Pachira macrocarpa Schltdl. & Cham., HPLC Profile, and Neuroprotective Potential via Regulation of JNK, miRNA132, and miRNA-125b

[Image: see text] In this study, we investigated the polyphenolic profile of Pachira macrocarpa Schltdl. & Cham. by HPLC analysis and we also isolated three compounds from the ethyl acetate leaf extract, which were identified by different spectral data as vitexin 1, luteolin 2, and ferulic acid 3. Moreover, we investigated the three isolated compounds and the plant extract for their therapeutic potential against AlCl(3) exposure-induced neurotoxicity in rats. This investigation aims to determine whether vitexin, luteolin, and ferulic acid in Pachira macrocarpa Schltdl. & Cham. extract (P. macrocarpa) have the ability to treat AlCl(3)-induced brain toxicity in rats. Six groups of rats were created: group 1 (normal group), group 2 treated with AlCl(3), and groups 3, 4, 5, and 6 treated with AlCl(3) with vitexin, luteolin, ferulic acid, and P. macrocarpa extract, respectively, for 28 days. Neurotoxicity was assessed by measuring plasma IL-8 and IL-33 as well as brain superoxide dismutase (SOD), glutathione reductase (GSR), B-cell lymphoma-2 (BcL-2), B-cell lymphoma-2 associated-x (Bax), and neurogranin using the ELISA technique and c-Jun N-terminal kinase (JNK), miRNA-125b, and miRNA-132 levels using western blot and PCR. HPLC analysis identified major phenolics and flavonoids. Among the phenolics identified, chlorogenic acid was prevalent (2159.14 μg/g), and regarding flavonoids, rutin was prevalent (204.69 μg/g). A significant elevation of IL-8 and IL-33 as well as brain Bax, neurogranin, and JNK levels and of miRNA-125b gene expression levels was observed following AlCl(3) exposure. However, significant depletion of SOD, GSR, BcL-2, total protein, and miRNA-132 gene expression was observed in AlCl(3)-treated rats. Administration of the P. macrocarpa extract and its isolated compounds significantly increased SOD, GSR, BcL-2, total protein, and miRNA132 gene expression and decreased IL-8 and IL-33 as well as brain Bax, neurogranin, and JNK levels and brain miRNA-125b gene expression compared to AlCl(3)-treated rats. P. macrocarpa extract and its isolated compounds ameliorated AlCl(3)-induced oxidative stress and neurotoxicity in rats.