Investigation of the effects of oridonin on motor and non-motor symptoms in an LPS-induced Parkinson's disease model

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized not only by motor system dysfunction but also by non-motor symptoms such as gastrointestinal dysfunction, depression, and anxiety. Neuroinflammation plays a critical role in the pathogenesis of PD, with the activation of immune response receptors such as Toll-like receptor 4 (TLR4) being particularly important in this process. Oridonin, a natural diterpenoid, is known for its anti-inflammatory and neuroprotective effects. This study aimed to investigate the effects of oridonin on motor and non-motor symptoms in a systemic lipopolysaccharide (LPS)-induced mouse model of PD and to evaluate the involvement of TLR4/α-synuclein-related mechanisms in these effects. Seventy-two male C57BL/6 mice were divided into control, LPS, low-dose oridonin (5 mg/kg), high-dose oridonin (10 mg/kg), and combination groups (LPS+O1, LPS+O2). A systemic neuroinflammatory PD model was established by intraperitoneal administration of LPS (0.3 mg/kg). Behavioral analyses included the forced swim test for depression, open field and elevated plus maze for anxiety and locomotor activity, the pole test for motor coordination, and colon motility assessment for gastrointestinal function. Immunohistochemical methods were used to evaluate α-synuclein and tyrosine hydroxylase (TH) levels in brain and colon tissues. LPS administration resulted in impaired motor coordination, depression- and anxiety-like behaviors, and decreased gastrointestinal motility. Oridonin treatment improved these parameters in a dose-dependent manner. While TH immunoreactivity was markedly reduced in the LPS group, preservation was observed in the oridonin groups, particularly in the substantia nigra pars compacta (SNpc), striatum, and dorsolateral motor nucleus of the vagus (DMV). Moreover, α-synuclein accumulation was suppressed by oridonin treatment. This study demonstrated that oridonin alleviated motor and non-motor symptoms in the LPS-induced PD model. The underlying mechanisms likely involve the suppression of neuroinflammation, reduction of α-synuclein accumulation, and preservation of dopaminergic neurons. These findings suggest that oridonin may represent a disease-modifying candidate for PD and warrants further investigation.