Sauchinone Suppresses Pro-inflammatory Mediators by Inducing Heme Oxygenase-1 in RAW264.7 Macrophages

Abstract

Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism responsible for catalyzing the split of free heme into carbon monoxide (CO), free iron and biliverdin/bilirubin. 1) Recent studies have shown that HO-1 has proven involvment in the resolution of inflammatory responses.2) HO-1 and its enzymatic by-products are the critical regulators of inflammation predominantly targeted against macrophages.3) Studies have shown that the anti-inflammatory action of HO-1 is mediated by inhibition of the production of pro-inflammatory cytokines and chemokines such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b) and interleukin (IL)-6 in activated macrophages. 4,5) Studies indicate that HO-1 and its product carbon monoxide (CO) can suppress the expression of the pro-inflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), thereby reducing COX-2-drived prostaglandin E 2 (PGE 2 ) and iNOS-derived nitric oxide (NO) production.6,7) Mitogen-activated protein kinases (MAPKs) is one of the most common signaling pathways that serve to coordinate the cellular response to a variety of extracellular stimuli. MAPKs have an important role in cellular processes, such as proliferation, stress responses, apoptosis and immune defense.8) The MAPK activation also modulates several gene and protein expression including the activation of HO-1. 9,10) Saururus chinensis (LOUR.) BAILL. (Saururaceae) has been traditionally used for the treatment of various diseases such as beriberi, pneumonia, urinary disorders, jaundice and gonorrhea. In Korea this plant is a known folk medicine, used for the treatment of edema.11) Sauchinone, a biologically active lignan isolated from the roots of S. chinensis, exibits various pharmacological activities, including hepatoprotective, antiinflammatory, cytoprotective and immunosuppressive effects.12-16) Moreover, several published studies demonstrate the inhibitory effect of sauchinone on LPS-induced expression of iNOS, iNOS-derived nitric oxide, TNF-a and COX-2 in murine macrophages.12,17) As a part of our ongoing research to identify phytochemicals isolated from natural sources that can induce HO-1 in vitro, 18,19) sauchinone was shown significantly induce the levels of HO-1 in RAW264.7 macrophages. In this study, we demonstrate that the effects of sauchinone on lipopolyscharride (LPS)-induced PGE 2 , NO, TNF-a and IL-1b production were partially reversed by the HO-1 inhibitor tin protoporphyrin. We further provided evidence to support the role of HO-1 in mediation of the antiinflammatory effects of sauchinone. Further this study provided evidence that HO-1 is a critical mechanism by which sauchinone exerts anti-inflammatory effects. Korea. Received April 7, 2011; accepted July 8, 2011; published online July 14, 2011 Sauchinone, a biologically active lignan isolated from the roots of Saururus chinensis (LOUR.) BAILL. (Saururaceae), is reported to exert a variety of biological activities, such as hepatoprotective, anti-inflammatory actions and inhibitory effects on...

Anti-Inflammatory Effect and Mechanism of the Green Fruit Extract ofSolanum integrifoliumPoir.

“…The use of specific inhibitors for MAPK pathways confirms the involvement of ERK pathway, but not of JNK pathway, in the anti-inflammatory action of ME. These data are in good agreement with other reports that numerous compounds, both natural and man-made ones, inhibit proinflammatory mediators through upregulation of HO-1 and ERK signaling [33–35]. …”

Anti-inflammatory effects of Saururus chinensis aerial parts in murine macrophages via induction of heme oxygenase-1

“…33 Jeong et al 34 also showed that sauchinone, an active lignan isolated from the roots of S. chinensis, upregulated HO-1 expression through the p38 MAPK-Nrf2/ARE-dependent pathway in t-butyl hydroperoxide-damaged HepG2 cells. However, Li et al 9 found that sauchinone induced HO-1 expression via the ERK pathway in LPS-stimulated RAW264.7 cells but did not affect the p38 MAPK and JNK pathways. The differences in the results can be attributed to the extract preparation method, the plant part used for extraction, and differences in experimental conditions (i.e.…”

“…In particular, sauchinone, a biologically active compound isolated from the root of S. chinensis, inhibits pro-inflammatory responses through HO-1-mediated anti-inflammatory effects of S. chinensis aerial parts 403 .......................................................................................................................... increased HO-1 expression via the ERK pathway. 9 However, the anti-inflammatory activity of the aerial parts of S. chinensis, and the cellular and molecular mechanisms involved (besides the ERK pathway) have not yet been determined. In the present study, we showed that the aerial parts of S. chinensis also inhibit LPS-induced proinflammatory mediators, activate p38 and Akt pathways, lead to nuclear translocation of NF-kB and Nrf2, and induce phosphorylation of the STAT1/3 pathway.…”

“…[3][4][5][6][7] Sauchinone, a diastereomeric ligand and a potential anti-inflammatory compound, has been isolated from the n-hexane fraction of S. chinensis root extract. 8,9 However, the cellular and molecular mechanisms of the extract of the aerial parts of this plant and its active compounds have not been extensively characterized.…”

Anti-inflammatory effect of methanol extract fromErigeron CanadensisL. may be involved with upregulation of heme oxygenase-1 expression and suppression of NFκB and MAPKs activation in macrophages

“…MAPKs are a group of serine/threonine protein kinases that are activated in response to diverse extracellular stimuli that mediate signal transduction from the cell surface to the nucleus [22]. MAPKs have been implicated in the signaling pathway relevant to LPS-induced inflammations.…”