Effect of Genistein on Heat Shock Protein 47 and Collagen Type IV in Diabetic Rat


Genistein, HSP 47 and Type IV Collagen.

How to Cite

Putri Dafriani, Nur Indrawati Lipoeto, Yanwirasti, AmriBakhtiar , & Roza Marlinda. (2018). Effect of Genistein on Heat Shock Protein 47 and Collagen Type IV in Diabetic Rat . Journal of Pharmacy and Nutrition Sciences, 8(4), 163–167. https://doi.org/10.29169/1927-5951.2018.08.04.2


Diabetes nephropathy (DN) is one of the most common complication in Diabetes Mellitus (DM). DN is an inflammatory process which involved immune cells and effect of genistein prevent this mechanism. However, the effects on HSP 47 and collagen type IV are not yet verified. The purpose of this study was to investigate whether the genistein can suppress HSP 47 and collagen type IV.
This study is experimental design used 25 rats. Rats were divided into five groups; normal group, hyperglycemia group, hyperglycemia by administering genistein 0.5 mg/kgw, 1mg/kgw, and 2 mg/kg. Streptozotocin induced 65 mg/kg administered intraperitoneal. Treatment duration is 4 weeks. After 4 weeks of blood was collected via the orbital vein and examined the levels of HSP 47 then rats’ kidneys were taken to see the levels of collagen type IV.
The average levels of HSP 47 in non diabetic control group was 1.7982 ng/ml, diabetic control 7.9424 ng/ml, STZ; G 0.5 mg/kgw 5.4192 ng/ml, STZ; G 1 mg/kgw 3.1152 ng/ml and STZ; G 2 mg/kgw 1.849 ng/ml, with p value 0.000 (p<0.05). While Type IV Collagen in non diabetic group was 10.006 ng/ml, diabetic group 26.864 ng/ml, STZ: G 0.5 mg/kgw 21.426 ng/ml, STZ; G 1 mg/kgw 17.352 ng/ml and STZ; G 2 mg/kgw 13.436 ng/ml with p value 0.000 (p<0.05).
Administer the genistein can reduce levels of HSP 47 and collagen type IV in diabetic rats. Genistein can reduce fibrotic mediators induced by NFkB and MAPK signaling by inhibiting the tyrosine kinase protein activation.



Packham DK, Alves TP, Dwyer JP, Atkins R, De Zeeuw D, Cooper M, Lambers Heerspink HJ. Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: Results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consor-tium) database. American Journal of Kidney Diseases 2012. http://doi.org/10.1053/j.ajkd.2011.09.017

Choi YE, Ahn SK, Lee WT, Lee JE, Park SH, Yoon BB, Park KA. Soybeans ameliolate diabetic nephropathy in rats. Evidence-Based Complementary and Alternative Medicine 2010. http://doi.org/10.1093/ecam/nen021

Sun Y-M, Su Y, Li J, Wang L-F. Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochemical and Biophysical Research Communications 2013. http://doi.org/10.1016/j.bbrc.2013.02.120

Lim AKH, Tesch GH. Inflammation in diabetic nephropathy. Mediators of Inflammation 2012a. http://doi.org/10.1155/2012/146154

Kanasaki K, Taduri G, Koya D. Diabetic nephropathy: The role of inflammation in fibroblast activation and kidney fibrosis. Frontiers in Endocrinology 2013. http://doi.org/10.3389/fendo.2013.00007

Kashihara N, Haruna Y, Kondeti V, Kanwar Y. Oxidative stress in diabetic nephropathy. Curr Med Chem 2010. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3708695/

Elmarakby AA, Sullivan JC. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovascular Therapeutics 2012. Retrieved from http:// www.scopus.com/inward/record.url?eid=2-s2.0-84856247093 &partnerID=40&md5=e0770becf40eec08fe6719232730679a

Lech M, Anders HJ. Macrophages and fibrosis: How resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochimica et Biophysica Acta - Molecular Basis of Disease 2013; 1832(7): 989-997. http://doi.org/10.1016/j.bbadis.2012.12.001

Sthaneshwar P, Chan SP. Urinary type IV collagen levels in diabetes mellitus. Malaysian Journal of Pathology 2010; 32(1): 43-47.

Taguchi T, Razzaque MS. The collagen-specific molecular chaperone HSP47: is there a role in fibrosis? Trends in Molecular Medicine 2007; 13(2): 45-53. http://doi.org/10.1016/j.molmed.2006.12.001

Ishihara K, Oyaizu S, Fukuchi Y, Mizunoya W, Segawa K, Takahashi M, Yasumoto K. A soybean peptide isolate diet promotes postprandial carbohydrate oxidation and energy expenditure in type II diabetic mice. The Journal of Nutrition 2003; 133: 752-757.

Taguchi T, Nazneen A, Al-Shihri AA, Turkistani K, Razzaque MS. Heat Shock Protein 47: A Novel Biomarker of Phenotypically Altered Collagen-Producing Cells. Acta Histochemica Et Cytochemica 2011; 44(2): 35-41. http://doi.org/10.1267/ahc.11001

Hu FB, Dam RM Van, Liu S. Diet and risk of Type II diabetes: the role of types of fat and carbohydrate 2001.

Hagiwara S, Iwasaka H, Matsumoto S, Noguchi T. Antisense oligonucleotide inhibition of heat shock protein (HSP) 47 improves bleomycin-induced pulmonary fibrosis in rats. Respiratory Research 2007; 8: 37. http://doi.org/10.1186/1465-9921-8-37

Shafi S, Tabassum N, Ahmad F. Diabetic nephropathy and herbal medicines 2012. Retrieved from https://www.researchgate.net/publication/216313356_Diabetic_nephropathy_and_herbal_medicines

Behloul N, Wu G. Genistein: A promising therapeutic agent for obesity and diabetes treatment. European Journal of Pharmacology 2013; 698(1-3): 31-38. http://doi.org/10.1016/j.ejphar.2012.11.013

Yang Z, Kulkarni K, Zhu W, Hu M. Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME. Anti-Cancer Agents in Medicinal Chemistry 2012. http://doi.org/10.2174/187152012803833107

Reeves PG. Committee Report AIN-93 Purified Diets for Laboratory Rodents?: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet 1993; 1939-1951.

Qi M-Y, Kai-Chen Liu H-R, Su Y, Yu S-Q. Protective effect of Icariin on the early stage of experimental diabetic nephropathy induced by streptozotocin via modulating transforming growth factor ?1 and type IV collagen expression in rats. Journal of Ethnopharmacology 2011; 138(3): 731-6. http://doi.org/10.1016/j.jep.2011.10.015

Ohashi S, Abe H, Takahashi T, Yamamoto Y, Takeuchi M, Arai H, Doi T. Advanced Glycation End Products Increase Collagen-specific Chaperone Protein in Mouse Diabetic Nephropathy. Journal of Biological Chemistry 2004; 279(19): 19816-19823. http://doi.org/10.1074/jbc.M310428200

Omri AEL, Han J, Ben Abdrabbah M, Isoda H. Down regulation effect of Rosmarinus officinalis polyphenols on cellular stress proteins in rat pheochromocytoma PC12 cells. Cytotechnology 2012; 64(3): 231-240. http://doi.org/10.1007/s10616-011-9352-y

He J, Ning C, Wang Y, Ma T, Huang H, Ge Y, Jiang Y. Natural plant flavonoid apigenin directly disrupts Hsp90/Cdc37 complex and inhibits pancreatic cancer cell growth and migration. Journal of Functional Foods 2015; 18: 10-21. http://doi.org/10.1016/j.jff.2015.06.052

Aalinkeel R, Bindukumar B, Reynolds JL, Sykes DE, Supriya D, Chadha KC, Schwartz SA. NIH Public Access. Prostate, The 2010; 68(16): 1773-1789. http://doi.org/10.1002/pros.20845.The

Ha TS, Hong EJ, Ahn EM, Ahn HY. Regulation of type IV collagen? chains of glomerular epithelial cells in diabetic conditions. Journal of Korean Medical Science 2009; 24(5): 837-843. http://doi.org/10.3346/jkms.2009.24.5.837

Yuan WJ, Jia FY, Meng JZ. Effects of genistein on secretion of extracellular matrix components and transforming growth factor beta in high-glucose-cultured rat mesangial cells. Journal of Artificial Organs 2009. http://doi.org/10.1007/s10047-009-0479-y

Cao C, Li S, Dai X, Chen Y, Feng Z, Zhao Y, Wu J. Genistein inhibits proliferation and functions of hypertrophic scar fibroblasts - Burns 2009; 35: 89-97. http://doi.org/10.1016/j.burns.2008.03.011

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Copyright (c) 2018 Putri Dafriani , Nur Indrawati Lipoeto , Yanwirasti , Amri Bakhtiar  , Roza Marlinda