Skip to main content
SpringerLink
Log in

Efficacy of Bee Products (Anzer Honey, Pollen and Propolis) in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells: Cytotoxic, Genotoxic and Biochemical Studies

  • Original Articles
  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Background and Objective

Although drugs are powerful therapeutic agents, they have a range of side effects. These side effects are sometimes cellular and not clinically noticeable. Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients. In this study, we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells “hTERT-HPNE”, and we aimed to improve these harmful effects by natural products. To benefit from the healing effect, we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey.

Methods

Cytotoxic and genotoxic effects of the drug were investigated by different tests, such as MTT, flow cytometry-apoptosis and comet assays. Anzer honey, pollen and propolis were analyzed by gas chromatography/mass spectrometry (G/C-MS). A total of 19 compounds were detected, constituting 99.9% of the samples.

Results

The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control (P<0.05). A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey, pollen and propolis in hTERT-HPNE cells (P<0.05).

Conclusion

This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells. In particular, Anzer honey, pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes atlas, 9th edition. Diabetes Res Clin Pract, 2019,157:107843

    Article  PubMed  Google Scholar 

  2. Chaudhury A, Duvoor C, Reddy Dendi VS, et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol, 2017,1:8

    Google Scholar 

  3. Liu YC, Nguyen PA, Humayun A, et al. Does long-term use of antidiabetic drugs changes cancer risk? Medicine, 2019,98(40):e17461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochem J, 2015,471:307–322

    Article  CAS  PubMed  Google Scholar 

  5. Petrie JR, Rossing PR, Campbell IW. Metformin and cardiorenal outcomes in diabetes: A reappraisal. Diabetes Obes Metab, 2020,22(6):904–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pratley RE, Salsali A. Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin, 2007,23(4):919–931

    Article  CAS  PubMed  Google Scholar 

  7. Croxtall JD, Keam SJ. Vildagliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs, 2008,68(16):2387–2409

    Article  CAS  PubMed  Google Scholar 

  8. Tahrani AA, Piya MK, Barnett AH. Drug evaluation: vildagliptin-metformin single-tablet combination. Adv Ther, 2009,26(2):138–154

    Article  CAS  PubMed  Google Scholar 

  9. Louveaux J, Maurizio A, Vorwohl G. Methods of melissopalynology. Bee World, 2015,59(4):139–157

    Article  Google Scholar 

  10. Onbaşli D, Çelik YG, Kahraman S, et al. Apitherapy and Effect on Human Health. J Erciyes Univ Faculty Veterinary Med, 2019,16(1):49–56

    Google Scholar 

  11. Samarghandian S, Farkhondeh T, Samini F. Honey and Health: A Review of Recent Clinical Research. Pharmacognosy Res, 2017,9(2):121–127

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ulbricht C, Conquer J, Giese N, et al. An evidencebased systematic review of bee pollen by the natural standard research collaboration. J Dietary Suppl, 2005,6(3):290–312

    Article  Google Scholar 

  13. Bankova V, Popova M, Bodganov S, et al. Chemical composition of european propolis: Expected and unexpected results. Z Naturforschung, 2002,57(5–6):530–533

    Article  CAS  Google Scholar 

  14. Nagai T, Sakai M, Inoue R, et al. Antioxidative activities of some commercially honeys, royal jelly, and propolis. Food Chem, 2001,75:237–240

    Article  CAS  Google Scholar 

  15. Fatrcová-Šramková K, Nôzková J, Kačániová M, et al. Antioxidant and antimicrobial properties of monofloral bee pollen. J Environ Sci Health Part B, 2013,48:133–138

    Article  Google Scholar 

  16. Yaghoobi R, Kazerouni A, Kazerouni O. Evidence for clinical use of honey in wound healing as an antibacterial, anti-inflammatory anti-oxidant and antiviral agent: A review. Jundishapur J Nat Pharm Prod, 2013,8:100–104

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ajibola A, Chamunorwa PJ, Erlwanger HK. Nutraceutical values of natural honey and its contribution to human health and wealth. Nutr Metab (Lond), 2012,9:61

    Article  PubMed  Google Scholar 

  18. Khalil MI, Sulaiman SA. The potential role of honey and its polyphenols in preventing heart diseases: A review. Afr J Tradit Complement Altern Med, 2010,7:315–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Akanmu MA, Olowookere TA, Atunwa SA, et al. Neuropharmacological effects of Nigerian honey in mice. Afr J Tradit Complement Altern Med, 2011,8(3):230–249

    Article  PubMed  PubMed Central  Google Scholar 

  20. Senyuk B, Boreyko L, Yurnyuk S. Correction of clinical and biochemical parameters using bee pollen in patients with diabetes. Unity Sci Int Sci Period J, 2016,4:137–139

    Google Scholar 

  21. Fuliang HU, Hepburn HR, Xuan H, et al. Effects of propolis on blood glucose, blood lipid and free radicals in rats with diabetes mellitus. Pharmacol Res, 2005,51(2):147–152

    Article  CAS  PubMed  Google Scholar 

  22. Murata K, Yatsunami K, Fukuda E, et al. Antihyperglycemic effects of propolis mixed with mulberry leaf extract on patients with type 2 diabetes. Altern Therap Health Med, 2004,10:78–79

    Google Scholar 

  23. Giovannucci E, Harlan DM, Archer MA, et al. Diabetes and cancer: a consensus report. Diabetes Care, 2010,33:1674–1685

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dankner R, Roth J. More recent, better designed studies have weakened links between antidiabetes medications and cancer risk. Diabet Med, 2020,37(2):194–202

    Article  CAS  PubMed  Google Scholar 

  25. Wild SH. Diabetes, treatments for diabetes and their effect on cancer incidence and mortality: attempts to disentangle the web of associations. Diabetologia, 2011,54(7):1589–1592

    Article  CAS  PubMed  Google Scholar 

  26. Gul OO, Cinkilic N, Gul CB, et al. Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: A cross-sectional, observational pilot study. Mutat Res, 2013,757:31–35

    Article  PubMed  Google Scholar 

  27. Zhu B, Qu S. The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms. Front Endocrinol (Lausanne), 2022,11(13):800995

    Article  Google Scholar 

  28. Maddika S, Ande RS, Panigrahi S, et al. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist Updates, 2007,10:13–29

    Article  CAS  Google Scholar 

  29. Colquhoun AJ, Venier NA, Vandersluis AD, et al. Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer Prostatic Dis, 2012,15:346–352

    Article  CAS  PubMed  Google Scholar 

  30. Zhuang Y, Miskimins WK. Metformin induces both caspase-dependent and poly (ADP-ribose) polymerase-dependent cell death in breast cancer cells. Mol Cancer Res, 2011,9(5):603–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Will MA, Palaniappan M, Peegel H, et al. Metformin: Direct inhibition of rat ovarian theca-interstitial cell proliferation. Fertil Steril, 2012,98(1):207–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Amritha CA, Kumaravelu P, Chellathai DD. Evaluation of Anti Cancer Effects of DPP-4 Inhibitors in Colon Cancer–An Invitro Study. J Clin Diagn Res, 2015,9(12):14–16

    Google Scholar 

  33. Kasurga CB, Elbistan M, Atmaca A, et al. In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin. Cytotechnology, 2019,71:1063–1077

    Google Scholar 

  34. Assessment Report European Medicines Agency. 20 September 2012. Available at: https://www.ema.europa.eu. Accessed 10 July 2022.

  35. Aghdai HM, Jamshidzadeh A, Nematizadeh M, et al. Evaluating the Effects of Dithiothreitol and Fructose on Cell Viability and Function of Cryopreserved Primary Rat Hepatocytes and HepG2 Cell Line. Hepat Mon, 2013,13(1):e7824

    Article  PubMed  PubMed Central  Google Scholar 

  36. Mao X, Yang Q, Chen D, et al. Benzoic Acid Used as Food and Feed Additives Can Regulate Gut Functions. BioMed Res Int, 2019,26:5721585

    Google Scholar 

  37. Anantharaju PG, Reddy BD, Padukudru MA, et al. Naturally occurring benzoic acid derivatives retard cancer cell growth by inhibiting histone deacetylases (HDAC). Cancer Biol Ther, 2017,18(7):492–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cuzzocre S, Costantino G, Mazzon E, et al. Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in zymosan-induced shock. Br J Pharmacol, 1999,128(6):1241–1251

    Article  Google Scholar 

  39. Almeida IT, Cortez-Pinto H, Fidalgo G, et al. Plasma total and free fatty acids composition in human nonalcoholic steatohepatitis. Clin Nutr, 2022,21:219–223

    Article  Google Scholar 

  40. Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes, 2011,18:139–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sampath H, Ntambi JM. The fate and intermediary metabolism of stearic acid. Lipids, 2005,40(2):1187–1191

    Article  CAS  PubMed  Google Scholar 

  42. Sawicka D, Car H, Borawska MH, et al. The anticancer activity of propolis. Folia Histochem Cytobiol, 2012,50(1):25–37

    Article  CAS  PubMed  Google Scholar 

  43. Tapani E, Taavitsainen M, Lindros K, et al. Toxicity of ethanol in low concentrations. Acta Radiol, 1996,37:923–926

    Article  CAS  PubMed  Google Scholar 

  44. Lay-flurrie K. Honey in wound care: Effects, clinical application and patient benefit. Br J Nurs, 2008,17(30):32–36

    Google Scholar 

  45. Popova M, Silici S, Kaftanoglu O, et al. Antibacterial activity of Turkish propolis and its qualitative and quantitative chemical composition. Phytomedicine, 2005,12(3):221–228

    Article  CAS  PubMed  Google Scholar 

  46. Silici S, Kutluca S. Chemical composition and antibacterial activity of propolis collected by three different races of honeybees in the same region. J Ethnopharmacol, 2005,99(1):69–73

    Article  CAS  PubMed  Google Scholar 

  47. Bobis O, Mărghitaş LA, Dezmirean D, et al. Quality Parameters and Nutritional Value of Different Commercial Bee Products. Bull Univ Agric Sci Vet Med Cluj-Napoca Anim Sci Biotechnol, 2010,67:1–2

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Faculty of Medicine, Ordu University, Ordu, 52200, Turkey

    Özlem Özdemir

  2. Department of Molecular Biology and Genetics, Faculty of Sciences and Letters, Ordu University, Ordu, 52200, Turkey

    Zinet Çöl & Ömer Ertürk

Authors
  1. Özlem Özdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zinet Çöl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ömer Ertürk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Özlem Özdemir.

Ethics declarations

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

This study was funded by Ordu University Scientific Project Coordination Department (ODUBAP, No. B-2139).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Özdemir, Ö., Çöl, Z. & Ertürk, Ö. Efficacy of Bee Products (Anzer Honey, Pollen and Propolis) in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells: Cytotoxic, Genotoxic and Biochemical Studies. CURR MED SCI 43, 1173–1182 (2023). https://doi.org/10.1007/s11596-023-2812-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-023-2812-8

Key words

Search

Navigation