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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (2): 145-150.doi: 10.3736/jcim20090210

• Original Experimental Research • Previous Articles     Next Articles

Salvianolic acid B in vitro inhibited matrix metalloproteinases-1, -2, and -9 activities

 Ya-hui Lianga, Ping Lib, Qi-fu Huanga, Jing-xia Zhaob, Xin Liub, Miao-ke Daib   

  1. a Department of Pathology, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
    b Department of Pathophysiology, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China
  • Received:2008-08-12 Accepted:2008-10-07 Online:2009-02-20 Published:2009-02-15

Objective

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all extracellular matrix components. The proteolytic property of the MMPs is important during wound healing to remove debris and facilitate cell migration. Targeting towards the decreased MMPs activities is a new treatment strategy for healing chronic wounds. Salvia miltiorrhiza is a popular Chinese herb that could promote chronic ulcers healing for topical use. Salvianolic acid B (Sal B) is the most abundant bioactive component in Salvia miltiorrhiza. The research was designed to explore the inhibitory effects of Sal B on MMP-1, MMP-2 and MMP-9 activities.
Methods

Pure human interstitial collagenase (MMP-1) or gelatinase A (MMP-2) was activated by p-aminophenylmercuric acetate (APMA), and was incubated with Sal B for 1 h. The activities were observed by quenched fluorescent substrate. Gelatinase B (MMP-9) is rich in polymorphonuclear neutrophils (PMN), so the rat PMN was used as a source of MMP-9 for MMPs activity assays. In vitro MMP-9 from rats' PMN lysate was incubated with Sal B for 1 h, and its activity was tested by gelatin zymography.
Results

Sal B dose-dependently inhibited the human MMP-1 and MMP-2 activities in the range of 0.002 4 to 0.3 g/L, with 50% inhibiting concentration (IC50) of (0.090±0.015) g/L and (0.080±0.005) g/L respectively. In the range of 0.003 to 0.3 g/L, Sal B could inhibit the MMP-9 activity (P<0.01).
Conclusion

The broad-spectrum inhibitory effects of Sal B on MMPs may reveal one of the mechanisms for the effects of Salvia miltiorrhiza on chronic wounds.

Key words: Salvia miltiorrhiza, Salviol, Matrix metalloproteinases, Rats

Figure 1

Effects of Sal B on the activity of MMP-1"

Figure 2

Effects of Sal B on the activity of MMP-2"

Figure 3

Inhibition ratios of different concentrations of Sal B on the activity of MMP-1"

Figure 4

Inhibition ratios of different concentrations of Sal B on the activity of MMP-2"

"

Group n Inhibition ratio of MMP-1 Inhibition ratio of MMP-2
Control 3 0 0
0.002 4 g/L Sal B 3 33.20±6.56** 34.17±3.15**
0.012 g/L Sal B 3 47.23±3.29** 43.97±2.67**
0.06 g /L Sal B 3 61.83±4.70** 71.27±6.21**
0.3 g /L Sal B 3 83.03±15.67** 90.83±3.09**

Figure 5

The lysis bands of MMP-9 1: Marker; 2, 3: 0 g/L Sal B; 4, 5: 0.003 g/L Sal B; 6, 7: 0.03 g/L Sal B; 8, 9: 0.3 g/L Sal B; 10, 11: 1, 10-phenanthroline."

"

Group n Relative activity of MMP-9
Control 4 1.124 2±0.145 9
0.003 g/L Sal B 4 0.862 3±0.189 2**
0.03 g/L Sal B 4 0.516 0±0.151 6**
0.3 g/L Sal B 4 0.283 9±0.125 3**
[1] Liu L, Zhang HQ . Advances in contemporary traditional Chinese medicine(TCM) pharmacology studies of active constituents of danshen(Salvia miltiorrhiza)[J]. Zhongguo Ye Sheng Zhi Wu Zi Yuan, 2003,22(6):1-4
柳丽, 张洪泉 . 丹参活性成分的现代中药药理研究进展[J]. 中国野生植物资源, 2003,22(6):1-4
[2] Falanga V . Chronic wounds: pathophysiologic and experimental considerations[J]. Invest Dermatol, 1993,100(5):721-725
doi: 10.1111/1523-1747.ep12472373
[3] Xue M, Le NT, Jackson CJ . Targeting matrix metalloproteases to improve cutaneous wound healing[J]. Expert Opin Ther Targets, 2006,10(1):143-155
doi: 10.1517/14728222.10.1.143
[4] Trengove NJ, Stacey MC, MacAuley S, Bennett N, Gibson J, Burslem F, Murphy G, Schultz G .Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors[J]. Wound Repair Regen, 1999,7(6):442-452
doi: 10.1046/j.1524-475X.1999.00442.x
[5] Ravanti L, Kähäri VM .Matrix metalloproteinases in wound repair[J]. Int J Mol Med, 2000,6(4):391-407
[6] Medina A, Scott PG, Ghahary A, Tredget EE . Pathophysiology of chronic nonhealing wounds[J]. J Burn Care Rehabil, 2005,26(4):306-319
doi: 10.1097/01.BCR.0000169887.04973.3A
[7] Bennett NT, Schultz GS . Growth factors and wound healing: Part Ⅱ. Role in normal and chronic wound healing[J]. Am J Surg, 1993,166(1):74-81
doi: 10.1016/S0002-9610(05)80589-6
[8] Nwomeh BC, Yager DR, Cohen IK . Physiology of the chronic wound[J]. Clin Plast Surg, 1998,25(3):341-356
[9] Lobmann R, Ambrosch A, Schultz G, Waldmann K, Schiweck S, Lehnert H . Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients[J]. Diabetologia, 2002,45(7):1011-1016
doi: 10.1007/s00125-002-0868-8
[10] Yager DR, Zhang LY, Liang HX, Diegelmann RF, Cohen IK . Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids[J]. J Invest Dermatol, 1996,107(5):743-748
doi: 10.1111/1523-1747.ep12365637
[11] Wysocki AB, Staiano-Coico L, Grinnell F . Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids[J]. J Invest Dermatol, 1993,101(1):64-68
doi: 10.1111/1523-1747.ep12359590
[12] Barone EJ, Yager DR, Pozez AL, Olutoye OO, Crossland MC, Diegelmann RF, Cohen IK . Interleukin-1α and collagenase activity elevated in chronic wounds[J]. Plast Reconstr Surg, 1998,102(4):1023-1027
doi: 10.1097/00006534-199809020-00015
[13] Weckroth M, Vaheri A, Lauharanta J, Sorsa T, Konttinen YT . Matrix metalloproteinases, gelatinase and collagenase, in chronic leg ulcers[J]. J Invest Dermatol, 1996,106(5):1119-1124
doi: 10.1111/1523-1747.ep12340167
[14] Drinkwater SL, Smith A, Burnand KG . What can wound fluids tell us about the venous ulcer microenvironment?[J]. Int J Low Extrem Wounds, 2002,1(3):184-190
doi: 10.1177/153473460200100307
[15] Mwaura B, Mahendran B, Hynes N, Defreitas D, Avalos G, Adegbola T, Adham M, Connolly CE, Sultan S . The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2, and PDGF-AA on the chronicity of venous leg ulcers[J]. Eur J Vasc Endovasc Surg, 2006,31(3):306-310
doi: 10.1016/j.ejvs.2005.08.007
[16] Parks WC . Matrix metalloproteinases in repair[J]. Wound Repair Reg, 1999,7(6):423-432
doi: 10.1046/j.1524-475X.1999.00423.x
[17] Luo P, Chen XH, Sun RS, Ran XZ . Effects of Radix Salviae millitiorrhizae on the wound healing in rats with whole-body radiation injury[J]. Zhongguo Lin Chuang Kang Fu, 2005,9(6):156-157
罗平, 陈晓红, 孙仁山, 冉新泽 . 丹参对复合全身放射损伤大鼠创面的影响[J]. 中国临床康复, 2005,9(6):156-157
[18] Chen JC, Shi ZM, Zhou XF, Zhang CH, Liu G, Wang YN, Lu KB . Clinical and experimental studies of external application of Radix Salviae militiorrhizae in acceleration of wound healing[J]. Zhongguo Zhong Xi Yi Jie He Wai Ke Za Zhi, 1998,4(4):209-210
陈建常, 史振满, 周雪峰, 张春浩, 刘刚, 王乐农, 卢开柏 . 丹参外用促进创面愈合的实验与临床研究[J]. 中国中西医结合外科杂志, 1998,4(4):209-210
[19] Wu HN, Sun H . Study on clinical therapeutic effect of composite Salvia Injection matched with Western medicine in treating diabetic foot[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2003,23(10):727-729
吴汉妮, 孙晖 . 复方丹参注射液配伍西药治疗糖尿病足临床疗效研究[J]. 中国中西医结合杂志, 2003,23(10):727-729
[20] Que HF, Wang YF, Shen L, Wang YL, Tang HJ . Treatment of chronic skin ulcers with traditional Chinese medicine: a report of five cases[J]. J Chin Integr Med, 2007,5(2):204-207
阙华发, 王云飞, 沈亮, 王永灵, 唐汉钧 . 中医药治疗慢性皮肤溃疡5例[J]. 中西医结合学报, 2007,5(2):204-207
[21] Saariaho-Kere UK . Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers[J]. Arch Dermatol Res, 1998,290(Supplement 1):S47-S54
doi: 10.1007/PL00007453
[22] Wall SJ, Sampson MJ, Levell N, Murphy G . Elevated matrix metalloproteinase-2 and -3 production from human diabetic dermal fibroblasts[J]. Br J Dermatol, 2003,149(1):13-16
[23] Mirastschijski U, Impola U, Jahkola T, Karlsmark T, AGren MS, Saarialho-Kere U . Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds[J]. Hum Pathol, 2002,33(3):355-364
doi: 10.1053/hupa.2002.32221
[24] Tao YY, Wang XL, Liu CH . Salvianolic acid-B effects on TGF-β1/ERK signaling transduction in NIH/3T3 fibroblast[J]. Shou Du Yi Ke Da Xue Xue Bao, 2007,28(2):192-195
陶艳艳, 王晓玲, 刘成海 . 丹酚酸B对NIH/3T3成纤维细胞TGF-β1/ERK胞内信号转导的影响[J]. 首都医科大学学报, 2007,28(2):192-195
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