Mangosteen peel extract attenuates aspartame-induced cerebral cortex, colon and female reproductive damages in Sprague Dawley rats

The aim of this study was to investigate the effect of mangosteen peel extract on aspartame-induced cerebral cortex, colon and female reproductive system injuries, with special focus on oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis pathways. Twenty-nine female Sprague Dawley rats were randomly divided into five groups: (i) normal diet with vehicle - control group (5 rats), (ii) low dose of aspartame group (LA) - 7 rats received 30 mg/kg body weight (bw) daily doses of aspartame, (iii) high dose of aspartame group (HA) - 7 rats received 60 mg/kg bw daily doses of aspartame, (iv) 5 rats received high dose (60 mg/kg bw) daily plus 15 mg/kg bw of mangosteen peel extract (HA+LM), and (v) 5 rats received high dose (60 mg/kg BW) plus 60 mg/kg bw of mangosteen peel extract (HA+HM). After 8 weeks, the results from LA and HA groups showed aspartame decreased the levels of BDNF and increased PGE2, COX-2 and glial fibrillary acidic protein (GFAP) expressions in brain including decreased the levels of antioxidant enzymes activity (SOD2, CAT), antioxidant marker (Nrf2), inflammatory response (IkB), mitochondrial biogenesis (Sirt1, PGC1α, Nrf1, TFAM), and apoptosis-related proteins (Bax, caspase-3) expressions. Aspartame administration also elevated oxidative stress levels (Malondialdehyde, MDA), pro-inflammatory cytokines (TNFα, IL6, IL1β), antioxidant marker expression (Keap1), inflammatory responses (iNOS, NFκB) in brain and colon. Moreover, in female reproductive system, aspartame administration changed the serum hormone level of GnRH, FSH and LH including the levels of estrogen and progesterone. However, no significantly difference was found in histological features of colon and ovary including the types and numbers of follicular cell in ovary. After 8 weeks, co-administration of aspartame with mangosteen peel extracts (HA+LM, HA+HM) attenuated aspartame-induced oxidative stress, inflammation, mitochondrial dysfunction and apoptosis through anti-inflammation, antioxidant, mitochondrial biogenesis and anti-apoptosis pathways, eventually contributing to enhanced survival of Pyramidal cells and astrocyte glia cells of cerebral cortex.