Schisantherin A Exhibits Anti-inflammatory Properties by Down-Regulating NF-κB and MAPK Signaling Pathways in Lipopolysaccharide-Treated RAW 264.7 Cells

Abstract

Schisantherin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent under the name of Wuweizi in Chinese traditional medicine. In the present study, we carry out a screening program to identify the anti-inflammatory potentials of schisantherin A. We found that schisantherin A reduced lipopolysaccharide (LPS (1 mg/L))-induced levels of TNF-alpha, IL-6, NO, and PGE2 (p<0.01 or p<0.05), and also reduced levels of iNOS and COX-2 in RAW 264.7 macrophages in a concentration-dependent manner. We further investigated signal transduction mechanisms to determine how schisantherin A affects. RAW264.7 cells were pretreated with 0.5, 2.5, or 25 mg/L of schisantherin A 1 h prior to treatment with 1 mg/L of LPS. Thirty minutes later, cells were harvested and mitogen activated protein kinases (MAPKs) activation and I kappaB alpha was measured by Western blot. Alternatively, cells were fixed and nuclear factor-kappaB (NF-kappaB) activation was measured using immunocytochemical analysis. Signal transduction studies showed that schisantherin A significantly inhibited extracellular signal-regulated kinase (ERK), p38, and c-jun NH2-terminal kinase (JNK) phosphorylation protein expression. Schisantherin A also inhibited p65-NF-kappaB translocation into the nucleus by I kappaB alpha degradation. By using specific inhibitors of ERK, JNK and p38, we found that schisantherin A may inhibit TNF-alpha mostly through ERK pathway. Therefore, schisantherin A may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kappaB and MAPKs signaling in RAW264.7 cells.

Lignans from Schisandra sphenathera Rehd. et Wils. and semisynthetic schisantherin A analogues: Absolute configuration, and their estrogenic and anti-proliferative activity

“…The EtOAc layer was repeatedly subjected to column chromatography on silica gel, Sephadex LH-20, and RP-18 to afford a new lignan, namely schisandrin A1 (1), together with 9 known ones. These known compounds were identified as schisantherin A (2) [12] (also known as gomisin C or wuweizi ester A) [14], wuweizisu C (3) [15], gomisin J (4) [16], schizandrin (5) [17], schisanbicolorin A (6) [18], (þ)-1-hydroxypinoresinol (7) [19], 8,8 0 -dihydroxypinoresinol (8) [20], clemaphenol A (9) [21], and (þ)-anwuligan (10) [22] (Fig. 1) by comparison with reported spectroscopic data.…”

“…Recent pharmacological studies have revealed that these compounds accounted for anti-oxidant [2,3], anti-HIV [4,5], antihepatitis B virus [6], and anti-proliferative multiple bio-effects [7]. In addition, schisantherin A (2) has been reported to exhibit anti-inflammatory properties by down-regulating NF-kappaB and MAPK signaling pathways in lipopolysaccharide-treated RAW 264.7 cells [8].…”

Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine

“…68 LPS triggers the translocation of NF-B leading to the expression of NF-B-regulated genes, including TNF-, IL-6, COX-2 and iNOS, in murine macrophage RAW 264.7 cells. 69 These results demonstrated that betaine treatment inhibited the LPS-induced expression of TNF-, IL-6, COX-2 and iNOS in RAW 264.7 cells. 65 These results suggest that betaine might be a candidate for a potential anti-inflammatory or cancer chemopreventive agent.…”

N-methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-κB signaling

“…The inhibition of the production of these inflammatory mediators is an important target in the treatment of inflammatory diseases. Hence, LPS-induced macrophages have usually been used as a model for evaluating the anti-inflammatory effects of various agents [12,13].…”