Neuroprotective Effect of Aqueous Extract of Selaginella delicatula as Evidenced by Abrogation of Rotenone-Induced Motor Deficits, Oxidative Dysfunctions, and Neurotoxicity in Mice.

Oxidative stress is one of the mechanisms
implicated to play a significant role in the pathophysiology
of Parkinson’s disease. Previously, we showed that an
aqueous extract of Selaginella delicatula (SDAE) offered
robust neuroprotection against rotenone (ROT) in a Drosophila
model. In furtherance in the present study, we validated
the neuroprotective efficacy of SDAE in a chronic
ROT exposure model in mice. Initially, we assessed the
propensity of SDAE to modulate the levels of endogenous
markers in striatal region of mice. Subsequently, the neuroprotective
efficacy of SDAE (100 mg/kg bw, 21 d) to
mitigate ROT-induced striatal motor deficits, oxidative
stress, and neurotoxicity was examined employing a coexposure
paradigm. We found significant attenuation of
ROT-induced motor deficits (stride length and landing foot
spread distance) among mice given SDAE supplements.
Biochemical analysis revealed that ROT-induced elevation
in the levels of oxidative markers in cytosol/mitochondria of
striatum were normalized with SDAE supplements. In
addition, SDAE also restored the ROT-induced elevation in
the levels of oxidized and nitrated proteins. Further, SDAE
also restored the activities of acetylcholinesterase and
butyrylcholinesterase indicating its effect on cholinergic
function. While ROT exposure caused significant perturbations
in the activity levels of mitochondrial electron
transport chain enzymes (complex I/II), membrane potential
and activity of ATPases, these functions were restored to
normalcy among mice receiving SDAE suggesting its
effects on mitochondrial function. Since these data corroborate
our previous findings in Drosophila system, we propose
that the neuroprotective property of SDAE may be
largely attributed to the antioxidant properties and its ability
to attenuate mitochondrial dysfunction. However, studies
employing dopaminergic cell models would enable us to
identify specific molecular mechanism, by which SDAE
exerts neuroprotective action.