The inhibitory effect of triterpenoid glycosides originating from Sanguisorba officinalis on tissue factor activity and the production of TNF-alpha.
We examined the inhibitory effects of novel triterpene glycoside compounds [ziyu-glycoside II (ZY-II) and its methyl ester (ZYM-201)], which originated from the roots of sanguisorba officinalis L. (Rosaceae), on tissue factor (TF) activity and tumor necrosis factor (TNF)-alpha production. In in vitro TF activity tests, ZY-II but not ZYM-201 strongly blocked lung TF activity with an IC50 value of 0.46 microM. By contrast, only ZYM-201 dose-dependently inhibited in vivo TF activity with an ED50 value of 1.7 mg/kg, when orally administered. Furthermore, ZYM-201 diminished both in vitro and in vivo TNF-alpha production with IC50 or ED50 values of 69.4 microM and 87.4 mg/kg, respectively. Therefore, these results suggest either that ZYM-201 may be developed as a potent inhibitor of both TF- and TNF-alpha-mediated diseases such as atherosclerosis and septic shock, or it may be a lead compound to be derivatized for further improvement of its curative efficacy.
Cho
Jae Youl
JY
School of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, South Korea. jaecho@kangwon.ac.kr
Yoo
Eun Sook
ES
Cha
Bae Cheon
BC
Park
Hwa-Jin
HJ
Rhee
Man Hee
MH
Han
Yong Nam
YN
D000284:Administration, Oral; D000818:Animals; D001685:Biological Factors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D031993:Sanguisorba; D013925:Thromboplastin / Q000096:biosynthesis* / Q000187:drug effects; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D001685:Biological Factors; D006027:Glycosides; D010936:Plant Extracts; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin