Anti-inflammatory and Antinociceptive Activity of Terminalia avicennioides Guill. & Perr. Stem Bark Extract is Distinct from the Antioxidant Effect Mediated by Its Phenolic-rich Fraction

Background: Terminalia avicennioides stem bark has been used in the management of pain and inflammatory disorders in northern Nigeria. This study evaluated the antinociceptive and anti-inflammatory properties of T. avicennioides stem bark extract and its fractions. The correlation of these effects to the presence and concentration of phenolics was also ascertained. Study Design: Experimental Design. Place and Duration of Study: Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development, Idu, Abuja, Nigeria. The study was conducted from October to December 2022. Methods: A 70%v/v ethanol extract of T. avicennioides stem bark was prepared. Aqueous and ethyl acetate fractions (AF, EF) and sub-fractions (EF1 – EF4) were also prepared. The antioxidant capacity of the extract and fractions were determined using DPPH radical scavenging test, while xylene-induced topical ear edema and formalin test were used to assess antinociceptive and anti-inflammatory activity. The ethyl acetate sub-fractions were further assessed using the egg albumin–induced inflammation. The extract and fractions were characterized by High-Performance Liquid Chromatography (HPLC), and phenolic content was quantified as gallic acid equivalent (GAE)/mg of extract or fraction. Results: The ethyl acetate and aqueous fractions showed higher antioxidant capacity compared to the parent ethanol extract. T. avicennioides ethanol extract significantly inhibited pain (p<0.001) and inflammatory responses (p<0.05) and these effects were more significant compared to those produced by the fractions. Fractions AF and EF exhibited similar activity, although EF produced better inhibition of pain and topical edema. The subfraction EF2 also showed anti-inflammatory activity but this effect was insignificant (p>0.05). The HPLC profiles of the extract and fractions showed peaks corresponding to caffeic acid, chlorogenic acid, and gallic acid. The EF and AF revealed higher peak areas corresponding to gallic acid and rutin respectively. This correlated with a comparatively high gallic acid content and antioxidant effect of the ethyl acetate fraction (GAE: 1.32/mg, IC50 = 0.036 mg/ml), relative to the extract (GAE: 0.88/mg, IC50 = 0.052 mg/ml). Conclusion: The constituents responsible for the antinociceptive and anti-inflammatory activity of T. avicennioides extract appear distinct from antioxidative principles in phenolics-rich fractions.