Anti-nociceptive effects of combined ethanol extracts of Ananas comosus, Citrus limon, and Zingiber officinale in Wistar rats

Abstract

The use of traditional medicine as an alternative to conventional therapeutic drugs for pain management remains highly prevalent in developing countries. This study investigated the antinociceptive effects of a combined ethanol extract of Ananas comosus, Citrus limon, and Zingiber officinale peels (EPLG) in male Wistar rats. Twenty male Wistar rats (150–180 g) were randomly assigned to four experimental groups (n = 5). Animals received oral administration of either normal saline (control) or EPLG at doses of 30, 60, or 90 mg/kg. Both reflexive (hot-plate and formalin-induced paw injection tests) and non-reflexive (open field test) pain-related behavioural assessments were conducted. Following behavioural testing, biochemical analyses of the prefrontal cortex and lumbar spinal cord (L4–L6) were performed to evaluate antioxidant enzyme activities, dopamine concentration, calcium ion levels, and nuclear factor kappa B (NF-κB). The hot-plate test showed that EPLG significantly increased thermal withdrawal latency. In the formalin test, EPLG markedly reduced hind paw flinching during both the neurogenic and inflammatory phases. Biochemical analyses revealed that EPLG significantly increased superoxide dismutase and catalase activities in the lumbar spinal cord while inhibiting NF-κB expression. Additionally, EPLG treatment reduced dopamine concentrations in the prefrontal cortex. Overall, these findings demonstrate that the combined extract of EPLG exerts significant antinociceptive effects, which may be mediated through enhanced antioxidant defence, suppression of inflammatory signalling, and modulation of dopaminergic activity.