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. 2020 Dec 22:2020:8856135.
doi: 10.1155/2020/8856135. eCollection 2020.

Comparation of Anti-Inflammatory and Antioxidantactivities of Curcumin, Tetrahydrocurcuminand Octahydrocurcuminin LPS-Stimulated RAW264.7 Macrophages

Qing-Feng Xie  1   2 , Juan-Juan Cheng  3 , Jin-Fen Chen  3 , Yu-Chao Feng  1   2 , Guo-Shu Lin  3 , Yang Xu  1   2
Affiliations

Comparation of Anti-Inflammatory and Antioxidantactivities of Curcumin, Tetrahydrocurcuminand Octahydrocurcuminin LPS-Stimulated RAW264.7 Macrophages

Qing-Feng Xie et al. Evid Based Complement Alternat Med. .

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.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The chemical structures of curcumin (a), tetrahydrocurcumin (b), and octahydrocurcumin (c).
Figure 2
Figure 2
Effects of CUR (a), THC (b), and OHC (c) on cell viability of RAW264.7 macrophages. Data are shown as mean ± SD (n = 3); ∗∗P < 0.01 vs. control group.
Figure 3
Figure 3
Effects of CUR, THC, and OHC on the productions of NO (a) and MCP-1 (b) and the mRNA expression of iNOS (c) and MCP-1 (d) in LPS-activated RAW264.7 cells. Data are shown as mean ± SD (n = 3); ##P < 0.01 vs. control group, ∗∗P < 0.01 vs. LPS group, and &&P < 0.01 vs. CUR of the same dose.
Figure 4
Figure 4
Effects of CUR, THC, and OHC on HO-1 (a), NQO-1 (b), GCLC (c), and GCLM (d) mRNA expression in LPS-stimulated RAW264.7 cells. Data are shown as mean ± SD (n = 3); ##P < 0.01 vs. control group, ∗∗P < 0.01 vs. LPS group, &P < 0.05, and &&P < 0.01 vs. CUR of the same dose.
Figure 5
Figure 5
Effects of ZnPP on the generation of HO-1 and ROS by CUR, THC, and OHC in LPS-stimulated RAW264.7 cells. Data are shown as mean ± SD (n = 3); ##P < 0.01 vs. control group, ∗P < 0.05, ∗∗P < 0.01 vs. LPS group, and &&P < 0.01 vs. CUR of the same dose.
Figure 6
Figure 6
Effects of CUR, THC, and OHC on protein expression levels of p-P38/P38 (b), p-ERK/ERK (c), and NF-κB (d) in LPS-stimulated RAW264.7 cells. (a) The representative expression bands. Data are shown as mean ± SD (n = 3); ##P < 0.01 vs. control group, ∗∗P < 0.01 vs. LPS group, &P < 0.05, and &&P < 0.01 vs. CUR of the same dose.
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