Syzygium cumini (L.) Skeels improves metabolic and ovarian parameters in female obese rats with malfunctioning hypothalamus-pituitary-gonadal axis.

BACKGROUND: Obesity is a chronic and multifactorial disease characterized by increased adipose tissue. In females, obesity leads to reduced ovulation and lower chances of conception in diseases like polycystic ovary syndrome, making it important to characterize complementary medicine to attenuate such deleterious effects. Therefore, the aim of this study was to assess the effects of a hydroethanolic extract from Syzigium cumini leaves in female reproductive impairments present in the obesity model of neonatal L-monosodium glutamate injection. METHODS: Newborn Wistar rats received saline (CTRL) or L-monosodium glutamate 4 mg/g BW (MSG). At 90 days of age, CTRL and some MSG rats received saline, while others received hydroethanolic extract of S. cumini leaves (HESc 500 mg/kg/day, MSG-Syz group) for 30 consecutive days. Estrous cycle was determined by daily vaginal washes. On days 26 and 28 of treatment, oral glucose tolerance test and blood collection were performed for biochemical assessment. At the end, animals were euthanized during estrous phase; blood was collected to measure sex hormones and organs collected for weighing and histological evaluation. RESULTS: MSG-Syz showed reduced Lee Index, retroperitoneal fat pads and restored gluco-insulin axis. Moreover, HESc treatment reduced serum cholesterol levels when compared to MSG. Treatment with HESc did not restore the oligociclicity observed in obese animals, though MSG-Syz reestablished ovarian follicle health back to CTRL levels, with proliferating primordial follicles - these effects were followed by a decrease on periovarian adipocyte area. CONCLUSIONS: This is the first report to show the reversibility of the reproductive dysfunctions seen in MSG female rats through ethnopharmacological treatment. Moreover, it expands the use of HESc as a prominent tool to treat metabolic and reproductive disorders. Finally, we provide novel evidence that, without a functioning hypothalamus-pituitary-gonads axis, metabolic improvement is ineffective for estrous cyclicity, but critical for ovarian follicle health.

Early onset and progression of non-alcoholic fatty liver disease in young monosodium l-glutamate-induced obese mice.

Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R 2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.