Saffron has a therapeutic effect on nephropathy by regulating the expression of TLR4, S100A8, and HMGB1 genes and reducing oxidative stress in diabetic rats
-
Abbas Alimoradian
,
Hadi Karami
,
Seied Amirhossein Latifi
,
Ali Ghazavi
,
Ahmad Akbari
,
Zahra Pilevar
,
Jamal Amri
Abstract
Objectives: Diabetic nephropathy (DN) is a major complication of diabetes that requires effective treatment options. This study explores the potential benefits of saffron extract as a remedy derived from medicinal plants, focusing on its effects on key inflammatory genes—Toll-like receptor 4 (TLR-4), S100 calcium-binding protein A8 (S100A8), and High Mobility Group Box 1 (HMGB1)—as well as its role in reducing oxidative stress in the kidney tissue of rats with type 1 diabetes
Methods: The rats were randomly divided into 8 groups of 6 each. Diabetes was induced using streptozotocin (55 mg/kg.bw). Diabetic and control groups were treated with three doses of saffron extract 100, 200 and 300 mg/kg for 60 days. Biochemical kits were used to evaluate Fasting blood Glucose (FBG), urea, creatinine, albumin, lipid profile, Malondialdehyde (MDA) and total antioxidant capacity (TAC). Expression of TLR-4, S100A8, and HMGB1 genes were evaluated by real-time PCR. ANOVA and Bonferroni post-hoc tests were used for data evaluation.
Results: Diabetes significantly impaired the FBG, lipid profile, creatinine, urea, and albumin levels (P<0.05). After treatment with the saffron extract, these parameters were significantly close to the normal range in all groups compared to the control group (P<0.05). Also, the saffron extract significantly decreased the expression levels of TLR-4, S100A8, and HMGB1 genes and improved oxidative stress markers (TAC and MDA) in kidney tissues when compared to the diabetic control group (P<0.05). In addition, the beneficial effects of saffron were dose-dependent.
Conclusion: Based on the obtained results, the saffron extract can lead to the improvement of nephropathy by reducing the expression of TLR-4, S100A8, and HMGB1 genes as well as improving oxidative stress. Thus, it may be used as an adjuvant treatment for diabetic complications.
1. Lim A. Diabetic nephropathy - complications and treatment. International journal of nephrology and renovascular disease. 2014;7:361-81. PubMed PMID: 25342915. Pubmed Central PMCID: PMC4206379. Epub 2014/10/25. eng.
2. Selby NM, Taal MW. An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines. Diabetes, Obesity and Metabolism. 2020;22(S1):3-15.
3. Dwivedi S, Sikarwar MS. Diabetic Nephropathy: Pathogenesis, Mechanisms, and Therapeutic Strategies. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2024 Nov 21. PubMed PMID: 39572154. Epub 2024/11/22. eng.
4. Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clinical journal of the American Society of Nephrology : CJASN. 2017 Dec 7;12(12):2032-45. PubMed PMID: 28522654. Pubmed Central PMCID: PMC5718284. Epub 2017/05/20. eng.
5. Natesan V, Kim SJ. Diabetic Nephropathy - a Review of Risk Factors, Progression, Mechanism, and Dietary Management. Biomolecules & therapeutics. 2021 Jul 1;29(4):365-72. PubMed PMID: 33888647. Pubmed Central PMCID: PMC8255138. Epub 2021/04/24. eng.
6. Banerjee D, Winocour P, Chowdhury TA, De P, Wahba M, Montero R, et al. Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021. BMC nephrology. 2022 Jan 3;23(1):9. PubMed PMID: 34979961. Pubmed Central PMCID: PMC8722287. Epub 2022/01/05. eng.
7. Sulaiman MK. Molecular mechanisms and therapeutic potential of natural flavonoids in diabetic nephropathy: Modulation of intracellular developmental signaling pathways. Current Research in Pharmacology and Drug Discovery. 2024 2024/01/01/;7:100194.
8. Ma J, Chadban SJ, Zhao CY, Chen X, Kwan T, Panchapakesan U, et al. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy. PloS one. 2014;9(5):e97985. PubMed PMID: 24842252. Pubmed Central PMCID: PMC4026484. Epub 2014/05/21. eng.
9. Tammaro A, Florquin S, Brok M, Claessen N, Butter LM, Teske GJD, et al. S100A8/A9 promotes parenchymal damage and renal fibrosis in obstructive nephropathy. Clinical and experimental immunology. 2018 Sep;193(3):361-75. PubMed PMID: 29746703. Pubmed Central PMCID: PMC6150262. Epub 2018/05/11. eng.
10. Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Experimental & Molecular Medicine. 2022 2022/02/01;54(2):91-102.
11. Sani A, Tajik A, Seiiedi SS, Khadem R, Tootooni H, Taherynejad M, et al. A review of the anti-diabetic potential of saffron. Nutrition and metabolic insights. 2022;15:11786388221095223. PubMed PMID: 35911474. Pubmed Central PMCID: PMC9335478. Epub 2022/08/02. eng.
12. Bolhassani A. Chapter 10 - Bioactive Components of Saffron and Their Pharmacological Properties. In: Atta ur R, editor. Studies in Natural Products Chemistry. 58: Elsevier; 2018. p. 289-311.
13. Mahmoudzadeh L, Najafi H, Ashtiyani SC, Yarijani ZM. Anti‐inflammatory and protective effects of saffron extract in ischaemia/reperfusion‐induced acute kidney injury. Nephrology. 2017;22(10):748-54.
14. Faul F, Erdfelder E, Lang A-G, Buchner A. G* Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior research methods. 2007;39(2):175-91.
15. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 1972 Jun;18(6):499-502. PubMed PMID: 4337382. Epub 1972/06/01. eng.
16. Ashrafi M, AFSAR Z, Erjaee H, Nazifi S. The effects of saffron (Crocus sativus) aqueous extract on TNF-α levels in liver, kidney, and lens tissues of diabetic rats. Turkish Journal of Endocrinology and Metabolism. 2018;22(4):217.
17. Karimi-Nazari E, Nadjarzadeh A, Masoumi R, Marzban A, Mohajeri SA, Ramezani-Jolfaie N, et al. Effect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trial. Clinical nutrition ESPEN. 2019 Dec;34:130-6. PubMed PMID: 31677703. Epub 2019/11/05. eng.
18. Karimi E, Oskoueian E, Hendra R, Jaafar HZ. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules. 2010;15(9):6244-56.
19. Soliman A, Mohamed A, Marie M. Effect of echinochrome on body weight, musculoskeletal system and lipid profile of male diabetic rats. Austin J Endocrinol Diabetes. 2016;3(2):1045.
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. Journal of basic and clinical physiology and pharmacology. 2020 Jan 22;31(2). PubMed PMID: 31967963. Epub 2020/01/23. eng.
21. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian heart journal. 2017 Mar-Apr;69(2):151-9. PubMed PMID: 28460761. Pubmed Central PMCID: PMC5414951. Epub 2017/05/04. eng.
22. Yaribeygi H, Zare V, Butler AE, Barreto GE, Sahebkar A. Antidiabetic potential of saffron and its active constituents. Journal of cellular physiology. 2019 Jun;234(6):8610-7. PubMed PMID: 30515777. Epub 2018/12/06. eng.
23. Bolhassani A. Bioactive Components of Saffron and Their Pharmacological Properties. Studies in Natural Products Chemistry. 58: Elsevier; 2018. p. 289-311.
24. Yaribeygi H, Mohammadi MT, Rezaee R, Sahebkar A. Crocin improves renal function by declining Nox-4, IL-18, and p53 expression levels in an experimental model of diabetic nephropathy. Journal of cellular biochemistry. 2018 Jul;119(7):6080-93. PubMed PMID: 29575259. Epub 2018/03/27. eng.
25. Altinoz E, Oner Z, Elbe H, Cigremis Y, Turkoz Y. Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats. Human & experimental toxicology. 2015 Feb;34(2):127-34. PubMed PMID: 24925368. Epub 2014/06/14. eng.
26. Amri J, Alaee M, Latifi SA, Alimoradian A, Salehi M. Amelioration of STZ-induced nephropathy in diabetic rats by saffron hydro alcoholic extract. Hormone molecular biology and clinical investigation. 2021 May 21;42(4):411-8. PubMed PMID: 34018383. Epub 2021/05/22. eng.
27. Ebrahimi F, Aryaeian N, Pahlavani N, Abbasi D, Hosseini AF, Fallah S, et al. The effect of saffron (Crocus sativus L.) supplementation on blood pressure, and renal and liver function in patients with type 2 diabetes mellitus: A double-blinded, randomized clinical trial. Avicenna journal of phytomedicine. 2019 Jul-Aug;9(4):322-33. PubMed PMID: 31309071. Pubmed Central PMCID: PMC6612249. Epub 2019/07/17. eng.
28. Milajerdi A, Jazayeri S, Bitarafan V, Hashemzadeh N, Shirzadi E, Derakhshan Z, et al. The effect of saffron (Crocus sativus L.) hydro-alcoholic extract on liver and renal functions in type 2 diabetic patients: A double-blinded randomized and placebo control trial. Journal of Nutrition & Intermediary Metabolism. 2017 2017/09/01/;9:6-11.
29. Abou-Hany HO, Atef H, Said E, Elkashef HA, Salem HA. Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats. Chemico-biological interactions. 2018 Mar 25;284:90-100. PubMed PMID: 29409856. Epub 2018/02/08. eng.
30. Gyurászová M, Kovalčíková AG, Renczés E, Kmeťová K, Celec P, Bábíčková J, et al. Oxidative Stress in Animal Models of Acute and Chronic Renal Failure. Disease markers. 2019;2019:8690805. PubMed PMID: 30886657. Pubmed Central PMCID: PMC6388331. Epub 2019/03/20. eng.
31. Abbasi-Oshaghi E, Khodadadi I, Mirzaei F, Ahmadi M, Tayebinia H, Goodarzi MT. Anethum graveolens L. Alleviates Sperm Damage by Limiting Oxidative Stress and Insulin Resistance in Diabetic Rats. The Open Medicinal Chemistry Journal. 2020;14(1).
32. Samarghandian S, Borji A. Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients. Pharmacognosy research. 2014;6(2):99.
33. Farahmand SK, Samini F, Samini M, Samarghandian S. Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver. Biogerontology. 2013;14(1):63-71.
34. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian heart journal. 2017;69(2):151-9.
35. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018 Feb;98:333-7. PubMed PMID: 29274590. Epub 2017/12/24. eng.
36. Kaur H, Chien A, Jialal I. Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy. American Journal of Physiology-Renal Physiology. 2012;303(8):F1145-F50.
37. Zhu T, Meng Q, Ji J, Zhang L, Lou X. TLR4 and Caveolin‐1 in Monocytes Are Associated With Inflammatory Conditions in Diabetic Neuropathy. Clinical and translational science. 2017;10(3):178-84.
38. Liu S-Y, Nie X-Z, Zhou W-Y, Chen J. Expression and effect of TLR4 in rats with diabetic nephropathy. Asian Pacific journal of tropical medicine. 2013;6(8):635-9.
39. Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohajeri SA, Mohammadi M. Crocus Sativus (Saffron): An immunoregulatory factor in the autoimmune and non-autoimmune diseases. Iranian Journal of Allergy, Asthma and Immunology. 2020.
40. Khedr L, Rahmo RM, Farag DB, Schaalan MF, Hekmat M. Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29. Food and Chemical Toxicology. 2020;140:111307.
41. Jin W, Zhang Y, Xue Y, Han X, Zhang X, Ma Z, et al. Crocin attenuates isoprenaline-induced myocardial fibrosis by targeting TLR4/NF-κB signaling: connecting oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg's Archives of Pharmacology. 2020;393:13-23.
42. Du L, Chen Y, Shi J, Yu X, Zhou J, Wang X, et al. Inhibition of S100A8/A9 ameliorates renal interstitial fibrosis in diabetic nephropathy. Metabolism. 2023;144:155376.
43. Chen Z, Chen L, Dai H. Mechanism of Resveratrol Improving Rheumatoid Arthritis Injury by Inhibiting S100A8/A9 Expression. Indian Journal of Pharmaceutical Sciences. 2023;85(2).
44. Yang L, Li D, Tang P, Zuo Y. Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein. Oncology Letters. 2020;19(1):83-92.
45. Liu T, Zhao H, Wang Y, Qu P, Wang Y, Wu X, et al. Serum high mobility group box 1 as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes. Frontiers in Immunology. 2024;15:1334109.
46. Chen X, Ma J, Kwan T, Stribos EG, Messchendorp AL, Loh YW, et al. Blockade of HMGB1 attenuates diabetic nephropathy in mice. Scientific reports. 2018;8(1):8319.
47. Ceylan T, Akın A, Kaymak E, Varinli Ş, Toluk A. Crocin Suppresses Inflammatory Response in LPS-Induced Acute Lung Injury (ALI) Via Regulation of HMGB1/TLR4 Inflammation Pathway. Journal of Basic and Clinical Health Sciences. 2024;8(2):271-8.
48. Zhang D, Qi B-y, Zhu W-w, Huang X, Wang X-z. Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways. Inflammation Research. 2020;69:267-78.
2. Selby NM, Taal MW. An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines. Diabetes, Obesity and Metabolism. 2020;22(S1):3-15.
3. Dwivedi S, Sikarwar MS. Diabetic Nephropathy: Pathogenesis, Mechanisms, and Therapeutic Strategies. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2024 Nov 21. PubMed PMID: 39572154. Epub 2024/11/22. eng.
4. Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clinical journal of the American Society of Nephrology : CJASN. 2017 Dec 7;12(12):2032-45. PubMed PMID: 28522654. Pubmed Central PMCID: PMC5718284. Epub 2017/05/20. eng.
5. Natesan V, Kim SJ. Diabetic Nephropathy - a Review of Risk Factors, Progression, Mechanism, and Dietary Management. Biomolecules & therapeutics. 2021 Jul 1;29(4):365-72. PubMed PMID: 33888647. Pubmed Central PMCID: PMC8255138. Epub 2021/04/24. eng.
6. Banerjee D, Winocour P, Chowdhury TA, De P, Wahba M, Montero R, et al. Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021. BMC nephrology. 2022 Jan 3;23(1):9. PubMed PMID: 34979961. Pubmed Central PMCID: PMC8722287. Epub 2022/01/05. eng.
7. Sulaiman MK. Molecular mechanisms and therapeutic potential of natural flavonoids in diabetic nephropathy: Modulation of intracellular developmental signaling pathways. Current Research in Pharmacology and Drug Discovery. 2024 2024/01/01/;7:100194.
8. Ma J, Chadban SJ, Zhao CY, Chen X, Kwan T, Panchapakesan U, et al. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy. PloS one. 2014;9(5):e97985. PubMed PMID: 24842252. Pubmed Central PMCID: PMC4026484. Epub 2014/05/21. eng.
9. Tammaro A, Florquin S, Brok M, Claessen N, Butter LM, Teske GJD, et al. S100A8/A9 promotes parenchymal damage and renal fibrosis in obstructive nephropathy. Clinical and experimental immunology. 2018 Sep;193(3):361-75. PubMed PMID: 29746703. Pubmed Central PMCID: PMC6150262. Epub 2018/05/11. eng.
10. Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Experimental & Molecular Medicine. 2022 2022/02/01;54(2):91-102.
11. Sani A, Tajik A, Seiiedi SS, Khadem R, Tootooni H, Taherynejad M, et al. A review of the anti-diabetic potential of saffron. Nutrition and metabolic insights. 2022;15:11786388221095223. PubMed PMID: 35911474. Pubmed Central PMCID: PMC9335478. Epub 2022/08/02. eng.
12. Bolhassani A. Chapter 10 - Bioactive Components of Saffron and Their Pharmacological Properties. In: Atta ur R, editor. Studies in Natural Products Chemistry. 58: Elsevier; 2018. p. 289-311.
13. Mahmoudzadeh L, Najafi H, Ashtiyani SC, Yarijani ZM. Anti‐inflammatory and protective effects of saffron extract in ischaemia/reperfusion‐induced acute kidney injury. Nephrology. 2017;22(10):748-54.
14. Faul F, Erdfelder E, Lang A-G, Buchner A. G* Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior research methods. 2007;39(2):175-91.
15. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 1972 Jun;18(6):499-502. PubMed PMID: 4337382. Epub 1972/06/01. eng.
16. Ashrafi M, AFSAR Z, Erjaee H, Nazifi S. The effects of saffron (Crocus sativus) aqueous extract on TNF-α levels in liver, kidney, and lens tissues of diabetic rats. Turkish Journal of Endocrinology and Metabolism. 2018;22(4):217.
17. Karimi-Nazari E, Nadjarzadeh A, Masoumi R, Marzban A, Mohajeri SA, Ramezani-Jolfaie N, et al. Effect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trial. Clinical nutrition ESPEN. 2019 Dec;34:130-6. PubMed PMID: 31677703. Epub 2019/11/05. eng.
18. Karimi E, Oskoueian E, Hendra R, Jaafar HZ. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules. 2010;15(9):6244-56.
19. Soliman A, Mohamed A, Marie M. Effect of echinochrome on body weight, musculoskeletal system and lipid profile of male diabetic rats. Austin J Endocrinol Diabetes. 2016;3(2):1045.
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. Journal of basic and clinical physiology and pharmacology. 2020 Jan 22;31(2). PubMed PMID: 31967963. Epub 2020/01/23. eng.
21. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian heart journal. 2017 Mar-Apr;69(2):151-9. PubMed PMID: 28460761. Pubmed Central PMCID: PMC5414951. Epub 2017/05/04. eng.
22. Yaribeygi H, Zare V, Butler AE, Barreto GE, Sahebkar A. Antidiabetic potential of saffron and its active constituents. Journal of cellular physiology. 2019 Jun;234(6):8610-7. PubMed PMID: 30515777. Epub 2018/12/06. eng.
23. Bolhassani A. Bioactive Components of Saffron and Their Pharmacological Properties. Studies in Natural Products Chemistry. 58: Elsevier; 2018. p. 289-311.
24. Yaribeygi H, Mohammadi MT, Rezaee R, Sahebkar A. Crocin improves renal function by declining Nox-4, IL-18, and p53 expression levels in an experimental model of diabetic nephropathy. Journal of cellular biochemistry. 2018 Jul;119(7):6080-93. PubMed PMID: 29575259. Epub 2018/03/27. eng.
25. Altinoz E, Oner Z, Elbe H, Cigremis Y, Turkoz Y. Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats. Human & experimental toxicology. 2015 Feb;34(2):127-34. PubMed PMID: 24925368. Epub 2014/06/14. eng.
26. Amri J, Alaee M, Latifi SA, Alimoradian A, Salehi M. Amelioration of STZ-induced nephropathy in diabetic rats by saffron hydro alcoholic extract. Hormone molecular biology and clinical investigation. 2021 May 21;42(4):411-8. PubMed PMID: 34018383. Epub 2021/05/22. eng.
27. Ebrahimi F, Aryaeian N, Pahlavani N, Abbasi D, Hosseini AF, Fallah S, et al. The effect of saffron (Crocus sativus L.) supplementation on blood pressure, and renal and liver function in patients with type 2 diabetes mellitus: A double-blinded, randomized clinical trial. Avicenna journal of phytomedicine. 2019 Jul-Aug;9(4):322-33. PubMed PMID: 31309071. Pubmed Central PMCID: PMC6612249. Epub 2019/07/17. eng.
28. Milajerdi A, Jazayeri S, Bitarafan V, Hashemzadeh N, Shirzadi E, Derakhshan Z, et al. The effect of saffron (Crocus sativus L.) hydro-alcoholic extract on liver and renal functions in type 2 diabetic patients: A double-blinded randomized and placebo control trial. Journal of Nutrition & Intermediary Metabolism. 2017 2017/09/01/;9:6-11.
29. Abou-Hany HO, Atef H, Said E, Elkashef HA, Salem HA. Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats. Chemico-biological interactions. 2018 Mar 25;284:90-100. PubMed PMID: 29409856. Epub 2018/02/08. eng.
30. Gyurászová M, Kovalčíková AG, Renczés E, Kmeťová K, Celec P, Bábíčková J, et al. Oxidative Stress in Animal Models of Acute and Chronic Renal Failure. Disease markers. 2019;2019:8690805. PubMed PMID: 30886657. Pubmed Central PMCID: PMC6388331. Epub 2019/03/20. eng.
31. Abbasi-Oshaghi E, Khodadadi I, Mirzaei F, Ahmadi M, Tayebinia H, Goodarzi MT. Anethum graveolens L. Alleviates Sperm Damage by Limiting Oxidative Stress and Insulin Resistance in Diabetic Rats. The Open Medicinal Chemistry Journal. 2020;14(1).
32. Samarghandian S, Borji A. Anticarcinogenic effect of saffron (Crocus sativus L.) and its ingredients. Pharmacognosy research. 2014;6(2):99.
33. Farahmand SK, Samini F, Samini M, Samarghandian S. Safranal ameliorates antioxidant enzymes and suppresses lipid peroxidation and nitric oxide formation in aged male rat liver. Biogerontology. 2013;14(1):63-71.
34. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian heart journal. 2017;69(2):151-9.
35. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018 Feb;98:333-7. PubMed PMID: 29274590. Epub 2017/12/24. eng.
36. Kaur H, Chien A, Jialal I. Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy. American Journal of Physiology-Renal Physiology. 2012;303(8):F1145-F50.
37. Zhu T, Meng Q, Ji J, Zhang L, Lou X. TLR4 and Caveolin‐1 in Monocytes Are Associated With Inflammatory Conditions in Diabetic Neuropathy. Clinical and translational science. 2017;10(3):178-84.
38. Liu S-Y, Nie X-Z, Zhou W-Y, Chen J. Expression and effect of TLR4 in rats with diabetic nephropathy. Asian Pacific journal of tropical medicine. 2013;6(8):635-9.
39. Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohajeri SA, Mohammadi M. Crocus Sativus (Saffron): An immunoregulatory factor in the autoimmune and non-autoimmune diseases. Iranian Journal of Allergy, Asthma and Immunology. 2020.
40. Khedr L, Rahmo RM, Farag DB, Schaalan MF, Hekmat M. Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29. Food and Chemical Toxicology. 2020;140:111307.
41. Jin W, Zhang Y, Xue Y, Han X, Zhang X, Ma Z, et al. Crocin attenuates isoprenaline-induced myocardial fibrosis by targeting TLR4/NF-κB signaling: connecting oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg's Archives of Pharmacology. 2020;393:13-23.
42. Du L, Chen Y, Shi J, Yu X, Zhou J, Wang X, et al. Inhibition of S100A8/A9 ameliorates renal interstitial fibrosis in diabetic nephropathy. Metabolism. 2023;144:155376.
43. Chen Z, Chen L, Dai H. Mechanism of Resveratrol Improving Rheumatoid Arthritis Injury by Inhibiting S100A8/A9 Expression. Indian Journal of Pharmaceutical Sciences. 2023;85(2).
44. Yang L, Li D, Tang P, Zuo Y. Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein. Oncology Letters. 2020;19(1):83-92.
45. Liu T, Zhao H, Wang Y, Qu P, Wang Y, Wu X, et al. Serum high mobility group box 1 as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes. Frontiers in Immunology. 2024;15:1334109.
46. Chen X, Ma J, Kwan T, Stribos EG, Messchendorp AL, Loh YW, et al. Blockade of HMGB1 attenuates diabetic nephropathy in mice. Scientific reports. 2018;8(1):8319.
47. Ceylan T, Akın A, Kaymak E, Varinli Ş, Toluk A. Crocin Suppresses Inflammatory Response in LPS-Induced Acute Lung Injury (ALI) Via Regulation of HMGB1/TLR4 Inflammation Pathway. Journal of Basic and Clinical Health Sciences. 2024;8(2):271-8.
48. Zhang D, Qi B-y, Zhu W-w, Huang X, Wang X-z. Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways. Inflammation Research. 2020;69:267-78.
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| Issue | Vol 2 No 2 (2024): . | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/abi.v2i2.17934 | |
| Keywords | ||
| Saffron Hydroalcoholic Extract Oxidative stress Gene Expression Diabetes Rat | ||
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How to Cite
1.
Alimoradian A, Karami H, Latifi SA, Ghazavi A, Akbari A, Pilevar Z, Amri J. Saffron has a therapeutic effect on nephropathy by regulating the expression of TLR4, S100A8, and HMGB1 genes and reducing oxidative stress in diabetic rats. ABI. 2024;2(2):78-86.
