HO-1 Is Essential for Tetrahydroxystilbene Glucoside Mediated Mitochondrial Biogenesis and Anti-Inflammation Process in LPS-Treated RAW264.7 Macrophages

Abstract

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an important monomer extracted from Polygonum multiflorum, can prevent a number of inflammation associated chronic diseases. However, the mechanism involved in TSG inducing anti-inflammatory role remains unclear. As an inducible antioxidant enzyme, Heme oxygenase-1 (HO-1), is crucial for protecting the mammalian cells against adverse stimuli. Here, we found that the TSG treatment strongly induces the expression of HO-1 in an NRF2-depended manner. Meanwhile, TSG increased the mitochondrial mass through upregulation of the mitochondrial biogenesis activators (PGC-1α, NRF1, and TFAM) as well as the mitochondrial complex IV. Furthermore, TSG attenuated Lipopolysaccharide (LPS) mediated RAW264.7 cells activation and secretion of proinflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Zinc Protoporphyrin (ZnPP), a selective inhibitor of HO-1 activity, was able to attenuate TSG mediated mitochondrial biogenesis and anti-inflammatory process. Finally, we observed that LPS induced obvious mtDNA depletion and ATP deficiency, which indicated a severe damage of mitochondria. TSG restored the LPS induced mitochondrial dysfunction via activation of the mitochondrial biogenesis. ZnPP treatment markedly reversed the inhibitory effects of TSG on mitochondrial damage and oxidative stress in LPS stimulated macrophages. Taken together, these findings suggest that TSG enhances mitochondrial biogenesis and function mainly via activation the HO-1. TSG can be developed as a potential drug for treatment of inflammatory diseases.

2,3,4′,5-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) Activates the Nrf2 Antioxidant Pathway and Attenuates Oxidative Stress-Induced Cell Death in Mouse Cochlear UB/OC-2 Cells

“…Previous studies found that THSG can restore or reverse mitochondrial biogenesis and mitochondrial function in mouse neuronal cells and RAW 246.7 macrophages through many different anti-inflammatory signaling pathways [30,31]. The JC-1 staining results obtained in our study also showed that THSG might have the ability to stabilize the mitochondrial membrane potential under conditions of H 2 O 2 -induced free radical damage in UB/OC-2 cells (Figure 5e).…”

“…Previous studies have shown that the cytoprotective effects of THSG are mediated by antioxidant/detoxifying enzymes and proteins such as HO-1, NQO1, and GSH. THSG protects against doxorubicin-induced nephropathy and cardiotoxicity by decreasing the ROS levels and inhibiting apoptotic signaling pathways in vivo and in vitro [29][30][31]. The current study also showed that THSG protected against H 2 O 2 -induced cell damage by attenuating oxidative stress in mouse cochlear UB/OC-2 cells.…”

Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

“…The cells were incubated in the atmosphere of 5% CO 2 and 37 C, and their culture medium was managed as DMEM complete medium that contained 10% FBS. 26 The THP-1 cells at the logarithmic phase were seeded at the concentration of 5.0 Â 10 6 /ml, and cell models of sepsis were built by stimulating the THP-1 cell line with 100 ng/ml LPS for 4 h. 27 Also, the THP-1 cells that grew to 70%-80% confluence were transfected with siRNAs against CRNDE, si-NC, miR-181a-5p mimic, miR-NC and si-TLR4 (Genepharma, China) (Supplemental Table 1). After 48 h, the cells were used for the following experiments.…”

Biological Effects of Tetrahydroxystilbene Glucoside: An Active Component of a Rhizome Extracted from Polygonum multiflorum

“…TSG treatment strongly induces the expression of HO-1 in an NRF2-dependent manner. Furthermore, TSG attenuates the LPS-mediated activation of RAW264.7 cells and the secretion of proinflammatory cytokines, including IL-6 and TNF- α [ 128 ]. NADPH oxidase is recognized as a key ROS-producing enzyme during inflammation and widely expressed in various immune cells, such as macrophages, eosinophils, microglia, and neutrophils [ 129 ].…”