Liying Wang1, Jinpo Gu2, Mingyue Zong1, Qingran Zhang1, Huixiang Li1, Danna Li1, Xiaofeng Mou1, Pan Liu1, Yanan Liu1, Feng Qiu3, Feng Zhao4. 1. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai, 264005, PR China. 2. Department of General Surgery, Yantai Hospital of Traditional Chinese Medicine, Yantai, 264000, PR China. 3. Tianjin State Key Laboratory of Modern Chinese Medicine, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, PR China. Electronic address: fengqiu20070118@163.com. 4. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai, 264005, PR China. Electronic address: ytuzhaofeng@163.com.
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.
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 inflammationmurine 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.