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.

Autor: Iqbal U; Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Pakistan., Malik A; Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Pakistan. abdul.malik@uos.edu.pk., Sial NT; Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Pakistan.; Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan., Mehmood MH; Department of Pharmaceutical Sciences, Government College University Lahore, Lahore, Pakistan.; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Lahore, Lahore, Pakistan., Nawaz S; The University of Lahore, Sargodha Campus, Sargodha, Pakistan., Papadakis M; Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany. drmariospapadakis@gmail.com., Fouad D; Department of Zoology, College of Science, King Saud University, PO Box 22452, 11495, Riyadh, Saudi Arabia., Ateyya H; Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt., Welson NN; Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef, 62511, Egypt., Alexiou A; University Centre for Research and Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India.; Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia.; Department of Research and Development, Funogen, 11741, Athens, Greece.; Department of Research and Development, AFNP Med, 1030, Vienna, Austria., Batiha GE; Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.
Jazyk: angličtina
Zdroj: Inflammopharmacology [Inflammopharmacology] 2024 Dec; Vol. 32 (6), pp. 3761-3784. Date of Electronic Publication: 2024 Sep 29.
DOI: 10.1007/s10787-024-01569-x
Abstrakt: 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, PGE 2 , 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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