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Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway.
J Ethnopharmacol. 2018 Jan 30; 211:366-374.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Entada phaseoloides (L.) Merr., a traditional Chinese folk medicine, has been used in treating diabetes and other inflammatory disorders. Our previous study revealed that the triterpene saponins in E.Phaseoloides possessed an antidiabetic effect in type 2 diabetic rats by activating AMP-activated protein kinase (AMPK). Entagenic acid, the principal aglycon, isolated from the seed kernels of E. phaseoloides, has been proposed to possess a significant role in the antidiabetic effect, however, its actual effect and pertinent mechanisms are still unknown.

AIM OF THE STUDY

The aim of the present study was to investigate the antidiabetic effect of entagenic acid in a type 2 diabetic animal model (C57BIKsj db/db mice) and its role in the regulation of glucose uptake in L6 myotubes, and to explore the possible molecular mechanisms.

MATERIALS AND METHODS

In vivo, average weekly body weight, daily water, food intake and postprandial blood glucose levels, the intraperitoneal insulin tolerance test, glucose tolerance test, serum lipid profiles and pancreatic histopathological changes in db/db mice treated with entagenic acid orally at different doses (5, 10 and 20mg/kg) were assessed and compared with wild-type littermates or vehicle- and metformin-treated db/db mice. In vitro, effects of entagenic acid on the glucose consumption and the phosphorylation of protein kinase B (AKT) and AMPK in L6 myotubes were evaluated.

RESULTS

In vivo, entagenic acid significantly lowered postprandial blood glucose levels but not the body weight, normalized the serum lipid imbalance, improved the impaired glucose tolerance, insulin resistance, as well as the pathological changes in pancreatic islets. In vitro, entagenic acid dose-dependently promoted glucose utilization and enhanced the translocation and expression of glucose transporter 4 (GLUT4), and phosphorylation of AMPK but not AKT.

CONCLUSIONS

The present study demonstrated that entagenic acid can markedly maintain the glucose homeostasis, improve insulin resistance and ameliorate dyslipidemia. Its antihyperglycemic effect could be caused by promoting AMPK mediated cellular signaling and GLUT4 translocation in muscles.

Authors+Show Affiliations

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, PR China.School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, PR China.Division of Pulmonary & Critical Care Medicine, Barnes-Jewish Hospital, St. Louis, MO 63110, USA; Department of Anesthesiology, The Center for the Study of Itch, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.School of Life Sciences, South-Central University for Nationalities, Wuhan 430074, PR China.School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, PR China.School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, PR China. Electronic address: meizhinan@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28993280

Citation

Xiong, Hui, et al. "Antidiabetic Activities of Entagenic Acid in Type 2 Diabetic Db/db Mice and L6 Myotubes Via AMPK/GLUT4 Pathway." Journal of Ethnopharmacology, vol. 211, 2018, pp. 366-374.
Xiong H, Zhang S, Zhao Z, et al. Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway. J Ethnopharmacol. 2018;211:366-374.
Xiong, H., Zhang, S., Zhao, Z., Zhao, P., Chen, L., & Mei, Z. (2018). Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway. Journal of Ethnopharmacology, 211, 366-374. https://doi.org/10.1016/j.jep.2017.10.004
Xiong H, et al. Antidiabetic Activities of Entagenic Acid in Type 2 Diabetic Db/db Mice and L6 Myotubes Via AMPK/GLUT4 Pathway. J Ethnopharmacol. 2018 Jan 30;211:366-374. PubMed PMID: 28993280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway. AU - Xiong,Hui, AU - Zhang,Shengnan, AU - Zhao,Zhongqiu, AU - Zhao,Ping, AU - Chen,Lvyi, AU - Mei,Zhinan, Y1 - 2017/10/07/ PY - 2017/04/11/received PY - 2017/08/30/revised PY - 2017/10/05/accepted PY - 2017/10/11/pubmed PY - 2018/7/22/medline PY - 2017/10/11/entrez KW - AMPK KW - Diabetes KW - Entagenic acid (PubChem CID: 21594206) KW - GLUT4 SP - 366 EP - 374 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 211 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Entada phaseoloides (L.) Merr., a traditional Chinese folk medicine, has been used in treating diabetes and other inflammatory disorders. Our previous study revealed that the triterpene saponins in E.Phaseoloides possessed an antidiabetic effect in type 2 diabetic rats by activating AMP-activated protein kinase (AMPK). Entagenic acid, the principal aglycon, isolated from the seed kernels of E. phaseoloides, has been proposed to possess a significant role in the antidiabetic effect, however, its actual effect and pertinent mechanisms are still unknown. AIM OF THE STUDY: The aim of the present study was to investigate the antidiabetic effect of entagenic acid in a type 2 diabetic animal model (C57BIKsj db/db mice) and its role in the regulation of glucose uptake in L6 myotubes, and to explore the possible molecular mechanisms. MATERIALS AND METHODS: In vivo, average weekly body weight, daily water, food intake and postprandial blood glucose levels, the intraperitoneal insulin tolerance test, glucose tolerance test, serum lipid profiles and pancreatic histopathological changes in db/db mice treated with entagenic acid orally at different doses (5, 10 and 20mg/kg) were assessed and compared with wild-type littermates or vehicle- and metformin-treated db/db mice. In vitro, effects of entagenic acid on the glucose consumption and the phosphorylation of protein kinase B (AKT) and AMPK in L6 myotubes were evaluated. RESULTS: In vivo, entagenic acid significantly lowered postprandial blood glucose levels but not the body weight, normalized the serum lipid imbalance, improved the impaired glucose tolerance, insulin resistance, as well as the pathological changes in pancreatic islets. In vitro, entagenic acid dose-dependently promoted glucose utilization and enhanced the translocation and expression of glucose transporter 4 (GLUT4), and phosphorylation of AMPK but not AKT. CONCLUSIONS: The present study demonstrated that entagenic acid can markedly maintain the glucose homeostasis, improve insulin resistance and ameliorate dyslipidemia. Its antihyperglycemic effect could be caused by promoting AMPK mediated cellular signaling and GLUT4 translocation in muscles. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/28993280/Antidiabetic_activities_of_entagenic_acid_in_type_2_diabetic_db/db_mice_and_L6_myotubes_via_AMPK/GLUT4_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(17)31430-7 DB - PRIME DP - Unbound Medicine ER -