Quercetin reduces TNF‐α‐induced mesangial cell proliferation and inhibits PTX3 production: Involvement of NF‐κB signaling pathway

Abstract

Lupus nephritis (LN) is an autoimmune disease caused by systemic lupus erythematosus. Excessive proliferation of mesangial cells is one of the most serious pathological manifestations of LN. In addition, the expression of PTX3 is elevated in the serum of patients with LN. Quercetin has good anti‐inflammatory effects and immunomodulatory activities. In this study, the result of MTT indicated that quercetin treatment alleviated the excessive proliferation of mesangial cells. ELISA and immunofluorescence experiments showed that quercetin treatment inhibited the expression of PTX3. Three doses of quercetin (20, 40, and 80 μM) were selected for the experiment. It is noteworthy that the efficacy of quercetin at 80 μM was significantly better than that of other dose groups. And the effect in inhibiting PTX3 expression was comparable with that of the PDTC (80 μM) positive control. Western blot and qRT‐PCR analysis revealed that quercetin treatment reduced the expression of nuclear factor‐κB p65 and IKKβ, increased the expression of IκBα, and inhibited the expression of PTX3. In conclusion, through inhibiting the activation of nuclear factor‐κB signaling pathway, quercetin treatment could reduce the expression of PTX3 and inhibit the excessive proliferation of mesangial cells, suggesting that quercetin is a potential therapeutic drug for LN.

SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis

“…Therefore, MG132 and other proteasome inhibitors are usually used to inhibit protein degradation by the UPS to better detect the ubiquitination signal. However, PTX3 is generated by the NF‐κB pathway, 35 and proteasome inhibitors such as MG132 and MG101 significantly promote IκBα accumulation and inhibit the NF‐κB pathway 36 . We confirmed that MG132 and MG101 substantially inhibit PTX3 expression, and we therefore transfected HA‐UBB into MSCs in an attempt to increase the ubiquitination of PTX3 for better detection.…”

“…Therefore, we detected the level of ubiquitinated PTX3 in HDMSCs and ASMSCs. PTX3 is generated by the NF‐κB pathway, 35 and proteasome inhibitors inhibit the NF‐κB pathway 36 . We initially confirmed that MG132 and MG101 substantially inhibited endogenous PTX3 expression (Supplementary Figure S2D).…”

Quercetin for COVID-19 and DENGUE co-infection: a potential therapeutic strategy of targeting critical host signal pathways triggered by SARS-CoV-2 and DENV

“…For the co-infection of SARS-COV-2 and DENV, firstly, quercetin has a wide range of antiviral properties and can interfere with the virulence of pathogens with multiple steps [ 63 ]. Secondly, quercetin, an anti-inflammatory component, is able to decrease the inflammatory response via dose-dependently inhibiting the NF-κB signaling pathway and effectively reduces the level of inflammatory factors TNF-α, IL-6 and IL-17 [ 62 , 64 , 65 ].…”

20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment

“…33 Studies have shown quercetin also exhibiting anti-inflammatory properties, [34][35][36] which could help mitigate the inflammatory response of cytokine and/or bradykinin storms provoked by COVID-19. A wide range of anti-viral/immunity benefits of quercetin have been identified, [37][38][39][40][41] as well as other health benefits that may address some comorbidities of COVID-19 [42][43][44] and some of its sequelae. 44,45 Role of vitamin C. Effects of vitamin C on the immune system (e.g., possible enhancement of activity of NK cells and of other effectors of immunity mechanisms) are well documented.…”