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Anti-hyperglycemic effects of Eryngium billardierei F. Delaroche extract on insulin-resistance HepG2 cells in vitro

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Abstract

Background

Insulin resistance as a major problem is associated with type 2 diabetes mellitus. This study investigated the effect of Eryngium billardierei on insulin-resistance induced HepG2 cells.

Methods and results

MTT method was used to evaluate the viability of HepG2 cells treated with various doses of E. billardierei extract. An insulin-resistance model was established in HepG2 cells. Next, MTT assay and Acridine orange staining were performed to investigate the viability of cells in the vicinity of different concentrations of insulin, pioglitazone, and E. billardierei extract in an insulin-resistance media. The glucose uptake test was performed to select the optimal insulin concentration. Expression levels of IR, G6Pase, and PEPCK genes were assessed by real-time RT-PCR. According to obtained data, E. billardierei at concentrations of 0.5 and 1 mg/mL show no toxicity on cells. Furthermore, based on MTT assay and glucose uptake test 10−5 mol/L insulin was chosen as the model group to induce insulin-resistance in HepG2 cells for gene expression analysis. Finally, 1 mg/mL E. billardierei not only induced no cytotoxicity but also showed an increase in the expression of IR as well as a reduction in G6Pase and PEPCK level compared to the control and model groups.

Conclusions

The obtained data indicated that 1 mg/mL E. billardierei might have an anti-insulin resistance effect on insulin-resistance HepG2 cells in vitro and could be a promising candidate with anti-hyperglycemic properties for diabetes treatments.

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Abbreviations

AO:

Acridine orange

CREB:

Cyclic adenosine monophosphate response element-binding protein

DMEM:

Dulbecco’s modified eagle’s medium

EB:

Ethidium bromide

FBS:

Fetal bovine serum

FoxO1:

Forkhead box O1

G6Pase:

Glucose-6-phosphatase

IR:

Insulin receptor

IR1:

Insulin receptor substrate 1

PEPCK:

Phosphoenolpyruvate carboxykinase

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

T2DM:

Type 2 diabetes mellitus

References

  1. Cuschieri S (2019) Type 2 diabetes: an unresolved disease across centuries contributing to a public health emergency. Diabetes Metab Syndr 13:450–453

    Article  PubMed  Google Scholar 

  2. Garcia-Compean D, Jaquez-Quintana JO, Gonzalez-Gonzalez JA, Maldonado-Garza H (2009) Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management. World J Gastroenterol 15:280–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Raddatz D, Ramadori G (2007) Carbohydrate metabolism and the liver: actual aspects from physiology and disease. Z Gastroenterol 45:51–62

    Article  CAS  PubMed  Google Scholar 

  4. Petersen MC, Shulman GI (2018) Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev 98:2133–2223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Beale EG (2013) Insulin signaling and insulin resistance. J Investigat Med 61:11–14

    Article  CAS  Google Scholar 

  6. Javeed N, Matveyenko AV (2018) Circadian etiology of type 2 diabetes mellitus. Physiology 33:138–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu J, Liu Z (2019) Muscle insulin resistance and the inflamed microvasculature: fire from within. Int J Mol Sci 20

  8. Tong T et al (2018) Theaflavins improve insulin sensitivity through regulating mitochondrial biosynthesis in palmitic acid-induced HepG2 cells. Molecules 23

  9. Wang B, Sun Y, Sang Y, Liu X, Liang J (2018) Comparison of dipeptidyl peptidase-4 inhibitors and pioglitazone combination therapy versus pioglitazone monotherapy in type 2 diabetes: a system review and meta-analysis. Medicine 97:e12633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. de Pablos-Velasco P (2010) Pioglitazone: beyond glucose control. Expert Rev Cardiovasc Ther 8:1057–1067

    Article  PubMed  Google Scholar 

  11. DeFronzo RA, Inzucchi S, Abdul-Ghani M, Nissen SE (2019) Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes. Diab Vasc Dis Res 16:133–143

    Article  CAS  PubMed  Google Scholar 

  12. Erdem SA, Nabavi SF, Orhan IE, Daglia M, Izadi M, Nabavi SM (2015) Blessings in disguise: a review of phytochemical composition and antimicrobial activity of plants belonging to the genus Eryngium. Daru 23:53

    Article  PubMed  PubMed Central  Google Scholar 

  13. Medbouhi A et al (2019) Essential oil of algerian eryngium campestre: chemical variability and evaluation of biological activities. Molecules 24

  14. Peña-Montes DJ, Huerta-Cervantes M, Ríos-Silva M, Trujillo X, Huerta M, Noriega-Cisneros R, Salgado-Garciglia R, Saavedra-Molina A (2019) Protective effect of the hexanic extract of eryngium carlinae inflorescences in vitro, in yeast, and in streptozotocin-induced diabetic male rats. Antioxidants 8

  15. Tan Y, Jin Y, Wu X, Ren Z (2019) PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism. BMC Mol Biol 20:24

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen L, Lin X, Fan X, Qian Y, Lv Q, Teng H (2020) Sonchus oleraceus Linn extract enhanced glucose homeostasis through the AMPK/Akt/ GSK-3β signaling pathway in diabetic liver and HepG2 cell culture. Food Chem Toxicol 136:111072

    Article  CAS  PubMed  Google Scholar 

  17. Abdul-Ghani MA, DeFronzo RA (2010) Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol 2010:476279

    Article  PubMed  PubMed Central  Google Scholar 

  18. Czech MP (2017) Insulin action and resistance in obesity and type 2 diabetes. Nat Med 23:804–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Banjari I, Misir A, Pavlić M, Herath PN, Waisundara VY (2019) Traditional herbal medicines for diabetes used in europe and asia: remedies from croatia and Sri Lanka. Altern Ther Health Med 25:40–52

    PubMed  Google Scholar 

  20. Fan X et al (2019) Investigations on the effects of ginsenoside-Rg1 on glucose uptake and metabolism in insulin resistant HepG2 cells. Eur J Pharmacol 843:277–284

    Article  CAS  PubMed  Google Scholar 

  21. Chen L, Teng H, Cao H (2019) Chlorogenic acid and caffeic acid from Sonchus oleraceus Linn synergistically attenuate insulin resistance and modulate glucose uptake in HepG2 cells. Food Chem Toxicol 127:182–187

    Article  CAS  PubMed  Google Scholar 

  22. Jiang B et al (2016) Protective effects of marein on high glucose-induced glucose metabolic disorder in HepG2 cells. Phytomedicine 23:891–900

    Article  CAS  PubMed  Google Scholar 

  23. Yang Z, Huang W, Zhang J, Xie M, Wang X (2019) Baicalein improves glucose metabolism in insulin resistant HepG2 cells. Eur J Pharmacol 854:187–193

    Article  CAS  PubMed  Google Scholar 

  24. Grover JK, Yadav S, Vats V (2002) Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol 81:81–100

    Article  CAS  PubMed  Google Scholar 

  25. Zheng Y et al (2020) Interactions between gut microbiota, host, and herbal medicines: a review of new insights into the pathogenesis and treatment of type 2 diabetes. Front Cell Infect Microbiol 10:360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang P, Su Z, Yuan W, Deng G, Li S (2012) Phytochemical constituents and pharmacological activities of Eryngium L. (Apiaceae)

  27. Thomas PS, Essien EE, Ntuk SJ, Choudhary MI (2017) Eryngium foetidum L. essential oils: chemical composition and antioxidant capacity. Medicines 4

  28. Pérez-Ramírez IF, Enciso-Moreno JA, Guevara-González RG, Gallegos-Corona MA, Loarca-Piña G, Reynoso-Camacho R (2016) Modulation of renal dysfunction by Smilax cordifolia and Eryngium carlinae, and their effect on kidney proteome in obese rats. J Funct Foods 20:545–555

    Article  Google Scholar 

  29. Daneshzadeh MS, Abbaspour H, Amjad L, Nafchi AM (2020) An investigation on phytochemical, antioxidant and antibacterial properties of extract from Eryngium billardieri F. Delaroche. J Food Measur Characteriz 14:708–715

    Article  Google Scholar 

  30. Chen L, Lin X, Teng H (2020) Emulsions loaded with dihydromyricetin enhance its transport through Caco-2 monolayer and improve anti-diabetic effect in insulin resistant HepG2 cell. J Funct Foods 64:103672

    Article  CAS  Google Scholar 

  31. Chen L, Gnanaraj C, Arulselvan P, El-Seedi H, Teng H (2019) A review on advanced microencapsulation technology to enhance bioavailability of phenolic compounds: based on its activity in the treatment of Type 2 Diabetes. Trends Food Sci Technol 85:149–162

    Article  CAS  Google Scholar 

  32. Posner BI (2017) Insulin signalling: the inside story. Can J Diabetes 41:108–113

    Article  PubMed  Google Scholar 

  33. Gu L et al (2019) Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1α pathway in high-fat-diet-induced rats and insulin resistant cells. Int J Biol Sci 15:2815–2829

    Article  PubMed  PubMed Central  Google Scholar 

  34. He L, Li Y, Zeng N, Stiles BL (2020) Regulation of basal expression of hepatic PEPCK and G6Pase by AKT2. Biochem J 477:1021–1031

    Article  CAS  PubMed  Google Scholar 

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Funding

The work was not supported by any Department.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Fatemeh Kheirollahzadeh & Elahe Eftekhari

  2. Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Marzieh Ghollasi

  3. Department of Microbiology, College of Basic Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran

    Payam Behzadi

Authors
  1. Fatemeh Kheirollahzadeh
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  2. Elahe Eftekhari
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  3. Marzieh Ghollasi
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  4. Payam Behzadi
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Corresponding authors

Correspondence to Marzieh Ghollasi or Payam Behzadi.

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All authors declare that they have no conflict ofinterest.

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This article does not contain any studies with human participants or animals performed by any of the authors. The HepG2 were purchased from The Stem Cell Technology Research Center.

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Kheirollahzadeh, F., Eftekhari, E., Ghollasi, M. et al. Anti-hyperglycemic effects of Eryngium billardierei F. Delaroche extract on insulin-resistance HepG2 cells in vitro. Mol Biol Rep 49, 3401–3411 (2022). https://doi.org/10.1007/s11033-022-07171-0

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