Skip to content
Research Article Open access CC BY 4.0

Ginsenoside Re, Produces Multi-targeted Potent Antidiabetic Effects Via Estrogen Receptor Signaling Pathway in Rat, an Alternative Multi-Targeted Therapeutic for Type 2 Diabetes

Jingxian Gao, Xianli Meng, Bayin Zabu, Yi Zhang, Siqinbilig Wu, Huhe Muren, Ni Ha, Qinnuan Sun, Tang Jisi, Changxi Bai

Journal of Pharmaceutical Research International · pp. 216–236 · Published 13 Dec 2021

10.9734/jpri/2021/v33i54B33782

Abstract

Aims: To identify more effective ginsenoside for type 2 diabetes (T2D) and clarify whether the ginsenoside characterizing estrogenic multi-targeted antidiabetic effects. Study Design: Identifying more effective ginsenoside through preclinical evaluation of antidiabetic effects of representative ginsenosides with T2D rat model, and further test pharmacological mechanism underlying the potent antidiabetic effects of the ginsenoside in the same model. Place and Duration of Study: Key laboratory for Pharmacy, Inner Mongolia Medical University, March 2018 to November 2020. Methodology: Used a total of 240 female adult rats. Rat model of T2D induced by high-fat diet fed and streptozotocin. Five tapes of representative ginsenosides (Rb1, Rd, Rg3, Re, Rg1) administrated at low (20 mg/kg daily) and high (40 mg/ kg daily) doses to T2D rats with orally for 4 weeks. Detect testing indexes with biochemical, histological, Quantitative Real-Time PCR, and western blots analysis. Results: Ginsenoside Re (Re), very significantly lowered blood glucose (P<0.01), lipids (P<0.001), free fatty acid (P<0.001), and glucagon (P<0.01) levels, markedly improved impaired insulin sensitivity (P<0.01), ameliorated oxidative stress (P<0.01) and inflammation (P<0.01) in T2D rats, exhibited potent antidiabetic effects. Moreover, Re, phosphorylate serine/threonine kinase (Akt) (P<0.01) and endothelial nitric oxide synthase (eNOS) (P<0.01), up regulates B-cell lymphoma-2 (P<0.01) and insulin gene expression (P<0.01), down regulates glucagon gene expression(P<0.01), reverse impaired glucagon-like peptide 1 (P<0.01); exhibits multi-targeted effects; these effects of Re were inhibited by estrogen receptor (ER) inhibitor (ICI-182,780) (P<0.01). Functionally, the antidiabetic effects of Re were sequentially inhibited by inhibitor of ER, Akt, and eNOS, respectively (P<0.01). Conclusion: These findings, revealed a novel pharmacological property of Re that characterized in multi-targeted potent antidiabetic effects mediated by ER/Akt/eNOS/NO signaling pathway, provide the first evidence for the potential use of Re, as a multi-targeted therapeutic for T2D, particularly, a novel candidate for replacement of estrogen therapy and NO therapy in diabetes.

Ginsenoside Re Type 2 diabetes Multiple targeted antidiabetic effects Estrogen receptor signaling pathway Nitric oxide An alternative multi - targeted therapy

References (40)

  1. 1 Insulin action and resistance in obesity and type 2 diabetes [DOI]
  2. 2 Meta‐analysis: effect of hormone‐replacement therapy on components of the metabolic syndrome in postmenopausal women [DOI]
  3. 3 Ginseng Compounds: An Update on their Molecular Mechanisms and Medical Applications [DOI]
  4. 4 Panax ginseng pharmacology: A nitric oxide link? [DOI]
  5. 5 Journal of Diabetes and Its Complications [DOI]
  6. 6 Estrogen Receptors and the Metabolic Network [DOI]
  7. 7 The Toxicology of Inhaled Nitric Oxide [DOI]
  8. 8 Estrogen and androgen receptors: regulators of fuel homeostasis and emerging targets for diabetes and obesity [DOI]
  9. 9 Treatment of type 2 diabetes: challenges, hopes, and anticipated successes [DOI]
  10. 10 Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats [DOI]
  11. 11 Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes [DOI]
  12. 12 Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies [DOI]
  13. 13 Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts [DOI]
  14. 14 Antiobesity and Antihyperglycemic Effects of Ginsenoside Rb1 in Rats [DOI]
  15. 15 Role of Nitric Oxide in Insulin Secretion and Glucose Metabolism [DOI]
  16. 16 Anti-diabetic effect of ginsenoside Re in ob/ob mice [DOI]
  17. 17 Review of Ginseng Anti-Diabetic Studies [DOI]
  18. 18 Pancreatic α-Cell Dysfunction in Type 2 Diabetes: Old Kids on the Block [DOI]
  19. 19 Loss of Inverse Relationship Between Pulsatile Insulin and Glucagon Secretion in Patients With Type 2 Diabetes [DOI]
  20. 20 Ginsenoside Re attenuates diabetes-associated cognitive deficits in rats [DOI]
  21. 21 The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice [DOI]
  22. 22 Anticarcinogenic Effects of Products of Heat-Processed Ginsenoside Re, a Major Constituent of Ginseng Berry, on Human Gastric Cancer Cells [DOI]
  23. 23 Non‐genomic effects of ginsenoside‐Re in endothelial cells via glucocorticoid receptor [DOI]
  24. 24 Possible mechanisms of the protection of ginsenoside Re against MPTP-induced apoptosis in substantia nigra neurons of Parkinson's disease mouse model [DOI]
  25. 25 Effects of ginsenoside Rg1 on glucose metabolism and liver injury in streptozotocin-induced type 2 diabetic rats [DOI]
  26. 26 Oxidative stress and inflammatory markers in type 2 diabetic patients [DOI]
  27. 27 Computational and experimental characterization of estrogenic activities of 20(S, R)-protopanaxadiol and 20(S, R)-protopanaxatriol [DOI]
  28. 28 Ginsenoside Re inhibits PDGF-BB-induced VSMC proliferation via the eNOS/NO/cGMP pathway [DOI]
  29. 29 Protective effects of ginsenoside Re on lipopolysaccharide-induced cardiac dysfunction in mice [DOI]
  30. 30 Insights on the current status and advancement of diabetes mellitus type 2 and to avert complications: An overview [DOI]
  31. 31 Antiobesogenic Role of Endothelial Nitric Oxide Synthase [DOI]
  32. 32 Estrogen replacement enhances insulin-induced AS160 activation and improves insulin sensitivity in ovariectomized rats [DOI]
  33. 33 AMP-activated protein kinase: A potential target for ginsenosides? [DOI]
  34. 34 Ginsenoside Re rapidly reverses insulin resistance in muscles of high-fat diet fed rats [DOI]
  35. 35 Structural insights into selective agonist actions of tamoxifen on human estrogen receptor alpha [DOI]
  36. 36 The Hot and Potential Targets of Type 2 Diabetes Mellitus Treatment in Recent Decade [DOI]
  37. 37 Effect of Ginsenoside Rg3 and Rh2 on Glucose Uptake in Insulin-resistant Muscle Cells [DOI]
  38. 38 For debate; pharmacological priorities in advanced type 2 diabetes [DOI]
  39. 39 [Estrogen receptor alpha in obesity and diabetes].
  40. 40 Ginsenoside Re promotes glucagons-like-peptide-1 amide secretion in diabetic rats

Cited by 0

No indexed citations yet.

Related research

Article metrics

Real usage data collected on this platform.

6

Page views

0

PDF downloads

0

Outbound clicks

0

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.