Saucerneol

Matrix Solid-Phase Dispersion Combined with HPLC-DAD for Simultaneous Determination of Nine Lignans in Saururus chinensis.[Pubmed:30272133]

J Chromatogr Sci. 2019 Feb 1;57(2):186-193.

A simple and rapid method, based on matrix solid-phase dispersion (MSPD) and high-performance liquid chromatography (HPLC) was developed for simultaneous determination of nine lignans, including (-)-(7R,8R)-machilin D (Wang, C., Wang, P., Chen, X., Wang, W., Jin, Y.; Saururus chinensis (Lour.) Baill blocks enterovirus 71 infection by hijacking MEK1-ERK signaling pathway; Antiviral Research, (2015); 119:47-56), dihydroguaiaretic acid (Quan, Z., Lee, Y.J., Yang, J.H., Lu,Y., Li,Y., Lee,Y.K., et al.; Ethanol extracts of Saururus chinensis suppress ovalbumin-sensitization airway inflammation; Journal of Ethnopharmacology, (2010); 132:143-149.), sauchinone (Zhuang, T., Liang, J.Y., Sun, J.B., Wu, Y., Huang, L.R., Qu, W.; Secondary metabolites from Saururus chinensis and their chemotaxonomic significance; Biochemical Systematics and Ecology, (2014); 56:95-98.), rel-(7S,8S,7'R,8'R)-3,3',4,4',5,5'-hexamethoxy-7.O.7',8.8'-lignan (Tsai, W.J., Shen, C.C., Tsai, T.H., Lin, L.C.; Lignans from the aerial parts of Saururus chinensis: isolation, structural characterization, and their effects on platelet aggregation; Journal of Natural Products, (2014); 77:125-131), licarin A (Cui, H., Xu, B., Wu, T., Xu, J., Yuan, Y., Gu, Q.; Potential antiviral lignans from the roots of Saururus chinensis with activity against Epstein-Barr virus lytic replication; Journal of Natural Products, (2014); 77:100-110.), manassantin A (Lu, Y., Piao, D., Zhang, H., Li, X., Chao, G.H., Park, S.J., et al.; Saucerneol F inhibits tumor necrosis factor-alpha and IL-6 production by suppressing Fyn-mediated pathways in FcepsilonRI-mediated mast cells; Food and Chemical Toxicology, (2013); 59:696-702.), saurucinol I (Kwon, O.E., Lee, H.S., Lee, S.W., Chung, M.Y., Bae, K.H., Rho, M.C., et al.; Manassantin A and B isolated from Saururus chinensis inhibit TNF-alpha-induced cell adhesion molecule expression of human umbilical vein endothelial cells; Archives of Pharmacal Research, (2005); 28:55-60.), manassantin B (Hwang, B.Y., Lee, J.H., Jung, H.S., Kim, K.S., Nam, J.B., Hong, Y.S., et al.; Sauchinone, a lignan from Saururus chinensis, suppresses iNOS expression through the inhibition of transactivation activity of RelA of NF-kappaB; Planta Medica, (2003); 69:1096-01.) and licarin B (Hwang, B.Y., Lee, J.H., Nam, J.B., Hong, Y.S., Lee, J.J.; Lignans from Saururus chinensis inhibiting the transcription factor NF-kappaB; Phytochemistry, (2003); 64:765-771.) in Saururus chinensis. The parameters of MSPD were optimized to be that 0.2 g of sample, blended with 0.4 g silica gel, and eluted with 5 mL of methanol. The separation was carried out on a C18 column with acidified aqueous acetonitrile gradients. The established method was fully validated in terms of linearity (r2 >/= 0.9994), sensitivity, precision (RSD

Lipid lowering agents of natural origin: An account of some promising chemotypes.[Pubmed:28987600]

Eur J Med Chem. 2017 Nov 10;140:331-348.

The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting naturally occurring compounds and their derivatives as potential hypolipidemic agents. Some of the interesting natural chemotypes that can control the increased levels of plasma lipids and discussed in this review are compactin, lovastatin, gugglesterone, berberine, lupeol, phytol, polyprenol, aegeline, 4-hydroxyisoleucine, alpha-asarone, resveratrol, esculeoside A, swertiamarin, rutin, Saucerneol B, curcumin and a clerodane diterpene.

Saucerneol D inhibits dendritic cell activation by inducing heme oxygenase-1, but not by directly inhibiting toll-like receptor 4 signaling.[Pubmed:25792017]

J Ethnopharmacol. 2015 May 26;166:92-101.

ETHNOPHARMACOLOGICAL RELEVANCE: Saururus chinensis is a medicinal plant used to treat jaundice, pneumonia, edema, fever, and several inflammatory diseases. Saucerneol D (SD), a lignan constituent of this plant, has antioxidant, anti-asthmatic, and anti-inflammatory activities. SD has been previously reported to inhibit the pro-inflammatory responses of RAW264.7 cells and primary mast cells. In this study, we investigated the effect of SD on the functions of dendritic cells (DCs). MATERIALS AND METHODS: SD was isolated from methanol extract of the roots of S. chinensis. Bone marrow-derived DCs were used as target cells. The effects of SD on the following DC functions were examined: surface molecule expression, cytokine expression, migration, allogenic T cell activation, heme oxygenase-1 expression, and Toll-like receptor 4 signaling. RESULTS: In lipopolysaccharide (LPS)-treated DCs, SD inhibited the expression of cell surface molecules (MHC I/II, CD40, CD80, and CD86), the production of inflammatory mediators (nitric oxide, IL-12, IL-1beta, and TNF-alpha), and allogenic T cell activation capacity. SD also inhibited DC migration toward MIP-3beta by down-regulating CCR7 expression. SD attenuated LPS-induced activation of NF-kappaB and MAPK signaling in DCs, but did not directly inhibit kinase activities of IRAK1, IRAK4, TAK1, or IKKbeta in enzymatic assays. SD did not inhibit LPS binding to myeloid differentiation protein-2, co-receptor of TLR4. SD increased the production of reactive oxygen species, Nrf-2, and heme oxygenase (HO)-1, which degrades the heme to immunosuppressive carbon monoxide and biliverdin, which may underlie the anti-inflammatory effects in SD-treated DCs. CONCLUSIONS: Taken together, these data suggest that SD suppresses LPS-induced activation of DCs through the induction of HO-1, but not by directly affecting Toll-like receptor 4 signaling.

Saucerneol F, a New Lignan Isolated from Saururus chinensis, Attenuates Degranulation via Phospholipase Cgamma 1 Inhibition and Eicosanoid Generation by Suppressing MAP Kinases in Mast Cells.[Pubmed:24009845]

Biomol Ther (Seoul). 2012 Nov;20(6):526-31.

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that Saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4), cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2), and on phospholipase Cgamma1 (PLCgamma1)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid (PGD2 and LTC4) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of PLCgamma1, intracellular Ca(2+) influx, the translocation of cytosolic phospholipase A2 (cPLA2) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular Ca(2+) influx by inhibiting PLCgamma1 phosphorylation and suppressing the nuclear translocations of cPLA2 and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

Saucerneol F inhibits tumor necrosis factor-alpha and IL-6 production by suppressing Fyn-mediated pathways in FcepsilonRI-mediated mast cells.[Pubmed:23851146]

Food Chem Toxicol. 2013 Sep;59:696-702.

The aim of this study was to investigate the effect of Saucerneol F (SF) on the productions of the pro-inflammatory cytokines, TNF-alpha and IL-6, in IgE/Ag-induced mouse bone marrow-derived mast cells (BMMCs). SF dose-dependently suppressed the transcriptions of these pro-inflammatory cytokines. To identify the molecular mechanisms responsible for these suppressions, we examined the effect of SF on three important transcription factors; activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and STAT5. It was found that SF inhibited the nuclear translocation of the p65 subunit of NF-kappaB to the nucleus and its DNA-binding ability. SF also attenuated mitogen-activated protein kinase (MAPK)-mediated AP-1 activation and STAT5 activation. Biochemical analysis of FcepsilonRI-mediated signaling pathways demonstrated that SF inhibited the phosphorylation of Fyn and multiple downstream signaling processes, including Syk, Gab2, and the Akt/IKK/IkappaB and MAPK pathways. Taken together, our results suggest that SF inhibits the production of pro-inflammatory cytokines by suppressing Fyn kinase-dependent signaling events.

Saucerneol D inhibits eicosanoid generation and degranulation through suppression of Syk kinase in mast cells.[Pubmed:22982805]

Food Chem Toxicol. 2012 Dec;50(12):4382-8.

Previously we reported that Saucerneol D (SD), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis) suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. The aim of this study was to elucidate whether SD modulates the generation of other inflammatory mediators in activated mast cells. We investigated the effects of SD on cyclooxygenase-2 (COX-2)-dependent prostaglandin D(2) (PGD(2)) and 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generations as well as degranulation in cytokine-stimulated mouse bone marrow-derived mast cells (BMMCs). Biochemical analyses of the cytokine-mediated signaling pathways showed that SD suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes including phospholipase Cgamma1 (PLCgamma1)-mediated intracellular Ca(2+) influx and activation of mitogen-activated protein kinases (MAPKs; including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH(2)-terminal kinase (JNK) and p38) and the nuclear factor-kappaB (NF-kappaB) pathway. Taken together, the present study suggests that SD suppresses eicosanoid generation and degranulation through Syk-dependent pathway in BMMCs.

Manipulating JNK signaling with (--)-zuonin A.[Pubmed:22916726]

ACS Chem Biol. 2012 Nov 16;7(11):1873-83.

Recently, in a virtual screening strategy to identify new compounds targeting the D-recruitment site (DRS) of the c-Jun N-terminal kinases (JNKs), we identified the natural product (-)-zuonin A. Here we report the asymmetric synthesis of (-)-zuonin A and its enantiomer (+)-zuonin A. A kinetic analysis for the inhibition of c-Jun phosphorylation by (-)-zuonin A revealed a mechanism of partial competitive inhibition. Its binding is proposed to weaken the interaction of c-Jun to JNK by approximately 5-fold, without affecting the efficiency of phosphorylation within the complex. (-)-Zuonin A inhibits the ability of both MKK4 and MKK7 to phosphorylate and activate JNK. The binding site of (-)-zuonin A is predicted by docking and molecular dynamics simulation to be located in the DRS of JNK. (+)-Zuonin A also binds JNK but barely impedes the binding of c-Jun. (-)-Zuonin A inhibits the activation of JNK, as well as the phosphorylation of c-Jun in anisomycin-treated HEK293 cells, with the inhibition of JNK activation being more pronounced. (-)-Zuonin A also inhibits events associated with constitutive JNK2 activity, including c-Jun phosphorylation, basal Akt activation, and MDA-MB-231 cell migration. Mutations in the predicted binding site for (-)-zuonin A can render it significantly more or less sensitive to inhibition than wild type JNK2, allowing for the design of potential chemical genetic experiments. These studies suggest that the biological activity reported for other lignans, such as Saucerneol F and zuonin B, may be the result of their ability to impede protein-protein interactions within MAPK cascades.

Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-kappaB and AP-1 inactivation in LPS-induced RAW264.7 cells.[Pubmed:22155103]

Int Immunopharmacol. 2012 Jan;12(1):175-81.

Saucerneol F (SF), a new tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, dose-dependently inhibited nitric oxide (NO) production, with concomitant reduction of inducible nitric oxide synthase (iNOS) protein and mRNA expression in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells. To elucidate the molecular mechanism underlying the inhibition of iNOS expression by SF, we assessed the effects of SF on nuclear factor-kappaB (NF-kappaB) DNA-binding activity, NF-kappaB-dependent reporter gene activity, inhibitory factor-kappaB (IkappaB) phosphorylation and degradation, and p65 nuclear translocation. Treatment with SF decreased the luciferase activities of NF-kappaB reporter promoters in a dose-dependent manner and translocation of NF-kappaB p65. In addition, pretreatment of SF reduced LPS-stimulated activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH(2)-terminal kinase (JNK). Furthermore, SF attenuated the luciferase activities of AP-1 reporter promoters and the DNA-binding capacity of AP-1. Taken together, the present results indicate that SF attenuates NO production and iNOS expression by blocking LPS-induced activation of NF-kappaB, MAPKs, and AP-1, suggesting that SF is potentially applicable as an anti-inflammatory drug.

Effect of saucerneol D on melanin production in cAMP-elevated melanocytes.[Pubmed:21910056]

Arch Pharm Res. 2011 Aug;34(8):1339-45.

Intracellular cAMP stimulates microphthalmia-associated transcription factor (MITF) induction in melanocytes through cAMP-responsive element binding protein (CREB), which plays a pivotal role in the gene expression of tyrosinase for melanin biosynthesis. In the present study, Saucerneol D as a lignan constituent of Saururus chinensis (Saururaceae family) efficiently inhibited melanin production with IC(50) values of 188-297 nM in B16 melanoma cells stimulated with alpha-melanocyte stimulating hormone (alpha-MSH) or other cAMP elevators. Moreover, Saucerneol D down-regulated alpha-MSH-induced gene expression of tyrosinase at the transcription level in B16 cells, but it did not directly inhibit the catalytic activity of cell-free tyrosinase. As to the molecular basis of hypopigmenting action, Saucerneol D inhibited alpha-MSH-induced phosphorylation of CREB in the cells, and sequentially suppressed MITF induction. Taken together, this study provides Saucerneol D down-regulated the gene expression of tyrosinase, resulting in the inhibition of cAMP-induced melanin biosynthesis, and suggests pharmacological potential of the lignan structure in skin hyperpigmentation.

Antioxidant and antiasthmatic effects of saucerneol D in a mouse model of airway inflammation.[Pubmed:21295171]

Int Immunopharmacol. 2011 Jun;11(6):698-705.

Chronic airway inflammation is a hallmark of asthma, which is an immune-based disease. We evaluated the ability of Saucerneol D, a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Furthermore, we determined whether heme oxygenase (HO)-1 was required for the protective activity of Saucerneol D. The airways of OVA-sensitized mice exposed to an OVA challenge developed eosinophilia and mucus hypersecretion and exhibited increased cytokine levels. Mice were administered Saucerneol D orally at doses of 20 and 40mg/kg once daily on days 26-30. Saucerneol D administered orally significantly inhibited the number of OVA-induced inflammatory cells and the production of immunoglobulin E as well as Th2-type cytokines. Histopathology studies revealed a marked decrease in lung inflammation and goblet cell hyperplasia after Saucerneol D treatment. In addition, Saucerneol D induced HO-1 and led to a marked decrease in OVA-induced reactive oxygen species and malondialdehyde and an increase in superoxide dismutase and glutathione in lung tissues. These antioxidant effects were correlated with HO-1 induction. In our experiments, Saucerneol D treatment reduced airway inflammation and suppressed oxidative stress in an OVA-induced asthma model.

Saucerneol G, a new lignan, from Saururus chinensis inhibits matrix metalloproteinase-9 induction via a nuclear factor kappaB and mitogen activated protein kinases in lipopolysaccharide-stimulated RAW264.7 cells.[Pubmed:21139230]

Biol Pharm Bull. 2010;33(12):1944-8.

This study was conducted to demonstrate the inhibitory effect of Saucerneol G (SG), a new lignan, isolated from the aerial part of Saururus chinensis (Saururaceae) on lipopolysaccharide (LPS)-stimulated matrix metalloproteinase-9 (MMP)-9 inductions in RAW 264.7 cells. Aimed at evaluating the mechanism of action by which SG inhibits the LPS-mediated induction of MMP-9, the effects of SG on nuclear factor-kappaB (NF-kappaB) DNA binding activity, NF-kappaB-dependent reporter gene activity, inhibitory factor-kappaB (IkappaB) phosphorylation, degradation and p65 nuclear translocation were assessed. SG profoundly suppressed the DNA binding activity and the reporter gene activity as well as translocation of NF-kappaB p65 subunit. Furthermore, SG also dose dependently inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). These findings suggest that SG may inhibit LPS-stimulated MMP-9 induction by blocking NF-kappaB and MAPKs activation.

Lignan, sesquilignans and dilignans, novel HIV-1 protease and cytopathic effect inhibitors purified from the rhizomes of Saururus chinensis.[Pubmed:19900481]

Antiviral Res. 2010 Feb;85(2):425-8.

Five lignans were isolated from the ethyl acetate extracts of Saururus chinensis rhizomes and evaluated for anti-HIV-1 activity. Their structures were elucidated as two dilignans, manassantin A (1), manassantin B (2), two sesquilignans, Saucerneol B (3) and Saucerneol C (4), and a new lignan, saururin B (5) by spectroscopic analysis. Of these components, manassantin A (1) and saururin B (5) showed dose-dependent inhibitory activities on HIV-1 protease with IC(50) values of 38.9 and 5.6 microM. In addition, manassantins A (1), B (2) and Saucerneol B (3) inhibited HIV-1-induced cytopathic effects in a human T lymphoblastoid cell line with IC(100) values of 1.0, 1.0 and 0.2 microM, respectively. Of these active constituents, Saucerneol B (3) showed the most potent and selective anti-HIV-1 activity (IC(100) of 0.2 microM, CC(0) of >125.0 microM, and SI of >520.8).

Inhibition of DNA topoisomerases I and II and cytotoxicity by lignans from Saururus chinensis.[Pubmed:19898804]

Arch Pharm Res. 2009 Oct;32(10):1409-15.

Thirteen lignans, erythro-austrobailignan-6 (1), meso-dihydroguaiaretic acid (2), sauchinone (3), 1'-epi-sauchinone (4), Saucerneol D (5), manassantin B (6), manassantin A (7), nectandrin B (8), machilin D (9), Saucerneol F (10), Saucerneol G (11), Saucerneol H (12) and Saucerneol I (13), were isolated from the ethyl acetate extract of the roots of Saururus chinensis. Among these compounds, 5 showed potent inhibitory activities against DNA topoisomerase I and II, and 5, 6, 7 and 10 showed mild cytotoxicities against HT-29 (IC(50) values; 13, 12, 11, and 10 microM, respectively) and HepG2 cell lines (IC(50) values; 16, 11, 12, and 11 microM, respectively).

Lignans from the roots of Saururus chinensis.[Pubmed:18841903]

J Nat Prod. 2008 Oct;71(10):1771-4.

Four new lignans, Saucerneol F (1), Saucerneol G (2), Saucerneol H (3), and Saucerneol I (4), were isolated from the EtOAc extract of the roots of Saururus chinensis, together with one known compound, Saucerneol D (5). The structures of compounds 1-4 were elucidated by spectroscopic analysis. These compounds showed cytotoxic activities against HT-29, MCF-7, and HepG-2 cell lines.

Inhibitory effect of (-)-saucerneol on osteoclast differentiation and bone pit formation.[Pubmed:18690659]

Phytother Res. 2009 Feb;23(2):185-91.

In this study, the effect of (-)-Saucerneol, one of the lignans isolated from Saururus chinensis, on osteoclast differentiation and bone resorption was evaluated in two in vitro models for osteoclast differentiation, the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-treated RAW264.7 cells and mouse BMMs treated with both RANKL and macrophage-colony stimulating factor. (-)-Saucerneol significantly inhibited the RANKL-induced activity of tartrate-resistance acid phosphatase (TRAP, an early marker of osteoclast formation) and formation of osteoclasts in a dose-dependent manner. Interestingly, (-)-Saucerneol was shown to inhibit the RANKL-induced activation of extracellular signal-regulated kinase in both in vitro models. In addition, (-)-Saucerneol inhibited the bone resorptive activity and the expression of transcription factors and genes essential for osteoclast formation and bone resorption as well. In conclusion, (-)-Saucerneol has a potential to inhibit the osteoclast differentiation via preventing the activation of ERK signaling pathway. In addition, its activity to inhibit the bone resorption activities of osteoclasts could result from its potential to inhibit RANKL-induced expression levels of transcription factors and genes essential for bone resorption.