title: A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db/db mouse.
abstract: BACKGROUND
  Gentiana scabra root extract (GS) is frequently prescribed as an internal remedy in traditional Korean medicine for treatment of diabetes mellitus. GS contains bitter iridoid glycosides including loganic acid, gentiopicrin, trifloroside, and rindoside. We previously reported that the intestinal bitter taste sensation stimulates GLP-1 secretion, and thereupon hypothesized that the blood glucose regulatory effect of GS is due to its GLP-1 secreting effect in enteroendocrine L cells.
  
  
  METHODS
  We studied GLP-1 secreting effect of GS treatment and its cellular downstream mechanism in human enteroendocrine NCI-H716 cells using the G protein-coupled receptor (GPCR) pathway inhibitors. Intracellular calcium assay also demonstrated the signal transduction pathway stimulated by the GS treatment. Using db/db mice, we performed oral glucose tolerance test (OGTT) to examine the blood glucose lowering effect of GS administration. We also collected the mouse plasma during the OGTT to measure the GLP-1 and insulin levels.
  
  
  RESULTS
  We demonstrated dose-dependent GLP-1 secreting effect of GS on the NCI-H716 cells. The GLP-1 secreting effect of GS is mediated by the G protein βγ-subunit and inositol triphosphate. Using db/db mice, we found that the effect of GS on lowering blood glucose is due to its GLP-1 secretion, and consequential insulinotropic effect. The chemical fingerprint of GS was obtained through a direct analysis in realtime mass spectrometry (DART-MS) and high-performance liquid chromatography (HPLC)/MS. Through the GLP-1 secretion study, we found that loganic acid, an iridoid glycoside, contributes to the GLP-1 secreting effect of GS.
  
  
  CONCLUSIONS
  The findings of this study highlight the potential of exploiting the antidiabetic effect of GS on type 2 diabetes mellitus patients.
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hyo-Weon
authors.initials: HW
authors.lastname: Suh
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Ki-Beom
authors.initials: KB
authors.lastname: Lee
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Ki-Suk
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hea Jung
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Choi
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Shin
authors.affiliation: Department of Microbiology, School of Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
authors.affiliation: Western Seoul Center, Korea Basic Science Institute, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 120-140, Republic of Korea.
authors.forename: Yun-Cheol
authors.initials: YC
authors.lastname: Na
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Young Pyo
authors.initials: YP
authors.lastname: Jang
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Um
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, Heogi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: hjjang@khu.ac.kr.
authors.forename: Hyeung-Jin
authors.initials: HJ
authors.lastname: Jang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D030012:Gentiana / Q000737:chemistry*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1
keywords: GLP-1; Gentiana scabra; Insulin; Loganic acid; NCI-H716