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Rhizoma Anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents.
J Ethnopharmacol. 2015 Aug 22; 172:368-76.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Rhizoma Anemarrhenae has been used in Asian countries for thousands of years to treat diabetes. Insulin resistance (IR) is the primary cause responsible for type 2 diabetes. The aim of this study was to to assess the hypoglycemic and insulin sensitizing properties of Rhizoma Anemarrhenae extract (TFA) in animal models of insulin resistance and/or diabetes and to delineate modes of action.

MATERIALS AND METHODS

In-vivo studies were performed on STZ-induced diabetic mice and KK-Ay mice, the former of which were given the extract alone or in combination with insulin for 7 days, and the latter of which were given the extract for 8 consecutive weeks. Fasting blood glucose and serum insulin levels were measured. Pancreatic tissue sections were examined using transmission electron micrographs. Further, hyperinsulinemic-euglycemic clamping study was conducted in BCG vaccine-induced insulin resistance rats, and glucose infusion rate was examined. Mechanisms of action were investigated in 3T3-L1 and Hela cells using Western blot analysis.

RESULTS

Our study showed that TFA enhanced the glucose-lowering effects of exogenous insulin administration in STZ-induced diabetic mice. Therapeutic administration of TFA significantly reduced fasting blood glucose, and serum insulin levels, and markedly increased the size and the number of insulin-producing beta cells in KK-Ay mice. Further, hyperinsulinemic-euglycemic clamping study showed that glucose infusion rate was significantly improved in TFA-treated BCG vaccine-induced insulin resistance rats. Study of mechanism of action revealed that TFA increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in 3T3-L1 cells. It activates AMPK in a LKB1-independent manner, providing a unified explanation for the beneficial effects of TFA.

CONCLUSIONS

This study that TFA mediates activation of AMPK and improves overall glucose and lipid metabolism in diabetic rodents, highlights the potential utility of TFA for the management of type 2 diabetes.

Authors+Show Affiliations

Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.New Drug Research Center, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China. Electronic address: chenwanshengsmmu@aliyun.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26162543

Citation

Han, Jun, et al. "Rhizoma Anemarrhenae Extract Ameliorates Hyperglycemia and Insulin Resistance Via Activation of AMP-activated Protein Kinase in Diabetic Rodents." Journal of Ethnopharmacology, vol. 172, 2015, pp. 368-76.
Han J, Yang N, Zhang F, et al. Rhizoma Anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents. J Ethnopharmacol. 2015;172:368-76.
Han, J., Yang, N., Zhang, F., Zhang, C., Liang, F., Xie, W., & Chen, W. (2015). Rhizoma Anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents. Journal of Ethnopharmacology, 172, 368-76. https://doi.org/10.1016/j.jep.2015.05.016
Han J, et al. Rhizoma Anemarrhenae Extract Ameliorates Hyperglycemia and Insulin Resistance Via Activation of AMP-activated Protein Kinase in Diabetic Rodents. J Ethnopharmacol. 2015 Aug 22;172:368-76. PubMed PMID: 26162543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rhizoma Anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents. AU - Han,Jun, AU - Yang,Na, AU - Zhang,Feng, AU - Zhang,Chuan, AU - Liang,Fengying, AU - Xie,WeiFen, AU - Chen,Wansheng, Y1 - 2015/07/07/ PY - 2015/01/08/received PY - 2015/05/04/revised PY - 2015/05/07/accepted PY - 2015/7/12/entrez PY - 2015/7/15/pubmed PY - 2016/6/2/medline KW - AMP-activated protein kinase KW - Animal experiment KW - Anti-diabetic compounds KW - Bacillus Calmette-Guérin (PubChem CID: 6451) KW - Carboxymethyl Cellulose Sodium (PubChem CID: 6328154) KW - Compound C (PubChem CID: 11524144) KW - Insulin sensitivity KW - Mangiferin (PubChem CID: 5281647) KW - Neomangiferin (PubChem CID: 6918448) KW - Pentobarbital Sodium (PubChem CID: 14075609) KW - Pioglitazone (PubChem CID: 4829) KW - STO-609 (PubChem CID: 16760660) KW - Streptozocin (PubChem CID: 29327) KW - Wortmannin (PubChem CID: 312145) SP - 368 EP - 76 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 172 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma Anemarrhenae has been used in Asian countries for thousands of years to treat diabetes. Insulin resistance (IR) is the primary cause responsible for type 2 diabetes. The aim of this study was to to assess the hypoglycemic and insulin sensitizing properties of Rhizoma Anemarrhenae extract (TFA) in animal models of insulin resistance and/or diabetes and to delineate modes of action. MATERIALS AND METHODS: In-vivo studies were performed on STZ-induced diabetic mice and KK-Ay mice, the former of which were given the extract alone or in combination with insulin for 7 days, and the latter of which were given the extract for 8 consecutive weeks. Fasting blood glucose and serum insulin levels were measured. Pancreatic tissue sections were examined using transmission electron micrographs. Further, hyperinsulinemic-euglycemic clamping study was conducted in BCG vaccine-induced insulin resistance rats, and glucose infusion rate was examined. Mechanisms of action were investigated in 3T3-L1 and Hela cells using Western blot analysis. RESULTS: Our study showed that TFA enhanced the glucose-lowering effects of exogenous insulin administration in STZ-induced diabetic mice. Therapeutic administration of TFA significantly reduced fasting blood glucose, and serum insulin levels, and markedly increased the size and the number of insulin-producing beta cells in KK-Ay mice. Further, hyperinsulinemic-euglycemic clamping study showed that glucose infusion rate was significantly improved in TFA-treated BCG vaccine-induced insulin resistance rats. Study of mechanism of action revealed that TFA increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in 3T3-L1 cells. It activates AMPK in a LKB1-independent manner, providing a unified explanation for the beneficial effects of TFA. CONCLUSIONS: This study that TFA mediates activation of AMPK and improves overall glucose and lipid metabolism in diabetic rodents, highlights the potential utility of TFA for the management of type 2 diabetes. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/26162543/Rhizoma_Anemarrhenae_extract_ameliorates_hyperglycemia_and_insulin_resistance_via_activation_of_AMP_activated_protein_kinase_in_diabetic_rodents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(15)00341-4 DB - PRIME DP - Unbound Medicine ER -