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 Schmiedebergs Arch Pharmacol. 2016 Nov;389(11):1183-1194. doi: 10.1007/s00210-016-1280-0. Epub 2016 Jul 28.

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.

Keywords: Blood vessel; Glucose; H2S; HDL-C; Kaempferia parviflora; Nitric oxide; Pentamethoxyflavone.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / enzymology
  • Administration, Oral
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / enzymology
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cholesterol, HDL / blood
  • Dose-Response Relationship, Drug
  • Flavones / administration & dosage*
  • Hydrogen Sulfide / metabolism
  • Lyases / metabolism*
  • Male
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / enzymology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism*
  • Rats, Wistar
  • Time Factors
  • Up-Regulation
  • Vasoconstriction / drug effects
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • 3,5,7,3',4'-pentamethoxyflavone
  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • Flavones
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Lyases
  • cystathionine beta-lyase
  • Hydrogen Sulfide