Quercetin's Restorative Properties in Male Mice with 3-Nitropropionic Acid-induced Huntington-like Symptoms: Molecular Docking, Behavioral, and Biochemical Assessment.

The neurotoxicity of 3-Nitropropionic acid (3-NP) is well known. Herein, the prophylactic versus therapeutic effects of quercetin (QCT) were investigated against 3-NP-induced behavioral anomalies and oxidative neural damage. Thirty male mice were assigned into five groups; the negative control group, the QCT group (25 mg/kg/day, p.o. for 21 days), the 3-NP group (17 days), the prophylactic group (QCT administration for 14 consecutive days, and then 3-NP was administrated), the therapeutic group (3-NP was administrated and then QCT for 21 days). At the end of the animal treatment, behavioral studies were assessed. Subsequently, the brain sample tissues were assessed for oxidative stress-related parameters and histological evaluation. Moreover, the potential interaction between 3-NP and tumor necrosis factor-alpha (TNF-α) was evaluated by using a molecular docking study. 3-NP markedly led to neurotoxicity which was indicated by behavioral deficits (motor behavior, depression-like behavior, memory dysfunction, and passive avoidance) and oxidative damage. Blind and targeted molecular docking results showed good interaction between 3-NP and TNF-α. However, the prophylactic effects of QCT were superior to the therapeutic effects for attenuating 3-NP-induced neurobehavioral and oxidative neural changes in experimental mice, which histological changes of the brain's striatum region approved our findings. Taken together, the antioxidant activity of QCT remarkably could attenuate 3-NP-induced neurobehavioral deficits and mitochondrial dysfunctions in mice.

Neuroprotective effects of silymarin in 3-nitropropionic acid-induced neurotoxicity in male mice: improving behavioral deficits by attenuating oxidative stress and neuroinflammation.

3-Nitropropionic acid (3-NP) is strongly believed to be an irreversible inhibitor of mitochondrial complex II, leading to neural damage. This study aimed to investigate the neuroprotective effects of silymarin against 3-NP-induced neurotoxicity in male mice. Six-week-old mice received subacute doses of 3-NP intraperitoneally for 17 days. Mice were given silymarin (70 mg/kg/day, P.O.) for 2 weeks before 3-NP administration or for 4 weeks after 3-NP administration. At the end of the treatment schedule, animals were evaluated for behavioral alterations. Subsequently, neuronal damage in the hippocampus region of the brain tissues, oxidative stress-related parameters (lipid peroxidation, nitric oxide, superoxide dismutase, glutathione, and total antioxidant capacity), and pro-inflammatory cytokine (TNF-α, IL-17, and IL-1ß) levels were evaluated. Our results indicated that 3-NP treatment significantly (p < 0.05) tended to reduce motor coordination, memory, and neuronal antioxidant status while increasing pro-inflammatory cytokine levels. However, silymarin in both treatment and pretreatment protocols markedly (p < 0.05) attenuated the behavioral deficits, oxidative stress status, and neuroinflammation. The results of the current study suggest that the neuroprotective effect of silymarin against 3-NP-induced neurotoxicity might be due to the mitigation of oxidative stress status and provide insight into the therapeutic potential of silymarin.