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- Title
7-Benzoylnimbocinol Isolated from Azadirachta indica Ameliorates Endoplasmic Reticulum (ER) Stress through the PERK Pathway.
- Authors
Mohamed, Mohamed Shabbir; Okechukwu, Patrick N.
- Abstract
Introduction: The endoplasmic reticulum (ER) is a large dynamic organelle present in eukaryotic cells, playing a vital role in processes such as protein synthesis, lipid metabolism and calcium storage. When the accumulation of misfolded proteins saturates the ER's natural capacity, it triggers ER stress, subsequently activating the unfolded protein response (UPR). This UPR mechanism is mediated through transmembrane signalling protein kinase R-like ER kinase (PERK). When the cell's coping mechanisms fall short, it can lead to apoptosis. Azadirachta indica, commonly known as Neem, is a fast-growing tree native to the Indian subcontinent and widely found throughout South Asia. A previous study from our research showed that Neem's crude extract could ameliorate ER stress by inhibiting the PERK pathway, with 7-benzoylnimbocinol identified as the major compound involved. The present study aims to evaluate the signalling pathway mediated by 7-benzoylnimbocinol in reducing ER stress in 3T3-L1 adipocyte. Method: ER stress in 3T3-L1 adipocytes was induced using 5 µg/mL of tunicamycin for 5 hours, prior to treating the cells with 10, 50 and 100 µM of 7-benzoylnimbocinol for 24 hours. Following treatment, protein extraction was performed using an appropriate lysis buffer. ELISA tests were conducted to determine the protein expression levels of PERK, ATF4, and GADD34. Results: The ELISA findings revealed that 7-benzoylnimbocinol effectively inhibited the expression of PERK and ATF4 proteins, while leading to an increase in GADD34 protein expression. Conclusion: The present results suggest that 7-benzoylnimbocinol has the potential to ameliorate ER stress by activating GADD34, while inhibiting PERK and ATF4, thus presenting a promising approach for further research in alleviating ER stress-related conditions.
- Subjects
SOUTH Asia; ENDOPLASMIC reticulum; NEEM; UNFOLDED protein response; CALCIUM metabolism; MEMBRANE proteins; PROTEIN kinases
- Publication
Malaysian Journal of Medicine & Health Sciences, 2024, Vol 20, p73
- ISSN
1675-8544
- Publication type
Abstract