Protocatechuic acid counteracts oxidative stress and inflammation in carrageenan-induced paw edema in mice

Protocatechuic acid (PCA), a phenolic compound found in teas, fruits, and vegetables, is widely recognized with its antioxidant and anti-inflammatory activities. Here, we verified the protective role of PCA on carrageenan (CGN)-induced paw edema in mice. Forty-five male Swiss albino mice were assigned into five groups: control group, CGN-injected group (1% w/v), PCA (25 mg/kg) + CGN group. PCA (50 mg/kg) + CGN group and diclofenac sodium (20 mg/kg) + CGN group. PCA and diclofenac sodium were administered orally for 5 consecutive days prior to the CGN injection. PCA pretreatment notably decreased the volume of the developed edema and alleviated the histopathological alterations induced by carrageenan. Additionally, PCA administration enhanced the cellular antioxidant capacity as demonstrated by the increased levels of catalase, superoxide dismutase, and reduced glutathione, in addition to the decreased malondialdehyde level in the edematous tissue. Interestingly, PCA administration was able significantly to suppress the developed inflammatory response upon carrageenan injection as indicated by the decreased levels and expression of pro-inflammatory cytokines and mediators including tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-II, prostaglandin E2, monocyte chemoattractant protein-1, myeloperoxidase and nuclear factor kappa B. These results collectively confirm the protective effect of PCA against carrageenan-induced paw edema owing to its antioxidant and anti-inflammatory characteristics.