Objective: This study aimed to evaluate the therapeutic potential of solid lipid nanoparticles (SLNs) containing hesperetin (HE-SLN), resveratrol (RE-SLN), and their co-administration (HE-RE-SLN) in combating oxidative stress in nigrostriatal tissue and improving neurobehavioral functions in a rotenone-induced rat model of Parkinson’s disease.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder primarily affecting older individuals, characterized by the progressive degeneration of nigrostriatal dopaminergic neurons. This degeneration leads to motor impairments, including tremors, rigidity, bradykinesia, and cognitive deficits.

Method: The double emulsion solvent displacement method was employed to prepare HE-RE-SLN vesicles. These vesicles were characterized to confirm the successful formation of drug-loaded particles and their potential for in vivo application. Rotenone was subcutaneously administered at a dose of 2 mg/kg body weight to Swiss albino rats to induce Parkinson’s disease-like symptoms. Behavioral tests, including the hang and catalepsy tests, were performed on the rats. Brain homogenates were used to assess biochemical parameters such as catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), and nitrites. Additionally, pro-inflammatory cytokines, inflammatory mediators, and histopathological analyses were conducted. The particle sizes of HE-SLN, RE-SLN, and HE-RE-SLN were found to be 134.3 ± 7, 138.3 ± 8, and 161.6 ± 5 nm, respectively.

Results: Chronic rotenone treatment caused motor deficits, reduced rearing behavior, mitochondrial dysfunction, and oxidative stress in the rat model. Surface methodology analysis showed that the optimal particle size for CE-SLN was 178.4 nm with a polydispersity index of 0.310. HE-RE-SLN treatment significantly (P<0.05) increased antioxidant levels (catalase, SOD, GPx) and reduced MDA and nitrite levels in nigrostriatal tissue. Additionally, CE-SLN improved neurobehavioral performance by increasing hanging time and reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and inflammatory mediators (iNOS, MPO, NF-kB).

Conclusion: These findings demonstrate that co-administered HE-RE-SLN alleviates oxidative stress and physiological abnormalities in rats, showing promising neuroprotective potential for the treatment of Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-effects-of-co-administered-hesperetin-and-resveratrol-nanoparticles-on-oxidative-stress-and-neurobehavioral-deficits-in-parkinsons-disease/