Neuroprotective Effect of Swertiamarin in a Rotenone Model of Parkinson’s Disease: Role of Neuroinflammation and Alpha-Synuclein Accumulation

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease with no permanent cure affecting around 1% of the population over 65. There is an urgency to search for a disease-modifying agent with fewer untoward effects. PD pathology involves the accumulation of toxic alpha-synuclein (α-syn) and neuronal inflammation leading to the degeneration of dopaminergic (DAergic) neurons. Swertiamarin (SWE), a well-studied natural product, possesses a strong anti-inflammatory effect. It is a secoiridoid glycoside isolated from Enicostemma littorale Blume. SWE showed a reversal effect on the α-syn accumulation in the 6-hydroxydopamine (6-OHDA)-induced Caenorhabditis elegans model of PD. However, there are no reports in the literature citing the effect of SWE as a neuroprotective agent in rodents. The present study aimed to evaluate the anti-inflammatory activity of SWE against lipopolysaccharide (LPS)-induced C6 glial cell activation and its neuroprotective effect in the intrastriatal rotenone mouse PD model. SWE treatment showed a significant reduction in interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels in LPS-induced C6 glial cell activation. Further, our studies demonstrated the suppression of microglial and astroglial activation in substantia nigra (SN) after administration of SWE (100 mg/kg, intraperitoneally) in a rotenone mouse model. Moreover, SWE alleviated the rotenone-induced α-syn overexpression in the striatum and SN. SWE ameliorated the motor impairment against rotenone-induced neurotoxicity and mitigated the loss of DAergic neurons in the nigrostriatal pathway. Therefore, SWE has the potential to develop as an adjunct therapy for PD, but it warrants further mechanistic studies.

Association of COVID-19 with Comorbidities: An Update

“…Furthermore, the accumulation of alpha-synuclein (α-Syn) is the major hallmark of PD. , According to previous findings, the entrance of SARS-CoV-2 into the CNS may upregulate this protein, causing aggregation. On the contrary, few studies have indicated α-Syn’s protective effect in blocking viral entry and propagation into the CNS .…”

Chemical composition and studying the possible neuroprotective effect of iridoids-rich fraction from Pentas lanceolata leaves using rotenone model of Parkinson’s disease in mice

“…The metabolite alleviated the rotenone-induced α-syn overexpression in the substantia nigra (SN) and striatum. The compound showed a reversal effect on the α-syn accumulation in the 6-hydroxydopamine-induced Caenorhabditis elegans model of PD (Sharma et al, 2022). The neuroprotective effect in the intrastriatal rotenone mouse PD model was reported and a suppression of microglial and astroglial activation in SN was exhibited after administration of this secoiridoid glycoside in a rotenone mouse model (Abdel-Salam et al, 2014).…”

Anti oxidative/neuro-inflammation properties of Withania somnifera root extract on rotenone induced stress in rat brain

“…Sharma et al . [ 32 ] has reported that just the enhanced activity of the antioxidant enzymes is not enough to control the impending damage in many conditions of oxidative stress. The observation made in the present study does corroborate with the results published by Saravanan et al .…”

“…In elderly rats, glial cell activation is more severe. A widespread increase in astrocytes and microglia is caused by unilateral rotenone infusion into the medial forebrain bundle, excluding the SN [ 32 ]. The microglial activation was observed in ROT intoxicated brains of the rat and the number of activated microglia ( Figure 5 ) were increasing with dose duration and age.…”