Saucerneol G, a New Lignan, from Saururus chinensis Inhibits Matrix Metalloproteinase-9 Induction via a Nuclear Factor .KAPPA.B and Mitogen Activated Protein Kinases in Lipopolysaccharide-Stimulated RAW264.7 Cells

Abstract

The Gram-negative bacteria cell wall component lipopolysaccharide (LPS) is considered as the most potent activators for macrophages. LPS-activated macrophages produces an array of proinflammatory cytokines such as tumor necrosis facto-a (TNF-a), interleukin (IL)-1b, IL-6 and other inflammatory mediators, such as nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) as well as matrix metalloproteinases (MMPs). [1][2][3][4][5] MMPs are a family of zinc requiring endopeptidases that play an important role in the turnover of extracellular matrix (ECM). Among them, MMP-2 and MMP-9 (92 kDa gelatinase) are capable of degrading basement membrane proteins. Various inflammatory cells such as macrophages, mast cells, lymphocytes, eosinophils and neutrophils produce and/or releases MMP-9 by LPS and other inflammatory mediators, such as TNF-a, IL-8, and granulocyte colony-stimulating factor. [6][7][8] Over expression or inappropriate expression of MMP-9 may contribute to the pathogenesis of conditions such as atherosclerosis, inflammation, tumor invasion and metastasis, rheumatoid arthritis, and periodontal disease. 9)It has been well established that MMP-9 induction is regulated by the transcription factor, nuclear factor-kB (NFkB).10,11) Inactive NF-kB is located in the cytoplasm by the inhibitor protein inhibitor of kB (IkB). When stimulated with any of a variety of stimuli, such as LPS, TNF-a, IL-1b and cellular stress, IkB is degraded and then NF-kB is translocated from the cytosol to the nucleus, and binds to its cognate DNA binding sites.12) LPS-stimulated macrophages activate several intracellular signaling pathways, including the NF-kB pathway and three of the mitogen-activated protein kinases (MAPKs) pathways such as extracellular signalregulated kinase (ERK) 1 and 2, c-Jun N-terminal kinase (JNK) and p38.12) Several lines of evidence have demonstrated that LPS also regulates MMP-9 expression via the MAPK signaling pathway. 13,14) Saururus chinensis (S. chinensis) has been traditionally used since long for the treatment of edema, jaundice, gonorrhea, pneumonia, and several inflammatory diseases. Previous published studies on the chemical nature of S. chinensis have reported a content of more than 20 lignans.15,16) Isolated tetrahydrofurans protect against cell adhesion, 17) inflammation, 18,19) hypercholesterolemia, 20) and sepsis. 21) Sesquinelignans such as saucerenol D inhibited the LPS-induced iNOS expression by blocking NF-kB activation.22) Previously, we had reported on isolation of compounds that protect against sepsis from this plant along with four new lignans including saucerneol G (SG) and their topoisomerase inhibitory activity.23) During the study of SG on anti-inflammatory effect using RAW264.7 cells, SG showed the MMP-9-inhibitory activity. However, the underlying mechanisms in the inhibitory activity of SG on MMP-9 induction in LPSstimulated macrophage cell line RAW264.7 cells have not been elucidated till date.Thus, in this study, we evaluated the effects of SG on LPSstimulated MMP-9 induction and co...

Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-κB and AP-1 inactivation in LPS-induced RAW264.7 cells

“…Until now, various natural compounds have been isolated from S. chinensis, and more than 20 lignans have been elucidated for their chemical natures [15,16,[28][29][30][31][32][33]. The isolated lignans from S. chinensis and S. cernuus showed potential anti-inflammatory, anti-metastatic, neuroleptic, and cholesterol-lowering activities [15,16,[28][29][30][31][32][33].…”

“…The isolated lignans from S. chinensis and S. cernuus showed potential anti-inflammatory, anti-metastatic, neuroleptic, and cholesterol-lowering activities [15,16,[28][29][30][31][32][33]. Additionally, these compounds exhibited hepatoprotective, antifibrotic, antiseptic, antioxidative, anti-tumor DNA replication, and anti-HIV effects [2,4,[34][35][36].…”

“…Recently, we demonstrated that a known sesquilignan, saucerenol D, inhibited LPS-induced iNOS expression and a new lignin, saucerneol G, inhibited matrix metalloproteinase-9 induction via NF-κB and MAPKs in LPS-stimulated RAW264.7 cells [15,16]. However, the underlying anti-inflammatory mechanisms of SF have not been elucidated.…”

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

“…Saururus chinensis (Lour.) Baill has been used in Chinese medicine for treating jaundice, gonorrhea and edema as well as reversing liver fibrosis [ 128 , 129 ]. Saururus chinensis (Lour.)…”

Potential of Phytomolecules in Alliance with Nanotechnology to Surmount the Limitations of Current Treatment Options in the Management of Osteoarthritis

“…They are most commonly acquired from roots, fruits, heartwoods, as well as resinous plant exudates. Lignans exhibiting therapeutic activity against OA by modulating the release of proinflammatory factors [159][160][161][162][163][164] and proliferation of MMP enzymes [165][166][167][168][169][170] are presented in Tables 3 and Table 4, respectively.…”