Curcumin's Metabolites, Tetrahydrocurcumin and Octahydrocurcumin, Possess Superior Anti-inflammatory Effects in vivo Through Suppression of TAK1-NF-κB Pathway.

Zhen-Biao Zhang,Zi-Ren Su,Jian-Hui Xie,Wei-Hai Liu,Yan-Fang Xian,Yu-Hong Liu,Xiao-Ping Lai,Jian-Nan Chen,Dan-Dan Luo,Zheng-Quan Lai,Zhi-Xiu Lin

doi:10.3389/fphar.2018.01181

Abstract

Curcumin (CUR), a promising naturally occurring dietary compound, is commonly recognized as the potential anti-inflammatory agent. While the application of CUR was hampered by its low stability and poor systemic bioavailability, it has been suggested that the biological activities of CUR are intimately related to its metabolites. In the current investigation, we aimed to comparatively explore the anti-inflammatory effects of tetrahydrocurcumin (THC), octahydrocurcumin (OHC), and CUR, and to elucidate the underlying action mechanisms on experimental mice models of acute inflammation, i.e., xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. The results showed that THC and OHC exerted significant and dose-dependent inhibitions on the formation of ear edema induced by xylene and paw edema provoked by carrageenan and inhibited the Evans blue dye leakage in peritoneal cavity elicited by acetic acid. Moreover, THC and OHC treatments were more effective than CUR in selectively inhibiting the expression of cyclooxygenase 2 (COX-2) and suppressing nuclear factor-κB (NF-κB) pathways via transforming growth factor β activated kinase-1 (TAK1) inactivation in the carrageenan-induced mouse paw edema model.

Highlights

Curcumin (CUR, C21H20O6, the molecular structure depicted in Figure 1), a food pigment derived from the curcuma species like dietary spice turmeric, has been commonly used as a flavoring agent in various foods
It has been found that oral administration with CUR in mice resulted in reduction to dihydrocurcumin, tetrahydrocurcumin (THC, C21H24O6, the chemical structure shown in Figure 1) and hexahydrocurcumin mediated by endogenous reductase (Zhongfa et al, 2012)
Previous studies have demonstrated that octahydrocurcumin (OHC, C21H28O6, the chemical structure shown in Figure 1), another important metabolite of CUR, exerted appreciable antiinflammatory properties in lipopolysaccharide (LPS)-challenged RAW 264.7 murine macrophages model (Zhao et al, 2015)

Summary

Introduction

Curcumin (CUR, C21H20O6, the molecular structure depicted in Figure 1), a food pigment derived from the curcuma species like dietary spice turmeric (rhizome of Curcuma longa), has been commonly used as a flavoring agent in various foods. Previous studies have demonstrated that octahydrocurcumin (OHC, C21H28O6, the chemical structure shown in Figure 1), another important metabolite of CUR, exerted appreciable antiinflammatory properties in lipopolysaccharide (LPS)-challenged RAW 264.7 murine macrophages model (Zhao et al, 2015). Despite OHC has been discovered in earlier studies, difficulties in its availability has hampered the studies on its biological properties. To solve this predicament, our previous study has developed a simple and highly effective way to produce OHC (Zhang et al, 2018), which made it possible to explore its biological activities

Objectives

Methods

Results

Conclusion