Antidiabetic and Protective Effects of Ferula assa-foetida L. oleo Gum Resin Ethanolic Extract on the Testis of Streptozotocin-Induced Diabetic Rats: A Histopathological Study

Document Type : Research Article

Authors

1 Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University, Mashhad, Iran.

2 Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University, Mashhad, Iran.

10.22067/ijvst.2024.85138.1317

Abstract

Diabetes is one of the most common metabolic diseases worldwide which affects all organs, including the reproductive system. Today, many researchers use medicinal plants instead of chemical agents to achieve fewer side effects. Ferula assa-foetida L. is one of the medicinal plants used to treat many diseases traditionally for years. The present study evaluated the antidiabetic and protective effects of Ferula assa-foetida L. on the testis of streptozotocin-induced diabetic male rats. The histomorphologic study of diabetic rats treated with Ferula assa-foetida L. extract showed a significant improvement in testes. Histological studies revealed that treatment with the Ferula assa-foetida L. extract significantly increased sperm count in the seminiferous tubules and reduced fibrosis. Our study confirmed the improving effects of Ferula assa-foetida L. on histomorphometric and biochemical parameters in diabetes and related testicular damage, which are partially attributed to the bioactive compounds and antioxidants in Ferula assa-foetida L.

Keywords

Main Subjects


1.    WHO, Global report on Diabetes—World Health Organization. 2016. https://www.who.int/publications-detail-redirect/9789241565257. 
2.     Vetere A, Choudhary A, Burns SM, Wagner BK. Targeting the pancreatic β-cell to treat diabetes. Nat Rev Drug Discov. 2014; 13(4): 278–289. Doi:10.1038/nrd4231"10.1038/nrd4231.
3.    American diabetes assiciation, Diagnosis and classification of diabetes mellitus, Diabetes Care,2010; 32: S64–S69. Doi:10.2337%2Fdc10-S062"10.2337/dc10-S062.
4.    Rosenbloom AL, Joe JR, Young RS, Winter WE. 1999. Emerging epidemic of type 2 diabetes in youth.Diabetes Care.1999;22: 345–354. Doi:  10.2337/diacare.22.2.345 .
5.     Kianifard D, Sadrkhanlou RA., Hasanzadeh Sh.The Histological, Histomorphometrical and Histochemical Changes of Testicular Tissue in the Metformin Treated and Untreated StreptozotocinInduced Adult Diabetic Rats. Veterinary Research Forum .2011;2(1):13 – 24. 
6.    Baccetti B, La Marca A, Piomboni P, Capitani S, Bruni E, Petraglia F, et al. Insulin-dependent diabetes in men is associated with hypothalamo–pituitary derangement and with impairment in semen quality. Hum. Reprod.2002;17: 2673–2677. Doi:10.1093/humrep/17.10.2673"10.1093/humrep/17.10.2673 .
7.    Dong Q, Lazarus RM, Wong LS, Vellios M, Handelsman DJ. Pulsatile LH secretion in streptozotocin-induced diabetes in the rat. J Endocrinol.1991;131: 49–55. Doi:10.1677/joe.0.1310049"10.1677/joe.0.1310049 .
8.     Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Current Diabetes Reviews.2008; 4(1): 46–54. Doi:10.2174/157339908783502398"10.2174/157339908783502398 .
9.    Agbaje IM, Rogers DA, McVicar CM,  McClure N, Atkinson AB,   Mallidis C, et al. Insulin dependent diabetes mellitus: implications for male reproductive function. Human Reproduction. 2007; 22:1871–1877. Doi:10.1093/humrep/dem077 .
10.     Maresch CC, Stute DC, Alves MJ. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review. Human Reproduction Update;2018: 24(1): 86–105. 
11.     Khamis T, Abdelalim AF, Abdallah SH, Saeed AA, Edress NM, Arisha AH. Early intervention with breast milk mesenchymal stem cells attenuates the development of diabetic-induced testicular dysfunction via hypothalamic Kisspeptin/Kiss1r-GnRH/GnIH system in male rats. 2020. Biochimica et Biophysica Acta - Molecular Basis of Disease,1866. 1, 165577. Doi:10.1016/j.bbadis.2019.165577"10.1016/j.bbadis.2019.165577.
12.      Sajadi E, DadrasS, Bayat M, Abdi S, Nazarian H, Ziaeipour S, et al. Impaired spermatogenesis associated with changes in spatial arrangement of Sertoli and spermatogonial cells following induced diabetes. Journal of Cellular Biochemistry.2020; 120(10): 17312– 17325. Doi:10.1002/jcb.28995"10.1002/jcb.28995 .
13.    Jiang YP, Ye RJ, Yang JM, Liu N, Zhang W, Ma L, et al. Protective effects of salidroside on spermatogenesis in streptozotocin induced type-1 diabetic male mice by inhibiting oxidative stress mediated blood-testis barrier damage. Chem Biol Interact.2020; 315, 108869. Doi: 10.1016/j.cbi.2019.108869.
14.    Kangralkar VA, Patil SD, Bandivadekar RM. Oxidative Stress and Diabetes: A Review. Int J Pharma Appl,2012; 1: 38-45. Doi:10.1002/jbt.10058"10.1002/jbt.10058 .
15.    Foretz M, He´ brard S, Leclerc J,  Zarrinpashneh E,  Soty M,   Mithieux G, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest.2010; 120: 2355–2369. Doi:  10.1172/JCI40671 .
16.    Liu Y, Yang Z,Kong D,  Zhang Y,  Zha W. Metformin Ameliorates Testicular Damage in Male Mice with Streptozotocin-Induced Type 1 Diabetes through the PK2/PKR Pathway. Oxidative Medicine and Cellular Longevity. 2019; Article ID 5681701, 14 pages, Doi:10.1155/2019/5681701"10.1155/2019/5681701 .
17.    Belhan SYS, Huyut Z, Özdek U, et al. Effects of curcumin on sperm quality, lipid profile, antioxidant activity and histopathological changes in streptozotocin induced diabetes in rats. Andrologia.2020. 52(6): e13584. https://pubmed.ncbi.nlm.nih.gov/32293755/.
18.    Belhan S,Yildirim S, Huyut Z, Özdek U, Oto G, Algul S. Effects of curcumin on sperm quality, lipid profile, antioxidant activity and histopathological changes in streptozotocin induced diabetes in rats. Andrologia.2020. 52(6): e13584. Doi:10.1111/and.13584"10.1111/and.13584 .
19.     Akang EN, Oremosu A A, Dosumu OO, et al. The effect of fluted pumpkin (Telferia occidentalis) seed oil (FPSO) on testis and semen parameters. Agriculture and Biology Journal of North America. 2010; 14:697-703. 
20.    Zahedi A, Fathiazad F, Khaki A, Ahmadnejad B. Protective Effect of Ginger on Gentamicin-Induced Apoptosis in Testis of Rats. Advanced Pharmaceutical Bulletin. 2012;2(2):197-200.Doi:10.5681%2Fapb.2012.030"10.5681/apb.2012.030.
21.     Dehpour A A, Ebrahimzadeh M A, Nabavi S F, Nabavi S M. Antioxidant activity of the methanol extract of Ferula assafoetida and its essential oil composition,Grasas Y Aceites 2009:60(4): 405–412.  Doi: 10.3989/gya.010109.
22.    Karimian V, Sepehry A, Barani H, et al. Productivity, essential oil variability and antioxidant activity of Ferula assa-foetida L. oleogum- resin during the plant exploitation period.J essen oil res.2020;32(6):545-555. Doi: 10.1016/j.foodchem.2012.11.131.
24.    Iranshahy M, Iranshahi M. Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin)-A review. J EthnoPharmacol. 2011; 134:1–10. Doi: 10.1016/j.jep.2010.11.067.
25.     Hofer O, Widhalm M, Greger H. Circular dichroism of sesquiterpene-umbelliferone ethers and structure elucidation of a new derivative isolated from the gum resin “Asa Foetida. Monatshefte Faƒa.rChemie-Chem.Mon.1984;115:1207–1218. 
26.    Bagheri S M, Yadegari M, Porentezari M, Mirjalili A, Hasanpor A, Dashti M H, et al. Effect of Ferula assa‑foetida oleo gum resin on spermatic parameters and testicular histopathology in male wistar rats.J Ayur & Integ Med.2015;6(3): 175-180. Doi: 10.4103/0975-9476.146552..
27.    Nejatbakhsh F, Shirbeigi L, Rahimi R, Abolhasani H. Review of local herbal compounds found in the Iranian traditional medicine known to optimise male fertility. Andrologia.2016; 48:8: 850-859. Doi:10.1111/and.12675"10.1111/and.12675.
28.    Latifi E, Mohammadpour A A, Fathi H B, Nourani H. Antidiabetic and antihyperlipidemic effects of ethanolic Ferula assa-foetida oleo-gum-resin extract in streptozotocin-induced diabetic wistar rats. Biomed pharmacother. 2019; 110:197-202.Doi:10.1016/j.biopha.2018.10.152"10.1016/j.biopha.2018.10.152.
29.    Rafiee S, Shafi MM, Molavi M, Nazemi S. Effect of Ethyl Acetate Extract of Ferula asafoetida Oleo-Gum Resin on the Glucose Level and Lipid Profile in Streptozotocin-Induced Diabetic Rats. Jundishapur J Nat Pharm Prod.2020;15,2. e67042. Doi:10.5812/jjnpp.67042" 10.5812/jjnpp.67042.
30.    Azizian H, Rezvani ME, Esmaeilidehaj M, Bagheri S M. Anti-Obesity, Fat Lowering and Liver Steatosis Protective Effects of Ferula asafoetida Gum in Type 2 Diabetic Rats: Possible Involvement of Leptin., Iranian Journal of Diabetes and Obesity. 2012; 4(3): 120-6.
31.    Tuomilehto J. The emerging global epidemic of type 1 diabetes, Current Diabetes Reports.2013;(13)6:795–804. Doi:10.1007/s11892-013-0433-5"10.1007/s11892-013-0433-5 .
32.    Gupta S, Kataria M, Gupta PK,   Murganandan S, Yashroy R C. Protective role of extracts of neem seeds in diabetes caused by streptozotocin in rats. J Ethnopharmacol.2004;90:185–189.Doi:10.1016/j.jep.2003.09.024"10.1016/j.jep.2003.09.024 .
33.    Kodikonda M, Naik PR. Ameliorative effect of borneol, a natural by cyclicmonoterpene against hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic Wistar rats. Biomed Pharmacother.2017;96:336–347. Doi:10.1016/j.biopha.2017.09.122"10.1016/j.biopha.2017.09.122.
34.    Chandran R, George BP, Abrahamse H, Parimelazhagan T. Therapeutic effects of Syzygium mundagam bark methanol extract on type-2 diabetic complications in rats. Biomed Pharmacother.2017;95:167–174.Doi:10.1016/j.biopha.2017.08.061"10.1016/j.biopha.2017.08.061.
35.     Luna LG. Manual of histologic staining methods of the Armed Forces Institute of Pathology. 3ed. NewYork: McGraw-Hill.1968. 
36.    Johnsen SG. Testicular biopsy score count-a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones. 1970;1(1):2-25.Doi:10.1159/000178170"10.1159/000178170.
37.    Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry.1974; 47(3):469–474. Doi:10.1111/j.1432-1033.1974. tb03714.x. 
38.    Sexton W J, Jarow J P. Effect of diabetes mellitus upon male reproductive function. Urology. 1997;49: 508–513. Doi:10.1016/s0090-4295(96)00573-0"10.1016/s0090-4295(96)00573-0.
39.    Singh A, Kukreti R, Luciano S, Kukreti S. Mechanistic Insight into Oxidative Stress-Triggered Signaling Pathways and Type 2 Diabetes. Molecules.2022;27(3):950. DOI:10.3390/molecules2703095040.
40.    Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today.1994;15: 7–10. Doi:10.1016/0167-5699(94)90018-3.
41.    Kianifard D, Sadrkhanlou RA, Hasanzadeh Sh. The ultrastructural changes of the sertoli and leydig cells following streptozotocin induced diabetes. Iran J Basic Med Sci.2012;15(1):623-35. PMID: 23493249.
42.    Shokoohi M, Gholami Farashah MS, Khaki A, Khaki A A, Ouladsahebmadarek E, Aref Nezhad R. Protective Effect of Fumaria parviflora Extract on Oxidative Stress and Testis Tissue Damage in Diabetic Rats. Crescent Journal of Medical and Biological Sciences. 2019; 6:355-360. https://www.cjmb.org/uploads/pdf/pdf_CJMB_375.pdf.
43.    Khaki A, Fathiazad F, Nouri M,  Khaki A A,  Maleki N A,  Jabbari Khamnei H, et al. Beneficial effects of quercetin on sperm parameters in streptozotocin-induced diabetic male rats. Phytother Res.2010; 24:1285–1291. Doi:10.1002/ptr.3100"10.1002/ptr.3100.
44.    Park JS, Han K. The spermatogenic effect of yacon extract and its constituents and their inhibition effect of testosterone metabolism. Biomol Ther (Seoul).2013;21: 153–160. Doi:10.4062%2Fbiomolther.2012.093"10.4062/biomolther.2012.093.
45.    Adedara IA, Abolaji A O, Ladipo E O, Fatunmibi OJ,  Farombi AO.4-Vinylcyclohexene diepoxide disrupts sperm characteristics, endocrine balance and redox status in testes and epididymis of rats. Redox Report.2016;22(6): 388–398. Doi:10.1080/13510002.2016.1259718"10.1080/13510002.2016.1259718.
46.    Rajkumar L, Srinivasan N, Balasubramanian K, Govindarajulu P. Increased degradation of dermal collagen in diabetic rats. Indian J Exp Biol.1991; 29:1081–1083.
47.    Proud CG. Regulation of protein synthesis by insulin. Biochemical Society Transactions.2006; 34: 213-216. Doi:10.1042/bst20060213"10.1042/BST20060213.
48.    Fuji J, Iuchi Y, Matsuki S, Ishii T. Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues. Asian J Androl.2003;5: 231–242. 
49.    Allam M, Khowailed A A, Elattar S, Mahmoud AM. Umbelliferone ameliorates oxidative stress and testicular injury, improves steroidogenesis and upregulates peroxisome proliferator-activated receptor gamma in type 2 diabetic   rat.  Journal of Pharmacy and Pharmacology.2022; 74: 573–584. Doi:10.1093/jpp/rgab083"10.1093/jpp/rgab083.
50.    Alotaibi M F, Al-Joufi F, Abou Seif H S, Alzoghaibi MA, Djouhri L, Ahmeda AF et al. Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and inflammation, and Improving Nrf2/HO-1 Signaling. Drug Des Dev and Ther.2020;14: 4003–4019. Doi: 10.2147%2FDDDT.S416910"10.2147/DDDT.S416910.
51.    Mahmoud AM, Hussein O E. Protective Effects of Umbelliferone in Experimental Testicular Ischaemia/Reperfusion Injury in Rats.Anat Physio: cur res.2015; 6:1. Doi:10.4172/2161-0940.1000189"10.4172/2161-0940.1000189.
CAPTCHA Image
Volume 16, Issue 3 - Serial Number 36
This issue XML files are being prepared.
September 2024
Pages 56-66
  • Receive Date: 20 November 2023
  • Revise Date: 10 July 2024
  • Accept Date: 29 July 2024