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Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2 diabetes mellitus in rats.
Biomed Pharmacother. 2017 Dec; 96:1427-1437.BP

Abstract

INTRODUCTION

Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. A lot of research has been done on this plant for its antidiabetic activity. However, there are no reports on flavonoids from E. littorale for its antidiabetic activity and their mechanism of action. Thus, the aim of this study is to evaluate the antidiabetic activity of Swertisin rich flavonoid fraction (SRF) from Enicostema littorale blume and their mechanism of action.

MATERIALS & METHODS

Type 2 Diabetes Mellitus rat model was established by inducing insulin resistance using high fat diet and low dose of streptozotacin injection and was authenticated by HOMA index. The antidiabetic effect of SRF was evaluated on diabetic rats to investigate its long term effects on fasting blood glucose, OGTT, weight of rats, insulin, liver profile, lipid profile, kidney profile, histopathology of liver and pancreas. In addition, antioxidant activity by lipid peroxidation and catalase assay, ex vivo assays and hepatic glycogen content were performed to determine its effect on glycogenesis and hepatic glucose production. Furthermore, the mechanism of action of SRF was evaluated by Real time PCR and the mRNA expression was quantified for Glucokinase (GCK), Insulin receptor substrate (IRS-1), Glucose transporter-2 (GLUT-2) and Glucose transporter-4 (GLUT-4) genes.

RESULTS

Treatment of diabetic rats with SRF demonstrated significant (p<0.0001) dose dependant hypoglycemic activity as compared to positive control metformin group. A decrease in liver, lipid and kidney function tests was seen as compared to diabetic control indicating normalization of organ function tests. Also, antioxidant activity showed significant decrease in malondialdehyde (MDA) content in liver (p<0.001) as compared to pancreas and increased catalytic activity in liver, kidney, spleen and pancreas. The hepatic glycogen content was significantly (p<0.001) increased in SRF treated rats indicating its inhibition of hepatic glucose production. Furthermore, ex vivo assays showed the significant (p<0.05) increase in glucose uptake by diaphragm. The mRNA expression for GCK, IRS-1, GLUT-2 and GLUT-4 genes showed significant up regulation as compared to diabetic control indicating its mechanism via insulin signalling pathway.

CONCLUSION

The studies suggest that SRF ameliorates the insulin resistance by increasing glucose uptake and sensitizing cells towards insulin via IRS1/PI3K/Akt2 pathway.

Authors+Show Affiliations

Department of Biological Sciences, NMIMS, Sunandan Divatia School of Science, SVKM's NMIMS University, Vile Parle (West), Mumbai 400056, India.Department of Pharmacology, Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai 400056, India.Department of Biological Sciences, NMIMS, Sunandan Divatia School of Science, SVKM's NMIMS University, Vile Parle (West), Mumbai 400056, India.Department of Chemistry, NMIMS, Sunandan Divatia School of Science, SVKM's NMIMS University, Vile Parle (West), Mumbai 400056, India. Electronic address: nancy.pandita@nmims.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29031588

Citation

Mokashi, Priyanka, et al. "Swertisin Rich Fraction From Enicostema Littorale Ameliorates Hyperglycemia and Hyperlipidemia in High-fat Fed Diet and Low Dose Streptozotacin Induced Type 2 Diabetes Mellitus in Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 96, 2017, pp. 1427-1437.
Mokashi P, Bhatt LK, Khanna A, et al. Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2 diabetes mellitus in rats. Biomed Pharmacother. 2017;96:1427-1437.
Mokashi, P., Bhatt, L. K., Khanna, A., & Pandita, N. (2017). Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2 diabetes mellitus in rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 96, 1427-1437. https://doi.org/10.1016/j.biopha.2017.09.153
Mokashi P, et al. Swertisin Rich Fraction From Enicostema Littorale Ameliorates Hyperglycemia and Hyperlipidemia in High-fat Fed Diet and Low Dose Streptozotacin Induced Type 2 Diabetes Mellitus in Rats. Biomed Pharmacother. 2017;96:1427-1437. PubMed PMID: 29031588.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2 diabetes mellitus in rats. AU - Mokashi,Priyanka, AU - Bhatt,Lokesh Kumar, AU - Khanna,Aparna, AU - Pandita,Nancy, Y1 - 2017/10/21/ PY - 2017/07/28/received PY - 2017/09/28/revised PY - 2017/09/29/accepted PY - 2017/10/17/pubmed PY - 2018/7/26/medline PY - 2017/10/17/entrez KW - Enicostema littorale KW - Glucose uptake KW - High fat diet KW - Hyperglycemia KW - Insulin resistance KW - Streptozotacin SP - 1427 EP - 1437 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 96 N2 - INTRODUCTION: Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. A lot of research has been done on this plant for its antidiabetic activity. However, there are no reports on flavonoids from E. littorale for its antidiabetic activity and their mechanism of action. Thus, the aim of this study is to evaluate the antidiabetic activity of Swertisin rich flavonoid fraction (SRF) from Enicostema littorale blume and their mechanism of action. MATERIALS & METHODS: Type 2 Diabetes Mellitus rat model was established by inducing insulin resistance using high fat diet and low dose of streptozotacin injection and was authenticated by HOMA index. The antidiabetic effect of SRF was evaluated on diabetic rats to investigate its long term effects on fasting blood glucose, OGTT, weight of rats, insulin, liver profile, lipid profile, kidney profile, histopathology of liver and pancreas. In addition, antioxidant activity by lipid peroxidation and catalase assay, ex vivo assays and hepatic glycogen content were performed to determine its effect on glycogenesis and hepatic glucose production. Furthermore, the mechanism of action of SRF was evaluated by Real time PCR and the mRNA expression was quantified for Glucokinase (GCK), Insulin receptor substrate (IRS-1), Glucose transporter-2 (GLUT-2) and Glucose transporter-4 (GLUT-4) genes. RESULTS: Treatment of diabetic rats with SRF demonstrated significant (p<0.0001) dose dependant hypoglycemic activity as compared to positive control metformin group. A decrease in liver, lipid and kidney function tests was seen as compared to diabetic control indicating normalization of organ function tests. Also, antioxidant activity showed significant decrease in malondialdehyde (MDA) content in liver (p<0.001) as compared to pancreas and increased catalytic activity in liver, kidney, spleen and pancreas. The hepatic glycogen content was significantly (p<0.001) increased in SRF treated rats indicating its inhibition of hepatic glucose production. Furthermore, ex vivo assays showed the significant (p<0.05) increase in glucose uptake by diaphragm. The mRNA expression for GCK, IRS-1, GLUT-2 and GLUT-4 genes showed significant up regulation as compared to diabetic control indicating its mechanism via insulin signalling pathway. CONCLUSION: The studies suggest that SRF ameliorates the insulin resistance by increasing glucose uptake and sensitizing cells towards insulin via IRS1/PI3K/Akt2 pathway. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29031588/Swertisin_rich_fraction_from_Enicostema_littorale_ameliorates_hyperglycemia_and_hyperlipidemia_in_high_fat_fed_diet_and_low_dose_streptozotacin_induced_type_2_diabetes_mellitus_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)33751-4 DB - PRIME DP - Unbound Medicine ER -