title: Diosgenin interferes coronary vasoconstriction and inhibits osteochondrogenic transdifferentiation of aortic VSMC in CRF rats.
abstract: Cardiovascular dysfunction and vascular calcification is the leading cause of death in chronic renal failure (CRF) patients. This study was designed to evaluate the effect of diosgenin on coronary flow resistance and to address the question whether the previously proven antivascular calcification potential of diosgenin is associated or not with the osteochondrogenic transdifferentiation of vascular smooth muscle cells (VSMC). In this study, CRF in Wistar rats was induced by fed with 0.75% adenine and diosgenin was treated everyday at the dose of 40 mg/kg. Langendorff based isolated heart protocol was employed to analyze the coronary flow resistance. Western blot method was used to explore the phosphorylation dynamics of endothelial nitric oxide synthase (eNOS) at the serine 1177 residue. In addition, cardiac nitric oxide metabolites level also assessed. Quantitative expression of VSMC and osteochondrogenic markers was also evaluated. Antioxidant potential of diosgenin was studied in vitro. The outcome of the present study explores that diosgenin treatment significantly improves the coronary resistance and increased the nitric oxide metabolites level compared with CRF. Further, diosgenin increases the phosphorylation of eNOS (peNOS ser1177). Moreover, diosgenin reduced the aortic expression of osteochondrogenic markers and improved the VSMC phenotype components. Further, diosgenin shows concentration dependent antioxidant potential. In conclusion, this study have proven that diosgenin have enough potential to improve the coronary function and interfere the osteochondrogenic transdifferentiation program of aortic VSMC which supports its antivascular calcification potential.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, 608 002, Tamilnadu, India.
authors.forename: Jeganathan
authors.initials: J
authors.lastname: Manivannan
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, 608 002, Tamilnadu, India.
authors.forename: Janakiraman
authors.initials: J
authors.lastname: Shanthakumar
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, 608 002, Tamilnadu, India.
authors.forename: Pandiyan
authors.initials: P
authors.lastname: Arunagiri
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, 608 002, Tamilnadu, India.
authors.forename: Boobalan
authors.initials: B
authors.lastname: Raja
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, 608 002, Tamilnadu, India. Electronic address: balamurugan_au@yahoo.co.in.
authors.forename: Elumalai
authors.initials: E
authors.lastname: Balamurugan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002114:Calcinosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054338:Cell Transdifferentiation / Q000235:genetics; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D004144:Diosgenin / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D004144:Diosgenin
keywords: Antioxidant; Diosgenin; Nitric oxide; Oxidative stress; VSMC