We evaluated the effects of intracerebroventricular administration (ICV) of brain estrogen and progesterone on menopausal symptoms and their effects on the secretion of follicle-stimulating hormone(FSH) and luteinizing hormone (LH) in estrogen-deficient rats. Three weeks after ovariectomy (OVX) or sham operation, OVX rats were given ICV infusions of either 17β-estradiol (4 μg/day; ICV-E), progesterone(0.8 μg/day; ICV-P), or vehicle (control) for 4 wk. OVX rats in the positive-control group were orally provided 150 μg 17β-estradiol·kg body wt·day. Sham rats had ICV vehicle infusion (normal-control). Serum 17β-estradiol levels of ICV-E and ICV-P groups were higher than the control group but much lower than the normal- and positive-control groups. Tail skin temperature was higher in the control group than the other groups. Serum FSH and LH levels were much higher in the control group than positive- and normal-control groups, but ICV-E and ICV-P lowered the levels similar to the normal-control treatment. ICV-E and ICV-P prevented the decreased energy expenditure in OVX rats. Homeostasis model assessment estimate of insulin resistance was lowered in the descending order of the control, positive-control, ICV-P, ICV-E, and normal-control treatments. The decreased bone mineral density was prevented by the positive-control, ICV-E, and ICV-P treatments. The control group exhibited decreased short-term memory and spatial memory compared with the other groups. Surprisingly, the control group exhibited a decreased richness of the gut microbiome compared with normal-control group, and ICV-E protected against the decrease the most. In conclusion, small amounts of brain estrogen and, to some extent, progesterone improved menopausal symptoms by decreasing serum FSH levels and maintaining the diversity of the gut microbiome in estrogen-deficient rats.

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Red mulberry (Morus alba) fruit is rich in anthocyanins, and mulberry leaves are used by silk worms to make silk protein. We determined that the water and ethanol extract of mulberry fruit and silk amino acids accelerated ethanol degradation and suppressed temporal cognitive dysfunction in acute alcohol administered rats. The mechanism was explored in rats with acute oral administration of silk protein and mulberry fruit extracts. Rats were given 0.3 g of dextrin (control) and water extract (WMB) and ethanol extract of mulberry (EMB), silk protein hydrolysates (SKA), and a commercial product (positive‑control) based on body weight. After 30 min, rats were administered 3 g ethanol/kg body weight and serum ethanol and acetaldehyde levels were measured. After 3 h movements were measured with a video tracking system and at 5 h cognitive function was measured by Y maze test. WMB contain much higher rutin, luteolin and quercetins than EMB. In SKA rats, serum alcohol concentrations slowly increased until 60 min, but were markedly elevated until 120 min. However, WMB rats exhibited rapidly increased serum alcohol levels until 60 min and showed the lowest peak of serum alcohol levels, indicating the highest degradation of alcohol. The patterns of serum acetaldehyde levels were similar to those of serum ethanol levels but WMB was more effective for reducing serum acetaldehyde levels than serum ethanol levels. WMB was most effective for increasing mRNA expression of alcohol dehydrogenase and acetaldehyde dehydrogenase. WMB and SKA decreased lipid peroxides by increasing activities of SOD and GSH‑Px in the liver and they also reduced pro‑inflammatory cytokines such as tumor necrosis factor‑α and interleukin‑6. WMB and SKA exerted better anti‑oxidant effects than the positive‑control. WMB containing higher flavonoids reduced pro‑inflammatory cytokines better than SKA. In conclusions, both WMB and SKA might reduce acute alcohol‑induced hangover and liver and brain damage by lowering serum alcohol and acetaldehyde levels.