Protective Effects of Myricetin Against Valproic Acid-Induced Endoplasmic Reticulum Stress, Apoptosis and Inflammation in Rats: Molecular Docking Analysis of PERK and IRE1
Year: 2026
Type: preprint
Abstract: Valproic acid (VPA) is a commonly prescribed broad-spectrum antiepileptic agent and remains an important first-line therapeutic option for the management of various seizure disorders. Despite its established clinical efficacy, prolonged or high-dose exposure to VPA has been associated with adverse effects on the liver and kidneys. This study aimed to investigate the potential protective effects of myricetin (MYR) against VPA-induced tissue damage and to elucidate its possible underlying mechanisms. Rats were randomly assigned to four groups: control, VPA (500 mg/kg), VPA+MYR50 (500 mg/kg VPA + 50 mg/kg MYR), and VPA+MYR100 (500 mg/kg VPA + 100 mg/kg MYR). Treatments were administered for 15 days. PERK, IRE1, p38 MAPK, Bcl-2, JNK, TNF-α, and IL-1β levels in liver and kidney tissues were determined by ELISA. Histopathological examinations were also performed. Additionally, molecular docking analyses were conducted to investigate the interactions of MYR with PERK and IRE1. VPA administration markedly increased hepatic and renal levels of PERK, IRE1, p38 MAPK, Bcl-2, MDA, TNF-α, and IL-1β compared with the control group. MYR treatment attenuated these VPA-induced alterations, with both MYR doses showing protective effects on the examined parameters. Histopathological findings were consistent with the biochemical results, demonstrating an improvement in VPA-induced tissue damage following myricetin treatment. Molecular docking analysis further indicated favorable interactions of MYR with PERK and IRE1, supporting its potential modulatory effects on VPA-induced endoplasmic reticulum stress. MYR attenuated VPA-induced hepatic and renal injury, potentially through the modulation of ER stress, inflammatory, and apoptotic pathways. The findings indicate that MYR may have therapeutic potential in preventing or reducing VPA-associated tissue toxicity.
Source: Research Square
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213894921