Abstract

Curcumin (CUR) possesses pronounced anti-inflammatory and antioxidant activities. Generally, the clinical application of CUR is restricted due to its apparent unstability and poor absorption, and the biological activities of CUR may be closely associated with its metabolites. Tetrahydrocurcumin (THC) and octahydrocurcumin (OHC) are two major hydrogenated metabolites of CUR with appreciable biological potentials. Here, we comparatively explored the anti-inflammatory and antioxidant activities of CUR, THC, and OHC in lipopolysaccharide- (LPS-) induced RAW264.7 macrophages. The results revealed that CUR, THC, and OHC dose-dependently inhibited the generation of NO and MCP-1 as well as the gene expression of MCP-1 and iNOS. Additionally, CUR, THC, and OHC significantly inhibited NF-κB activation and p38MAPK and ERK phosphorylation, while substantially upregulated the Nrf2 target gene expression (HO-1, NQO-1, GCLC, and GCLM). Nevertheless, zinc protoporphyrin (ZnPP), a typical HO-1 inhibitor, significantly reversed the alleviative effect of CUR, THC, and OHC on LPS-stimulated ROS generation. These results demonstrated that CUR, THC, and OHC exerted beneficial effect on LPS-stimulated inflammatory and oxidative responses, at least partially, through inhibiting the NF-κB and MAPKs pathways and activating Nrf2-regulated antioxidant gene expression. Particularly, THC and OHC might exert superior antioxidant and anti-inflammatory activities to CUR in LPS-stimulated RAW264.7 cells, which can be further explored to be a promising novel effective agent for inflammatory treatment.

Highlights

  • Turmeric derives from the root of Curcuma longa (Zingiberaceae), which is widely used for the therapy of various inflammatory diseases [1]

  • Greiss reagent and enzymelinked immunosorbent assay (ELISA) kits for reactive oxygen species (ROS) were purchased from Beijing Cheng Lin Biotechnology Technology Co., Ltd. (Beijing, China). e following primary antibodies for Western blot: nuclear factor-κB (NF-κB) (#8242), Mitogen-activated protein kinases (MAPKs)-p-p38 (#4511), MAPK-p-extracellular signal-regulated kinase (ERK) (#8690), β-tubulin, and secondary antibodies were purchased from Cell Signaling Technology MA, USA. e primer sequences for monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), NQO-1, glutamatecysteine ligase catalytic (GCLC), and GCLM were from Sangon Biotech Co., Ltd. (Shanghai, China)

  • The viability of RAW264.7 cells was significantly reduced by CUR at 64 μM, while THC and OHC at concentrations ranging from 2 to 64 μM exhibited no cytotoxic effects on the viability of RAW264.7 cells. erefore, 2, 4, and 8 μM were used in the subsequent experiments

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Summary

Introduction

Turmeric derives from the root of Curcuma longa (Zingiberaceae), which is widely used for the therapy of various inflammatory diseases [1]. Accumulating evidence has indicated that CUR exerts an array of health-beneficial effects in vitro and in vivo [2,3,4,5]. CUR and THC possess identical phenolic groups, THC lacks α, β dienes [9]. Compared to CUR, OHC lacks α, β dienes, while it has more phenolic groups [10]. They have been reported to possess stronger pharmacological and biological effects against various diseases such as anti-inflammatory [10, 11], antidiabetic [12], and antioxidant properties [13,14,15,16].

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