title: Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by massive enlargement of fluid-filled cysts in the kidney. However, there is no effective therapy yet for this disease. To examine whether ginkgolide B, a natural compound, inhibits cyst development, a Madin-Darby canine kidney (MDCK) cyst model, an embryonic kidney cyst model, and a PKD mouse model were used. Interestingly, ginkgolide B significantly inhibited MDCK cyst formation dose dependently, with up to 69% reduction by 2 μM ginkgolide B. Ginkgolide B also significantly inhibited cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse model. To determine the underlying mechanisms, the effect of ginkgolide B on MDCK cell viability, proliferation, apoptosis, chloride transporter CFTR activity, and intracellular signaling pathways were also studied. Ginkgolide B did not affect cell viability, proliferation, and expression and activity of the chloride transporter CFTR that mediates cyst fluid secretion. Ginkgolide B induced cyst cell differentiation and altered the Ras/MAPK signaling pathway. Taken together, our results demonstrate that ginkgolide B inhibits renal cyst formation and enlargement, suggesting that ginkgolide B might be developed into a novel candidate drug for ADPKD.
authors.affiliation: Dept. of Pharmacology. School of Basic Medical Sciences, Peking Univ., 38 Xueyuan Lu, Haidian District, Beijing 100191, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Xuejun
authors.initials: X
authors.lastname: Li
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D046934:Ginkgolides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D007783:Lactones / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010936:Plant Extracts / Q000494:pharmacology; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D011247:Pregnancy; D011493:Protein Kinase C / Q000235:genetics
chemical_list: D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; C045856:ginkgolide B; D000242:Cyclic AMP; C089212:protein kinase D; D011493:Protein Kinase C