# Chrysin Modulates Behavior and Hippocampal Histopathology in Adult Male Hypoandrogenic Rats: The Regulatory Role of miR‐30a, miR‐375, and miR‐204

## TL;DR

Chrysin, a flavonoid, may help reduce memory loss and brain cell damage in male rats with hypoandrogenism by regulating specific microRNAs.

## Contribution

The study shows chrysin modulates miR-30a, miR-375, and miR-204 to reduce cell death and improve memory in hypoandrogenic rats.

## Key findings

- Hypoandrogenism increased apoptosis, autophagy, oxidative stress, and dark neurons while reducing memory and microRNA levels.
- Chrysin at 75 mg/kg reduced cell death, oxidative stress, and improved memory by modulating miR-30a, miR-375, and miR-204.
- Chrysin treatment reversed neurodegeneration and memory deficits caused by hypoandrogenism.

## Abstract

Hypoandrogenism, a condition linked to oxidative stress and hippocampal cell death, can lead to learning and memory disorders in aging men or those with hypogonadism. Recently, microRNAs such as miR‐30a, miR‐375, and miR‐204 have been identified as regulators of cell death and memory formation. Flavonoid antioxidants that modulate microRNA expression offer a potential therapeutic approach for neurodegenerative conditions. This study examines the effects of the flavonoid chrysin on these microRNAs, cell death processes, and memory under hypoandrogenic stress.

Rats were assigned to six groups: control, hypoandrogenic, hypoandrogenic treated with chrysin (50 mg/kg and 75 mg/kg), and chrysin treated alone (50 mg/kg and 75 mg/kg). After 14 days, memory changes were assessed using the Morris water maze test, along with evaluations of oxidative stress enzymes, apoptosis and autophagy, miR‐30a, miR‐375, and miR‐204 gene expression, and the number of dark neurons.

Hypoandrogenism increased apoptosis and autophagy gene expression, dark neurons, oxidative stress enzymes, and decreased memory and microRNA expression compared to controls. Treatment with chrysin (75 mg/kg) significantly reduced apoptosis and autophagy gene expression, dark neurons, and oxidative stress enzymes, and improved memory and learning. This group also showed modulation of miR‐30a, miR‐375, and miR‐204 levels compared to the hypoandrogenic group.

Hypoandrogenism led to neurodegeneration and memory impairment, likely due to oxidative stress affecting miR‐30a, miR‐375, and miR‐204 regulation. Chrysin (75 mg/kg) potentially mitigates cell death processes and memory deficits in hypoandrogenism by modulating these microRNAs.

Hypoandrogenism with expression disorder of miR‐30a, miR‐375, and miR‐204 leads to neurodegeneration, apoptosis, and autophagy, as well as learning and memory disorders. Chrysin mitigates cell death processes and memory deficits in hypoandrogenism by modulating these microRNAs.