2. Academic Validation
  3. Cardamonin retards progression of autosomal dominant polycystic kidney disease via inhibiting renal cyst growth and interstitial fibrosis

Cardamonin retards progression of autosomal dominant polycystic kidney disease via inhibiting renal cyst growth and interstitial fibrosis

  • Pharmacol Res. 2020 May;155:104751. doi: 10.1016/j.phrs.2020.104751.
Jinzhao He 1,  Hong Zhou 2,  Jia Meng 1,  Shun Zhang 1,  Xiaowei Li 1,  Shuyuan Wang 1,  Guangying Shao 1,  William Jin 3,  Xiaoqiang Geng 1,  Shuai Zhu 1,  Baoxue Yang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
  • 2 State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China.
  • 3 Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, MA 02118, USA.
  • 4 State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. Electronic address: [email protected].
PMID: 32151678 DOI: 10.1016/j.phrs.2020.104751
Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic inherited kidney disease characterized by renal progressive fluid-filled cysts and interstitial fibrosis. Inhibiting renal cyst development and interstitial fibrosis has been proven effective in delaying the progression of ADPKD. The purpose of this study was to discover effective drugs from Natural Products for preventing and treating ADPKD. Candidate compounds were screened from a natural product library by virtual screening. The Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model, and orthologous mouse model of ADPKD were utilized to determine the pharmacological activities of the candidate compounds. Western blot and morphological analysis were used to investigate underlying mechanisms. The experimental results showed that 0.625, 2.5, and 10 μM cardamonin dose-dependently reduced formation and enlargement in MDCK cyst model. Cardamonin also significantly attenuated renal cyst enlargement in ex vivo mouse embryonic kidneys and PKD mouse kidneys. We found that cardamonin inhibited renal cyst development and interstitial fibrosis by downregulating the MAPK, Wnt, mTOR, and Transforming Growth Factor-β/SMAD2/3 signaling pathways. Cardamonin significantly inhibits renal cyst development and interstitial fibrosis, suggesting that cardamonin shows promise as a potential therapeutic drug for preventing and treating ADPKD.

Keywords

3-acetamidocoumarin (PubChem CID: 136620); ADPKD; Cardamonin; Cardamonin (PubChem CID: 641785); Drug discovery; Esculetin (PubChem CID: 5281416); Fibrosis; Natural drug; Renal cyst.

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