The possible benefits of Garcinia kola and curcumin on diabetes-induced aorta damage in the male rats with transected sciatic nerve: An experimental study

Öz

Background: The aim of this study is to evaluate the degenerative effects of diabetes on the aorta and the potential therapeutic advantages of herbal agents halting the progression of diabetes, using morphoquantitative, light, and electron microscopy, and immunohistochemical methods. In diabetic rats with sciatic nerve transection, severe systemic inflammation can lead to significant changes in vascular morphology. Therefore, it was hypothesized that the combination of neuropathic pain and diabetes would create a more clinically significant pathophysiological picture. Methods: The study groups consisted of 35 randomly selected Wistar albino rats: Healthy control group (Cont) (n=7), Sham that underwent the operation (n=7), Diabetes mellitus group induced by streptozotocin (DM) (n=7), diabetes treated with 200 mg/kg/day Garcinia kola (GK) (DM+GK) (n=7), and 300 mg/kg/day Curcumin (Cur) is administered to treat diabetes in the DM+Cur group (n=7). A neuropathic pain model was induced by performing a vein graft after sciatic nerve incision in all groups except the control group. 50 mg/kg (a single dose) of streptozotocin has been used for the induction of diabetes. Histopathological, ultrastructural, and immunostaining for anti-caspase-3 and anti-VEGF-A were evaluated. Results: Degenerative changes were found in the diabetic aorta. Partial disruption of elastic fiber integrity in the tunica media was observed in the GK-treated group. Anti-caspase-3 positivity was intense in the DM rats. Anti-VEGF-A staining was low in the DM but higher in DM+Cur compared with DM+GK. The tunica media thickness decreased significantly in the DM and treatment groups compared to the Sham group. Conclusion: Diabetes damages aortic elastic fibers. Cur can induce anti-VEGF-A expression, which is reduced in diabetes. Both curcumin and GK inhibit diabetes-induced apoptosis, with Cur exerting a more substantial protective effect on the aorta.

Anahtar Kelimeler

• Aorta
• Apoptosis
• Curcumin
• Diabetes Mellitus
• Garcinia Kola

Etik Beyan

All experimental methods involving live animals used in the current study were approved by the Ondokuz Mayıs University Local Animal Experiments Ethics Committee (Approval number: 2019/49, date: October 22, 2019). Additionally, formal approval was obtained for the use of aortic cadaver tissues (Application number: 68489742-604.01.03-E.2607, dated January 31, 2020).

Kurkumin ve Garcinia Kola'nın diyabetik aort hasarı üzerindeki iyileştirici etkileri: Deneysel bir çalışma

Öz

Giriş: Bu çalışmanın amacı, diyabetin aort üzerindeki dejeneratif etkilerini ve terapötik bitkilerin diyabetin ilerlemesini durdurucu potansiyel terapötik avantajlarını, morfokantitatif, ışık ve elektron mikroskopi ile immünohistokimyasal yöntemler kullanarak değerlendirmektir. Siyatik sinir kesisi modeli oluşturulan diyabetik sıçanlarda gelişen şiddetli sistemik inflamasyon, vasküler morfolojide önemli değişikliklere yol açabilir. Bu nedenle, nöropatik ağrı modeli ile diyabet hastalığının birlikte klinik açıdan daha anlamlı bir patofizyolojik tablo oluşturacağı düşünülmüştür. Yöntemler: Çalışma grupları rastgele seçilmiş 35 Wistar albino sıçandan oluşmuştur: Sağlıklı kontrol grubu (Kont) (n=7), cerrahi kontrol grubu olan Sham grubu (n=7), streptozotosin ile indüklenen diyabet grubu (DM) (n=7), 200 mg/kg/gün Garcinia kola (GK) ile tedavi edilen diyabet grubu (DM+GK) (n=7) ve DM+Kur grubunda diyabeti tedavi etmek için 300 mg/kg/gün Kurkumin (Kur) uygulanan grup (n=7). Kontrol grubu hariç tüm gruplarda siyatik sinir insizyonundan sonra ven grefti uygulanarak nöropatik ağrı modeli oluşturulmuştur. Diyabet indüksiyonu için 50 mg/kg (tek doz) streptozotosin kullanılmıştır. Histopatolojik, ultrastrüktürel ve anti-kaspaz-3 ve anti-VEGF-A için immün boyama değerlendirilmiştir. Bulgular: Diyabetik aortada dejeneratif değişiklikler saptandı. GK ile tedavi edilen grupta tunika media'da elastik lif bütünlüğünde kısmi bozulma gözlemlendi. Anti-kaspaz-3 pozitifliği DM sıçanlarında yoğundu. Anti-VEGF-A boyaması DM grubunda düşük, ancak DM+Kur grubunda DM+GK grubuna kıyasla daha yüksekti. Tunika media kalınlığı, Sham grubuna kıyasla DM ve tedavi gruplarında anlamlı derecede azaldı. Sonuç: Diyabet, aortun elastik liflerine zarar verir. Kur, diyabette azalan anti-VEGF-A ekspresyonunu tetikleyebilir. Hem Kur hem de GK, diyabetin neden olduğu apoptozu inhibe eder; ancak Kur aort üzerinde daha belirgin bir koruyucu etki gösterir.

Anahtar Kelimeler

• Aort
• Apoptoz
• Kurkumin
• Diabetes Mellitus
• Garcinia Kola.

Kaynakça

1. 1.Glovaci D, Fan W, Wong ND. Epidemiology ofdiabetes mellitus and cardiovascular disease. CurrCardiol Rep 2019; 21(4): 21.
2. 2.American Diabetes A. Diagnosis and classificationof diabetes mellitus. Diabetes Care 2009; 32 (Suppl1): S62–7.
3. 3. Strain WD, Paldanius PM. Diabetes, cardiovasculardisease and the microcirculation. CardiovascDiabetol 2018; 17(1): 57.
4. 4.Petrie JR, Guzik TJ, Touyz RM. Diabetes,hypertension, and cardiovascular disease: clinicalinsights and vascular mechanisms. Can J Cardiol2018; 34 (5): 575–84.
5. 5.Beckman JA, Creager MA, Libby P. Diabetes andatherosclerosis: epidemiology, pathophysiology,and management. JAMA 2002; 287(19): 2570–81.
6. 6.Androulakis AE, Andrikopoulos GK, Kartalis AN, etal. Relation of coronary artery ectasia to diabetesmellitus. Am J Cardiol 2004; 93 (9): 1165–7.
7. 7.Lederle FA, Johnson GR, Wilson SE, et al. Theaneurysm detection and management studyscreening program - Validation cohort and finalresults. Arch Intern Med 2000; 160 (10): 1425–30.
8. 8.Chen XF, Wang JA, Lin XF, et al. Diabetes mellitus:is it protective against aortic root dilatation?Cardiology 2009; 112 (2): 138–43.

9. 9.Liu Y, Wei J, Ma KT, et al. Carvacrol protectsagainst diabetes-induced hypercontractility in theaorta through activation of the PI3K/Akt pathway.Biomed Pharmacother 2020; 125: 109825.
10. 10.Endemann DH, Schiffrin EL. Endothelialdysfunction. J Am Soc Nephrol 2004; 15 (8): 1983–92.
11. 11.Shibuya M. Vascular endothelial growth factor(VEGF) and its receptor (VEGFR) signaling inangiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2011; 2 (12):1097–105.
12. 12.Senger DR. Vascular endothelial growth factor:much more than an angiogenesis factor. Mol Biol Cell2010; 21(3): 377–9.
13. 13.Aggarwal BB, Sundaram C, Malani N, Ichikawa H.Curcumin: The Indian solid gold. Adv Exp Med Biol2007; 595: 1–75.
14. 14.Wang ME, Chen YC, Chen IS, et al. Curcuminprotects against thioacetamide-induced hepaticfibrosis by attenuating the inflammatory responseand inducing apoptosis of damaged hepatocytes. JNutr Biochem 2012; 23(10): 1352–66.
15. 15.Liu Y, Wang Y, Miao X, et al. Inhibition of JNK bycompound C66 prevents pathological changes of theaorta in STZ-induced diabetes. J Cell Mol Med 2014;18(6): 1203–12.
16. 16.Dehghan MH, Mirmiranpour H, Faghihi-KashaniS, et al. Inhibitory effect of curcumin on angiogenesis in a streptozotocin-induced diabetic rat model: Anaortic ring assay. J Tradit Complement Med 2016; 6(4): 437–41.
17. 17.Adaramoye OA. Antidiabetic effect of kolaviron,a biflavonoid complex isolated from Garcinia kolaseeds, in wistar rats. Afr Health Sci 2012; 12 (4):498–506.
18. 18.Hamour HM, Marangoz AH, Altun G, Kaplan S.Neuroprotective effects of Garcinia kola andcurcumin on diabetic transected sciatic nerve.Biomed Mater 2025; 20 (3).
19. 19.Lee HY, Kim SW, Lee GH, et al. Turmeric extractand its active compound, curcumin, protect againstchronic CCl4-induced liver damage by enhancingantioxidation. BMC Complement Altern Med 2016;16 (1): 316.
20. 20.Ajayi SA, Ofusori DA, Ojo GB, et al. Themicrostructural effects of aqueous extract ofGarcinia kola (Linn) on the hippocampus andcerebellum of malnourished mice. Asian Pac J TropBiomed 2011; 1 (4): 261–5.
21. 21.Oyagbemi AA, Omobowale TO, Olopade JO,Farombi EO. Kolaviron and Garcinia kola attenuatedoxorubicin-induced cardiotoxicity in Wistar rats. JComplement Integr Med 2017;15(1):/j/jcim.2018.15.issue-1/jcim-2016-0168/jcim-2016-0168.xml.
22. 22.Park J, Kim M, Sun K, et al. VEGF-A-expressingadipose tissue shows rapid beiging and enhancedsurvival after transplantation and confers IL-4-independent metabolic improvements. Diabetes2017; 66 (6): 1479–90.
23. 23.Kiguchi N, Kobayashi Y, Kadowaki Y, et al.Vascular endothelial growth factor signaling ininjured nerves underlies peripheral sensitization inneuropathic pain. J Neurochem 2014; 129 (1): 169–78.
24. 24.Laddha AP, Kulkarni YA. VEGF and FGF-2:Promising targets for the treatment of respiratorydisorders. Respir Med 2019;156: 33-46.
25. 25.Asselbergs FW, de Boer RA, Diercks GF, et al.Vascular endothelial growth factor: the link between cardiovascular risk factors and microalbuminuria?Int J Cardiol 2004; 93 (2-3): 211–5.
26. 26. Hovind P, Tarnow L, Oestergaard PB, Parving HH.Elevated vascular endothelial growth factor in type1 diabetic patients with diabetic nephropathy.Kidney Int Suppl 2000; 75: S56–61.
27. 27.Aiello LP, Wong JS. Role of vascular endothelialgrowth factor in diabetic vascular complications.Kidney Int Suppl 2000; 77: S113–9.
28. 28.Wang TY, Chen JX. Effects of Curcumin on Vesselformation insight into the pro- and antiangiogenesisof curcumin. Evid-Based Compl Alt 2019; 1390795.
29. 29.Muhammad A, Funmilola A, Aimola IA, et al.Kolaviron shows anti-proliferative effect and downregulation of vascular endothelial growth factor-Cand toll like receptor-2 in infected bloodlymphocytes. J Infect Public Heal 2017; 10 (5): 661–6.
30. 30.Barber AJ, Gardner TW, Abcouwer SF. Thesignificance of vascular and neural apoptosis to thepathology of diabetic retinopathy. InvestOphthalmol Vis Sci 2011; 52 (2): 1156–63.
31. 31.Li X, Fang Q, Tian X, et al. Curcumin attenuatesthe development of thoracic aortic aneurysm byinhibiting VEGF expression and inflammation. MolMed Rep. 2017; 16 (4): 4455–62.
32. 32.Lopresti AL. The problem of curcumin and itsbioavailability: could its gastrointestinal influencecontribute to its overall health-enhancing effects?Adv Nutr 2018; 9(1): 41-50.
33. 33.Akbarzadeh A, Norouzian D, Mehrabi MR, et al.Induction of diabetes by streptozotocin in rats.Indian J Clin Biochem 2007; 22(2): 60-4.
34. 34.Adaramoye OA, Adeyemi EO. Hypoglycaemic andhypolipidaemic effects of fractions from kolaviron, abiflavonoid complex from Garcinia Kola instreptozotocin-induced diabetes mellitus rats. JPharm Pharmacol 2006; 58(1):121-8.
35. 35.Testa R, Bonfigli AR, Prattichizzo F, et al. The"Metabolic Memory" theory and the early treatmentof hyperglycemia in prevention of diabeticcomplications. Nutrients 2017;9(5):437.