The Selected Traditional Chinese Medicinal Formulas for Treating Diabetic Nephropathy: Perspective of Modern Science

10.4103/2225-4110.114893

Thing-Fong Tzeng；Shorong-Shii Liou；I-Min Liu

Danggui-Buxue-Tang ； Danggui-Shaoyao-San ； Diabetic nephropathy ； Traditional Chinese medicine ； Wu-Ling-San

Journal of Traditional and Complementary Medicine

3卷3期（2013 / 07 / 01）

152 - 158

英文

With the increasing patients and limited therapeutic options, diabetic nephropathy (DN) is a long-term complication of diabetic mellitus. The precise mechanism of DN is not yet fully understood and the effective blockade of the progression of nephropathy remains a therapeutic challenge. Application of traditional Chinese medicine (TCM) for diabetes and its related complications has received increasing attention due to its wide availability, low side effects, and proven therapeutic mechanisms and benefits. In the current review, we mainly focus on the recent laboratory studies of the TCM formulas including Wu-Ling-San (Poria Five Powder; 五苓散 Wǔ Líng Sǎn), Danggui-Buxue-Tang (Tangkuei and Astragalus Decoction; 當歸補血湯 Dāng Guī Bǔ Xuè Tang), and Danggui-Shaoyao-San (Tangkuei and Paeonia Formula; 當歸芍藥散 Dāng Guī Sháo Yào Sǎn), conducted by the Committee on Chinese Medicine and Pharmacy at the Department of Health of Taiwan Government, in the amelioration of DN. These selected TCM formulas have anti-diabetic properties, with antihyperglycemic activity accompanied by amelioration of advanced glycation end product-mediated renal damage in streptozotocin-induced diabetic rats. However, the renoprotective effects of the selected TCM formulas did not correlate with suppressing renal renin-angiotensin system hyperactivity in diabetic rats. These TCM formulas also have the capacity to ameliorate the defective antioxidative defense system, leading to modulation of the oxidative stress, thereby resulting in downregulation of nuclear factor-kB as well as transforming growth factor-β_1 and, consequently, attenuation of extracellular matrix components such as fibronectin or type IV collagen expression in diabetic renal cortex tissue. More detailed mechanistic researches and long-term clinical evaluations, as well as evaluation of safety of the selected TCM formulas are needed for their future applications in DN therapy.

1. Arredondo, A.(2013).Diabetes: A global challenge with high economic burden for public health systems and society.Am J Public Health,103,e1-e2.
2. Benigni, A,Zoja, C,Corna, D,Zatelli, C,Conti, S,Campana, M(2003).Add‑on anti‑TGF‑beta antibody to ACE inhibitor arrests progressive diabetic nephropathy in the rat.J Am Soc Nephrol,14,1816-1824.
3. Chen, DA(1998).Treating 27 cases of edema in the lower limbs with Wu Ling San.Xinjiang Zhong Yi Yao,16,19-20.
4. Chen, L,Qi, J,Chang, YX,Zhu, D,Yu, B(2009).Identification and determination of the major constituents in Traditional Chinese Medicinal formula Danggui‑Shaoyao‑San by HPLC‑DAD‑ESI‑MS/MS.J Pharm Biomed Anal,50,127-137.
5. Cheng, JT(2000).Review: Drug therapy in Chinese traditional medicine.J Clin Pharmacol,40,445-450.
6. Cruzado, JM,Lloberas, N,Torras, J,Riera, M,Fillat, C,Herrero‑Fresneda, I(2004).Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats.Diabetes,53,1119-1127.
7. De Angelis, C,Drazen, JM,Frizelle, FA,Haug, C,Hoey, J,Horton, R(2004).Clinical trial registration: A statement from the international committee of medical journal editors.N Z Med J,117,U1054.
8. Dominguez, JH,Tang, N,Xu, W,Evan, AP,Siakotos, AN,Agarwal, R(2000).Studies of renal injury III: Lipid‑induced nephropathy in type II diabetes.Kidney Int,57,92-104.
9. Dong, H,He, L,Huang, M,Dong, Y(2008).Anti‑inflammatory components isolated from Atractylodes macrocephala Koidz.Nat Prod Res,22,1418-1427.
10. Dong, TT,Zhao, KJ,Gao, QT,Ji, ZN,Zhu, TT,Li, J(2006).Chemical and biological assessment of a chinese herbal decoction containing Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having optimized properties.J Agric Food Chem,54,2767-2774.
11. Falk, RJ,Scheinman, JI,Mauer, SM,Michael, AF(1983).Polyantigenic expansion of basement membrane constituents in diabetic nephropathy.Diabetes,32,34-39.
12. Fu, MX,Requena, JR,Jenkins, AJ,Lyons, TJ,Baynes, JW,Thorpe, SR(1996).The advanced glycation end product, Nepsilon‑(carboxymethyl) lysine, is a product of both lipid peroxidation and glycoxidation reactions.J Biol Chem,271,9982-9986.
13. Glandt, M,Bloomgarden, ZT(2011).Hypertension in diabetes: Treatment considerations.J Clin Hypertens,13,314-318.
14. Guangdong Medical Journal Editorial Department(1982).Clinical observation of curative effects of Wu Ling San for treatment of glaucoma.Guangdong Yi Xue,3,40.
15. Hatip‑Al‑Khatib, I,Egashira, N,Mishima, K,Iwasaki, K,Iwasaki, K,Kurauchi, K(2004).Determination of the effectiveness of components of the herbal medicine Toki‑Shakuyaku‑San and fractions of Angelica acutiloba in improving the scopolamine‑induced impairment of rat’s spatial cognition in eight‑armed radial maze test.J Pharmacol Sci,96,33-41.
16. Hattori, T,Fujitsuka, N,Kurogi, A,Shindo, S(1997).Sairei‑to may inhibit the synthesis of endothelin‑1 in nephritic glomeruli.Nippon Jinzo Gakkai Shi,39,121-128.
17. He, L,Rong, X,Jiang, JM,Liu, PQ,Li, Y(2008).Amelioration of anti‑cancer agent adriamycin‑induced nephrotic syndrome in rats by Wulingsan (Gorei‑San), a blended traditional Chinese herbal medicine.Food Chem Toxicol,46,1452-1460.
18. Hodge, HC,Downs, WL,Panner, BS,Smith, DW,Maynard, EA(1967).Oral toxicity and metabolism of diuron (N‑(3,4‑dichlorophenyl)‑N’, N’‑dimethylurea) in rats and dogs.Food Cosmet Toxicol,5,513-531.
19. Hong, SW,Isono, M,Chen, S,Iglesias‑De La Cruz, MC,Han, DC,Ziyadeh, FN(2001).Increased glomerular and tubular expression of transforming growth factor‑beta1, its type II receptor, and activation of the Smad signaling pathway in the db/db mouse.Am J Pathol,158,1653-1663.
20. Hsieh, CC,Lin, WC,Lee, MR,Hsu, SL,Liu, HS,Kao, ST(2003).Dang‑Gui‑Bu‑Xai‑Tang modulated the immunity of tumor bearing mice.Immunopharmacol Immunotoxicol,25,259-271.
21. Huang, WY,Sheu, SJ(2006).Separation and identification of the organic acids in Angelicae Radix and Ligustici Rhizoma by HPLC and CE.J Sep Sci,29,2616-2624.
22. Huang, YT,Huang, DM,Chueh, SC,Teng, CM,Guh, JH(2006).Alisol B acetate, a triterpene from Alismatis rhizoma, induces Bax nuclear translocation and apoptosis in human hormone‑resistant prostate cancer PC‑3 cells.Cancer Lett,231,270-278.
23. Huntley, AL,Ernst, E(2003).A systematic review of herbal medicinal products for the treatment of menopausal symptoms.Menopause,10,465-476.
24. Janero, DR,Burghardt, B(1988).Analysis of cardiac membrane phospholipid peroxidation kinetics as malondialdehyde: Nonspecificity of thiobarbituric acid‑reactivity.Lipids,23,452-458.
25. Janiak, P,Bidouard, JP,Cadrouvele, C,Poirier, B,Gouraud, L,Grataloup, Y(2006).Long‑term blockade of angiotensin AT1 receptors increases survival of obese Zucker rats.Eur J Pharmacol,534,271-279.
26. Jiang, H,Shen, Y,Wang, XG(2010).Current progress of Chinese medicinal treatment of endometriosis.Chin J Integr Med,16,283-288.
27. Kano, Y,Takaguchi, S,Nohno, T,Hiragami, F,Kawamura, K,Iwama, MK(2002).Chinese medicine induces neurite outgrowth in PC12 mutant cells incapable of differentiation.Am J Chin Med,30,287-295.
28. Kanwar, YS,Wada, J,Sun, L,Xie, P,Wallner, EI,Chen, S(2008).Diabetic nephropathy: Mechanisms of renal disease progression.Exp Biol Med,233,4-11.
29. Kikuchi, T,Uchiyama, E,Ukiya, M,Tabata, K,Kimura, Y,Suzuki, T(2011).Cytotoxic and apoptosis‑inducing activities of triterpene acids from Poria cocos.J Nat Prod,74,137-144.
30. Kolasinska‑Malkowska, K,Filipiak, KJ,Gwizdala, A,Tykarski, A(2008).Current possibilities of ACE inhibitor and ARB combination in arterial hypertension and its complications.Expert Rev Cardiovasc Ther,6,759-771.
31. Kotani, N,Oyama, T,Sakai, I,Hashimoto, H,Muraoka, M,Ogawa, Y(1997).Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea‑a double‑blind study.Am J Chin Med,25,205-212.
32. Koya, D,Hayashi, K,Kitada, M,Kashiwagi, A,Kikkawa, R,Haneda, M(2003).Effects of antioxidants in diabetes‑induced oxidative stress in the glomeruli of diabetic rats.J Am Soc Nephrol,14,S250-S253.
33. Lee, BC,Choi, JB,Cho, HJ,Kim, YS(2009).Rehmannia glutinosa ameliorates the progressive renal failure induced by 5 ⁄ 6 nephrectomy.J Ethnopharmacol,122,131-135.
34. LeRoith, D,Rayfield, EJ(2007).The benefits of tight glycemic control in type 2 diabetes mellitus.Clin Cornerstone,8(Suppl 7),S19-S29.
35. Li, JH,Huang, XR,Zhu, HJ,Johnson, R,Lan, HY(2003).Role of TGF‑beta signaling in extracellular matrix production under high glucose conditions.Kidney Int,63,2010-2019.
36. Liu, IM,Tzeng, TF,Liou, SS(2011).A Chinese herbal decoction, Dang Gui Bu Xue Tang, prepared from Radix Astragali and Radix Angelicae sinensis, ameliorates insulin resistance induced by a high‑fructose diet in rats.Evid Based Complement Alternat Med,2011,248231.
37. Liu, IM,Tzeng, TF,Liou, SS,Chang, CJ(2009).The amelioration of streptozotocin diabetes‑induced renal damage by Wu‑Ling‑San (Hoelen Five Herb Formula), a traditional Chinese prescription.J Ethnopharmacol,124,211-218.
38. Liu, IM,Tzeng, TF,Liou, SS,Chang, CJ(2012).Beneficial effect of traditional chinese medicinal formula danggui‑shaoyao‑san on advanced glycation end‑product‑mediated renal injury in streptozotocin‑diabetic rats.Evid Based Complement Alternat Med,2012,140103.
39. Liu, QL,Sato, S,Kishikawa, T,Matsuzaki, H,Yamanaka, N(2001).Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats.Med Electron Microsc,34,103-114.
40. Lv, ZM,Wang, Q,Wan, Q,Lin, JG,Hu, MS,Liu, YX(2011).The role of the p38 MAPK signaling pathway in high glucose‑induced epithelial‑mesenchymal transition of cultured human renal tubular epithelial cells.PLoS One,6,e22806.
41. Mima, A,Matsubara, T,Arai, H,Abe, H,Nagai, K,Kanamori, H(2006).Angiotensin II‑dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy.Lab Invest,86,927-939.
42. Miyazono, K.(2000).TGF‑beta signaling by Smad proteins.Cytokine Growth Factor Rev,11,15-22.
43. Monkawa, T,Hiromura, K,Wolf, G,Shankland, SJ(2002).The hypertrophic effect of transforming growth factor‑beta is reduced in the absence of cyclin‑dependent kinase‑inhibitors p21 and p27.J Am Soc Nephrol,13,1172-1178.
44. Ning, L,Chen, CX,Jin, RM,Wu, YP,Zhang, HG,Sun, CL(2002).Effect of components of dang‑gui‑bu‑xue decoction on hematopenia.Zhongguo Zhong Yao Za Zhi,27,50-53.
45. Okazaki, T,Sakon, S,Sasazuki, T,Sakurai, H,Doi, T,Yagita, H(2003).Phosphorylation of serine 276 is essential for p65 NF‑kappaB subunit‑dependent cellular responses.Biochem Biophys Res Commun,300,807-812.
46. Poon, TY,Ong, KL,Cheung, BM(2011).Review of the effects of the traditional Chinese medicine Rehmannia six formula on diabetes mellitus and its complications.J Diabetes,3,184-200.
47. Rossing, P(2006).Diabetic nephropathy: Worldwide epidemic and effects of current treatment on natural history.Curr Diab Rep,6,479-483.
48. Satchell, SC,Tooke, JE(2008).What is the mechanism of microalbuminuria in diabetes: A role for the glomerular endothelium?.Diabetologia,51,714-725.
49. Schnaper, HW,Hayashida, T,Hubchak, SC,Poncelet, AC(2003).TGF‑beta signal transduction and mesangial cell fibrogenesis.Am J Physiol Renal Physiol,284,243-252.
50. Schrijvers, BF,De Vriese, AS(2007).Novel insights in the treatment of diabetic nephropathy.Acta Clin Belg,62,278-290.
51. Schrijvers, BF,De Vriese, AS,Flyvbjerg, A(2004).From hyperglycemia to diabetic kidney disease: The role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines.Endocr Rev,25,971-1010.
52. Seifried, HE,Anderson, DE,Fisher, EI,Milner, JA(2007).A review of the interaction among dietary antioxidants and reactive oxygen species.J Nutr Biochem,18,567-579.
53. Song, ZH,Ji, ZN,Lo, CK,Dong, TT,Zhao, KJ,Li, OT(2004).Chemical and biological assessment of a traditional chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis: Orthogonal array design to optimize the extraction of chemical constituents.Planta Med,70,1222-1227.
54. Tian, YC,Fraser, D,Attisano, L,Phillips, AO(2003).TGF‑beta1‑mediated alterations of renal proximal tubular epithelial cell phenotype.Am J Physiol Renal Physiol,285,130-142.
55. Tsai, HY,Lin, YT,Tsai, CH,Chen, YF(2001).Effects of paeoniflorin on the formalin‑induced nociceptive behaviour in mice.J Ethnopharmacol,75,267-271.
56. Vivian, EM(2006).Type 2 diabetes in children and adolescents‑the next epidemic?.Curr Med Res Opin,22,297-306.
57. Yamagishi, S,Matsui, T(2010).Advanced glycation end products, oxidative stress and diabetic nephropathy.Oxid Med Cell Longev,3,101-108.
58. Yoshimura, K,Miyake, O,Okuyama, A,Yoshioka, T,Honda, M,Yamaguchi, S(1998).Effect of chorei‑to and gorei‑san on calcium oxalate crystallization in human urine.Hinyokika Kiyo,44,13-16.
59. Zhang, YW,Xie, D,Xia, B,Zhen, RT,Liu, IM,Cheng, JT(2006).Suppression of transforming growth factor‑beta1 gene expression by Danggui buxue tang, a traditional Chinese herbal preparation, in retarding the progress of renal damage in streptozotocin‑induced diabetic rats.Horm Metab Res,38,82-88.