Investigation of the Antidiabetic Effects of Bee Bread (Perga) in Diabetic Rats: A Histopathological, Immunohistochemical, and Biochemical Study

Öz

Diabetes mellitus is a major public health concern. Bee bread (Perga), rich in bioactive compounds, has gained attention in apitherapy for its potential therapeutic properties. This study aimed to investigate the antidiabetic potential of bee bread in streptozotocin (STZ)-induced diabetic rats through histopathological, immunohistochemical, and biochemical analyses. A total of 40 male Wistar albino rats were randomly divided into five groups: Control, perga (0.5 g/kg), diabetes (STZ, 55 mg/kg), diabetes+perga (STZ, 55 mg/kg+perga, 0.5 g/kg), and diabetes+acarbose (STZ, 55 mg/kg+acarbose, 20 mg/kg). Experimental diabetes was induced by a single intraperitoneal STZ injection. Perga and acarbose were administered daily via oral gavage throughout the experiment. Blood glucose levels were monitored periodically from tail vein samples. Pancreatic tissues were examined histopathologically and immunohistochemically. Serum levels of ALT, AST, ALP, LDH, total cholesterol, triglyceride, creatinine, urea, and glucose were analyzed using an automated analyzer with commercial kits. STZ administration resulted in marked pancreatic damage and a significant decrease in insulin expression. Biochemical analyses revealed notable diabetes-related alterations. Perga treatment partially alleviated hyperglycemia, improved pancreatic histopathology, and enhanced insulin immunoexpression. However, adverse alterations in liver enzyme levels were observed in the Perga-treated diabetic group. These findings suggest that bee bread may exert only limited antidiabetic effects in STZ-induced experimental diabetes. Nevertheless, the observed hepatic effects warrant further comprehensive studies to clarify the safety and efficacy of bee bread as an antidiabetic agent.

Anahtar Kelimeler

• Bee Bread (Perga)
• Diabetes Mellitus
• Streptozotocin (STZ)
• Antidiabetic Effect
• Histopathology
• Immunohistochemistry

Diyabetik Sıçanlarda Arı Ekmeğinin (Perga) Antidiyabetik Etkilerinin Araştırılması: Histopatolojik, İmmünohistokimyasal ve Biyokimyasal Bir Çalışma

Öz

Diabetes mellitus, önemli bir halk sağlığı sorunu olarak öne çıkmaktadır. Biyoaktif bileşenler açısından zengin olan arı ekmeği (Perga), apiterapide potansiyel tedavi edici etkileri nedeniyle ilgi görmektedir. Bu çalışmada, streptozotosin (STZ) ile oluşturulan deneysel diyabet modelinde arı ekmeğinin antidiyabetik potansiyelinin histopatolojik, immünohistokimyasal ve biyokimyasal olarak değerlendirilmesi amaçlanmıştır. Çalışmada 40 adet erkek Wistar albino sıçanı rastgele beş gruba ayrılmıştır: Kontrol, perga (0.5 g/kg), diyabet (STZ, 55 mg/kg), diyabet+perga (STZ, 55 mg/kg+perga, 0.5 g/kg) ve diyabet+akarboz (STZ, 55 mg/kg+akarboz, 20 mg/kg). Diyabet, tek doz STZ enjeksiyonu ile indüklenmiştir. Perga ve akarboz uygulamaları deney süresi boyunca günlük olarak gastrik gavaj yöntemiyle gerçekleştirilmiştir. Deney süresince belirli aralıklarla kuyruk veninden kan glukoz düzeyleri ölçülmüş; deney sonunda pankreas dokuları histopatolojik ve immünohistokimyasal olarak incelenmiştir. Serumda ALT, AST, ALP, LDH, total kolesterol, trigliserid, kreatinin, üre ve glukoz düzeyleri otoanalizör ve ticari kitler kullanılarak analiz edilmiştir. STZ uygulaması, pankreas dokusunda belirgin histopatolojik lezyonlara ve immunohistokimyasal olarak insülin ekspresyonunda anlamlı azalmaya yol açmıştır. Biyokimyasal analizlerde diyabete bağlı olarak önemli değişiklikler gözlenmiştir. Perga uygulaması, hiperglisemiyi kısmen baskılayarak kan glukoz düzeylerinde azalma sağlamış; pankreatik histopatolojik bulgularda ve insülin immunekspresyonunda iyileştirici etkiler göstermiştir. Ancak, perga ile tedavi grubunda karaciğer enzim düzeylerinde olumsuz değişiklikler saptanmıştır. Elde edilen bulgular, perganın STZ ile oluşturulan deneysel diyabet modelinde yalnızca sınırlı antidiyabetik etkiler gösterebileceğini ortaya koymaktadır. Bununla birlikte, karaciğer üzerine gözlemlenen etkiler dikkate alındığında, perganın antidiyabetik etkinliğinin ve güvenirliliğinin daha ileri çalışmalarla desteklenmesi gerekmektedir.

Anahtar Kelimeler

• Arı Ekmeği (Perga)
• Diabetes Mellitus
• Streptozotosin (STZ)
• Antidiyabetik Etki
• Histopatoloji
• İmmünohistokimya

Kaynakça

1. Aboulghazi A, Fadil M, Touzani S, et al (2024). Phenolic screening and mixture design optimization for in vitro assessment of antioxidant and antimicrobial activities of honey, propolis, and bee pollen. J Food Biochem, 2024(1), 8246224.
2. Ahrens B (2011). Antibodies in metabolic diseases. New biotechnology, 28(5), 530-537.
3. Aksoy A, Altunatmaz SS, Aksu F et al. (2024). Bee bread as a functional product: phenolic compounds, amino acid, sugar, and organic acid profiles. Foods, 13(5), 795.
4. Almdal TP, Vilstrup H (1988). Strict insulin therapy normalises organ nitrogen contents and the capacity of urea nitrogen synthesis in experimental diabetes in rats. Diabetologia, 31, 114-118.
5. Alvarez JF, Barbera A, Nadal B, et al (2004). Stable and functional regeneration of pancreatic beta-cell population in n-STZ rats treated with tungstate. Diabetologia, 47, 470-477.
6. Borycka K, Grabek-Lejko D, Kasprzyk I (2015). Antioxidant and antibacterial properties of commercial bee pollen products. J Apic Res, 54, 1-12.
7. Calcutt N, Cooper M, Kern T, Schmidt AM (2009). Therapies for hyperglycaemia- induced diabetic complications: from animal models to clinical trials. Nat Rev Dru Discov, 8(5), 417-429.
8. Ceriello A, Morocutti A, Franceschina M, et al (2000). Defective intracellular Antioxidant Enzyme Production in Type 1 Diabetic Patients with Nephropathy. Am Diabetes Assoc. 49(12), 2170-2177.

9. Doğan A, Çelik İ (2016). Healing effects of sumac (Rhus coriaria) in streptozotocin-induced diabetic rats. Pharm biol, 54(10), 2092-2102.
10. Dubsky M, Veleba J, Sojakova D, et al (2023). Endothelial dysfunction in diabetes mellitus: new insights. Int J Mol Sci, 24(13), 10705.
11. Fatrcová-Šramková K, Nôžková J, Kačániová M, et al (2013). Antioxidant and antimicrobial properties of monofloral bee pollen. J Environ Sci Health B, 48(2), 133-138.
12. Ijaola TO, Osunkiyesi AA, Taiwo AA, et al (2014). Antidiabetic effect of Ipomoea batatas in normal and alloxan-induced diabetic rats. IOSR-JAC, 7(5), 16-25.
13. Jin L, Xue HY, Jin LJ, Li SY, Xu YP (2008). Antioxidant and pancreas-protective effect of aucubin on rats with streptozotocin-induced diabetes. Eur J Pharmacol, 582(1-3), 162-167.
14. Kieliszek M, Piwowarek K, Kot AM et al (2018). Pollen and bee bread as new health-oriented products: A review. Trends Food Sci Technol, 71, 170-180.
15. Komosinska-Vassev K, Olczyk P, Kaźmierczak J, Mencner L, Olczyk K (2015). Bee pollen: chemical composition and therapeutic application. Evid Based Complement Alternat Med, 2015(1), 297425.
16. Kosedag M, Gulaboglu M (2023). Pollen and bee bread expressed highest anti-inflammatory activities among bee products in chronic inflammation: an experimental study with cotton pellet granuloma in rats. Inflammopharmacology, 31, 1967-1975.
17. Lenzen S (2008). The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia, 51(2), 216-226.
18. Markiewicz-Zukowska R, Naliwajko SK, Bartosiuk E et al (2013). Chemical composition and antioxidant activity of beebread, and its influence on the glioblastoma cell line (U87MG). J Apic Sci, 57(2), 147.
19. Nagai T, Nagashima T, Suzuki N, Inoue, R (2005). Antioxidant activity and angiotensin I–converting enzyme inhibition by enzymatic hydrolysates from bee bread. Zeitschrift für Naturforschung C, 60(1-2), 133–138.
20. Oguntibeju OO (2019a). Hypoglycaemic and anti-diabetic activity of selected African medicinal plants. Int J Physiol Pathophysiol Pharmacol, 11(6), 224-237.
21. Oguntibeju OO (2019b). Type 2 diabetes mellitus, oxidative strees and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol, 11(3), 45–63.
22. Ohkuwa T, Sato Y, Naoi M (1995). Hydroxyl radical formation in diabetic ratöinduced by streptozotocin. Life Sci, 56, 1789-1798.
23. Poretsky L (2010). Principles of Diabetes Mellitus. 2nd ed., Springer, Boston, MA, USA.
24. Sobral F, Calhelha RC, Barros L et al (2017). Flavonoid Composition and Antitumor Activity of Bee Bread Collected in Northeast Portugal. Molecules, 22, 248.
25. Szkudelski T (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res, 50(6), 537-546.
26. Viuda-Martos M, Ruiz-Navajas Y, Fernández-López J et al (2008). Functional properties of honey, propolis, and royal jelly. J Food Sci, 73(9), R117-R124.
27. Yaman T, Doğan A (2016). Streptozotosin ile diyabet oluşturulan sıçanlarda meşe palamudu (Quercus branti Lindl.) ekstraktların karaciğer ve pankreası koruyucu etkileri. Dicle Üniv Vet Fak Der, 1(2), 7-15.
28. Yaman T, Kömüroğlu, AU (2018). Effects of Juniperus communis L. Oil on Nephropathy in Experimental Diabetic Rats. Harran Üniv Vet Fak Derg, 7(2), 192-199.
29. Yaman T, Uyar A, Celik I et al (2017). Histopathological and immunohistochemical study of antidiabetic effects of Heracleum persicum extract in experimentally diabetic rats. IJPER, 51(3), 450-457.
30. Yazdi H (2019). Liver dysfunction and oxidative stress in streptozotocin-induced diabetic rats: protective role of Artemisia turanica. J Pharmacopuncture, 22(2), 109.
31. Zakaria Z, Othman ZA, Suleiman JB (2021). Hepatoprotective effect of bee bread in metabolic dysfunction-associated fatty liver disease (MAFLD) rats: Impact on oxidative stress and inflammation. Antioxidants, 10(12), 2031.