Curcumin, a secondary metabolite from the turmeric plant is one of the most promising natural products, which has been studied extensively for decades. It has demonstrated several pharmacological activities in vitro and in vivo. Various studies have indicated that the pharmacological activity of curcumin is contributed by its metabolites.

Atherosclerosis, a chronic inflammatory disease defined by plaque formation in artery walls, is still a significant cause of cardiovascular morbidity and mortality globally. Despite advancements in conventional medicines, the search for natural substances with several therapeutic applications continues. Curcumin, a polyphenol produced from Curcuma longa, has emerged as a promising anti-atherosclerosis treatment due to its powerful anti-inflammatory, antioxidant, lipid-modulating, and endothelial-protective characteristics. This article explores how curcumin reduces atherosclerosis by inhibiting NF-κB and MAPK signaling pathways, reducing oxidative stress, modulating lipid metabolism, and increasing nitric oxide bioavailability. Curcumin has been shown in preclinical studies to reduce aortic lesion area, inhibit pro-inflammatory cytokines, and improve endothelial function, and clinical trials show that it has the potential to improve vascular health in at-risk groups. However, issues such as low bioavailability demand additional research into improved formulations. By integrating current information, this article highlights curcumin's therapeutic potential and advocates for robust clinical trials to validate its efficacy and establish standardized dose regimens for cardiovascular disease prevention and treatment.

Curcumin is a hydrophobic polyphenol derived from turmeric with potent anti-oxidant, anti-microbial, anti-inflammatory and anti-carcinogenic effects. Curcumin is degraded into various derivatives under in vitro and in vivo conditions, and it appears that its degradation may be responsible for the pharmacological effects of curcumin. The primary risk factor for the cause of gastric cancer is Helicobacter pylori (H. pylori). A virulence factor vacuolating cytotoxic A (VacA) is secreted by H. pylori as a 88 kDa monomer (p88), which can be fragmented into a 33 kDa N-terminal domain (p33) and a 55 kDa C-terminal domain (p55). Recently it has been reported that curcumin oxidation is required to inhibit the activity of another major H.pylori toxin CagA. We performed molecular docking of curcumin and its oxidative derivatives with p33 and p55 domains of VacA. Further, we have examined the effect of the oxidation of curcumin on the vacuolation activity of VacA protein. We observed the binding of curcumin to the p55 domain of VacA at five different sites with moderate binding affinities. Curcumin did not bind to p33 domain of VacA. Remarkably, cyclobutyl cyclopentadione and dihydroxy cyclopentadione, which are oxidized products of curcumin, showed a higher binding affinity with VacA protein at all sites except one as compared to parent curcumin itself. However, cyclobutyl cyclopentadione showed a significant binding affinity for the active site 5 of the p55 protein. Active site five (312–422) of p55 domain of VacA plays a crucial role in VacA-mediated vacuole formation. Invitro experiments showed that curcumin inhibited the vacuolation activity of H. pylori in human gastric cell line AGS cells whereas acetyl and diacetyl curcumin, which cannot be oxidized, failed to inhibit the vacuolation in AGS cells after H. pylori infection. Here our data showed that oxidation is essential for the activity of curcumin in inhibiting the vacuolation activity of H. pylori. Synthesis of these oxidized curcumin derivatives could potentially provide new therapeutic drug molecules for inhibiting H. pylori-mediated pathogenesis.