Abstract 1504: Harnessing the power of mangifera indica: Activation of Nrf2 by leaf-derived oxylipins

Abstract Mangifera indica L., a member of the Anacardiaceae family, is grown all over the world and is known for its therapeutic properties because of its abundance of bioactive chemicals. In the current study, we investigated the effect of mango leaf extract on oxidative stress in HeLa cells. At a concentration of 100 µg/mL, the n-hexane fraction (MLHx) significantly increased antioxidant response element (ARE)-luciferase activity, surpassing other fractions. Furthermore, via raising nuclear NRF2 levels, MLHx enhanced the HO-1 mRNA expression. Increased phosphorylation of ERK1/2 and stability of NRF2 are the fundamental mechanisms. Through bioactivity-guided isolation, six oxylipins were identified: 13(R)-hydroxy-octadeca-(9Z, 11E, 15Z)-trienoic acid (C-1), 9(R)-hydroxy-octadeca-(10E, 12Z, 15Z)-trienoic acid (C-2), 13(R)-hydroxy-(9Z, 11E)-octadecadienoic acid (C-3), 9(R)-hydroxy-(10E, 12Z)-octadecadienoic acid (C-4), 9-oxo-(10E, 12E)-octadecadienoic acid (C-5), and 9-oxo-(10E, 12Z)-octadecadienoic acid (C-6). Their structures were confirmed by advance spectroscopic methods, such as 1H NMR and MS. Additionally, the structures of compounds C-7 (9-oxo-(10E, 12Z, 15Z)-octadecatrienoic acid) and C-8 (13-oxo-(9E, 11E)-octadecadienoic acid) were characterized via LC-MS/MS mass fragmentation. This work is the first to disclose the isolation of components 1-6 from M. indica. In HeLa cells, compounds 3, 5, and 6 showed significant, dose-dependent stimulation of ARE-luciferase activity when tested for their impact on NRF2 activity Citation Format: Atif Ali Khan Khalil, Min Seok Woo, Jung-Hwan Kim. Harnessing the power of mangifera indica: Activation of Nrf2 by leaf-derived oxylipins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1504.