Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease
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Issued Date
2022-06-01
Resource Type
eISSN
14203049
Scopus ID
2-s2.0-85132566452
Pubmed ID
35744960
Journal Title
Molecules
Volume
27
Issue
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecules Vol.27 No.12 (2022)
Suggested Citation
Khunpatee N., Bhukhai K., Chatsudthipong V., Yuajit C. Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease. Molecules Vol.27 No.12 (2022). doi:10.3390/molecules27123837 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83708
Title
Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
Abnormal cell proliferation and accumulation of fluid-filled cysts along the nephrons in polycystic kidney disease (PKD) could lead to a decline in renal function and eventual end-stage renal disease (ESRD). Gambogic acid (GA), a xanthone compound extracted from the brownish resin of the Garcinia hanburyi tree, exhibits various pharmacological properties, including anti-inflammation, antioxidant, anti-proliferation, and anti-cancer activity. However, its effect on inhibiting cell proliferation in PKD is still unknown. This study aimed to determine the pharmacological effects and detailed mechanisms of GA in slowing an in vitro cyst growth model of PKD. The results showed that GA (0.25–2.5 µM) significantly retarded MDCK cyst growth and cyst formation in a dose-dependent manner, without cytotoxicity. Using the BrdU cell proliferation assay, it was found that GA (0.5–2.5 µM) suppressed MDCK and Pkd1 mutant cell proliferation. In addition, GA (0.5–2.5 µM) strongly inhibited phosphorylation of ERK1/2 and S6K expression and upregulated the activation of phosphorylation of AMPK, both in MDCK cells and Pkd1 mutant cells. Taken together, these findings suggested that GA could retard MDCK cyst enlargement, at least in part by inhibiting the cell proliferation pathway. GA could be a natural plant-based drug candidate for ADPKD intervention.