Protective effect of berberine on renal fibrosis caused by diabetic nephropathy

Li,Zhong; Zhang,Wei

doi:10.3892/mmr.2017.6707

Protective effect of berberine on renal fibrosis caused by diabetic nephropathy

Authors:
- Zhong Li
- Wei Zhang
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Affiliations: The Clinical Teaching and Research Department, School of Zhang Zhongjing Traditional Chinese Medicine, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China
Published online on: June 7, 2017 https://doi.org/10.3892/mmr.2017.6707
Pages: 1055-1062
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Berberine (BBR) is a material extracted from Chinese herbs, which has been used in the treatment of diabetes in Chinese medicine for thousands of years. However, the importance of BBR in renal fibrosis remains to be elucidated. In the present study, streptozotocin‑induced diabetic nephropathy (DN) rats were used to determine the effect of BBR on renal fibrosis. The pathology of the kidneys was examined using periodic acid‑Schiff (PAS) and Masson staining. The expression levels of transforming growth factor‑β (TGF‑β) and α smooth muscle actin (α‑SMA) in kidneys were observed using immunohistochemical staining. The mRNA and protein expression levels of TGF‑β, α‑SMA, vimentin, nuclear factor‑κB were examined using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. PAS and Masson staining revealed that there was notable glomerular hypertrophy and mesangial matrix expansion in DN rats. Immunohistochemistry revealed that there was a significant increase in TGF‑β and α‑SMA expression levels in the renal tubulointerstitium and the extracellular matrix. However, treatment with BBR may significantly reduce kidney injury. The protein and mRNA expression levels of TGF‑β, vimentin and α‑SMA were significantly increased in DN rats compared with the control group; however, this increase was reduced following treatment with BBR. The present study revealed that BBR may inhibit fibrosis and ameliorate the symptoms of DN. The current findings indicated that BBR may be used as a potential treatment for patients with DN.

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1	Atkins RC and Zimmet P: Diabetic kidney disease: Act now or pay later. Kidney Int. 77:375–377. 2010. View Article : Google Scholar : PubMed/NCBI
2	Cooper ME: Diabetes: Treating diabetic nephropathy-still an unresolved issue. Nat Rev Endocrinol. 8:515–516. 2012. View Article : Google Scholar : PubMed/NCBI
3	Reidy K, Kang HM, Hostetter T and Susztak K: Molecular mechanisms of diabetic kidney disease. J Clin Invest. 124:2333–2340. 2014. View Article : Google Scholar : PubMed/NCBI
4	Badal SS and Danesh FR: New insights into molecular mechanisms of diabetic kidney disease. Am J Kidney Dis. 63 2 Suppl 2:S63–S83. 2014. View Article : Google Scholar : PubMed/NCBI
5	Fan Y, Li X, Xiao W, Fu J, Harris RC, Lindenmeyer M, Cohen CD, Guillot N, Baron MH, Wang N, et al: BAMBI elimination enhances alternative TGF-β signaling and glomerular dysfunction in diabetic mice. Diabetes. 64:2220–2233. 2015. View Article : Google Scholar : PubMed/NCBI
6	Du J, Hong S, Dong L, Cheng B, Lin L, Zhao B, Chen YG and Chen X: Dynamic sialylation in transforming growth factor-β (TGF-β)-induced epithelial to mesenchymal transition. J Biol Chem. 290:12000–12013. 2015. View Article : Google Scholar : PubMed/NCBI
7	Chen KH, Hung CC, Hsu HH, Jing YH, Yang CW and Chen JK: Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats. Chem Biol Interact. 190:45–53. 2011. View Article : Google Scholar : PubMed/NCBI
8	Chen X, Zhang Y, Zhu Z, Liu H, Guo H, Xiong C, Xie K, Zhang X and Su S: Protective effect of berberine on doxorubicin-induced acute hepatorenal toxicity in rats. Mol Med Rep. 13:3953–3960. 2016.PubMed/NCBI
9	Adil M, Kandhare AD, Dalvi G, Ghosh P, Venkata S, Raygude KS and Bodhankar SL: Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Ren Fail. 38:996–1006. 2016. View Article : Google Scholar : PubMed/NCBI
10	Liu C, Wang Z, Song Y, Wu D, Zheng X, Li P, Jin J, Xu N and Li L: Effects of berberine on amelioration of hyperglycemia and oxidative stress in high glucose and high fat diet-induced diabetic hamsters in vivo. Biomed Res Int. 2015:3138082015.PubMed/NCBI
11	Zhang H, Li P, Burczynski FJ, Gong Y, Choy P, Sha H and Li J: Attenuation of diabetic nephropathy in otsuka long-evans tokushima fatty (OLETF) rats with a combination of Chinese herbs (Tangshen Formula). Evid Based Complement Alternat Med. 2011:6137372011. View Article : Google Scholar : PubMed/NCBI
12	Zhao TT, Zhang HJ, Lu XG, Huang XR, Zhang WK, Wang H, Lan HY and Li P: Chaihuang-Yishen granule inhibits diabetic kidney disease in rats through blocking TGF-β/Smad3 signaling. PLoS One. 9:e908072014. View Article : Google Scholar : PubMed/NCBI
13	Hou CC, Wang W, Huang XR, Fu P, Chen TH, Sheikh-Hamad D and Lan HY: Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney. Am J Pathol. 166:761–771. 2005. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Liu SF, Chang SY, Lee TC, Chuang LY, Guh JY, Hung CY, Hung TJ, Hung YJ, Chen PY, Hsieh PF and Yang YL: Dioscorea alata attenuates renal interstitial cellular fibrosis by regulating Smad- and epithelial-mesenchymal transition signaling pathways. PLoS One. 7:e474822012. View Article : Google Scholar : PubMed/NCBI
16	Renno WM, Abdeen S, Alkhalaf M and Asfar S: Effect of green tea on kidney tubules of diabetic rats. Br J Nutr. 100:652–659. 2008. View Article : Google Scholar : PubMed/NCBI
17	Kuo CW, Shen CJ, Tung YT, Chen HL, Chen YH, Chang WH, Cheng KC, Yang SH and Chen CM: Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling. Life Sci. 135:77–86. 2015. View Article : Google Scholar : PubMed/NCBI
18	Wang J, Liu H, Li N, Zhang Q and Zhang H: The protective effect of fucoidan in rats with streptozotocin-induced diabetic nephropathy. Mar Drugs. 12:3292–3306. 2014. View Article : Google Scholar : PubMed/NCBI
19	Mapanga RF, Tufts MA, Shode FO and Musabayane CT: Renal effects of plant-derived oleanolic acid in streptozotocin-induced diabetic rats. Ren Fail. 31:481–491. 2009. View Article : Google Scholar : PubMed/NCBI
20	Rodell CB, Rai R, Faubel S, Burdick JA and Soranno DE: Local immunotherapy via delivery of interleukin-10 and transforming growth factor β antagonist for treatment of chronic kidney disease. J Control Release. 206:131–139. 2015. View Article : Google Scholar : PubMed/NCBI
21	Yang Y, Kim B, Park YK, Koo SI and Lee JY: Astaxanthin prevents TGFβ1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells. Biochim Biophys Acta. 1850:178–185. 2015. View Article : Google Scholar : PubMed/NCBI
22	Lu J, Shi J, Li M, Gui B, Fu R, Yao G, Duan Z, Lv Z, Yang Y, Chen Z, et al: Activation of AMPK by metformin inhibits TGF-β-induced collagen production in mouse renal fibroblasts. Life Sci. 127:59–65. 2015. View Article : Google Scholar : PubMed/NCBI
23	Hinz B, Celetta G, Tomasek JJ, Gabbiani G and Chaponnier C: Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell. 12:2730–2741. 2001. View Article : Google Scholar : PubMed/NCBI
24	Ramos AM, González-Guerrero C, Sanz A, Sanchez-Niño MD, Rodríguez-Osorio L, Martín-Cleary C, Fernández-Fernández B, Ruiz-Ortega M and Ortiz A: Designing drugs that combat kidney damage. Expert Opin Drug Discov. 10:541–556. 2015. View Article : Google Scholar : PubMed/NCBI
25	Meng XM, Tang PM, Li J and Lan HY: TGF-β/Smad signaling in renal fibrosis. Front Physiol. 6:822015. View Article : Google Scholar : PubMed/NCBI
26	Meng LQ, Tang JW, Wang Y, Zhao JR, Shang MY, Zhang M, Liu SY, Qu L, Cai SQ and Li XM: Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive nephropathy. Br J Pharmacol. 162:1805–1818. 2011. View Article : Google Scholar : PubMed/NCBI
27	Yao J, Kong W and Jiang J: Learning from berberine: Treating chronic diseases through multiple targets. Sci China Life Sci. 58:854–859. 2015. View Article : Google Scholar : PubMed/NCBI
28	Singh IP and Mahajan S: Berberine and its derivatives: A patent review (2009–2012). Expert Opin Ther Pat. 23:215–231. 2013. View Article : Google Scholar : PubMed/NCBI