The mechanisms underlying the neuroprotective effects of hesperidin in a murine model of PD are not fully elucidated. The current study was carried out to investigate the ability of hesperidin in modulating proinflammatory cytokines, neurotrophic factors, and neuronal recovery in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic neuronal loss. Adult male C57BL/6 mice were randomly assigned into four groups: (I) sham/vehicle, (II) sham/hesperidin, (III) 6-OHDA/vehicle, and (IV) 6-OHDA/hesperidin. Mice received a unilateral intrastriatal injection of 6-OHDA and treated with hesperidin (50 mg/kg; per oral) for 28 days. After hesperidin treatment, mice were submitted to behavioral tests and had the striatum removed for neurochemical assays. Our results demonstrated that oral treatment with hesperidin ameliorated the anxiety-related and depressive-like behaviors in 6-OHDA-lesioned mice (p < 0.05). It also attenuated the striatal levels of proinflammatory cytokines tumor necrosis factor-α, interferon-gamma, interleukin-1β, interleukin-2, and interleukin-6 and increased the levels of neurotrophic factors, including neurotrophin-3, brain-derived neurotrophic factor, and nerve growth factor in the striatum of 6-OHDA mice (p < 0.05). Hesperidin treatment was also capable to increase striatal levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid and protects against the impairment of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (p < 0.05). In conclusion, this study indicated that hesperidin exerts anxiolytic-like and antidepressant-like effect against 6-OHDA-induced neurotoxicity through the modulation of cytokine production, neurotrophic factors levels, and dopaminergic innervation in the striatum.

尚不能完全阐明橙皮苷在PD小鼠模型中的神经保护作用的潜在机制。当前的研究是为了研究橙皮苷在6-羟基多巴胺（6-OHDA）诱导的黑色素多巴胺能神经元丢失中调节促炎细胞因子，神经营养因子和神经元恢复的能力。将成年雄性C57BL / 6小鼠随机分为四组：（I）假手术/车辆，（II）假手术/橙皮苷，（III）6-OHDA /车辆和（IV）6-OHDA /橙皮苷。小鼠单侧纹状体内注射6-OHDA，并用橙皮苷（50 mg / kg；口服）治疗28天。橙皮苷处理后，对小鼠进行行为测试，并取出纹状体进行神经化学测定。p  ＜0.05）。它还减弱了促炎性细胞因子肿瘤坏死因子-α，干扰素-γ，白介素-1β，白介素-2和白介素-6的纹状体水平，并增加了神经营养因子的水平，包括神经营养蛋白3，脑源性神经营养因子，和6-OHDA小鼠纹状体中的神经生长因子（p  <0.05）。橙皮苷治疗还能够增加纹状体多巴胺及其代谢物3,4-二羟基苯基乙酸，并保护黑质致密部（SNpc）中的多巴胺能神经元受损（p <0.05）。总之，这项研究表明橙皮苷通过调节细胞因子的产生，神经营养因子水平和纹状体的多巴胺能神经支配，对6-OHDA诱导的神经毒性具有抗焦虑和抗抑郁样作用。