Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced neurocognitive, biochemical, morphological and histological alterations in Wistar rats.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE\nIn the traditional system of Indian medicine, the whole plant and roots of Achyranthes aspera L have been extensively used to treat neurological conditions such as epilepsy and stroke by the various ethnic communities of India.\n\n\nAIM OF THE STUDY\nThe present study was aimed to evaluate the cerebroprotective potential of methanol extract of A. aspera aerial parts (MeAA).\n\n\nMATERIALS AND METHODS\nInitially the MeAA was evaluated for total phenolic content and subjected to detailed liquid chromatography-mass spectrometry analysis. Additionally, it was evaluated for in vitro antioxidant activity in ferric reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity assays. Furthermore, in RAW 264.7 cell lines the effect of MeAA was evaluated on lipopolysaccharide-induced generation of reactive oxygen species, nitrite and tumor necrosis factor-α. Finally, the MeAA (400 and 800\u202fmg/kg) was evaluated against ischemia-reperfusion (I/R)-induced brain injury in rats. In brief, male Wistar rats were allocated in to five groups (G-I to G-V, n\u202f=\u202f10). G-I and G-II assigned as sham control and I/R control, and received only vehicle (carboxy methyl cellulose 0.5% w/v, 10\u202fml/kg, p.o.). G-III received quercetin (20\u202fmg/kg, p.o.) and assigned as reference standard. G-IV and G-V group animals received 400 and 800\u202fmg/kg oral doses of MeAA, respectively. All the treatments were given orally for a period of seven days and the parameters such as functional (neurological, cognitive and motor), morphological (edema and infarct area), biochemical (superoxide dismutase, catalase, reduced glutathione, lipid peroxidation, cytokines), and histopathological evaluations of the brain tissue was performed.\n\n\nRESULTS\nThe MeAA exhibited 72.48\u202fmg gallic acid equivalents/g of total phenolic content and the LC-MS/MS analysis showed acteoside, apigenin, and pentagalloyl glucose as major ingredients in the MeAA. In in vitro antioxidant assays, the MeAA showed good antioxidant activity with IC50 of 126.50\u202fμg/ml in DPPH assay; FRAP and ORAC values of 759.65 and 979.4 in FRAP and ORAC assays, respectively. Further, the MeAA significantly suppressed the generation of ROS, nitrite and TNF-α in LPS activated RAW 264.7 cell lines. Besides, sixty mins of global cerebral ischemia followed by 24\u202fh of reperfusion produced considerable alterations in neurobehavioral functions in the I/R control group compared to sham control, with a significant reduction in catalase and superoxide dismutase enzyme activities. Moreover, there was a significant reduction in reduced glutathione levels with increased lipid peroxidation. Furthermore, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10) decreased. I/R insult increased the brain volume and aggravated cerebral infarct formation. Histopathological examination of the brain tissue revealed vascular congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis. Interestingly, seven days pretreatment with MeAA (800\u202fmg/kg, p.o.) has offered significant protection against I/R-induced functional, morphological, biochemical and histopathological alterations in Wistar rats.\n\n\nCONCLUSIONS\nThese findings suggest that the MeAA possesses potent cerebroprotective action through its antioxidant and anti-inflammatory mechanisms.