An ethanolic extract of Lindera obtusiloba stems, YJP-14, improves endothelial dysfunction, metabolic parameters and physical performance in diabetic db/db mice

PLoS One. 2013 Jun 3;8(6):e65227. doi: 10.1371/journal.pone.0065227. Print 2013.

Abstract

Lindera obtusiloba is a medicinal herb traditionally used in Asia for improvement of blood circulation, treatment of inflammation, and prevention of liver damage. A previous study has shown that an ethanolic extract of Lindera obtusiloba stems (LOE) has vasoprotective and antihypertensive effects. The possibility that Lindera obtusiloba improves endothelial function and metabolic parameters in type 2 diabetes mellitus (T2DM) remains to be examined. Therefore, the aim of the present study was to determine the potential of LOE to prevent the development of an endothelial dysfunction, and improve metabolic parameters including hyperglycemia, albuminuria and physical exercise capacity in db/db mice, an experimental model of T2DM. The effect of LOE (100 mg/kg/day by gavage for 8 weeks) on these parameters was compared to that of an oral antidiabetic drug, pioglitazone (30 mg/kg/day by gavage). Reduced blood glucose level, body weight and albumin-creatinine ratio were observed in the group receiving LOE compared to the control db/db group. The LOE treatment improved endothelium-dependent relaxations, abolished endothelium-dependent contractions to acetylcholine in the aorta, and normalized the increased vascular oxidative stress and expression of NADPH oxidase, cyclooxygenases, angiotensin II, angiotensin type 1 receptors and peroxynitrite and the decreased expression of endothelial NO synthase in db/db mice. The angiotensin-converting enzyme (ACE) activity was reduced in the LOE group compared to that in the control db/db group. LOE also inhibited the activity of purified ACE, COX-1 and COX-2 in a dose-dependent manner. In addition, LOE improved physical exercise capacity. Thus, the present findings indicate that LOE has a beneficial effect on the vascular system in db/db mice by improving endothelium-dependent relaxations and vascular oxidative stress most likely by normalizing the angiotensin system, and also on metabolic parameters, and these effects are associated with an enhanced physical exercise capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / prevention & control
  • Angiotensin II / genetics
  • Angiotensin II / metabolism
  • Animals
  • Aorta / drug effects
  • Aorta / physiopathology
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Ethanol / chemistry
  • Exercise Tolerance / drug effects*
  • Gene Expression / drug effects
  • Humans
  • Hyperglycemia / prevention & control
  • Hypoglycemic Agents / pharmacology*
  • Lindera / chemistry*
  • Male
  • Mice
  • Mice, Transgenic
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Pioglitazone
  • Plant Extracts / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Thiazolidinediones / pharmacology

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Plant Extracts
  • Receptor, Angiotensin, Type 1
  • Thiazolidinediones
  • Angiotensin II
  • Ethanol
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Prostaglandin-Endoperoxide Synthases
  • NADPH Oxidases
  • Pioglitazone

Grants and funding

The study was supported, in part, by The Ministry of Knowledge Economy, Republic of Korea, under the Leading Industry Development for Gangwon Economic Region (LIDGER) program (number 70007579), and by Hanwha Pharma. Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.