Home Allium jesdianum hydro alcoholic extract ameliorates diabetic nephropathy by suppressing connective tissue growth factor (CTGF) and receptor for advanced glycation endproducts (RAGE) gene expression in diabetic rats with streptozotocin
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Allium jesdianum hydro alcoholic extract ameliorates diabetic nephropathy by suppressing connective tissue growth factor (CTGF) and receptor for advanced glycation endproducts (RAGE) gene expression in diabetic rats with streptozotocin

  • Mona Alaee , Jamal Amri , Hadi Karami , Seyed Amirhossein Latifi , Zahra Salemi and Mehdi Salehi EMAIL logo
Published/Copyright: May 20, 2021
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 42 Issue 2

Abstract

Objectives

Diabetic nephropathy is one of the major complications of diabetes, the use of medicinal plants is increasing due to fewer side effects. This study was designed to examine antidiabetic effects of Allium jesdianum (A. jesdianum) ethanolic extract and evaluate its effects on oxidative stress markers and the expression of connective tissue growth factor (CTGF) and receptor for advanced glycation endproducts (RAGE) genes in the kidney of type 1 diabetic rats.

Methods

In this study, we randomly divided 24 rats into four groups with six rats in each group as follows: Cnt group: normal control receiving normal saline, Dibt group: diabetic control receiving normal saline daily, Dibt + A. jesdianum 250 group: diabetic rats receiving A. jesdianum at a dose of 250 mg/kg bw daily, Dibt + A. jesdianum 500 group: diabetic rats receiving A. jesdianum at a dose of 500 mg/kg bw daily. To induce diabetes, we used 55 mg/kg bw dose of streptozotocin intraperitoneally. The concentration of fasting blood glucose (FBG) and serum urea, creatinine and albumin, SOD, MDA (using spectrophotometric methods) and gene expression of CTGF and RAGE in kidney tissue (using real-time PCR methods) were quantified in the diabetic rats that received A. jesdianum for 42 days, and were compared to control rats.

Results

The results showed that in the diabetic group the FBG and serum urea, creatinine and expression of kidney CTGF and RAGE genes and the levels of SOD and MDA significantly increased and serum albumin significantly decreased compared to the Cnt group (p<0.001). Administration of A. jesdianum significantly improved the FBG and serum urea, creatinine and albumin compared to Dibt group (p<0.05). It was shown the A. jesdianum significantly decrease the kidney expression levels of CTGF and RAGE genes and improve oxidative stress (increased SOD and decreased MDA) in the kidney tissues when compared to Dibt group (p<0.001). Also, it was found that the beneficial effects of the A. jesdianum were dose-dependent.

Conclusions

The results of this study showed that administration of A. jesdianum for 42 days has beneficial anti-diabetic and anti-nephropathic effects in diabetic rats and can be used as an adjunct therapy in the treatment of diabetes.

Keywords: Allium jesdianum; CTGF; diabetic nephropathy; oxidative stress; RAGE
Corresponding author: Mehdi Salehi, Member of Traditional and Complementary Medicine Research Center, Faculty of Medicine, Arak University of Medical Sciences, Arak, 3848176941, I.R. Iran, Phone: +98 8634173505 (436), Fax: +98 8634173521, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Animal procedures were carried out considering the Guide for the Care and Use of Laboratory that approved by the Committee on Animal Research of Arak University of Medical Sciences. The grant number was 3485.

References

1. Lim, AK. Diabetic nephropathy-complications and treatment. Int J Nephrol Renovasc Dis 2014;7:361–81. https://doi.org/10.2147/ijnrd.s40172.Search in Google Scholar

2. Yee, J. Diabetic kidney disease: chronic kidney disease and diabetes. Diabetes Spectr 2008;21:8. https://doi.org/10.2337/diaspect.21.1.8.Search in Google Scholar

3. Dabla, PK. Renal function in diabetic nephropathy. World J Diabetes 2010;1:48–56. https://doi.org/10.4239/wjd.v1.i2.48.Search in Google Scholar PubMed PubMed Central

4. Kashihara, N, Haruna, Y, Kondeti, VK, Kanwar, YS. Oxidative stress in diabetic nephropathy. Curr Med Chem 2010;17:4256–69. https://doi.org/10.2174/092986710793348581.Search in Google Scholar PubMed PubMed Central

5. Mason, RM. Connective tissue growth factor (CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it? J Cell Commun Signal 2009;3:95–104. https://doi.org/10.1007/s12079-009-0038-6.Search in Google Scholar PubMed PubMed Central

6. Wang, S, Li, B, Li, C, Cui, W, Miao, L. Potential renoprotective agents through inhibiting CTGF/CCN2 in diabetic nephropathy. J Diabetes Res 2015;2015:962383. https://doi.org/10.1155/2015/962383.Search in Google Scholar PubMed PubMed Central

7. Sanajou, D, Ghorbani Haghjo, A, Argani, H, Aslani, S. AGE-RAGE axis blockade in diabetic nephropathy: current status and future directions. Eur J Pharmacol 2018;833:158–64. https://doi.org/10.1016/j.ejphar.2018.06.001.Search in Google Scholar PubMed

8. Singh, VP, Bali, A, Singh, N, Jaggi, AS. Advanced glycation end products and diabetic complications. Kor J Physiol Pharmacol 2014;18:1–14. https://doi.org/10.4196/kjpp.2014.18.1.1.Search in Google Scholar PubMed PubMed Central

9. Yamagishi, S-I, Matsui, T. Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev 2010;3:101–8. https://doi.org/10.4161/oxim.3.2.11148.Search in Google Scholar PubMed PubMed Central

10. Ott, C, Jacobs, K, Haucke, E, Navarrete Santos, A, Grune, T, Simm, A. Role of advanced glycation end products in cellular signaling. Redox Biol 2014;2:411–29. https://doi.org/10.1016/j.redox.2013.12.016.Search in Google Scholar PubMed PubMed Central

11. Rines, AK, Sharabi, K, Tavares, CDJ, Puigserver, P. Targeting hepatic glucose metabolism in the treatment of type 2 diabetes. Nat Rev Drug Discov 2016;15:786–804. https://doi.org/10.1038/nrd.2016.151.Search in Google Scholar

12. Ekor, M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 2014;4:177. https://doi.org/10.3389/fphar.2013.00177.Search in Google Scholar

13. Marrelli, M, Amodeo, V, Statti, G, Conforti, F. Biological properties and bioactive components of Allium cepa L.: focus on potential benefits in the treatment of obesity and related comorbidities. Molecules 2018;24:119. https://doi.org/10.3390/molecules24010119.Search in Google Scholar

14. Kim, S, Kim, DB, Jin, W, Park, J, Yoon, W, Lee, Y, et al.. Comparative studies of bioactive organosulphur compounds and antioxidant activities in garlic (Allium sativum L.), elephant garlic (Allium ampeloprasum L.) and onion (Allium cepa L.). Nat Prod Res 2018;32:1193–7. https://doi.org/10.1080/14786419.2017.1323211.Search in Google Scholar

15. Sohrabinezhad, Z, Dastan, D, Asl, SS, Nili-Ahmadabadi, A. Allium jesdianum extract improve acetaminophen-induced hepatic failure through inhibition of oxidative/nitrosative stress. J Pharmacopuncture 2019;22:239–47. https://doi.org/10.3831/KPI.2019.22.032.Search in Google Scholar

16. Mehrabadi, ME, Salemi, Z, Babaie, S, Panahi, M. Effect of biochanin A on retina levels of vascular endothelial growth factor, tumor necrosis factor-alpha and interleukin-1beta in rats with streptozotocin-induced diabetes. Can J Diabetes 2018;42:639–44. https://doi.org/10.1016/j.jcjd.2018.03.008.Search in Google Scholar

17. Nasiri, A, Ziamajidi, N, Abbasalipourkabir, R, Goodarzi, MT, Saidijam, M, Behrouj, H, et al.. Beneficial effect of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of type 1 diabetic rats. Indian J Clin Biochem 2017;32:329–36. https://doi.org/10.1007/s12291-016-0621-6.Search in Google Scholar

18. Ghasemi, H, Einollahi, B, khiripour, N, Hosseini-Zijoud, S-R, Farhadiannezhad, M. Protective effects of curcumin on diabetic nephropathy via attenuation of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) expression and alleviation of oxidative stress in rats with type 1 diabetes. Iran J Basic Med Sci 2019;22:376–83. https://doi.org/10.22038/ijbms.2019.31922.7674.Search in Google Scholar

19. Oyedemi, SO, Adewusi, EA, Aiyegoro, OA, Akinpelu, DA. Antidiabetic and haematological effect of aqueous extract of stem bark of Afzelia africana (Smith) on streptozotocin-induced diabetic Wistar rats. Asian Pac J Trop Biomed 2011;1:353–8. https://doi.org/10.1016/S2221-1691(11)60079-8.Search in Google Scholar

20. Alaee, M, Akbari, A, Karami, H, Salemi, Z, Amri, J, Panahi, M. Antidiabetic and protective effects of Scrophularia striata ethanolic extract on diabetic nephropathy via suppression of RAGE and S100A8 expression in kidney tissues of streptozotocin-induced diabetic rats. J Basic Clin Physiol Pharmacol 2020;31. https://doi.org/10.1515/jbcpp-2019-0186.Search in Google Scholar PubMed

21. Roh, S-S, Kwon, OJ, Yang, JH, Kim, YS, Lee, SH, Jin, J-S, et al.. Allium hookeri root protects oxidative stress-induced inflammatory responses and β-cell damage in pancreas of streptozotocin-induced diabetic rats. BMC Complement Altern Med 2016;16:63. https://doi.org/10.1186/s12906-016-1032-1.Search in Google Scholar PubMed PubMed Central

22. Zolfaghari, B, Shokoohinia, Y, Ramezanlou, P, Sadeghi, A, Mahmoudzadeh, M, Minaiyan, M. Effects of methanolic and butanolic fractions of Allium elburzense Wendelbo bulbs on blood glucose level of normal and STZ-induced diabetic rats. Res Pharm Sci 2012;7:201–7.Search in Google Scholar

23. Chang, W-C, Wu, JS-B, Chen, C-W, Kuo, P-L, Chien, H-M, Wang, Y-T, et al.. Protective effect of vanillic acid against hyperinsulinemia, hyperglycemia and hyperlipidemia via alleviating hepatic insulin resistance and inflammation in high-fat diet (HFD)-Fed rats. Nutrients 2015;7:9946–59. https://doi.org/10.3390/nu7125514.Search in Google Scholar PubMed PubMed Central

24. Matboli, M, Eissa, S, Ibrahim, D, Hegazy, MGA, Imam, SS, Habib, EK. Caffeic acid attenuates diabetic kidney disease via modulation of autophagy in a high-fat diet/streptozotocin- induced diabetic rat. Sci Rep 2017;7:2263. https://doi.org/10.1038/s41598-017-02320-z.Search in Google Scholar PubMed PubMed Central

25. Yusuf, M, Nasiruddin, M, Sultana, N, Akhtar, J, Khan, MI, Ahmad, M. Regulatory mechanism of caffeic acid on glucose metabolism in diabetes. Res J Pharm Technol 2019;12:4735–40. https://doi.org/10.5958/0974-360x.2019.00816.3.Search in Google Scholar

26. Asmat, U, Abad, K, Ismail, K. Diabetes mellitus and oxidative stress-a concise review. Saudi Pharmaceut J 2016;24:547–53. https://doi.org/10.1016/j.jsps.2015.03.013.Search in Google Scholar PubMed PubMed Central

27. Matough, FA, Budin, SB, Hamid, ZA, Alwahaibi, N, Mohamed, J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J 2012;12:5–18. https://doi.org/10.12816/0003082.Search in Google Scholar PubMed PubMed Central

28. Ni, Z, Guo, L, Liu, F, Olatunji, OJ, Yin, M. Allium tuberosum alleviates diabetic nephropathy by supressing hyperglycemia-induced oxidative stress and inflammation in high fat diet/streptozotocin treated rats. Biomed Pharmacother 2019;112:108678. https://doi.org/10.1016/j.biopha.2019.108678.Search in Google Scholar PubMed

29. Beretta, HV, Bannoud, F, Insani, M, Berli, F, Hirschegger, P, Galmarini, CR, et al.. Relationships between bioactive compound content and the antiplatelet and antioxidant activities of six allium vegetable species. Food Technol Biotechnol 2017;55:266–75. https://doi.org/10.17113/ftb.55.02.17.4722.Search in Google Scholar PubMed PubMed Central

30. Andersen, S, van Nieuwenhoven, FA, Tarnow, L, Rossing, P, Rossing, K, Wieten, L, et al.. Reduction of urinary connective tissue growth factor by Losartan in type 1 patients with diabetic nephropathy. Kidney Int 2005;67:2325–9. https://doi.org/10.1111/j.1523-1755.2005.00337.x.Search in Google Scholar PubMed

31. Gojo, A, Utsunomiya, K, Taniguchi, K, Yokota, T, Ishizawa, S, Kanazawa, Y, et al.. The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats. Eur J Pharmacol 2007;568:242–7. https://doi.org/10.1016/j.ejphar.2007.04.011.Search in Google Scholar PubMed

32. Han, KH, Kang, YS, Han, SY, Jee, YH, Lee, MH, Han, JY, et al.. Spironolactone ameliorates renal injury and connective tissue growth factor expression in type II diabetic rats. Kidney Int 2006;70:111–20. https://doi.org/10.1038/sj.ki.5000438.Search in Google Scholar PubMed

33. Li, G-S, Jiang, W-L, Yue, X-D, Qu, G-W, Tian, J-W, Wu, J, et al.. Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro. Planta Med 2009;75:1470–5. https://doi.org/10.1055/s-0029-1185802.Search in Google Scholar PubMed

Received: 2020-09-24
Accepted: 2021-01-19
Published Online: 2021-05-20

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hmbci-2020-0072
Keywords for this article
Allium jesdianum; CTGF; diabetic nephropathy; oxidative stress; RAGE

Articles in the same Issue

  1. Frontmatter
  2. Special Section: "Progestogen-only pill and its therapeutic indications and effects"; Guest Editors: Adolf E- Schindler and René Druckmann
  3. Original Articles
  4. Peritoneal fluid biomarkers in patients with endometriosis: a cross-sectional study
  5. Safety, influence on the endometrium, sonographic changes and bleeding profile after 13 cycles with the new drospirenone only pill (DOP) for contraception
  6. Review Articles
  7. A progestin isn’t a progestin: dienogest for endometriosis as a blueprint for future research – Review as a contribution for discussion -
  8. Progestogens in luteal support
  9. Mini Review
  10. Progestogen-only pills: which progestogen would be ideal
  11. Regular Issue
  12. Original Articles
  13. Outcomes of surgical and/or medical treatment in patients with prolactinomas during long-term follow-up: a retrospective single-centre study
  14. PPARGC1A promoter DNA-methylation level and glucose metabolism in Ecuadorian women with Turner syndrome
  15. Allium jesdianum hydro alcoholic extract ameliorates diabetic nephropathy by suppressing connective tissue growth factor (CTGF) and receptor for advanced glycation endproducts (RAGE) gene expression in diabetic rats with streptozotocin
  16. Changes in serum levels of Apo AIV in patients with newly diagnosed hyperthyroidism and hypothyroidism: a preliminary study
  17. The study of ischemia modified albumin as an early biomarker of epilepsy in adolescent population: a cross-sectional study
  18. Short Communications
  19. The effect of water-based rhythmic exercise training on glucose homeostasis and thyroid hormones in postmenopausal women with metabolic syndrome
  20. Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome
  21. Case Report
  22. A rare association of two endocrine tumours: non-functional oncocytic adrenocortical carcinoma and Papillary thyroid carcinoma
  23. Mini Review
  24. Vitamin D and new insights into pathophysiology of type 2 diabetes
  25. Review Articles
  26. Sex steroids-induced neurogenesis in adult brain: a better look at mechanisms and mediators
  27. Genetic variants and risk of thyroid cancer among Iranian patients
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