Pasala Praveen Kumar, Dsnbk Prasanth, Rudrapal Mithun, Challa Ranadheer Reddy, Ahmad Sheikh F, Vallamkonda Bhaskar, R Ram Babu
Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, JNTUA, Anantapur, Andhra Pradesh, India.
School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Jadcherla, Hyderabad, India.
Nat Prod Res. 2024 Apr 22:1-10. doi: 10.1080/14786419.2024.2344740.
Parkinson's disease (PD) is characterised by the gradual demise of dopaminergic neurons. In recent years, there has been significant interest in herbal treatments. In this study, hesperetin nanoparticles (HTN) were developed and compared their anti-PD potential with hesperetin (HT) on rotenone induced PD rats. Molecular docking was also performed to evaluate the binding affinity of hesperetin on pathological protein, i.e. D2 dopamine receptors (DR2), using Auto Dock Vina tools. The results showed a higher binding relationship of HTN on dopamine receptors (-7.2 kcal/mol) compared to L-dopa (-6.4 kcal/mol), supporting their potential as drug candidates for PD therapy. HTN was effectively synthesised using the fabrication technique and characterised by zeta potential and SEM analysis. HTN had favourable characteristics, including a size of 249.8 ± 14.9 nm and a Z-potential of -32.9 mV. After being administered orally, HTN demonstrated a notable anti-Parkinsonian effects, indicated by the significant improvement in motor function as assessed by the rota rod test ( < .001***), pole test ( < .001***), stair test ( < .01**), wood walk test ( < .01**) and an increase in substantia nigra (SN) antioxidant levels, CAT ( < .001***), SOD ( < .001***), GSH ( < .01**). Additionally, HTN led to increased dopamine levels ( < .01**) and a decrease in the oxidant system, MDA levels ( < .01**). Furthermore, histopathological examination revealed decreased SN neuronal necrosis in diseased animals treated with HTN compared to those treated with HT in a rat model of Parkinson's disease. Therefore, HTN can be regarded as a viable platform for efficient therapy of PD.
帕金森病(PD)的特征是多巴胺能神经元逐渐死亡。近年来,人们对草药治疗产生了浓厚兴趣。在本研究中,制备了橙皮素纳米颗粒(HTN),并将其与橙皮素(HT)对鱼藤酮诱导的帕金森病大鼠的抗PD潜力进行了比较。还使用自动对接Vina工具进行了分子对接,以评估橙皮素对病理蛋白即D2多巴胺受体(DR2)的结合亲和力。结果表明,与左旋多巴(-6.4kcal/mol)相比,HTN与多巴胺受体的结合关系更高(-7.2kcal/mol),这支持了它们作为帕金森病治疗候选药物的潜力。通过制备技术有效地合成了HTN,并通过zeta电位和扫描电子显微镜分析对其进行了表征。HTN具有良好的特性,包括尺寸为249.8±14.9nm和Z电位为-32.9mV。口服给药后,HTN表现出显著的抗帕金森病作用,通过转棒试验(<0.001***)、杆试验(<0.001***)、楼梯试验(<0.01**)、木走试验(<0.01**)评估的运动功能显著改善,以及黑质(SN)抗氧化水平、CAT(<0.001***)、SOD(<0.001***)、GSH(<0.01**)升高表明了这一点。此外,HTN导致多巴胺水平升高(<0.01**),氧化系统丙二醛水平降低(<0.01**)。此外,组织病理学检查显示,在帕金森病大鼠模型中,与用HT治疗的患病动物相比,用HTN治疗的患病动物SN神经元坏死减少。因此,HTN可被视为帕金森病有效治疗的可行平台。