ABSTRACT
Glehnia littoralis (Umbelliferae) has been used traditionally in Korean, Japanese, and Chinese medicine for the treatment of immune-related diseases; however, its anti-inflammatory activity and underlying mechanism remain to be defined. We investigated the anti-inflammatory effect and inhibitory mechanism on inflammation by the methylene chloride fraction from Glehnia littoralis extract (MCF-GLE), which was more effective than Glehnia littoralis extract (GLE). MCF-GLE inhibited 12-O-Tetradecanoyl-phorbol-13-acetate (TPA)-induced inflammation in an inflammatory edema mouse model. Also, MCF-GLE strongly inhibited the releases of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) and significantly suppressed the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW 264.7 macrophage cells in a dose-dependent manner. Furthermore, MCF-GLE suppressed NF-kappaB activation and IkappaB-alpha degradation. MCF-GLE also attenuated the activation of ERK and JNK in a dose-dependent manner. These results indicate that MCF-GLE has an inhibitory effect on the in vivo and in vitro inflammatory reaction and is a possible therapeutic agent. Our results suggest that the anti-inflammatory properties of MCF-GLE may result from the inhibition of pro-inflammatory mediators, such as NO, PGE(2), TNF-alpha, and IL-1beta via suppression of NF-kappaB- and mitogen-activated protein kinases-dependent pathways.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apiaceae , Methylene Chloride/pharmacology , Mitogen-Activated Protein Kinases/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Edema/drug therapy , Edema/metabolism , Edema/pathology , Male , Methylene Chloride/therapeutic use , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Roots , Protein Kinase Inhibitors/isolation & purification , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic useABSTRACT
AIMS OF STUDY: Although the flowers of Chrysanthemum indicum Linné (Asteraceae) have long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of a 70% ethanolic extract of C. indicum (CIE) on the activities of cellular signaling molecules that mediate inflammatory responses. MATERIALS AND METHODS: Production of NO, PGE(2), TNF-alpha, and IL-1beta by ELISA, mRNA and protein expression of iNOS and COX-2, phosphorylation of MAPKs, and activation of NF-kappaB by RT-PCR and Western blotting were examined in LPS-induced RAW 264.7 macrophages. RESULTS: The CIE strongly inhibited NO, PGE(2), TNF-alpha, and IL-1beta production, and also significantly inhibited mRNA and protein expression of iNOS and COX-2 in LPS-induced RAW 264.7 macrophages, in a dose-dependent manner. Furthermore, the CIE clearly suppressed nuclear translocation of NF-kappaB p65 subunits, which correlated with an inhibitory effect on IkappaBalpha phosphorylation. The CIE also attenuated the activation of ERK1/2 and JNK in a dose-dependent manner. CONCLUSION: Our results suggest that the anti-inflammatory properties of CIE might result from the inhibition of inflammatory mediators, such as NO, PGE(2), TNF-alpha, and IL-1beta, via suppression of MAPKs and NF-kappaB-dependent pathways.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Chrysanthemum , Macrophages/drug effects , Mitogen-Activated Protein Kinases/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Plant Extracts/pharmacology , Active Transport, Cell Nucleus/drug effects , Animals , Cell Line , Cell Survival/drug effects , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Dinoprostone/metabolism , Flowers , I-kappa B Proteins/antagonists & inhibitors , Lipopolysaccharides , Mice , Mitogen-Activated Protein Kinases/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Phosphorylation/drug effects , RNA, Messenger/metabolismABSTRACT
AIM OF THE STUDY: Although Chrysanthemum indicum Linné (Compositae) has long been used in traditional Korean, Chinese, Japanese medicine to treat various immune-related diseases the underlying mechanism(s) by which these effects are induced remains to be defined in vivo model system. We investigated the effects of 70% ethanolic extract from Chrysanthemum indicum Linné (CIE) on skin inflammation in mice. MATERIALS AND METHODS: Production of pro-inflammatory cytokines (TNF-alpha and IL-1 beta), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. RESULTS: CIE inhibited topical edema in the mouse ear, following administration at 200mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. Furthermore, CIE was effective at reducing inflammatory damage induced by chronic TPA exposure. CONCLUSIONS: These results demonstrate that CIE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the extract may have therapeutic potential in a variety of immune-related cutaneous diseases.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Chrysanthemum/chemistry , Dermatitis/prevention & control , Plant Extracts/pharmacology , Acute Disease , Animals , Anti-Inflammatory Agents/therapeutic use , Chronic Disease , Enzyme Activation , Inflammation Mediators/metabolism , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred C57BL , Peroxidase/metabolism , Plant Extracts/therapeutic use , Tetradecanoylphorbol Acetate/toxicity , Tumor Necrosis Factor-alpha/metabolismABSTRACT
AIMS OF STUDY: Although Asparagus cochinchinensis Merrill (Liliaceae) has long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of 70% ethanolic extract from Asparagus cochinchinensis Merrill (ACE) on skin inflammation in mice. MATERIALS AND METHODS: Production of pro-inflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability test. RESULTS: ACE inhibited topical edema in the mouse ear, following administration at 200mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase (MPO) activity, and various histopathological indicators. Furthermore, ACE was effective at reducing inflammatory damage induced by chronic TPA exposure and evoked a significant inhibition of vascular permeability induced by acetic acid in mice. CONCLUSION: These results demonstrate that ACE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the compound may have therapeutic potential in a variety of immune-related cutaneous diseases.