Ho, Keat Lam and Yong, Phaik Har and Wang, Chee Woon and Lim, Siew Huah and Kuppusamy, Umah Rani and Arumugam, Bavani and Ngo, Chek Tung and Ng, Zhi Xiang (2024) In vitro anti-inflammatory activity and molecular docking of Peperomia pellucida (L.) Kunth extract via the NF-κB and PPAR-γ signalling in human retinal pigment epithelial cells. Bioorganic Chemistry, 153. p. 107969. ISSN 0045-2068, DOI https://doi.org/10.1016/j.bioorg.2024.107969.
Full text not available from this repository.Abstract
This study aims to elucidate the anti-inflammatory mechanism of Peperomia pellucida (L.) Kunth in human retinal pigment epithelial cell line (ARPE-19) as stimulated by high glucose (34 mM and 68 mM), and advanced glycation end product (AGE) under different glucose (17 mM, 34 mM and 68 mM) environments via the nuclear factor kappa B (NF-kappa B) and peroxisome proliferator activated receptor gamma (PPAR-gamma) signalling pathways. The cytotoxicity of P. pellucida in ARPE-19 cells was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The genes and proteins expression of nine pro-inflammatory, angiogenic and antioxidant markers, including glutathione peroxidase (GPx), interleukin 8, matrix metalloproteinase 2, monocyte chemoattractant protein 1, NF-kappa B, PPAR-gamma, receptor for AGE (RAGE), soluble RAGE (sRAGE), and vascular endothelial growth factor in P. pellucida-treated ARPE-19 cells were compared to non-treated control via realtime polymerase chain reaction and western blot. Both P. pellucida methanolic extract (1.5 mg/mL and 3 mg/ mL) and ethyl acetate fraction (4 mg/mL) were non-toxic to ARPE-19 cells and demonstrated cytoprotective effect against the high glucose (34 mM) and AGE (17 mM glucose)-induced cellular stress. High glucose and AGE activated the pro-inflammatory signalling in ARPE-19 cells, as evidenced by the increased NF-kappa B p65 phosphorylation, up-regulation of pro-inflammatory and angiogenic mediators (p<0.05) but reduced GPx, PPAR-gamma and sRAGE protein expression. Both P. pellucida methanolic extract (3 mg/mL) and ethyl acetate fraction (4 mg/ mL) suppressed (p<0.05) the pro-inflammatory and angiogenic markers expression under high glucose and AGE environment. The main phytochemicals identified in P. pellucida were dillapiole, 2,4,5-trimethoxystyrene, 9octadecenoic acid, and pheophorbide A-methyl ester which displayed relatively strong binding affinity towards NF-kappa B p65 and PPAR-gamma proteins in molecular docking analysis. This study has demonstrated that P. pellucida is a potential alternative anti-inflammatory source for managing diabetic retinopathy via NF-kappa B and PPAR-gamma signalling.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Malaysia (FRGS/1/2019/SKK06/UNIM/02/1), Malaysia Toray Science Foundation (210521STRG0121) |
| Uncontrolled Keywords: | Cytokine; Diabetes; Medicinal plant; Phytochemical; Retinopathy; Toxicity |
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine > Biomedical Science Department Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 24 Feb 2025 01:48 |
| Last Modified: | 24 Feb 2025 01:48 |
| URI: | http://eprints.um.edu.my/id/eprint/47298 |
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