Anti‐inflammatory function of Withangulatin A by targeted inhibiting COX‐2 expression via MAPK and NF‐κB pathways

Abstract

Withangulatin A (WA), an active component isolated from Physalis angulata L., has been reported to possess anti-tumor and trypanocidal activities in model systems via multiple biochemical mechanisms. The aim of this study is to investigate its anti-inflammatory potential and the possible underlying mechanisms. In the current study, WA significantly suppressed mice T lymphocytes proliferation stimulated with LPS in a dose- and time-dependent manner and inhibited pro-inflammation cytokines (IL-2, IFN-gamma, and IL-6) dramatically. Moreover, WA targeted inhibited COX-2 expression mediated by MAPKs and NF-kappaB nuclear translocation pathways in mice T lymphocytes, and this result was further confirmed by the COX-1/2 luciferase reporter assay. Intriguingly, administration of WA inhibited the extent of mice ear swelling and decreased pro-inflammatory cytokines production in mice blood serum. Based on these evidences, WA influences the mice T lymphocytes function through targeted inhibiting COX-2 expression via MAPKs and NF-kappaB nuclear translocation signaling pathways, and this would make WA a strong candidate for further study as an anti-inflammatory agent.

Erythromycin EnhancesCD4+Foxp3+Regulatory T-Cell Responses in a Rat Model of Smoke-Induced Lung Inflammation

“…Erythromycin can inhibit mitogen-stimulated human T-cell proliferation and cytokine production, which are associated with inhibition of the MAPK and NF- κ B activation [18, 19]. Furthermore, erythromycin can ameliorate chronic inflammation in various animal models [20, 21].…”

Intestinal anti-inflammatory activity of Ground Cherry (Physalis angulataL.) standardized CO2phytopharmaceutical preparation

“…The main group of sterols in this plant are the seco-sterols (named physalins) and molecules derived from ergostane[9,58], which were identified as active compounds from P. angulata , reducing vascular permeability, neutrophil infiltration[59], inflammatory cytokine production such as of IFN-γ and IL-6, and modulating the expression of Mapks[60], as observed in our experiments. Indeed, administration of seco-sterols of P. angulata has been useful to treat autoimmune diseases, allergies or in cases of transplant rejection with lower toxicity when compared to glucocorticoids[59].…”

Amelioration of systemic lupus erythematosus by withangulatin A in MRL/lpr mice

“…Intriguingly, it has been demonstrated that WA inhibits mice T lymphocytes proliferation stimulated with LPS and pro-inflammation cytokines, including IL-2, IFN-g, and IL-6 in vitro [Sun et al, 2010], as well as WA significantly suppressed the over-proliferation of ConA-induced T lymphocytes and markedly reduced Th1-type cytokines and increased Th2-type cytokines to obtain Th1/Th2 balance [Sun et al, 2011]. WA also attenuated the lymphadenopathy in MRL/lpr mice.…”

“…Here we show that WA, isolated out from Physalis angulata L., exerts pleiotropic therapeutic effect. In our previous work, we reported the mechanism of anti-inflammatory [Sun et al, 2010] and immunosuppressive effect [Sun et al, 2011] of WA, which might protect against autoimmune disorder diseases. This study showed WA could improve the life quality and renal histopathologic characteristics, as well as reduce the accumulation of proteinuria symptoms and levels of anti-double-stranded DNA antibodies in MRL/lpr mice, which suggested a potential application of this active constituent in the treatment of SLE.…”