Averrhoa Carambola L. Fruit and Stem Metabolites Profiling and Immunostimulatory Action Mechanisms Against Cyclosporine Induced Toxic Effects in Rat Model As Analyzed Using UHPLC/MS-MS-based Chemometrics and Bioassays.

The Averrhoa carambola L. tree encompasses a myriad of phytochemicals contributing to its nutritional and health benefits. The current study aims at investigating the A. carambola L. the metabolite profile grown in tropical and temperate regions represented by fruit and stem, for the first time using UPLC/MS-based molecular networking and chemometrics. Asides, assessment of the immunostimulatory effect of ripe fruit and stem, was compared in relation to metabolite fingerprints. Eighty metabolites were identified, 8 of which are first-time to be reported including 3 dihydrochalcone-C-glycosides, 4 flavonoids, and one phenolic. Multivariate data analysis revealed dihydrochalcones as origin-discriminating metabolites between temperate and tropical grown fruits. Further, an in vivo immunomodulatory assay in a cyclosporine A-induced rat model revealed a potential immune-enhancing effect as manifested by down-regulation of inflammatory markers (IL-6, INF-γ, IL-1, TLR4, and ESR) concurrent with the up-regulation of CD4 level and the CD4/CD8 ratio. Moreover, both extracts suppressed elevation of liver and kidney functions in serum as well as reduction in oxidative stress with concurrent increased levels of T-protein, albumin, globulin, and A/G ratio. This study pinpoints differences in secondary metabolite profiles amongst A. carambola L. accessions from different origins and organ type and its immunomodulatory action mechanisms.