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β-keto amyrin isolated from Cryptostegia grandiflora R. br. inhibits inflammation caused by Daboia russellii viper venom: Direct binding of β-keto amyrin to phospholipase A 2 .
- Source :
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Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Apr; Vol. 241, pp. 107679. Date of Electronic Publication: 2024 Mar 05. - Publication Year :
- 2024
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Abstract
- The search for mechanism-based anti-inflammatory therapies is of fundamental importance to avoid undesired off-target effects. Phospholipase A <subscript>2</subscript> (PLA <subscript>2</subscript> ) activity is a potential molecular target for anti-inflammatory drugs because it fuels arachidonic acid needed to synthesize inflammation mediators, such as prostaglandins. Herein, we aim to investigate the molecular mechanism by which β-keto amyrin isolated from a methanolic extract of Cryptostegia grandiflora R. Br. Leaves can inhibit inflammation caused by Daboia russellii viper (DR) venom that mainly contains PLA <subscript>2</subscript> . We found that β-keto amyrin neutralizes DR venom-induced paw-edema in a mouse model. Molecular docking of PLA <subscript>2</subscript> with β-keto amyrin complex resulted in a higher binding energy score of -8.86 kcal/mol and an inhibition constant of 611.7 nM. Diclofenac had a binding energy of -7.04 kcal/mol and an IC50 value of 620 nM, which predicts a poorer binding interaction than β-keto amyrin. The higher conformational stability of β-keto amyrin interaction compared to diclofenac is confirmed by molecular dynamics simulation. β-keto amyrin isolated from C. grandiflora inhibits the PLA <subscript>2</subscript> activity contained in Daboia russellii viper venom. The anti-inflammatory property of β-keto amyrin is due to its direct binding into the active site of PLA <subscript>2</subscript> , thus inhibiting its enzyme activity.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Mice
Anti-Inflammatory Agents pharmacology
Diclofenac pharmacology
Diclofenac therapeutic use
Molecular Docking Simulation
Phospholipases A2 drug effects
Phospholipases A2 metabolism
Apocynaceae chemistry
Daboia
Inflammation chemically induced
Inflammation drug therapy
Oleanolic Acid analogs & derivatives
Oleanolic Acid pharmacology
Oleanolic Acid therapeutic use
Viper Venoms chemistry
Viper Venoms toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3150
- Volume :
- 241
- Database :
- MEDLINE
- Journal :
- Toxicon : official journal of the International Society on Toxinology
- Publication Type :
- Academic Journal
- Accession number :
- 38447765
- Full Text :
- https://doi.org/10.1016/j.toxicon.2024.107679