Pharmacodynamic interaction profile of apigenin with diclofenac in an experimental model of inflammation in rats

Objectives: Chronic use of non-steroidal anti-inflammatory drugs(NSAID’s) is often limited by their side effect, necessitating the development of safer therapeutic alternatives. Apigenin, A plant flavonoid, has shown potential in enhancing the efficacy of NSAIDs while potentially reducing their adverse effects. This study aimed to evaluate the synergistic effects of apigenin combined with a subtherapeutic dose of diclofenac on inflammation in a rat model, to determine whether such a combination can improve anti-inflammatory effectiveness and reduce the drug dose required. Materials and Methods: A total of 42 Wistar albino rats were randomised into seven groups to receive various treatments including control (normal saline), standard diclofenac (100 mg/kg), three doses of apigenin (10, 20 and 40 mg/kg), a subtherapeutic dose of diclofenac (50 mg/kg) and a combination of apigenin (20 mg/kg) with diclofenac (50 mg/kg). Inflammation was induced using carrageenan, and paw volume was measured at multiple time points to assess oedema. The percentage change from baseline paw volume and percentage protection against paw oedema was calculated for each group. Results: The study found that the combination of 20 mg/kg apigenin with 50 mg/kg diclofenac significantly enhanced the anti-inflammatory response, achieving a peak reduction in paw volume of up to 49.66% at 3 h post-administration. This was superior to the responses seen with apigenin or diclofenac alone, where the maximal dose of apigenin (40 mg/kg) only managed a peak reduction of 28.18%, and the standard dose of diclofenac (100 mg/kg) reached a peak inhibition of 66.66% at 6 h. The subtherapeutic dose of diclofenac (50 mg/kg), used alone, showed a lower peak effect of 21.47% at 3 h. These results underscore the enhanced efficacy of the combination therapy, potentially allowing for lower doses of diclofenac while maintaining effective anti-inflammatory action. Conclusion: The findings suggest that combining apigenin with diclofenac enhances anti-inflammatory responses, supporting the potential of flavonoid-NSAID combinations as more effective and safer anti-inflammatory therapies. Future studies should explore the long-term effects and mechanisms of action to fully understand the benefits and limitations of such combinations in managing chronic inflammation.