Santamarin, a sesquiterpene lactone isolated from Saussurea lappa, represses LPS-induced inflammatory responses via expression of heme oxygenase-1 in murine macrophage cells.

Saussurea lappa C.B. Clarke (Compositae) is indigenous to India and Pakistan. The dried root of S. lappa has been traditionally used for alleviating pain in abdominal distention and tenesmus, indigestion with anorexia, dysentery, nausea, and vomiting. Santamarin is a sesquiterpene lactone isolated from S. lappa. In the present study, santamarin inhibited inducible nitric oxide synthase (iNOS) protein, reduced iNOS-derived nitric oxide (NO), suppressed COX-2 protein and reduced COX-derived PGE(2) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and murine peritoneal macrophages. Similarly, santamarin reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production. In addition, santamarin suppressed the phosphorylation and degradation of IκB-α as well as the nuclear translocation of p65 in response to LPS in RAW264.7 cells. Furthermore, santamarin induced heme oxygenase (HO)-1 expression mRNA and protein level that plays a cytoprotective role against inflammation. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various agents is mediated by the nuclear transcription factor E2-related factor 2 (Nrf2), master regulator of antioxidant responses. Unbound Nrf2 translocates into the nucleus and binds to the antioxidant response element (ARE) in the upstream promoter region of many antioxidative genes, where it initiates their transcription. The effects of santamarin on LPS-induced NO, PGE(2), TNF-α, and IL-1β production were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Therefore, our data suggest that the anti-inflammatory effect of santamarin in macrophages may be exerted through a novel mechanism that involves HO-1 expression.

Choi HG ，Lee DS ，Li B ，Choi YH ，Lee SH ，Kim YC ... -  《-》

Pulchellamin G, an amino acid-sesquiterpene lactone, from Saussurea pulchella suppresses lipopolysaccharide-induced inflammatory responses via heme oxygenase-1 expression in murine peritoneal macrophages.

Saussurea pulchella (Asteraceae) is widely distributed in Korea and has been used in Korean folk medicine for the treatment of inflammation, hypertension, hepatitis, and arthritis. Pulchellamin G is an amino acid-sesquiterpene lactone conjugate isolated from S. pulchella. In the present study, we focused on the anti-inflammatory effect of pulchellamin G, which acts by inducing the expression of heme oxygenase (HO)-1. HO-1 plays important roles in cytoprotection since it has antioxidant, anti-inflammatory, antiproliferative, and antiapoptotic properties. Pulchellamin G inhibited the mRNA and protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), and cyclooxygenase (COX)-2 and COX-derived prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. The compound also reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production and suppressed the phosphorylation and degradation of IκB-α and nuclear translocation of p65 in murine peritoneal macrophages in response to LPS stimulus. The inhibitory effects of pulchellamin G on nuclear factor kappa B (NF-κB) translocation was impaired by co-treatment of the cells with HO activity inhibitor tin protoporphyrin (SnPP). By using SnPP, we verified that the inhibitory effects of pulchellamin G on the pro-inflammatory mediators NO, PGE2, TNF-α, and IL-1β are associated with induction of HO-1 expression. Our data suggest that pulchellamin G might have potent therapeutic effects and it should be considered in the development of treatments for various inflammatory diseases.

Lee DS ，Choi HG ，Wan Woo K ，Kang DG ，Lee HS ，Oh H ，Ro Lee K ，Kim YC ... -  《-》

Inhibitory Effects of Aucklandia lappa Decne. Extract on Inflammatory and Oxidative Responses in LPS-Treated Macrophages.

Lim JS ，Lee SH ，Lee SR ，Lim HJ ，Roh YS ，Won EJ ，Cho N ，Chun C ，Cho YC ... -  《MOLECULES》

Anti-inflammatory effects of sulfuretin from Rhus verniciflua Stokes via the induction of heme oxygenase-1 expression in murine macrophages.

Rhus verniciflua Stokes (Anacardiaceae) has traditionally been used as an ingredient in East Asian medicines used to treat oxidative damage and cancer. Sulfuretin is one of the major flavonoid components isolated from R. verniciflua. In the present study, we isolated sulfuretin from R. verniciflua and demonstrated that sulfuretin inhibited inducible nitric oxide synthase (iNOS) protein and mRNA expression, reduced iNOS-derived NO, suppressed COX-2 protein and mRNA expression, and reduced COX-derived PGE(2) production in lipopolysaccharide (LPS)-stimulated RAW264.7 and murine peritoneal macrophages. Similarly, sulfuretin reduced tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) production. In addition, sulfuretin suppressed the phosphorylation and degradation of I kappaB-alpha as well as the nuclear translocation of p65 by the stimulation of LPS in RAW264.7 macrophages. Furthermore sulfuretin induced heme oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf)2 and increased heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of sulfuretin on LPS-induced NO, PGE(2), TNF-alpha, and IL-1 beta production were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Therefore, it is suggested that sulfuretin-induced HO-1 expression plays a role of the resulting anti-inflammatory effects in macrophages. This indicated that the anti-inflammatory effects of sulfuretin in macrophages might be exerted through a novel mechanism that involves HO-1 expression.

Lee DS ，Jeong GS ，Li B ，Park H ，Kim YC ... -  《-》

Asperlin from the marine-derived fungus Aspergillus sp. SF-5044 exerts anti-inflammatory effects through heme oxygenase-1 expression in murine macrophages.

Lee DS ，Jeong GS ，Li B ，Lee SU ，Oh H ，Kim YC ... -  《-》