Antioxidant and anti-inflammatory properties of marmelosin from Bael (Aegle marmelos L.); Inhibition of TNF-α mediated inflammatory/tumor markers.

Abstract

Oxidative stress and inflammation are important critical factors that are implicated in almost all life style disorders such as diabetes, cardiovascular disease, ulcer and cancer. Current study aimed at isolation and characterization of a furanocoumarin from Bael (Aegle marmelos L.) fruit that can modulate both oxidative stress and inflammation effectively. Ethyl acetate extract of Bael fruit (EAFB) was subjected to HPLC for identification, purified and characterized using FTIR, NMR and ESI-MS analysis. Predominant peak of EAFB at RT 12.54 min on HPLC was identified as marmelosin with molecular weight of m/z ∼ 271.2. Marmelosin was evaluated for antioxidant, antiproliferative, apoptotic, cancer (Tyrosinase & Galectin-3) and immunomodulatory (NO, TNF-α) potentials employing standard assay systems. Marmelosin possessed potent antioxidant activity with IC50 of ∼ 15.4 ± 0.32 μM as opposed to standard - gallic acid (IC50 1.1 ± 0.08 μM), antiproliferative activity with IC50 of ∼ 6.24 ± 0.16 μM as opposed to deferoxamine (∼10.8 ± 0.28 μM) and protected cells against cellular/DNA damage. Anti-inflammatory property was evident with significant reduction in the release of NO (∼3.9 fold) and TNF-α (∼3.4 fold), a pro-inflammatory cytokine, in addition to the inhibition of NFκB (∼2.7 fold), a transcription factor in Raw 264.7 cells. Marked down regulation of galectin-3 (∼5.5 folds) and tyrosinase (∼11.1 folds) by gene expression analysis substantiated by tyrosinase inhibition (IC50 - 20.3 ± 1.26 μM Vs. Kojic acid - IC50 - 24.1 ± 1.41 μM) and molecular docking studies strengthened the cancer modulatory property of marmelosin. In addition, marmelosin induced apoptotic bodies, chromatin condensation and nulcear blebbing in Raw 264.7 cells commending the apoptotic effect of marmelosin. Marmelosin thus displayed potential multi-potent antioxidant, anti-inflammatory and anticancer properties via TNF-α mediated Akt signaling pathway.

• Authors: Hasitha Pynam, Shylaja M Dharmesh
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 106 Pg. 98-108 (Oct 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29957472 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents, Phytogenic
• Antioxidants
• Furocoumarins
• Galectin 3
• Inflammation Mediators
• Lgals3 protein, mouse
• NF-kappa B
• Plant Extracts
• Tumor Necrosis Factor-alpha
• marmelosin
• Nitric Oxide
• Monophenol Monooxygenase
• Proto-Oncogene Proteins c-akt

Topics

• Aegle (chemistry)
• Animals
• Anti-Inflammatory Agents (isolation & purification, pharmacology)
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Antioxidants (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism, pathology)
• Fibroblasts (drug effects, metabolism, pathology)
• Fruit
• Furocoumarins (chemistry, isolation & purification, pharmacology)
• Galectin 3 (metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Macrophages (drug effects, metabolism, pathology)
• Mice
• Monophenol Monooxygenase (metabolism)
• NF-kappa B (metabolism)
• NIH 3T3 Cells
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects)
• Phytotherapy
• Plant Extracts (isolation & purification, pharmacology)
• Plants, Medicinal
• Proto-Oncogene Proteins c-akt (metabolism)
• RAW 264.7 Cells
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)