Euscaphic acid

The dried fruit of Ziziphus jujuba

Euscaphic acid isolated from roots of Rosa rugosa inhibits LPS-induced inflammatory responses via TLR4-mediated NF-kappaB inactivation in RAW 264.7 macrophages.[Pubmed:22234926]

J Cell Biochem. 2012 Jun;113(6):1936-46.

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of Euscaphic acid (19alpha-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2, TNF-alpha, and IL-1beta mRNA were inhibited by EA in a concentration-dependent manner. In addition, EA attenuated LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-kappaB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Balpha (IkappaBalpha) and consequently by decreased nuclear translocation of p65 subunit of NF-kappaB. Pretreatment with EA significantly inhibited the LPS-induced phosphorylation of IkappaB kinase beta (IKKbeta), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS-induced clustering of TNF receptor-associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor-beta-activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF-kappaB activations.

Euscaphic acid, a new hypoglycemic natural product from Folium Eriobotryae.[Pubmed:18972842]

Pharmazie. 2008 Oct;63(10):765-7.

Folium Eriobotryae has been used as a medicinal plant for a long time, and it is known to have many physiological actions such as anti-inflammatory, anti-tussive, expectorant and anti-diabetic. We have reported that the 70% ethanol extract of Folium Eriobotryae exerted a significant hypoglycemic effect to alloxan-diabetic mice. In this study, we isolated Euscaphic acid, a natural product from Folium Eriobotryae, and investigated its hypoglycemic effect in normoglycemic and alloxan-diabetic mice. All effects had been compared with those of gliclazide. The plasma glucose levels were significantly lowered in normoglycemic mice treated with Euscaphic acid compared to mice treated with 0.5% CMC-Na solution only. Moreover, the dosage of 50 mg/kg exerted a significant (P < 0.05) hypoglycemic effect in alloxan-diabetic mice after orally administration. The research proved that Euscaphic acid is one of the active hypoglycemic constituents in Folium Eriobotryae, but the details of the mechanism need to be investigated further.

Euscaphic acid, a DNA polymerase inhibitor, is a triterpene from the root of the R. alceaefolius Poir. Euscaphic inhibits calf DNA polymerase α (pol α) and rat DNA polymerase β (pol β) with IC50 values of 61 and 108 μM. Euscaphic acid induces apoptosis.

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