Pinostrobin inhibits renal CFTR-mediated Cl<sup>−</sup> secretion and retards cyst growth in cell-derived cyst and polycystic kidney disease rats
Issued Date
2022-04-01
Resource Type
ISSN
13478613
eISSN
13478648
Scopus ID
2-s2.0-85125759506
Pubmed ID
35300812
Journal Title
Journal of Pharmacological Sciences
Volume
148
Issue
4
Start Page
369
End Page
376
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Pharmacological Sciences Vol.148 No.4 (2022) , 369-376
Suggested Citation
Tonum K., Chabang N., Fongsupa S., Chantawarin S., Jiarpinitnun C., Tuchinda P., Soodvilai S. Pinostrobin inhibits renal CFTR-mediated Cl<sup>−</sup> secretion and retards cyst growth in cell-derived cyst and polycystic kidney disease rats. Journal of Pharmacological Sciences Vol.148 No.4 (2022) , 369-376. 376. doi:10.1016/j.jphs.2022.02.003 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83787
Title
Pinostrobin inhibits renal CFTR-mediated Cl<sup>−</sup> secretion and retards cyst growth in cell-derived cyst and polycystic kidney disease rats
Author's Affiliation
Other Contributor(s)
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) plays crucial role in renal cyst expansion via increase in fluid accumulation. Inhibition of CFTR has been proposed to retard cyst development and enlargement in polycystic kidney disease (PKD). Pinostrobin, a bioactive natural flavonoid, possesses several pharmacological effects. The present study investigated pharmacological effects of pinostrobin on CFTR-mediated Cl− secretion and renal cyst expansion in in vitro and in vivo models. Pinostrobin (10 and 50 μM) reduced number of MDCK cell-derived cyst colonies and inhibited cyst expansion via inhibition of cell proliferation and CFTR-mediated Cl− secretion. The inhibitory effect of pinostrobin was not due to the decrease in cell viability and activity of Na+-K+-ATPase. We also investigated the natural analogue pinocembrin as well as the synthetic analogue pinostrobin oxime. Both pinocembrin and pinostrobin oxime did not reduce CFTR-mediated Cl− secretion. In PKD rats, oral administration of pinostrobin (40 mg/kg/day) exhibited a decreasing in cystic area compared to vehicle-treated rats. Pinostrobin treatment inhibited renal expression of CFTR protein in PKD rats. Our findings highlighted the potential therapeutic application of pinostrobin in PKD.