammatory, anti-oxidant, and gastro-protective effects of β-Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE_2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.

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β-香茅醇：一种潜在的抗炎和胃保护剂--通过体外、体内、硅学和网络药理学研究，深入了解其对 COX-II、5-LOX、eNOS 和 ICAM-1 通路的调节作用。

研究背景本研究旨在利用体外、体内试验和硅学方法评估β-香茅醇的抗炎、抗氧化和明显的胃保护活性：方法：以吡罗昔康为标准，进行了牛血清白蛋白变性、鸡蛋蛋白变性和人类红血细胞（RBC）膜稳定等体外检测。在体内评估中，使用组胺（0.1 毫升，1% w/v）和甲醛（0.1 毫升，2% v/v）来介导炎症。在吲哚美辛诱导（25 毫克/千克 i.p.）的大鼠胃溃疡中，采用了分子对接和网络药理学方法，以 25、50 和 100 毫克/千克的剂量探究了介导β-香茅醇胃保护作用的可能靶基因。此外，还对胃组织进行了形态学、组织病理学和生化分析评估，包括 PGE2、COX-I、COX-II、5-LOX、eNOS、ICAM-1、无氧自由基清除剂（SOD、CAT）和氧化应激标记物（MDA）。香茅醇能减轻大鼠爪水肿。网络药理学和对接研究显示，香茅醇可能通过花生四烯酸途径靶向 COX-I、COX-II、PGE2 和 5-LOX 起到胃保护作用。香茅醇降低了溃疡指数和组织病理学变化。此外，β-香茅醇（50 和 100 毫克/千克）增加了胃 PGE2、COX-1 和 eNOS，同时抑制了 COX-2、5-LOX 和 ICAM-1。香茅醇明显提高了离体大鼠胃组织的氧化平衡：结论：β-香茅醇通过介导 COX-I、COX-II、PGE2、5-LOX、eNOS 和 ICAM-1 等炎症标志物，对吲哚美辛诱导的大鼠胃溃疡模型具有抗炎、抗氧化和胃保护作用。

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

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]