Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle.
BACKGROUND
Ginseng (Panax ginseng C. A. Meyer, Araliaceae) has been used as a traditional medicine for thousands of years for the treatment of a wide variety of diseases, including diabetes. Processed ginseng named Black ginseng exhibits more potent biological activities than white and red ginseng. The aim of this study was to investigate the effects of black ginseng extract (GBG05-FF) on hyperglycemia and glucose tolerance in streptozotocin (STZ)-induced diabetic mice.


METHODS
Black ginseng was produced by a repeated steaming and drying process, subsequent extraction with 70% ethanol, filtration, and lyophilization. The effect of GBG05-FF on glucose uptake and related protein expression and phosphorylation were determined in C2C12 cells. Furthermore, we evaluated the anti-diabetic effects of GBG05-FF in STZ-induced diabetic mice.


RESULTS
GBG05-FF significantly (p<0.05) increased glucose uptake in C2C12 myotubes via AMPK, Sirt1 and PI3-K pathway. In addition, GBG05-FF improved the fasting blood glucose levels and glucose tolerance in STZ-induced diabetic mice. GBG05-FF decreased blood parameters such as glycated hemoglobin, triglyceride and total cholesterol. Quantitative RT-PCR assay revealed that in the STZ-induced diabetic mice treated with GBG05-FF, the expression of hepatic genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase)), glycogenolysis (liver glycogen phosphorylase (LGP)) and glycogenesis (glycogen synthase (GS)) was suppressed, while the expression of the genes involved in glucose uptake (glucose transporter (GLUT) 1, GLUT4) and β-oxidation (acyl-CoA oxidase (ACO), carnitine palmitoyl transferase 1a (CPT1a), mitochondrial medium chain acyl-CoA dehydrogenase (MCAD)) in muscle were increased. GBG05-FF delayed diabetes-associated muscle atrophy by activating mTOR. The major bioactive compounds including ginsenoside Rg1, Rg3(S), Rg3(R), Rg5, Rk1 and Rh4 were evaluated for glucose uptake effect in C2C12 myotubes; the data indicated that Rh4 significantly (p<0.05) increased glucose uptake.


CONCLUSIONS
Collectively, the results suggested that GBG05-FF is a potentially useful agent for treatment of diabetes by increasing glucose uptake.
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Yun-Soo
YS
Seo
International Ginseng and Herb Research Institute, Geumsan, 312-804, Republic of Korea.
Mi-Yae
MY
Shon
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Ryong
R
Kong
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Ok-Hwa
OH
Kang
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Tian
T
Zhou
International Ginseng and Herb Research Institute, Geumsan, 312-804, Republic of Korea.
Do-Yeon
DY
Kim
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address: sssimi@wku.ac.kr.
Dong-Yeul
DY
Kwon
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008813:Mice, Inbred ICR; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology; D005894:Panax / Q000737:chemistry* / Q000145:classification; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D013311:Streptozocin; C558406:HbA(1c) protein, mouse
Black ginseng; Diabetes mellitus; Glucose tolerance; Insulin signaling; Skeletal muscle