Activation of the Nrf2/HO‐1 Pathway by Amomum villosum Extract Suppresses LPS‐Induced Oxidative Stress In Vitro and Ex Vivo

Abstract

Despite its deleterious effects on living cells, oxidative stress plays essential roles in normal physiological processes and provides signaling molecules for cell growth, differentiation, and inflammation. Macrophages are equipped with antioxidant mechanisms to cope with intracellular ROS produced during immune response, and Nrf2 (NF-E2-related factor 2)/HO-1 (heme oxygenase-1) pathway is an attractive target due to its protective effect against ROS-induced cell damage in inflamed macrophages. We investigated the effects of ethanol extract of A. villosum (AVEE) on lipopolysaccharide- (LPS-) stimulated inflammatory responses generated via the Nrf2/HO-1 signaling pathway in murine peritoneal macrophages and RAW 264.7 cells. AVEE was found to suppress the NF-κB signaling pathway, thus, to reduce proinflammatory cytokine, nitric oxide, and prostaglandin levels in peritoneal macrophages and Raw 264.7 cells treated with LPS, and to enhance HO-1 expression by activating Nrf2 signaling. Furthermore, these anti-inflammatory effects of AVEE were diminished when cells were pretreated with SnPP (a HO-1 inhibitor). HPLC analysis revealed AVEE contained quercetin, a possible activator of the Nrf2/HO-1 pathway. These results show A. villosum ethanol extract exerts anti-inflammatory effects by activating the Nrf2/HO-1 pathway in LPS-stimulated macrophages.

Calycosin alleviatesH2O2‐induced astrocyte injury by restricting oxidative stress through the Akt/Nrf2/HO‐1 signaling pathway

“…Previously studies show that ROS regulates changes in levels of molecules involved in mediating oxidative stress via different signaling cascades, such as the Nrf2/HO-1 signaling axis. 18,44,45 Nrf2 is a transcription factor that regulates the expression of variety of cytoprotective molecules, and HO-1 protects cells by reducing ROS. [18][19][20] Previous reports indicate that under normal physiological circumstances, Nrf2 is mainly present in the cytoplasm; however, elevated ROS levels promote its nuclear translocation and transcription of genes encoding proteins involved in controlling oxidative stress, including HO-1.…”

Artemisia argyiextract amelioratesIL‐17A‐induced inflammatory response by regulation of NF‐κB and Nrf2 expression inHIG‐82 synoviocytes

“…Furthermore, inflammatory protein modifications may regulate by NF-κB during different signaling cascades, such as the nuclear factor erythroid 2-related factor (Nrf2) signaling pathway. [17][18][19][20] Nrf2 activation and absence may regulate the expression of NF-κB and pro-inflammatory cytokines. [20][21][22] Moreover, previous studies have shown that Nrf2 can protect cells by reducing inflammation through Nrf2 and heme oxygenase-1 (HO-1) pathway.…”

Purification, Structural Characterization and Immunomodulatory Effects of Polysaccharides from Amomumvillosum Lour. on RAW 264.7 Macrophages

“…A. villosum is widely distributed in South and East Asia [ 2 ]. Accumulating studies demonstrated that the major bioactive components of A. villosum included volatile oils, flavonoids, terpenoids and polysaccharides, which showed anti-inflammation, anti-oxidant, anti-ulceration and anti-microbial activities [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”