Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock

Abstract

Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6 N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E 2 in a dose-dependent manner, while CA up to 200 mM did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of IkB-a and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-kB to the nucleus, transcription of the NF-kB minimal promoter and NF-kB DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-a, IL-6, and IL-1b in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-kB and MAPK signaling pathways, suggesting that CA may be used as a potential antiinflammatory agent for the prevention and treatment of inflammatory diseases.

Cynandione�A inhibits lipopolysaccharide-induced cell adhesion via suppression of the protein expression of VCAM‑1 in human endothelial cells

“…1A), has been isolated in a number of studies (19,20). In addition, several studies investigating the biological and pharmaceutical activity of cA have revealed it exhibits protective activity against toxicity by various stimulant agents in rat hepatocytes and cortical neurons (21)(22)(23). Among investigations on the inhibitory effects of CA on anti-inflammatory activity, few have reported on the molecular mechanism underlying the anti-adhesion effects of CA in vascular inflammation.…”

Hyperbaric oxygen preconditioning attenuates brain injury after intracerebral hemorrhage by regulating microglia polarization in rats

“…Studies confirm lipopolysaccharide (LPS) induces inflammatory response in microglia/macrophage by activating several signaling pathways. Lipopolysaccharide first binds with membrane‐bound Toll‐like receptor 4 (TLR4), to activate its downstream signaling molecules, mainly mitogen‐activated protein kinases (MAPKs) and NF‐κB, through induction by phosphorylation . Phosphorylated MAPKs activate their downstream molecules, which can be translocated into the nucleus and contribute to expression of inflammatory molecules .…”

“…Lipopolysaccharide first binds with membrane-bound Toll-like receptor 4 (TLR4), to activate its downstream signaling molecules, mainly mitogen-activated protein kinases (MAPKs) and NF-κB, through induction by phosphorylation. [28][29][30] Phosphorylated MAPKs activate their downstream molecules, which can be translocated into the nucleus and contribute to expression of inflammatory molecules. 31 MAPKs consist of the JNK, p38 MAPK, and p42/p44 MAPKs.…”

Discrimination and Proper Use of Polygoni Multiflori Radix, Cynanchi Wilfordii Radix, and Cynanchi Auriculati Radix in Korea: A Descriptive Review

“…The components of CWR are as follows: cynandione A [19], cynanoneside B, p-hydroxyacetophenone, 2,5-dihydroxyacetophenone, 2,4-dihydroxyacetophenone, wilfoside K1N, wilfoside C1N [20], β -sitosterol, wilfoside C3N, methyleugenol, wilfoside C1G, cynauriculoside A, daucosterol, acetovanillone, sucrose, geniposide, succinic acid, bungeiside A [21], and cynanchone A [22]. …”

“…The components of CAR are the following: cynandione A [19]; cynanoneside B; p-hydroxyacetophenone; 2,5-dihydroxyacetophenone; 2,4-dihydroxyacetophenone; wilfoside K1N; wilfoside C1N [20]; C21-steroidal glycoside [23]; cyanoauriculosides F, G, and H [24]; wilfoside C3N [25]; taraxasterol acetate; cynanchone A; succinic acid; betulinic acid; kidjoranin [25]; auriculoside A [26]; caudatin; metaplexigenin; azelaic acid; wilforibiose; sucrose; 1-O-hexadecanolenin; beta-amyrin acetate; acetylquinol; beta-sitosterol; and daucosterol [27]. …”