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
{"title":"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。","authors":"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","doi":"10.1007/s10787-024-01569-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sub>2,</sub> COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA).</p><p><strong>Results: </strong>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, PGE<sub>2</sub>, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100 mg/kg) increased gastric PGE<sub>2,</sub> COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues.</p><p><strong>Conclusions: </strong>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<sub>2,</sub> 5-LOX, eNOS, and ICAM-1 inflammatory markers.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":"3761-3784"},"PeriodicalIF":4.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550294/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1007/s10787-024-01569-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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<sub>2,</sub> COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA).</p><p><strong>Results: </strong>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, PGE<sub>2</sub>, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100 mg/kg) increased gastric PGE<sub>2,</sub> COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues.</p><p><strong>Conclusions: </strong>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<sub>2,</sub> 5-LOX, eNOS, and ICAM-1 inflammatory markers.</p>\",\"PeriodicalId\":13551,\"journal\":{\"name\":\"Inflammopharmacology\",\"volume\":\" \",\"pages\":\"3761-3784\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550294/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Inflammopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10787-024-01569-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10787-024-01569-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/29 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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 PGE2, 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 PGE2, 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, PGE2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.
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 [...]
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