Harpagophytum Procumbens Ethyl Acetate Fraction Reduces Fluphenazine-Induced Vacuous Chewing Movements and Oxidative Stress in Rat Brain

Abstract

Long-term treatment with fluphenazine is associated with manifestation of extrapyramidal side effects, such as tardive dyskinesia. The molecular mechanisms related to the pathophysiology of TD remain unclear, and several hypotheses, including a role for oxidative stress, have been proposed. Harpagophytum procumbens is an herbal medicine used mainly due to anti-inflammatory effects, but it also exhibits antioxidant effects. We investigated the effect of ethyl acetate fraction of H. procumbens (EAF HP) in fluphenazine-induced orofacial dyskinesia by evaluating behavioral parameters at different times (vacuous chewing movements (VCM's) and locomotor and exploratory activity), biochemical serological analyses, and biochemical markers of oxidative stress of the liver, kidney, cortex, and striatum. Chronic administration of fluphenazine (25 mg/kg, intramuscular (i.m) significantly increased the VCMs at all analyzed times (2, 7, 14, and 21 days), and this was inhibited by EAF HP (especially at a dose of 30 mg/kg). Fluphenazine decreased locomotion and exploratory activity, and EAF HP did not improve this decrease. Fluphenazine induced oxidative damage, as identified by changes in catalase activity and ROS levels in the cortex and striatum, which was reduced by EAF HP, especially in the striatum. In the cortex, EAF HP was protective against fluphenazine-induced changes in catalase activity but not against the increase in ROS level. Furthermore, EAF HP was shown to be safe, since affected serum biochemical parameters or parameters of oxidative stress in the liver and kidney. These findings suggest that the H. procumbens is a promising therapeutic agent for the treatment of involuntary oral movements.

Alteration of Cytokines Levels in the Striatum of Rats: Possible Participation in Vacuous Chewing Movements Induced by Antipsycotics

“…Recently, our group showed that treatment with Harpagophytum procumbens, a plant known for its anti-inflammatory properties, reduced the number of VCMs induced by fluphenazine in rats [70], once again suggesting that the development and progression of these motor disorders may be linked with inflammation at CNS.…”

Protective Effects Induced by Microwave-Assisted Aqueous Harpagophytum Extract on Rat Cortex Synaptosomes Challenged with Amyloid β-Peptide

“…This results in an early and sharp increase in membrane oxidative injury. Actually, the observed inhibitory effects on MDA production could be related to the radical scavenging activities of Harpagophytum (Grant et al , ; Schaffer et al , ). In addition, we observed an inhibitory effect induced by Harpagophytum extract on 3‐HK level, a marker of neurotoxicity synthesized by kynurenine monooxygenase (KMO) which generates free radicals in the brain (Maddison and Giorgini, ).…”

Optimization of Aqueous Extraction and Biological Activity of Harpagophytum procumbens Root on Ex Vivo Rat Colon Inflammatory Model

“…The same authors also observed a direct scavenging activity. On the other hand, Harpagophytum extract (ethyl acetate fraction) treatment could also stimulate catalase activity, a well‐established anti‐oxidative marker (Schaffer et al , ). 5‐HT pro‐inflammatory role in IBDs has been previously suggested (Regmi et al , ), possibly involving the activation of 5‐HT3 receptors (Mousavizadeh et al , 2009).…”

“…The rationale for the traditional use is consistent, albeit in part, with the down-regulation of multiple pathways involved in inflammation, including ROS, cytokines and prostaglandin production (Huang et al, 2006;Grant et al, 2009;Fiebich et al, 2012;Schaffer et al, 2013;Schaffer et al, 2016Günther et al, 2006. On the other hand, the possible hepatic cytotoxic effects induced by Harpagophytum and harpagoside should be taken in consideration (Biazi et al, 2016).…”