Effects of Tang Shen 2 Hao Fang, a Traditional Chinese Medicine, on Diabetic Nephropathy in Sprague–Dawley Rats doi.org/10.26538/tjnpr/v5i10.20
Main Article Content
Abstract
Diabetic nephropathy is a chronic disease characterized by a reduced glomerular filtration rate. Kidney disease is a microvascular complication of diabetes mellitus, which can eventually lead to end-stage renal disease and threaten patient health. This study aimed to evaluate the effects of Tang Shen 2 Hao Fang (TS2HF), a traditional Chinese medicine formulation, on rats with diabetic nephropathy induced by streptozotocin injection and a high-fat diet. Rats were given TS2HF at doses of 11.57 and 23.14 g/kg/day. Rat weight, blood glucose levels, and blood lipid indices were measured, and renal function was assessed by blood urea, creatinine, and 24-hour urine albumin. Antioxidant effects were evaluated via serum superoxide dismutase (SOD) activity and glutathione (GSH). The anti-inflammatory effects of TS2HF were evaluated by measuring the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF- ????) using quantitative ELISA. The kidney weights and kidney/body weight ratios were also determined. The results demonstrated that TS2HF reduced kidney injury complications. TS2HF decreased triglycerides, total cholesterol, and low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL). TS2HF decreased the cytokines IL-6 and TNF-???? and increased SOD and GSH levels in rat serum. It also protected against weight loss, decreased the glomerular size, decreased glomerular and interstitial fibrosis, and reduced the proliferation of endothelial and intercapillary cells in rats with diabetic nephropathy. These results suggest that TS2HF has anti-diabetic and anti-nephropathic activities.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Xu Y, Wang L, He J, Bi Y, Li M, Wang T, Wang L, Jiang Y, Dai M, Lu J, Xu M, Li Y, Hu N, Li J, Mi S, Chen CS, Li G, Mu
Y, Zhao J, Kong L, Chen J, Lai S, Wang W, Zhao W, Ning G. 2010 China Noncommunicable Disease Surveillance Group.
Prevalence and control of diabetes in Chinese adults. J Am Med Assoc. 2013; 310(9):948-959.
Zhang L, Long J, Jiang W, Shi Y, He X, Zhou Z, Li Y, Yeung RO, Wang J, Matsushita K, Coresh J, Zhao MH, Wang H.
Trends in Chronic Kidney Disease in China. N Engl J Med. 2016; 375(9):905-906.
Li G, Qiao Y, Lu Y, Liu S, Ding Y, Chen X, Ke C. Role of handgrip strength in predicting new-onset diabetes: findings
from the survey of health, ageing and retirement in Europe. BMC Geriatr. 2021; 21(1):445.
Lu CC, Hu ZB, Wang R, Hong ZH, Lu J, Chen PP, Zhang JX, Li XQ, Yuan BY, Huang SJ, Ruan XZ, Liu BC, Ma KL. Gut
microbiota dysbiosis-induced activation of the intrarenal reninangiotensin system is involved in kidney injuries i rat diabetic nephropathy. Acta Pharmacol Sin. 2020; 41(8):1111-1118.
Satirapoj B and Adler SG. Prevalence and Management of Diabetic Nephropathy in Western Countries. Kidney Dis. 2015; 1(1):61-70.
Tomino Y and Gohda T. The Prevalence and Management of Diabetic Nephropathy in Asia. Kidney Dis (Basel). 2015;
(1):52-60.
Wolf G and Ziyadeh FN. Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Nephron Physiol. 2007; 106(2):26-31.
Al-Waili N, Al-Waili H, Al-Waili T, Salom K. Natural antioxidants in the treatment and prevention of diabetic
nephropathy; a potential approach that warrants clinical trials. Redox Rep. 2017; 22(3):99-118
Pofi R, Di Mario F, Gigante A, Rosato E, Isidori AM, Amoroso A, Cianci R, Barbano B. Diabetic Nephropathy: Focus on
Current and Future Therapeutic Strategies. Curr Drug Metab. 2016; 17(5):497-502.
Tang G, Li S, Zhang C, Chen H, Wang N, Feng Y. Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management. Acta Pharm Sin B. 2021; 11(9):2749-2767.
Nair AB and Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm.
; 7(2):27-31.
Peng L, Li J, Xu Y, Wang Y, Du H, Shao J, Liu Z. The Protective Effect of Beraprost Sodium on Diabetic Nephropathy
by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats. Int J Endocrinol. 2016; 2016:1690474.
Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM. A new rat model of type 2 diabetes:
the fat-fed, streptozotocin-treated rat. Metab. 2000; 49(11):1390-1394.
Mansor LS, Gonzalez ER, Cole MA, Tyler DJ, Beeson JH, Clarke K, Carr CA, Heather LC. Cardiac metabolism in a new
rat model of type 2 diabetes using high-fat diet with low dose streptozotocin. Cardiovasc Diabetol. 2013; 12:136.
Guo XX, Wang Y, Wang K, Ji BP, Zhou F. Stability of a type 2 diabetes rat model induced by high-fat diet feeding with lowdose streptozotocin injection. J Zhejiang Univ Sci B. 2018; 19(7):559-569.
Wen W, Lin Y, Ti Z. Antidiabetic, Antihyperlipidemic, Antioxidant, Anti-inflammatory Activities of Ethanolic Seed
Extract of Annona reticulata L. in Streptozotocin Induced Diabetic Rats. Front Endocrinol (Lausanne). 2019; 10:716.
Ni Z, Guo L, Liu F, Olatunji OJ, Yin M. Allium tuberosum alleviates diabetic nephropathy by supressing hyperglycemiainduced oxidative stress and inflammation in high fat diet/streptozotocin treated rats. Biomed Pharmacother. 2019; 112:108678.
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/StreptozotocinInduced Diabetic Rat. Sci Rep. 2017;7(1):2263.
Zhou X, Sun X, Gong X, Yang Y, Chen C, Shan G, Yao Q. Astragaloside IV from Astragalus membranaceus ameliorates
renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кB in vivo and in vitro. Int Immunopharmacol. 2017;
:18-24.
Shahzad M, Shabbir A, Wojcikowski K, Wohlmuth H, Gobe GC. The Antioxidant Effects of Radix Astragali (Astragalus
membranaceus and Related Species) in Protecting Tissues from Injury and Disease. Curr Drug Targets. 2016; 17(12):1331-1340.
Elsherbiny NM, Said E, Atef H, Zaitone SA. Renoprotective effect of calycosin in high fat diet-fed/STZ injected rats: Effect on IL-33/ST2 signaling, oxidative stress and fibrosis suppression. Chem Biol Interact. 2020; 315:108897.
Zhai X, Lenon GB, Xue CC, Li CG. Euonymus alatus: A Review on Its Phytochemistry and Antidiabetic Activity. Evid
Based Complement Alternat Med. 2016; 2016:9425714.
Chang B, Jin C, Zhang W, Kong L, Yang JH, Lian FM, Li QF, Yu B, Liu WK, Yang LL, Zhao P, Zhen Z. Euonymus alatus in
the treatment of diabetic nephropathy in rats. Am J Chin Me. 2012; 40(6):1177-1187.
Oh BK, Mun J, Seo HW, Ryu SY, Kim YS, Lee BH, Oh KS. Euonymus alatus extract attenuates LPS-induced NF-κB
activation via IKKβ inhibition in RAW 264.7 cells. J Ethnopharmacol. 2011;134(2):288-293.
Chen K, Deng D, Huang Y, Ma X, Li X, Zhang W, Li Z, Liu Y, Wang W, Chen J, Zhao HH. Combination of Astragalus
membranaceus and Euonymus alatus (THUNB.) SIEB. for treatment of diabetes: A network-based pharmacology research. J Tradit Chinese Med Sci. 2016; 3(3):184-191.
Zeng JY, Wang Y, Miao M, Bao XR. The Effects of Rhubarb for the Treatment of Diabetic Nephropathy in Animals: A Systematic Review and Meta-analysis. Front Pharmacol. 2021; 12:602816.
Cheng FR, Cui HX, Fang JL, Yuan K, Guo Y. Ameliorative Effect and Mechanism of the Purified Anthraquinone-Glycoside Preparation from Rheum palmatum L. on Type 2 Diabetes Mellitus. Molecules. 2019; 24(8):1454.
Jin D, Huang WJ, Meng X, Yang F, Bao Q, Zhang MZ, Yang YN, Ni Q, Lian FM, Tong XL. Chinese herbal medicine
Tangshen Formula treatment for type 2 diabetic kidney disease in the early stage: study protocol for a randomized controlled trial. Trials. 2019; 20:756.
Fan XM, Huang CL, Wang YM, Li N, Liang QL, Luo GA. Therapeutic Effects of Tangshen Formula on Diabetic
Nephropathy in db/db Mice Using Cytokine Antibody Array. J Diabetes Res. 2018; 2018:8237590.
Huang M, Xie Y, Chen L, Chu K, Wu S, Lu J, Chen X, Wang Y, Lai X. Antidiabetic effect of the total polyphenolic acids
fraction from Salvia miltiorrhiza Bunge in diabetic rats. Phytother Res. 2012; 26(6):944-948.
Su CY, Ming QL, Rahman K, Han T, Qin LP. Salvia miltiorrhiza: Traditional medicinal uses, chemistry, and
pharmacology. Chin J Nat Med. 2015; 13(3):163-182. 32. Mir MA, Upadhyay S, Mir BA. Inhibition of alpha amylase and alpha glycosidase enzymes by various earth worm extracts. Biomed Pharmacol J. 2018; 11(3):1261-1268.
Gupta M, Mazumder UK, Kumar RS, Gomathi P, Rajeshwar Y, Kakoti BB, Selven VT. Anti-inflammatory, analgesic and
antipyretic effects of methanol extract from Bauhinia racemosastem bark in animal models. J Ethnopharmacol. 2005;
(3):267-273.
Balamurugan M, Parthasarathi K, Cooper EL, Ranganathan LS. Anti-inflammatory and anti-pyretic activities of earthworm extract-Lampito mauritii (Kinberg). J Ethnopharmacol. 2009; 121(2):330-332.
Chen Z, Yuan Y, Zou X, Hong M, Zhao M, Zhao Y, Liu Y, Li G, Zhu Y, Luo L, Bao B, Bu S. Radix Puerariae and Fructus
Crataegi mixture inhibits renal injury in type 2 diabetes via decreasing of AKT/PI3K. BMC Compl Altern Med. 2017;
(1):454.
Fang ZH, Duan XC, Zhao JD, Wu YJ, Liu MM. Novel Polysaccharide H-1-2 from Pseudostellaria heterophylla Alleviates Type 2 Diabetes Mellitus. Cell Physiol Biochem. 2018; 49(3):996-1006.
Ebefors K, Granqvist A, Ingelsten M, Mölne J, Haraldsson B, Nyström J. Role of glomerular proteoglycans in IgA
nephropathy. PLoS One. 2011; 6(4):e18575.
Xia M, Liu D, Peng L, Li Y, Liu H, Wu L, Chen G, Liu Y, Liu H. Coagulation parameters are associated with the prognosis of immunoglobulin a nephropathy: a retrospective study. BMC Nephrol. 2020; 21(1):447.