Biological Evaluation of Aegle marmelos Fruit Extract and Isolated Aegeline in Alleviating Pain–Depression Dyad: In Silico Analysis of Aegeline on MAO-A and iNOS
Autor: | Rajbir Bhatti, Lovedeep Singh, Amrit Pal Singh, Palwinder Singh |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Drug
biology Chemistry General Chemical Engineering media_common.quotation_subject In silico fungi General Chemistry Glutathione Oxidative phosphorylation Pharmacology Article Lipid peroxidation chemistry.chemical_compound Monoamine neurotransmitter Threshold of pain biology.protein Monoamine oxidase A QD1-999 media_common |
Zdroj: | ACS Omega ACS Omega, Vol 6, Iss 3, Pp 2034-2044 (2021) |
ISSN: | 2470-1343 |
Popis: | Pain and depression have been assessed to co-occur in up to 80% of patients, and this comorbidity is more debilitating and pricier for the patients as compared to either of these disorders alone. Aegle marmelos is a well-known medicinal plant with a broad spectrum of pharmacological activities. Aegeline is a relatively unexplored molecule present in Aegle marmelos. Therefore, the current investigation aims to explore the potential of Aegle marmelos fruit extract (AMFE) and isolated aegeline against the reserpine-induced pain-depression dyad. In the current investigation, aegeline was isolated from AMFE, followed by spectroscopic characterization, i.e., using NMR and mass analyses. AMFE (200 mg kg-1 p.o) and aegeline (10 mg kg-1 p.o.) were administered to reserpinized (0.5 mg kg-1 s.c.) mice, and clorgyline (3 mg kg-1 i.p.) was taken as the standard drug. AMFE and aegeline significantly alleviated the reserpine-induced reduction in a pain threshold and an increase in immobility as observed in behavioral tests of pain and depression, respectively. In silico molecular docking studies of aegeline showed a good binding interaction at the active sites of MAO-A and iNOS. The in vivo analysis showed that AMFE and aegeline treatment significantly decreased the monoamine oxidase-A (MAO-A) activity, serum interleukin-6 (IL-6) level, and lipid peroxidation, along with an increase in the reduced glutathione level in comparison to the reserpine-treated group. Immunofluorescence studies also showed that AMFE and aegeline abrogated the reserpine-induced increase in iNOS expression. Conclusively, the results delineate that AMFE and aegeline might exert a protective effect via downregulating the MAO-A hyperactivity, IL-6 level, oxidative and nitrosative stress. |
Databáze: | OpenAIRE |
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