PMID- 23755196 OWN - NLM STAT- MEDLINE DCOM- 20150113 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 6 DP - 2013 TI - An ethanolic extract of Lindera obtusiloba stems, YJP-14, improves endothelial dysfunction, metabolic parameters and physical performance in diabetic db/db mice. PG - e65227 LID - 10.1371/journal.pone.0065227 [doi] LID - e65227 AB - 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. FAU - Lee, Jung-Ok AU - Lee JO AD - UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculte de Pharmacie, Universite de Strasbourg, Illkirch, France. FAU - Auger, Cyril AU - Auger C FAU - Park, Dong Hyun AU - Park DH FAU - Kang, Moonkyu AU - Kang M FAU - Oak, Min-Ho AU - Oak MH FAU - Kim, Kyoung Rak AU - Kim KR FAU - Schini-Kerth, Valerie B AU - Schini-Kerth VB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130603 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Plant Extracts) RN - 0 (Receptor, Angiotensin, Type 1) RN - 0 (Thiazolidinediones) RN - 11128-99-7 (Angiotensin II) RN - 3K9958V90M (Ethanol) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, mouse) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) RN - EC 1.6.3.- (NADPH Oxidases) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Albuminuria/prevention & control MH - Angiotensin II/genetics/metabolism MH - Animals MH - Aorta/drug effects/physiopathology MH - Blood Glucose/metabolism MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism/physiopathology MH - Disease Models, Animal MH - Endothelium, Vascular/*drug effects/metabolism MH - Ethanol/chemistry MH - Exercise Tolerance/*drug effects MH - Gene Expression/drug effects MH - Humans MH - Hyperglycemia/prevention & control MH - Hypoglycemic Agents/*pharmacology MH - Lindera/*chemistry MH - Male MH - Mice MH - Mice, Transgenic MH - NADPH Oxidases/genetics/metabolism MH - Nitric Oxide Synthase Type III/genetics/metabolism MH - Pioglitazone MH - Plant Extracts/*pharmacology MH - Prostaglandin-Endoperoxide Synthases/genetics/metabolism MH - Receptor, Angiotensin, Type 1/genetics/metabolism MH - Thiazolidinediones/pharmacology PMC - PMC3670856 COIS- Competing Interests: Jung-Ok Lee, Moonkyu Kang and Kyoung Rak Kim are all employees of Hanwha Pharma. Co., Ltd, Chuncheon, Republic of Korea, whose company provided funding toward this study. Dong Hyun Park is an employee of YangJi Chemicals, Suwon, Republic of Korea, which is a daughter company of Hanwha. Hanwha has filed a European and US patent on YJP14 and endothelial dysfunction. The Korean FDA have approved further clinical studies regarding YJP-14 and endothelial dysfunction in diabetes. At present there are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2013/06/12 06:00 MHDA- 2015/01/15 06:00 PMCR- 2013/06/03 CRDT- 2013/06/12 06:00 PHST- 2012/10/29 00:00 [received] PHST- 2013/04/24 00:00 [accepted] PHST- 2013/06/12 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2015/01/15 06:00 [medline] PHST- 2013/06/03 00:00 [pmc-release] AID - PONE-D-12-33944 [pii] AID - 10.1371/journal.pone.0065227 [doi] PST - epublish SO - PLoS One. 2013 Jun 3;8(6):e65227. doi: 10.1371/journal.pone.0065227. Print 2013.