Targeted anti-inflammatory effects of folic acid-conjugated chitosan-ZnO NPs: Modulation of inflammatory cytokines and oxidative stress.

Abstract

Inflammation-driven disorders remain a major therapeutic challenge, partly because conventional anti-inflammatory drugs are often limited by adverse effects, poor target specificity, and incomplete modulation of oxidative and inflammatory pathways. This study developed a green, plant-based targeted nanoplatform using methanolic extracts of Cuminum cyminum and Carum carvi for the synthesis of ZnO NPs, followed by chitosan coating and folic acid functionalization to improve biocompatibility, stability, and inflammatory-cell targeting. The resulting ZnO, CS-ZnO, and FA-CS-ZnO NPs were characterized by FTIR, XRD, FESEM, TEM, and EDX analyses. Their anti-inflammatory, antioxidant, and hepatoprotective activities were evaluated in a carrageenan-induced acute inflammation model in mice. Structural analyses confirmed successful ZnO formation, chitosan coating, and folic acid conjugation, with FA-CS-ZnO NPs showing nanoscale morphology and preserved crystalline features. In vivo, both plant extracts reduced paw edema and hepatic injury, confirming their intrinsic bioactivity. However, nanoformulation markedly enhanced these effects, with FA-CS-ZnO NPs producing the strongest reduction in paw swelling and the greatest improvement in liver histoarchitecture. Mechanistically, carrageenan induced oxidative stress and inflammation by increasing Tnf-α, Nf-κb, and Cox-2 while suppressing Il-10, Nrf2, Sod, and antioxidant enzyme activities. FA-functionalized nanoparticles, particularly the C. carvi-based formulation, most effectively reversed these changes, in some parameters matching or surpassing indomethacin. These findings highlight the novelty of combining green-synthesized ZnO NPs, chitosan-based delivery, and folate-mediated targeting to enhance the therapeutic performance of medicinal plant extracts. Overall, FA-CS-ZnO NPs represent a promising multifunctional strategy for targeted management of inflammation-associated oxidative tissue damage.