Therapeutic Potential of Hexahydrocurcumin in the Regeneration and Protection of the Retinal Pigment Epithelium

Abstract

Hexahydrocurcumin (HHC), the primary metabolite of curcumin, shows promising therapeutic potential due to its antioxidant and anti-inflammatory properties. The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis; however, its dysfunction-linked to oxidative stress and chronic inflammation-contributes to the progression of degenerative diseases such as age-related macular degeneration (AMD). This review highlights the therapeutic potential of HHC in protecting and regenerating RPE cells. It explores the effects of oxidative stress on the RPE, the mechanisms underlying its damage, and the involvement of reactive oxygen species (ROS) and inflammatory mediators. HHC has demonstrated the ability to modulate these pathways by activating nuclear factor erythroid 2-related factor 2 (NRF2), enhancing antioxidant defenses, and inhibiting pro-inflammatory cytokine production. Preclinical studies suggest that HHC mitigates vascular remodeling and endothelial dysfunction by reducing the expression of transforming growth factor β (TGF-β1) and matrix metalloproteinase-9 (MMP-9). Moreover, HHC improves nitric oxide bioavailability and promotes nitric oxide synthase expression, thereby counteracting oxidative stress-induced vascular damage. Emerging evidence indicates that HHC may be a promising candidate for the treatment of retinal degenerative diseases, particularly those associated with oxidative stress and inflammation. However, further studies, including clinical trials, are essential to confirm its efficacy and elucidate the precise mechanisms underlying HHC's protective effects on RPE cells.

Keywords: age-related macular degeneration; hexahydrocurcumin; inflammation; oxidative stress; retinal pigment epithelium.

Figure 1

Schematic representation of the structure of the retinal pigment epithelium. The figure was partly generated using Servier Medical Art, provided by Servier and licensed under a Creative Commons Attribution 4.0 unported license.

Figure 2

Schematic representation of the role of macrophage-regulated immune inflammation in the pathogenesis of age-related macular degeneration. The factors involved in the immune response include macrophages, monocytes, autoantibodies, lymphocytes (Th1, Th17, B, CD8+), and activated microglia. Inflammatory mediators such as interleukins are also highlighted. The role of complement anaphylatoxins, C3a and C5a, which may contribute to inflammatory and degenerative processes, is also emphasized. The figure was partly generated using Servier Medical Art, provided by Servier and licensed under a Creative Commons Attribution 4.0 unported license.

Figure 3

Structure of curcumin and its metabolites.

Figure 4

Structure dependence of hexahydrocurcumin on its biological activity.