Antinociceptive, Anti-Inflammatory And Antipyretic Effects Of Solanum Incanum (Linnaeus), Craterostigma Pumilum (Hochst) And Euclea Divinorum (Hiern) In Animal Models.

ABSTRACT

Solanum incanum, Craterostigma pumilum and Euclea divinorum have been used for generations as folklore medicine for various ailments associated with pain and inflammation in humans in Kenya. However, there is scarcity of data on scientific studies done on their effectiveness, modes of action, toxicity and their phytochemical composition. The aims of this study was to evaluate the antinociceptive, anti-inflammatory and antipyretic potential of these plants crude extracts, to determine the antinociceptive and anti-inflammatory mechanisms of action, toxicity as well as the phytochemical composition of alkaloid rich fractions of these plants. Antinociceptive and anti-inflammatory effect assays were carried out using formalin test and formalin induced paw edema in rats. Pyrexia was induced in rats using lipopolysaccharid and rectal temperature taken using a digital thermometer. Alkaloid rich fractions of S. incanum and E. divinorum were screened using formalin pain and inflammation tests in mice while antipyretic effect of S. incanum alkaloids was tested on rats. The antinociceptive mode of action assays involved injection of various receptor agonists and antagonists which included atropine an antagonist for M2 muscarinic receptors, and ketamine an N-methyl D-aspartate receptor blocker. Evaluation of anti-inflammatory mode of actions involved carrageenan leukocyte migration assay and histamine induced pedal edema. Phytochemical assay was carried out using standard procedures while LC-QToF MS was used in identification of the metabolites in alkaloid rich fractions. Extracts from the three plants caused significant (p < 0.05) anti-inflammatory effects while only the S. incanum and E. divinorum extract exhibited significant (p < 0.05) antinociceptive effect. The alkaloids rich fraction of S. incanum exhibited significant antipyretic effect. Antinociception was significantly attenuated by atropine and ketamine in S. incanum and E. divinorum alkaloids treated animals respectively. Alkaloids from S. incanum showed no toxic effect unlike those from E. divinorum. The extracts contained several types of metabolites of varying quantities. QToF-MS results for S. incanum showed presence of tri- and tetra glycosides identified as solamargine and its derivatives E. divinorum contained an unidentified xylose containing glycosidic alkaloids. Hence S. incanum and E. divinorum contains alkaloids and perhaps other metabolites with analgesic and anti-inflammatory effects. The analgesic and anti-inflammatory of S. incanum alkaloids involved inhibition of M2 receptors and leukocyte migration respectively. E. divinorum alkaloids inhibited pain via NMDA receptors and inflammation via either or both H1 and H4 receptors. The finding lenders support to traditional use of these plant parts for relief of pain pain and inflammation. Further investigation may lead to development of novel drugs for management of these conditions.