Possible mechanisms involved in the antinociceptive 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 support 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 intraplantar injection of TNF-a (F4,120¼ 10.86, p < 0.0001), IL-1b (F4,120¼ 14.71, p < 0.0001), bradykinin (F4,80 ¼ 12.52, p < 0.0001) and prostaglandin E2 (F5,144¼ 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.