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.

Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats.

Paraquat (PQ) is a nonselective herbicide that induces oxidative reactions and multiple-organ failure on exposure. Crocin, a carotenoid obtained from saffron, has demonstrated many therapeutic effects against neural conditions because of its antioxidant properties. In this study, 30 male Wistar rats were divided into 6 groups to evaluate the protective effects of crocin and crocin-loaded niosomes (NC) against PQ in the brain. The levels of total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), superoxide dismutase (SOD), and catalase (CAT) activity were measured as the markers of redox status. Histopathological changes in the CA1 region of the hippocampus were evaluated by cresyl violet staining. Results indicated that both crocin and NC were able to attenuate the adverse effects of PQ at the histopathological level, which was following the changes in LPO (P < 0.0001), TAC (P < 0.01), and TTG (P < 0.05) level. The activity of CAT (P < 0.01) and SOD (P < 0.01) could be restored either by crocin or NC. Also, results indicated that nanoformulation of crocin in niosomes appears to be more promising. In conclusion, both crocin and NC showed favourable effects of PQ in the brain of rats, and were determined to be excellent agents to prevent acute toxicities of PQ. Furthermore, these two compounds can be known to provide neuroprotection.