Anti-inflammatory action of physalin A by blocking the activation of NF-κB signaling pathway. (1st March 2021)

• Record Type: Journal Article
• Authors: Wang, Liying; Gu, Jinpo; Zong, Mingyue; Zhang, Qingran; Li, Huixiang; Li, Danna; Mou, Xiaofeng; Liu, Pan; Liu, Yanan; Qiu, Feng; Zhao, Feng
• Is Part Of: Journal of ethnopharmacology. Volume 267(2021)
• Publication Date: 2021-03-01
• Subjects: Physalin A -- Anti-inflammatory activity -- NF-κB -- MAPKs -- iNOS -- NO; TCM traditional Chinese medicine -- NO nitric oxide -- LPS lipopolysaccharide -- TNF-α tumor necrosis factor-α -- PGE2 prostaglandin E2 -- ELISA enzyme-linked immuno sorbent assay -- iNOS inducible nitric oxide synthase -- COX-2 cyclooxygenase-2 -- NF-κB nuclear factor kappa B -- IκB-α inhibitor of nuclear factor kappa B alpha -- MAPKs mitogenactivated protein kinases -- ERK extracellular signal-regulated kinase -- JNK c-Jun N-terminal kinase -- FBS fetal bovine serum -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- HSS hydrocortisone sodium succinate; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113490
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Physalis Calyx seu Fructus is typically used to treat inflammatory diseases such as upper respiratory tract infection and acute tonsillitis in clinical practice of China. Physalin A, a main active ingredient of this traditional Chinese medicine (TCM), has been reported for its significant anti-tumor activity. However, most reports focused on the studies of its anti-tumor activity, the anti-inflammatory activity of physalin A and its molecular mechanism are still not elucidated clearly. Aim of the study: The aim of the study was to investigate the anti-inflammatory activities both in vitro and in vivo and molecular mechanism of physalin A. Materials and methods: The potential anti-inflammatory properties of physalin A were evaluated in vitro by lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells, and in vivo via two typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by enzyme-linked immuno sorbent assay (ELISA) and Western blotting. Results: The results showed that physalin A inhibited carrageenan-induced paw edema of rats and capillary permeability of mice induced by acetic acid in vivo . Furthermore, physalin A also significantly reduced the release of inflammatory mediators nitric oxide (NO), prostaglandin E2 (PGE2 ), and tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW 264.7 in vitro . Further investigations indicated that physalin A can down-regulate the high expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Physalin A remarkably blocked the degradation of inhibitor of nuclear factor kappa B alpha (IκB-α) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 induced by LPS in RAW 264.7 cells. However, physalin A did not significantly inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) family proteins c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) or p38. Conclusions: All the results clearly illustrated that the anti-inflammatory action of physalin A is due to the inactivation of NF-κB signal pathway, but is irrelevant to the MAPKs pathway. Graphical abstract: Image 1 Highlights: Physalin A significantly inhibited the overproduction of NO induced by LPS. Physalin A significantly inhibited the overproduction of PGE2 induced by LPS. Physalin A significantly inhibited the overproduction of TNF-α induced by LPS. Physalin A down-regulated the expression of iNOS and COX-2 proteins. Physalin A exerts anti-inflammatory effects by blocking the NF-κB pathway.