Protective Effect of Lignans against Sepsis from the Roots of <i>Saururus chinensis</i>

Abstract

Lipopolysaccharide (LPS) is an endotoxin which induces septic shock syndrome and stimulates the production of inflammatory mediators such as NO, tumor necrosis factor-a (TNF-a), interleukins, prostanoids and leukotrienes. [1][2][3] These mediators frequently result from excessive stimulation of the host immune system through complex signal transductions and lead to hypotension and multiorgan dysfunction with a high mortality rate. 4,5) In patients with sepsis, TNF-a plays a major role in the associated systemic toxicity.6) Loss of hepatic function is one of the hallmarks of the development of multiple-organ failure associated with severe sepsis. 7,8) There have been reports that the synthetic compounds IRFI 042, 9) tyrphostin AG 126, 10) and SR 27388 11) show significant protection against lethality due to septic shock, and lysophosphatidylcholine (LPC) can effectively prevent and treat sepsis and microbial infections. 12) Recently, protective compounds against sepsis have been reported from medicinal plants. 13,14) The protective activity against sepsis-induced lethality of the methanol extracts of about 100 Korean medicinal plants was determined based on the sepsis model induced by lipopolysaccharide/D-galactosamine, from which Saururus chinensis (Saururaceae) was chosen as one of the active plants. Saururus chinensis (Saururaceae) is a perennial herbaceous plant with potential therapeutic utility in treatment of various diseases such as edema, jaundice, gonorrhea, anti-pyretic, diuretic, and anti-inflammatory agents in Korean folk medicine.15) Previous chemical studies of the genus Saururus have shown the presence of more than 20 lignans, [16][17][18][19] some of which exhibited neuroleptic, 20) hepatoprotective, 21) and antifeedant activities. 22) A triene, 12,13-dehydrogeranylgeraniol, was recently demonstrated to inhibit intracellular reactive oxygen species (ROS)-catalyzed oxidation within HL-60 cells.23) Different types of compounds have also been isolated from Saururus species including aristolactams, flavonoids, anthraquinones, and fruanoditerpenes. [24][25][26][27] In this paper, the isolation and activity of twelve known lignans as anti-septic shock agents from the roots of this plant are described. MATERIALS AND METHODS General ProceduresMelting points were measured by Fisher-Johns melting point apparatus and are uncorrected. Optical rotations were measured using a JASCO DIP-1000 (Tokyo, Japan) automatic digital polarimeter. The NMR spectra were recorded on a Bruker 250 MHz (DMX 250, Germany) spectrometer using Bruker's standard pulse program. Samples were dissolved in CDCl 3 -d 1 or CD 3 OD, and chemical-shifts were reported in ppm downfield from TMS. The FABMS spectrum was measured by VG TRIO 2A mass spectrometer. Stationary phases for column chromatography (Silica gel 60, 70-230 and 230-400 mesh and Lichroprep RP-18 gel, 40-63 mm, Merck) and TLC plates (Silica-gel 60 F 254 and RP-18 F 254, 0.25 mm, Merck) were purchased from Merck KGaA (Darmstadt, Germany). Spots were detected under UV radiation ...

The dineolignan from Saururus chinensis, manassantin B, inhibits tumor-induced angiogenesis via downregulation of matrix metalloproteinases 9 in human endothelial cells

“…MB, a neolignan isolated from the roots of S. chinensis, has been demonstrated to exhibit a range of activities, including anti-inflammatory (10,(19)(20)(21), antiseptic (22) and antitumor activities (11,23). Furthermore, MB was shown to inhibit PMA-induced ICAM-1 expression in HL-60 cells (15) and to prevent monocyte adhesion to HUVECs through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-α (24).…”

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

“…1,2 Previous reports have shown that an extract of S. chinensis roots has various positive effects, including antioxidant, anti-inflammatory, antiviral, antihypertensive, anti-septic, and anti-cancer activities. [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.…”

Inhibition of Phenotypic and Functional Maturation of Dendritic Cells by Manassantin A

“…Manassantin A (MSA), a dineolignan isolated from Saururus cernuus, was known to inhibit NF-κB activation and nitric oxide production in macrophages (10,11). In addition, MSA inhibited hypoxia-inducible factor-1α (HIF-1α) by blocking protein accumulation without affecting mRNA levels.…”