Devil's claw (Harpagophytum procumbens) ameliorates the neurobehavioral changes and neurotoxicity in female rats exposed to arsenic

Abstract

Over 200 million people are exposed to arsenic worldwide in their daily lives. Arsenic is a toxic ubiquitous metalloid distributed in the ground water. From the last few decades it is obtaining considerable attention for its severe neurotoxic properties. In this study the neuroprotective efficacy of devil's claw (DCW), a potent antioxidant has been investigated against arsenic induced neurotoxicity in female rats. Neurotoxicity was established by oral administration of 13 mg/kg sodium arsenite. The animals were divided into five groups (n = 6) including normal control, disease/arsenic control, standard treatment (Apocynin, 10 mg/kg), DCW treatment I (DCW, 200 mg/kg) and DCW treatment II (DCW, 400 mg/kg). Exploratory, anxiety and motor coordination related behavior of the animals was assessed using hole-board, forced swimming, beam walk and elevated plus maze tests. Findings revealed that DCW treatment ameliorated anxiety and motor in-coordination in the rats compared to the arsenic control group. In addition, arsenic induced a significant oxidative stress in arsenic only treated group, whereas co-administration with DCW the oxidative stress was reduced prominently. Arsenic control group produced gliosis and nuclear pyknosis of the brain cells which were prominently suppressed with the treatment of DCW for 21 days. The activity of DCW was in correlation with the concentration of harpagoside in the serum estimated by the HPLC method, supports that harpagoside was the active constituent responsible for neuroprotective effect. Further findings are required to understand the molecular mechanisms involved in neuroprotective effect of harpagoside and DCW.

Keywords: Arsenic; Devil's claw; Harpagophytum procumbens; Harpagoside; Neurobehavior and neurotoxicity; Neuroscience.

Figure 1

Effect of DCW on hole-board, forced swimming, beam walk and EPM tests A) Hole-board test B) Forced swim test C) Beam walk test D) % Time spent in Open field of EPM E) % Open field entries of EPM [Data was expressed as mean ± SD (n = 6); analysed by two way ANOVA followed by Bonferroni's post test.∗ = p < 0.05, considered statistically significant when compared to the normal and # = p < 0.05 when compared to the Disease control].

Figure 2

Estimation of harpagoside levels in serum by HPLC A) Standard plot of harpagoside with different concentrations B) Typical chromatogram of harpagoside C) Chromatogram of DCW 200 mg/kg serum sample D) Chromatogram of DCW 400 mg/kg Serum Sample.

Figure 3

Effect of DCW on CRP level and protein carbonyl levels A) CRP (mg/ml) in serum sample B) Protein carbonyl content (nmol/ml) in brain homogenate. [Data was expressed as mean ± SD (n = 6); analyzed by one way ANOVA followed by Bonferroni's post test.∗ = p < 0.05, considered statistically significant when compared to the normal and # = p < 0.05 when compared to the disease control].

Figure 4

Effect of DCW on brain histopathological alterations A) Normal control with normal brain histology and black arrow indicates the normal brain cells B) Arsenic control group showing pyknotic cells (green arrow) and hyperemic blood vessels (blue arrow) C) Arsenic + Apocynin 10 mg/kg D) Arsenic + DCW 200 mg/kg pyknotic cells (green arrow) and normal neuronal cells (black arrow) and E) Arsenic + DCW 400 mg/kg.