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Title: Fungus-Derived 3-Hydroxyterphenyllin and Candidusin A Ameliorate Palmitic Acid-Induced Human Podocyte Injury via Anti-Oxidative and Anti-Apoptotic Mechanisms
Authors: Suchada Kaewin
Karn Changsorn
Titiwat Sungkaworn
Peraya Hiranmartsuwan
Wiriya Yaosanit
Vatcharin Rukachaisirikul
Chatchai Muanprasat
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Mahidol University
Thammasat University
Prince of Songkla University
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Apr-2022
Citation: Molecules. Vol.27, No.7 (2022)
Abstract: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. An elevated fatty acid plasma concentration leads to podocyte injury and DN progression. This study aimed to identify and characterize cellular mechanisms of natural compounds that inhibit palmitic acid (PA)–induced human podocyte injury. By screening 355 natural compounds using a cell viability assay, 3-hydroxyterphenyllin (3-HT) and candidusin A (CDA), isolated from the marine-derived fungus Aspergillus candidus PSU-AMF169, were found to protect against PA-induced podocyte injury, with half-maximal inhibitory concentrations (IC50) of ~16 and ~18 µM, respectively. Flow cytometry revealed that 3-HT and CDA suppressed PA-induced podocyte apoptosis. Importantly, CDA significantly prevented PA-induced podocyte barrier impairment as determined by 70 kDa dextran flux. Reactive oxygen species (ROS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) direct scavenging assays indicated that both compounds exerted an anti-oxidative effect via direct free radical–scavenging activity. Moreover, 3-HT and CDA upregulated the anti-apoptotic Bcl2 protein. In conclusion, 3-HT and CDA represent fungus-derived bioactive compounds that have a novel protective effect on PA-induced human podocyte apoptosis via mechanisms involving free radical scavenging and Bcl2 upregulation.
ISSN: 14203049
Appears in Collections:Scopus 2022

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