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Increased vascular eNOS and cystathionine-γ-lyase protein after 6 weeks oral administration of 3, 5, 7, 3′, 4′-pentamethoxyflavone to middle-aged male rats

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Abstract

Effects of treatment of middle-aged male rats with 3, 5, 7, 3′, 4′-pentamethoxyflavone (PMF) on vascular and perivascular adipose tissue (PVAT) functions and blood chemistry were investigated. Rats received PMF (22 mg/kg), orally or vehicle, twice a day for 6 weeks. The PMF-treated rats had lower serum glucose, higher HDL-C levels, but no change in other parameters. Thoracic aortic and mesenteric rings of PMF treated rats produced lower maximal contraction to phenylephrine that was normalized by NG-nitro-L-arginine (L-NA) or endothelial removal. The aortic- and mesenteric rings of the PMF treated rats showed improved relaxation to acetylcholine, but not to glyceryl trinitrate, and had higher eNOS protein. DL-propargylglycine (PAG) caused greater increase in the baseline tension of the PMF-treated aortic ring and higher contraction to low concentrations of phenylephrine. PVAT lowered the contractile response of the L-NA pretreated aortic rings to phenylephrine for both groups, but PAG had no effect. The cystathionine-γ-lyase (CSE) protein of the thoracic rings, but not of the PVAT, shows increased expression after PMF treatment. Overall, PMF treatment of middle aged rats appeared to increase production of NO and H2S from the blood vessels by upregulating the expression of eNOS and CSE. PMF also decreased fasting serum glucose and increased HDL-C levels, with no toxicity to liver and kidney functions. Thus, PMF is a novel compound for possible use as a health product to prevent and/or to reduce the development of diabetes type II and/or cardiovascular disease.

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Acknowledgments

This work was supported by the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission. The authors thank Prof. Poungpen Sirirugsa, Department of Biology, Faculty of Science, for her kind help in identifying the plant; the Central Equipment Unit, Faculty of Science, for facilitating use of the HPLC equipment; Miss Srisurat Duangsai for technical assistance, Dr. Brian Hodgson for English assistance, and Prof. Michael J. Mulvany, Aarhus University, Denmark, for his valuable comments and editing the manuscript.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat-Yai, Thailand

    Somruedee Yorsin & Kanyanatt Kanokwiroon

  2. Natural Product Research Centre of Excellence, Prince of Songkla University, Hat-Yai, 90112, Thailand

    Somruedee Yorsin & Chaweewan Jansakul

  3. The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Hat-Yai, Thailand

    Kanyanatt Kanokwiroon

  4. Department of Anatomy, Faculty of Science, Prince of Songkla University, Hat-Yai, Thailand

    Nisaudah Radenahmad

  5. Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat-Yai, Thailand

    Chaweewan Jansakul

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  1. Somruedee Yorsin
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  2. Kanyanatt Kanokwiroon
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  3. Nisaudah Radenahmad
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  4. Chaweewan Jansakul
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Yorsin, S., Kanokwiroon, K., Radenahmad, N. et al. Increased vascular eNOS and cystathionine-γ-lyase protein after 6 weeks oral administration of 3, 5, 7, 3′, 4′-pentamethoxyflavone to middle-aged male rats. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1183–1194 (2016). https://doi.org/10.1007/s00210-016-1280-0

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