Evaluation of the anti-inflammatory effects of the hydroethanolic extract of Holarrhena Floribunda in Murine Models of inflammation

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Holarrhena floribunda in Ghanaian folk medicine is claimed to be used to treat inflammatory diseases. To validate its anecdotal use, a 70% ethanolic extract of Holarrhena floribunda (HFE) was prepared and evaluated on murine models of inflammation. The effect of HFE on acute inflammation was evaluated using the carrageenan-induced paw oedema model in rats. HFE (50, 200 and 500 mg/kg) dose-dependently and significantly inhibited paw oedema. The total paw oedema induced over 4 h was inhibited by 39.85 ± 11.19, 61.00 ± 7.35 and 65.41 ± 3.85 % respectively prophylactically and by 33.43 ± 6.83, 48.33 ± 6.83 and 56.55 ± 2.05 % respectively when administered therapeutically. Administration of HFE dose- dependently suppressed compound 48/80-induced mouse systemic anaphylactic shock (0, 16 and 50 % respectively for the 50, 200 and 500 mg/kg HFE). HFE dose dependently protected rats from LPS-induced anaphylactic shock on both prophylactic and therapeutic approaches with maximum protection of 20 % and 40 % respectively. Pinnal inflammation reaction model was employed in the passive cutaneous anaphylaxis study. The antigen-induced inflammation was significantly (p<0.001) suppressed in a dose dependent (44.77%, 69.89% and 80.69%) manner. The anti-arthritic effect of HFE was evaluated using the adjuvant-induced arthritis model in rats. HFE (50, 200 and 500 mg/kg) dose-dependently and significantly inhibited swelling of the injected paw and prevented the systematic spread of arthritis to the uninjected paw. The maximal inhibition in total paw oedema in rats given prophylactic and therapeutic treatments was observed to be 78.21 % and 67.92 % respectively. HFE also showed inflammation alleviation properties in indices monitored such body weight, radiology, histology, and haematology. HFE dose dependently inhibited histamine-induced paw oedema and exhibited an indirect anti-histaminic activity in clonidine-induced catalepsy test. HFE also showed inhibitory effects on serotonin and prostaglandin E2-induced paw oedema. HFE inhibited the serum expression of IL-1α, IL-6 and protein kinase C and enhanced the expression of IL-10, Cyclic adenosine monophosphate and protein kinase A levels in chronic inflammation. Phytochemical screening of the ethanolic extract of the stem bark of Holarrhena floribunda indicated the presence of saponins, phenolic compounds, alkaloids and reducing sugars which possibly could be responsible for its observed inhibitory effects on acute and chronic inflammation.
A thesis submitted in partial fulfilment of the requirements for the degree of Master of Philosophy in The Department of Pharmacology, 2016