Sauchinone

Int Immunopharmacol. 2013 Oct;17(2):471-7.

Sauchinone, a lignan from Saururus chinensis, attenuates neutrophil pro-inflammatory activity and acute lung injury.[Pubmed: 23928505]

Previous studies have shown that Sauchinone modulates the expression of inflammatory mediators through mitogen-activated protein kinase (MAPK) pathways in various cell types. However, little information exists about the effect of Sauchinone on neutrophils, which play a crucial role in inflammatory process such as acute lung injury (ALI).
METHODS AND RESULTS:
We found that Sauchinone decreased the phosphorylation of p38 MAPK in lipopolysaccharide (LPS)-stimulated murine bone marrow neutrophils, but not ERK1/2 and JNK. Exposure of LPS-stimulated neutrophils to Sauchinone or SB203580, a p38 inhibitor, diminished production of tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-2 compared to neutrophils cultured with LPS. Treatment with Sauchinone decreased the level of phosphorylated ribosomal protein S6 (rpS6) in LPS-stimulated neutrophils. Systemic administration of Sauchinone to mice led to reduced levels of phosphorylation of p38 and rpS6 in mice lungs given LPS, decreased TNF-α and MIP-2 production in bronchoalveolar lavage fluid, and also diminished the severity of LPS-induced lung injury, as determined by reduced neutrophil accumulation in the lungs, wet/dry weight ratio, and histological analysis.
CONCLUSIONS:
These results suggest that Sauchinone diminishes LPS-induced neutrophil activation and ALI.

Biol Pharm Bull. 2013;36(7):1134-9.

Sauchinone, a lignan from Saururus chinensis, protects human skin keratinocytes against ultraviolet B-induced photoaging by regulating the oxidative defense system.[Pubmed: 23811562]

Ultraviolet (UV) radiation from sunlight induces matrix metalloproteinase (MMP) expression, which are responsible for collagenous extracellular matrix proteins breakdown in skin, causing photoaging. Sauchinone is reported to have various bioactivity such as antioxidative, hepatoprotective, and anti-inflammatory effects. In the present study, we investigated the protective effect of Sauchinone against UVB (50 mJ/cm(2))-induced photoaging in HaCaT human epidermal keratinocytes.
METHODS AND RESULTS:
Sauchinone, at 5-40 μM, significantly protected keratinocytes against UVB-induced damage as assessed by cell viability and toxicity assay. Additionally, Sauchinone, at 20-40 μM, prevented the upregulation of MMP-1 proteins and reduction of type 1 collagen induced by UVB. Other assays revealed that, in keratinocytes, Sauchinone decreased reactive oxygen species (ROS) production and increased glutathione levels and heme oxygenase-1. Sauchinone also inhibited UVB-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling pathways.
CONCLUSIONS:
These results demonstrated that Sauchinone protects skin keratinocytes through inhibition of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK signaling via upregulation of oxidative defense enzymes.

Biol Pharm Bull. 2003 Oct;26(10):1428-30.

Sauchinone, a lignan from Saururus chinensis, inhibits staurosporine-induced apoptosis in C6 rat glioma cells.[Pubmed: 14519949]

Neuronal apoptosis may contribute to pathologic neuronal loss in certain disease states such as neurodegenerative diseases. Staurosporine (ST), a nonselective protein kinase inhibitor, has been shown to induce apoptosis in a variety of cells including nerve cell lines. In this study, we investigated the neuroprotective effect of Sauchinone, which is a unique lignan from Saururus chinensis, on ST-induced apoptosis in C6 rat glioma cells.
METHODS AND RESULTS:
Sauchinone attenuated ST-induced apoptosis of C6 glioma cells as evidenced by DNA fragmentation. We also provide evidence that the inhibitory effect of Sauchinone on ST-induced apoptosis involves a dose-dependent upregulation of an antiapoptotic protein, Bcl-2. Mounting evidence shows that the activation of caspases, especially caspase-3, triggers the apoptotic process. The activity of caspase-3 of ST-pretreated cells was significantly decreased upon Sauchinone treatment in a dose-dependent manner.
CONCLUSIONS:
Taken together, the data demonstrate that Sauchinone protects C6 glioma cells from ST-induced apoptosis in a caspase-3 dependent manner. Our findings may be critical for developing a strategy to protect nerve cells from apoptosis, suggesting the potential development of Sauchinone as a neuroprotective agent.

Eur J Pharmacol. 2014 Apr 5;728:176-82.

Effect of sauchinone, a lignan from Saururus chinensis, on bacterial phagocytosis by macrophages.[Pubmed: 24486706]

AMP-activated protein kinase (AMPK) plays an important role in inflammation in various cells and increases the phagocytic ability of macrophages.
METHODS AND RESULTS:
In this study, we found that Sauchinone increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in mouse peritoneal macrophages. Sauchinone increased macrophage phagocytosis of fluorescent Escherichia coli, which was blocked by compound C, an AMPK inhibitor. Sauchinone also increased the phosphorylation of p38 mitogen activated protein kinase (MAPK) in cultured macrophages in a concentration-dependent fashion, which was not blocked by compound C. However, the increase of Sauchinone-induced phagocytosis was prevented by SB203580. An inhibitor of the upstream kinase TGF-beta-activated kinase (TAK1), (5z)-7-oxozeaenol, abolished the phosphorylation of ACC and p38 MAPK. Systemic administration of Sauchinone to mice led to increased phosphorylation of AMPK and p38 MAPK in the lung, and enhanced phagocytosis of fluorescent E. coli in bronchoalveolar lavage fluid as compared with control mice.
CONCLUSIONS:
These results suggest Sauchinone to be a useful adjunctive treatment for bacterial infection.

Phytomedicine. 2014 Jan 15;21(2):101-8.

Sauchinone from Saururus chinensis protects vascular inflammation by heme oxygenase-1 induction in human umbilical vein endothelial cells.[Pubmed: 24035224]

Sauchinone, a diastereomeric 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 bone resorption.
METHODS AND RESULTS:
In this study, we investigated the effect of Sauchinone in suppressing cell adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression in high glucose stimulated human umbilical vein endothelial cells (HUVEC). Sauchinone inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by the stimulation of high glucose. In addition, Sauchinone induced heme oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2-related factor 2 in HUVEC. The effects of Sauchinone on the high glucose-induced expression of VCAM-1 and ICAM-1 and nuclear translocation of NF-κB p65 were partially reversed by transfection of the cells with HO-1 siRNA.
CONCLUSIONS:
These findings suggest that Sauchinone-induced HO-1 expression plays a key role in the vascular protective effects of Sauchinone in HUVEC.

Toxicol In Vitro. 2011 Mar;25(2):505-12.

Sauchinone protects pancreatic β cells against cytokine-mediated toxicity.[Pubmed: 21167929 ]

Sauchinone has been shown to exert potent hepatoprotective, anti-inflammatory and inhibitory effects on bone resorption. In this study, we investigated the effect of Sauchinone on IL-1β (5 ng/ml) and IFN-γ (100 U/ml)-induced β-cell damage.
METHODS AND RESULTS:
Pre-treatment with Sauchinone increased the viability of cytokine-treated RINm5F cells at concentrations of 20-40 μM. Sauchinone prevented nitric oxide (NO) production, and this effect was correlated with reduced levels of protein expression of the inducible form of NO synthase (iNOS). The molecular mechanism by which Sauchinone inhibits iNOS gene expression appeared to involve the inhibition of NF-κB activation. Moreover, pancreatic β-cells treated with cytokines upregulated the phosphorylation of STAT-1, STAT-3 and STAT-5, however, pre-treatment with Sauchinone attenuated these effects. Additionally, in a second set of experiments in which rat islets were used, the protective effects of Sauchinone in rat islets were essentially the same as those observed when RINm5F cells were used. Sauchinone prevented cytokine-induced NO production, iNOS expression, JAK/STAT activation, and NF-κB activation and inhibition of glucose-stimulated insulin secretion (GSIS).
CONCLUSIONS:
Collectively, these results suggest that Sauchinone can be used for the prevention of functional β-cell damage.

Chem Biol Interact. 2014 Oct 16;224C:58-67.

Sauchinone attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway.[Pubmed: 25451574]

Hepatic stellate cells (HSCs) are key mediators of fibrogenesis, and the regulation of their activation is now viewed as an attractive target for the treatment of liver fibrosis. Here, the authors investigated the ability of Sauchinone, an active lignan found in Saururus chinensis, to regulate the activation of HSCs, to prevent liver fibrosis, and to inhibit oxidative stress in vivo and in vitro.
METHODS AND RESULTS:
Blood biochemistry and histopathology were assessed in CCl4-induced mouse model of liver fibrosis to investigate the effects of Sauchinone. In addition, transforming growth factor-β1 (TGF-β1)-activated LX-2 cells (a human HSC line) were used to investigate the in vitro effects of Sauchinone. Sauchinone significantly inhibited liver fibrosis, as indicated by decreases in regions of hepatic degeneration, inflammatory cell infiltration, and the intensity of α-smooth muscle actin staining in mice. Sauchinone blocked the TGF-β1-induced phosphorylation of Smad 2/3 and the transcript levels of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 as well as autophagy in HSCs. Furthermore, Sauchinone inhibited oxidative stress, as assessed by stainings of 4-hydroxynonenal and nitrotyrosine: these events may have a role in its inhibitory effects on HSCs activation.
CONCLUSIONS:
Sauchinone attenuated CCl4-induced liver fibrosis and TGF-β1-induced HSCs activation, which might be, at least in part, mediated by suppressing autophagy and oxidative stress in HSCs.