A new metabolite: The effects of aminated tetrahydrocurcumin on inducible nitric oxide synthase and cyclooxygenase-2

Background: Curcumin and its metabolite, tetrahydrocurcumin (THC), have been widely studied due to their compelling capabilities in the prevention of various diseases. However, these compounds face some shortcomings, including the bioavailability of curcumin and comparatively weaker anti-inflammatory effects of THC. The amination of natural compounds in the hosts' colons has garnered attention because these aminated compounds retain and even increase their bioactivity relative to their original counterparts. Materials and Methods: The existence of THC-NH2 as a metabolite of THC in mice feces was analyzed by using LC-MS. Three-week DSS-induced colitis in mice experiment was designed to confirm the ameliorative effect of THC-NH2 on inflammatory bowel disease. The anti-inflammatory effect of THC-NH2 on LPS-treated murine macrophage RAW264.7 cell line was further clarified in vitro. Results: In this study, the metabolite 3-amino-3-deoxytetrahydrocurcumin (THC-NH2) was discovered in the feces of mice administered with THC. Compared to THC, THC-NH2 exhibits greater anti-inflammatory effects in terms of nitric oxide production. In a study of dextran sulfate sodium-induced colitis in which animal subjects were supplied with both THC and THC-NH2, each sample displayed encouraging but not compelling effects on inflammation reduction. In vitro research revealed that intervention using THC-NH2 could significantly reduce protein expression levels of nitric oxide synthase (iNOS) but cause the accumulation of cyclooxygenase-2 (COX-2). By using cycloheximide, THC-NH2 was found to retard the degradation of COX-2 by increasing its stability. However, mRNA levels of COX-2 and concentrations of prostaglandin E2 (PGE2) in spent medium indicated that COX-2 activity did not increase alongside its accumulated protein level, though no significant effects on the reduction of COX-2 activity were seen. Conclusion: As the current body of research is inadequate, in order to ensure that all things are considered, the efficacy and safety of THC-NH2 as a pharmaceutical drug require further investigation. Nevertheless, recent results showed that THC-NH2 can be used in multi-targeting anti-inflammation drugs to inhibit iNOS levels and reduce the side effects of COX-2 inhibitors by acting as a competitive inhibitor.