Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Evaluating Pharmacological Effects of Two Major Components of Shuangdan Oral Liquid: Role of Danshensu and Paeonol in Diabetic Nephropathy Rat

  • Chen, Ying (Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University) ;
  • Liu, Zhuying (State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, Fourth Military Medical University) ;
  • Zhou, Fuxing (Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University) ;
  • Zhao, Hang (Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University) ;
  • Yang, Qian (Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University) ;
  • Li, Hua (Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University) ;
  • Sun, Jiyuan (Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University) ;
  • Wang, Siwang (Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University)
  • Received : 2015.11.26
  • Accepted : 2016.06.30
  • Published : 2016.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms.

Keywords

References

  1. Ayo, S. H., Radnik, R. A., Garoni, J. A., Glass, W. F., 2nd and Kreisberg, J. I. (1990) High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am. J. Pathol. 136, 1339-1348.
  2. Azadbakht, L. and Esmaillzadeh, A. (2009) Soy-protein consumption and kidney-related biomarkers among type 2 diabetics: a crossover, randomized clinical trial. J. Ren. Nutr. 19, 479-486. https://doi.org/10.1053/j.jrn.2009.06.002
  3. Azadbakht, L., Atabak, S. and Esmaillzadeh, A. (2008) Soy protein intake, cardiorenal indices, and C-reactive protein in type 2 diabetes with nephropathy: a longitudinal randomized clinical trial. Diabetes Care 31, 648-654. https://doi.org/10.2337/dc07-2065
  4. Chan, K., Chui, S. H., Wong, D. Y., Ha, W. Y., Chan, C. L. and Wong, R. N. (2004) Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction. Life Sci. 75, 3157-3171. https://doi.org/10.1016/j.lfs.2004.06.010
  5. Dai, M., Liu, Q. Y., Gu, C. G. and Zhang, H. Y. (2000) Inhibitory effect of paeonol on lipid peroxidational reaction and oxidational decorate of low density lipoprotein. Zhongguo Zhong Yao Za Zhi 25, 625-627.
  6. Dewanjee, S., Das, A. K., Sahu, R. and Gangopadhyay, M. (2009) Antidiabetic activity of Diospyros peregrina fruit: effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes. Food Chem. Toxicol. 47, 2679-2685. https://doi.org/10.1016/j.fct.2009.07.038
  7. Giacco, F. and Brownlee, M. (2010) Oxidative stress and diabetic complications. Circ. Res. 107, 1058-1070. https://doi.org/10.1161/CIRCRESAHA.110.223545
  8. Gregg, E. W., Li, Y., Wang, J., Burrows, N. R., Ali, M. K., Rolka, D., Williams, D. E. and Geiss, L. (2014) Changes in diabetes-related complications in the United States, 1990-2010. N. Engl. J. Med. 370, 1514-1523. https://doi.org/10.1056/NEJMoa1310799
  9. Guan, Y., Wu, X. X., Duan, J. L., Yin, Y., Guo, C., Wei, G., Wang, Y. H., Zhu, Y. R., Weng, Y., Xi, M. M. and Wen, A. D. (2015) Effects and mechanism of combination of rhein and danshensu in the treatment of chronic kidney disease. Am. J. Chin. Med. 43, 1381-1400. https://doi.org/10.1142/S0192415X15500780
  10. Haffner, S. M. and Miettinen, H. (1997) Insulin resistance implications for type II diabetes mellitus and coronary heart disease. Am. J. Med. 103, 152-162. https://doi.org/10.1016/S0002-9343(97)00027-2
  11. Han, J. Y., Horie, Y., Fan, J. Y., Sun, K., Guo, J., Miura, S. and Hibi, T. (2009) Potential of 3,4-dihydroxy-phenyl lactic acid for ameliorating ischemia-reperfusion-induced microvascular disturbance in rat mesentery. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G36-G44. https://doi.org/10.1152/ajpgi.90284.2008
  12. Hu, J., Li, Y. L., Li, Z. L., Li, H., Zhou, X. X., Qiu, P. C., Yang, Q. and Wang, S. W. (2012) Chronic supplementation of Paeonol combined with danshensu for the improvement of vascular reactivity in the cerebral basilar artery of diabetic rats. Int. J. Mol. Sci. 13, 14565-14578. https://doi.org/10.3390/ijms131114565
  13. Hu, P., Luo, G. A., Zhao, Z. and Jiang, Z. H. (2005) Quality assessment of radix Salviae miltiorrhizae. Chem. Pharm. Bull. 53, 481-486. https://doi.org/10.1248/cpb.53.481
  14. Ji, H. S., Yu, F. and Yang, J. (2008) Comparative research on pharmacodynamics of Danshen co-microemulsion on hemorheology in rats with hyperlipidemia. Zhong Yao Cai 31, 566-569.
  15. Lam, F. F., Yeung, J. H., Chan, K. M. and Or, P. M. (2007) Relaxant effects of danshen aqueous extract and its constituent danshensu on rat coronary artery are mediated by inhibition of calcium channels. Vascul. Pharmacol. 46, 271-277. https://doi.org/10.1016/j.vph.2006.10.011
  16. Lau, C. H., Chan, C. M., Chan, Y. W., Lau, K. M., Lau, T. W., Lam, F. C., Law, W. T., Che, C. T., Leung, P. C., Fung, K. P., Ho, Y. Y. and Lau, C. B. (2007) Pharmacological investigations of the antidiabetic effect of cortex moutan and its active component Paeonol. Phytomedicine 14, 778-784. https://doi.org/10.1016/j.phymed.2007.01.007
  17. Levey, A. S., Coresh, J., Balk, E., Kausz, A. T., Levin, A., Steffes, M. W., Hogg, R. J., Perrone, R. D., Lau, J. and Eknoyan, G.; National Kidney Foundation (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann. Intern. Med. 139, 137-147. https://doi.org/10.7326/0003-4819-139-2-200307150-00013
  18. Li, H., Wang, S. W., Zhang, B. L., Xie, Y. H., Yang, Q., Cao, W. and Wang, J. B. (2011) Simultaneous quantitative determination of 9 active components in traditional Chinese medicinal preparation ShuangDan oral liquid by RP-HPLC coupled with photodiode array detection. J. Pharm. Biomed. Anal. 56, 820-824. https://doi.org/10.1016/j.jpba.2011.07.016
  19. Li, H., Wang, S., Zmhang, B., Xie, Y., Wang, J., Yang, Q., Cao, W., Hu, J. and Duan, L. (2012) Influence of co-administered danshensu on pharmacokinetic fate and tissue distribution of Paeonol in rats. Planta Med. 78, 135-140. https://doi.org/10.1055/s-0031-1280269
  20. Liu, J., Yang, C. F., Lee, B. L., Shen, H. M., Ang, S. G. and Ong, C. N. (1999) Effect of Salvia miltiorrhiza on aflatoxin B1-induced oxidative stress in cultured rat hepatocytes. Free Radic. Res. 31, 559-568. https://doi.org/10.1080/10715769900301131
  21. Liu, Z., Li, J., Zeng, Z., Liu, M. and Wang, M. (2008) The antidiabetic effects of cysteinyl metformin, a newly synthesized agent, in alloxan-and streptozocin-induced diabetic rats. Chem. Biol. Interact. 173, 68-75. https://doi.org/10.1016/j.cbi.2007.11.012
  22. Lu, T., Yang, J., Gao, X.,Chen, P., Du, F., Sun, Y., Wang, F., Xu, F., Shang, H., Huang, Y., Wang, Y., Wan, R., Liu, C., Zhang, B. and Li, C. (2008) Plasma and urinary tanshinol from Salvia miltiorrhiza (Danshen) can be used as pharmacokinetic markers for cardiotonic pills, a cardiovascular herbal medicine. Drug Metab. Dispos. 36, 1578-1586. https://doi.org/10.1124/dmd.108.021592
  23. Mi, X. J., Chen, S. W., Wang, W. J., Wang, R., Zhang, Y. J., Li, W. J. and Li, Y. L. (2005) Anxiolytic-like effect of Paeonol in mice. Pharmacol. Biochem. Behav. 81, 683-687. https://doi.org/10.1016/j.pbb.2005.04.016
  24. Moon, E., Lee, SO., Kang, T. H., Kim, H. J., Choi, S. Z., Son, M. W. and Kim, S. Y. (2014) Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice. Biomol. Ther. (Seoul) 22, 445-452. https://doi.org/10.4062/biomolther.2014.051
  25. Pang, B., Zhao, L. H., Zhou, Q., Zhao, T. Y., Wang, H., Gu, C. J. and Tong, X. L. (2015) Application of berberine on treating type 2 diabetes mellitus. Int. J. Endocrinol. 2015, 905749.
  26. Perkins, B. A., Ficociello, L. H., Silva, K. H., Finkelstein, D. M., Warram, J. H. and Krolewski, A. S. (2003) Regression of microalbuminuria in type 1 diabetes. N. Engl. J. Med. 348, 2285-2293. https://doi.org/10.1056/NEJMoa021835
  27. Rajavel, V., Abdul Sattar, M. Z., Abdulla, M. A., Kassim, N. M. and Abdullah, N. A. (2012) Chronic administration of oil palm (elaeis guineensis) leaves extract attenuates hyperglycaemic-induced oxidative stress and improves renal histopathology and function in experimental diabetes. Evid. Based Complement. Alternat. Med. 2012, 195367.
  28. Ritz, E., Rychlik, I., Locatelli, F. and Halimi, S. (1999) End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am. J. Kidney Dis. 34, 795-808. https://doi.org/10.1016/S0272-6386(99)70035-1
  29. Sakamoto, K., Kawamura, M., Kohro, T., Omura, M., Watanabe, T., Ashidate, K., Horiuchi, T., Hara, H., Sekine, N., Chin, R., Tsujino, M., Hiyoshi, T., Tagami, M., Tanaka, A., Mori, Y., Inazawa, T., Hirano, T., Yamazaki, T. and Shiba, T.; RESEARCH Study Group (2015) Effect of ezetimibe on LDL-C lowering and atherogenic lipoprotein profiles in type 2 diabetic patients poorly controlled by statins. PLoS ONE 10, e0138332. https://doi.org/10.1371/journal.pone.0138332
  30. Subash-Babu, P., Alshatwi, A. A. and Iqnacimuthu, S. (2014) Beneficial antioxidative and antiperoxidative effect of cinnamaldehyde protect streptozotocin-induced pancreatic ${\beta}$-cells damage in wistar rats. Biomol. Ther. (Seoul) 22, 47-54. https://doi.org/10.4062/biomolther.2013.100
  31. Verbeke, F., Lindley, E., Van Bortel, L., Vanholder, R., London, G., Cochat, P., Wiecek, A., Fouque, D. and Van Biesen, W. (2014) A european renal best practice (ERBP) position statement on the kidney disease: improving global outcomes (KDIGO) clinical practice guideline for the management of blood pressure in non-dialysis-dependent chronic kidney disease: an endorsement with some caveats for real-life application. Nephrol. Dial. Transplant. 29, 490-496. https://doi.org/10.1093/ndt/gft321
  32. Wang, Y., Liu, L., Hu, C. and Cheng, Y. (2007) Effects of salviae mitiorrhizae and cortex moutan extract on the rat heart after myocardial infarction: a proteomic study. Biochem. Pharmacol. 74, 415-424. https://doi.org/10.1016/j.bcp.2007.04.017
  33. Wu, J. B., Song, N. N., Wei, X. B., Guan, H. S. and Zhang, X. M. (2008) Protective effects of paeonol on cultured rat hippocampal neurons against oxygen-glucose deprivation-induced injury. J. Neurol. Sci. 264, 50-55. https://doi.org/10.1016/j.jns.2007.06.057
  34. Wu, L., Qiao, H., Li, Y. and Li, L. (2007) Protective roles of puerarin and Danshensu on acute ischemic myocardial injury in rats. Phytomedicine 14, 652-658. https://doi.org/10.1016/j.phymed.2007.07.060
  35. Yang, Q., Wang, S., Xie, Y., Wang, J., Li, H., Zhou, X. and Liu, W. (2010) Effect of salvianolic acid B and paeonol on blood lipid metabolism and hemorrheology in myocardial ischemia rabbits induced by pituitruin. Int. J. Mol. Sci. 11, 3696-3704. https://doi.org/10.3390/ijms11103696
  36. Yano, N., Suzuki, D., Endoh, M., Cao, T. N., Dahdah, J. R., Tseng, A., Stabila, J. P., McGonnigal, B. G., Padbury, J. F. and Tseng, Y. T. (2009) High ambient glucose induces angiotensin-independent AT-1 receptor activation, leading to increases in proliferation and extracellular matrix accumulation in MES-13 mesangial cells. Biochem. J. 423, 129-143. https://doi.org/10.1042/BJ20082277
  37. Zhang, Q., Xiao, X., Li, M., Li, W., Yu, M., Zhang, H., Sun, X., Mao, L. and Xiang, H. (2013) Attenuating effect of fufang xueshuantong capsule on kidney function in diabetic nephropathy model. J. Nat. Med. 67, 86-97. https://doi.org/10.1007/s11418-012-0654-y
  38. Zhao, B. L., Jiang, W., Zhao, Y., Hou, J. W. and Xin, W. J. (1996) Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemiareperfusion injury. Biochem. Mol. Biol. Int. 38, 1171-1182.
  39. Zitkus, B. S. (2014) Update on the american diabetes association standards of medical care. Nurse Pract. 39, 22-32; quiz 32-23.

Cited by

  1. Qi-Zhu-Xie-Zhuo-Fang reduces serum uric acid levels and ameliorates renal fibrosis in hyperuricemic nephropathy rats vol.91, 2017, https://doi.org/10.1016/j.biopha.2017.04.031
  2. Noninvasive Real-Time Characterization of Renal Clearance Kinetics in Diabetic Mice after Receiving Danshensu Treatment vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/8267560
  3. Paeonol reverses promoting effect of the HOTAIR/miR‐124/Notch1 axis on renal interstitial fibrosis in a rat model vol.234, pp.8, 2019, https://doi.org/10.1002/jcp.28137
  4. Paeonol protects against hypertension in spontaneously hypertensive rats by restoring vascular endothelium vol.83, pp.11, 2016, https://doi.org/10.1080/09168451.2019.1648203