Ethanolic Extracts of Cissus quadrangularis Linn. (Vitaceae) Attenuate Vincristine-Induced Peripheral Neuropathy in Rats: An Evidence of the Antioxidant, Calcium Inhibitory, and Neuromodulatory Properties

Cissus quadrangularis Linn. (C. quadrangularis, Vitaceae) is a plant reported to treat injured tendons, broken bones, asthma, stomach ache, scurvy, and digestive disorders. The present study evaluated the antihyperalgesic effects of ethanolic extract of C. quadrangularis Linn. Vincristine sulfate (100 μg/kg, i.p.) was administered in rats for 10 days with 2 days break to induce painful peripheral neuropathy. Mechanical hyperalgesia and allodynia tests were performed to assess the threshold of painful neuropathy. Calcium levels in the sciatic nerve, oxidant stress markers, and levels of GABA and 5-HT were also determined in the brain and spinal cord after 15 days. Ethanolic extract of C. quadrangularis (180 and 360 mg/kg) and pregabalin (50 mg/kg) were administered for 15 consecutive days. The results revealed that the extract significantly (p<0.001) inhibited hyperalgesia and allodynia in animals after vincristine administration. The extract decreased total calcium levels in the sciatic nerve, MDA levels while increasing GSH activity, 5-HT level, as well as GABA levels in the brain and spinal cord. The results of this study suggest that the ethanolic extract of C. quadrangularis uses antioxidant capacity, calcium inhibitory action, and neuromodulation of GABA and 5-HT to prevent the development of painful neuropathy after vincristine administration. This demonstrates that C. quadrangularis is a promising molecule for the management of peripheral neuropathic pain induced by anticancer drugs.