Possible mechanisms involved in the anti- nociceptive effects of hydro-ethanolic leaf extract of Ziziphus abyssinica

Abstract

Context: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to sup- port the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. Purpose: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE. Materials and methods: The effect of EthE (30, 100 and 300 mg/kg) on intraplantar injection of pain mediators such as interleukin-1b, tumour necrosis factor-a, prostaglandin E2 and bradykinin was evaluated in male Sprague Dawley rats using Randall–Selitto test for 5 h. The effect of specific antagonists to the opioidergic, adenosinergic, ATP-sensitive Kþ channels, nitric oxide, serotonergic, muscarinic, adrenergic and voltage-gated calcium channel on the anti-nociceptive effect of EthE (100 mg/kg) was evaluated using the formalin test in male imprinting control region (ICR) mice for 1 h. Results: Pretreatment of the rats with EthE significantly reversed the hypernociception induced by intra- plantar injection of TNF-a (F4,120 ¼ 10.86, p < 0.0001), IL-1b (F4,120 ¼ 14.71, p < 0.0001), bradykinin (F4,80 ¼ 12.52, p < 0.0001) and prostaglandin E2 (F5,144 ¼ 6.165, p ¼ 0.0001). The anti-nociceptive effect exhibited by EthE in the formalin test was reversed by systemic administration of NG-L-nitro-arginine methyl ester, naloxone, theophylline and glibenclamide. Conclusions: EthE inhibits hypernociception induced by TNF-a, IL-1b, bradykinin and prostaglandin E2. EthE exhibited anti-nociceptive effects possibly mediated through opioidergic, adenosinergic, ATP-sensitive potassium channels and nitric oxide cyclic GMP pathways.