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

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.

Diminished CCl 4 ‐induced hepatocellular carcinoma, oxidative stress, and apoptosis by co‐administration of curcumin or selenium in mice

“…This study proved the protective effect of curcumin and selenium, alone and in combination with each other, this finding in agreement with previous studies where curcumin showed multiple pharmacological activities, including anti‐inflammation and antioxidant (Xie et al, 2020), and have an essential role in inhibiting the progression of HCC through various pathways (Tan & Norhaizan, 2019; Zhang et al., 2018). Previous studies have shown a potential inverse relationship between selenium levels and the occurrence of HCC (Cheng et al., 2019).…”

Docosahexaenoic acid-acylated curcumin diester alleviates cisplatin-induced acute kidney injury by regulating the effect of gut microbiota on the lipopolysaccharide- and trimethylamine-N-oxide-mediated PI3K/Akt/NF-κB signaling pathway in mice

“…A large number of studies have shown that dietary curcumin reduced the mRNA expression and secretion of IL-1β, IL-6, TNFα, and MCP-1 in LPS stimulated RAW 264.7 cells and cisplatin-treated mice. 29,30 Our previous studies verified that the orally-administered DHA enriched phospholipids and triglycerides could decrease the level of inflammatory cytokines, including IL-1β and TNF-α in mice with dextran sodium sulfate-induced colitis. 31 The above results indicated that the intervention of DHA or Cur could inhibit the inflammatory response in the kidney of AKI mice, and it is worth mentioning that DHA-acylated curcumin esters exhibited good anti-inflammatory activities compared with the recombination of Cur and DHA or Cur and DHA alone.…”

Suppressive Effect of Tetrahydrocurcumin on Pseudomonas aeruginosa Lipopolysaccharide-Induced Inflammation by Suppressing JAK/STAT and Nrf2/HO-1 Pathways in Microglial Cells

“…The major metabolite of curcumin, THC, is reported to exhibit stable activity and absorption efficiency and to possess a more favourable bioavailability than that of curcumin [10,26,27]. Xie et al have demonstrated that THC exerts more notable anti-inflammatory and antioxidant activities in LPS-stimulated RAW264.7 macrophages than curcumin does [14]. Moreover, compared with curcumin, THC more effectively suppresses pathways for COX-2 and transforming growth factor β, activated kinase-1, and NF-κB in vivo [13].…”

“…Neurodegenerative disorders are commonly associated with oxidative stress-induced inflammation [28,29]. Under LPS stimulation, the TLR4-mediated NF-κB and mitogenactivated protein kinases are activated and iNOS-mediated proinflammatory NO is produced in activated macrophages [14]. LPS is also known to induce COX-2 production in vitro and in vivo [30][31][32].…”

“…Additionally, in a paw edema mouse model, THC inhibits the COX-2-NFκB pathway by inactivating transforming growth factor, which eventually reduces inflammation [13]. In LPS-stimulated RAW264.7 cells, THC exerts potent anti-inflammatory and antioxidant activities through the inhibition of the generation of ROS, NO, and monocyte chemotactic protein-1 [14]. Many previous studies have indicated that inhibition of the anus kinase-(JAK-) signal transducer and activator of transcription protein (STAT) signaling pathway can reduce LPS-induced inflammation [15][16][17].…”