Ginkgo biloba extract modulates astrocytic and microglial recruitment in the hippocampus and hypothalamus of menopause-induced ovariectomized rats.

Background: Changes in steroid hormone levels associated with menopause are known to affect body composition, with increased accumulation of visceral fat and impaired actions of appetite-regulating neuropeptides. Anti-obesogenic, antioxidant, anti-inflammatory and neuromodulatory properties have been attributed to Ginkgo biloba extract (GbE) oral supplementation. Hypothesis / Purpose: We investigated in menopause-induced ovariectomized rats the effects of GbE oral supplementation on microglial reactivity and astrocyte recruitment in hippocampal and hypothalamic subregions involved in the regulation of feeding behavior and energy homeostasis. Study Design / Methods: Ovariectomy (Ovx) or false-Ovx (Sham) surgery were performed in 2-month-old female Wistar rats. Sixty days after surgery, Ovx rats were gavaged daily for 14 days with either saline (Ovx+Veh) or GbE 500mg/Kg (Ovx+GbE). Rats were subsequently sacrificed, brains harvested and subjected to immunohistochemistry and immunofluorescence analyses. Results: Ovx increased microglial reactivity in CA1, CA3 and dentate gyrus (DG) in the dorsal hippocampal formation (dHF), as well as in DG in the ventral hippocampal formation (vHF). Additionally, Ovx reduced astrocyte count in dHF CA3. The disturbances found in Ovx+Veh versus Sham were not found in Ovx+GbE versus Sham. Furthermore, higher astrocyte counts in DG of both dHF and vHF were found in Ovx+GbE as compared to Ovx+Veh. In the hypothalamus, Ovx+Veh showed reduced microglial reactivity in the arcuate (ARC) and ventromedial (VMH) nuclei as compared to Ovx+GbE. Ovx+GbE rats presented higher astrocyte counts in ARC compared to Sham rats. Conclusion: Our results show for the first time in a rodent model of menopause that GbE supplementation modulates astrocyte and microglial recruitment and reactivity in hippocampal and hypothalamic subregions involved in feeding behavior and energy homeostasis. Future research employing other experimental models may further elucidate whether GbE supplementation possesses therapeutic properties upon glial cell reactivity to potentially alleviate changes in energy homeostasis associated with menopause

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment