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Thromb Haemost 1982; 48(03): 301-306
DOI: 10.1055/s-0038-1657286
Original Article
Schattauer GmbH Stuttgart

The Effect of a Medicinal Chinese Herb on Platelet Function

Z Wang
1   The Department of Pharmacology, Institute of Basic Medical Sciences, The Chinese Academy of Medical Sciences, Beijing
,
J M Roberts
2   The People's Republic of China, Department of Obstetrics and Gynecology, University of California School of Medicine, San Francisco, CA, U.S.A.
,
P G Grant
3   Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, U.S.A.
,
R W Colman
3   Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, U.S.A.
,
A D Schreiber
4   Hematology-Oncology Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
› Author Affiliations
Further Information

Publication History

Received 27 November 1981

Accepted 28 October 1982

Publication Date:
13 July 2018 (online)

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Summary

We investigated the effect of the Chinese herb Injectio Salvia Miltiorrhizae (ISM) on human platelet function in vitro. ISM inhibited platelet aggregation and serotonin release induced by either ADP or epinephrine in a dose dependent manner. This effect of ISM was observed with both gel-filtered platelets (ID50 = 8–30 μg ISM/ml gel-filtered platelets) and platelets in plasma (ID50 = 400–900 μg ISM/ml of platelet-rich plasma). The active molecule(s) in ISM was heat stable, resistant to acid, base and proteolysis and fractionated on Sephadex 6-25 at MW ~ 280. ISM did not interact with the platelet α-adrenergic receptor, but increased cAMP in intact platelets. The results are consistent with the concept that ISM inhibition of platelet aggregation and release is mediated by an increase in platelet cAMP. The exact mechanism whereby ISM increases platelet cAMP appears to be that of inhibition of cyclic AMP phosphodiesterase. The effect of ISM on platelet function is one mechanism which might explain the therapeutic effect of ISM in experimental and clinical coronary artery disease.

Keywords

Injectio salvia miltiorrhizae (ISM) - Platelet-rich plasma (PRP) - Platelet aggregation - ADP and platelet cAMP
 

  • References

  • 1 Shanghai first med. coll.. A study of the therapeutic effect of Salvia Miltiorrhiza on coronary heart disease and the mechanism of promoting blood circulation and relieving stasis. Chin J Med 1976; 711: 689-697
    PubMedGoogle Scholar
  • 2 Jin Lan, Dai Yuhua, Liao Jiazheng. Combination of Western Medicine with traditional Chinese medicine in the treatment of acute myocardial infarction. The analysis of the therapeutic effect of five years. Chin J Int Med 1978; 5: 335-345
    PubMedGoogle Scholar
  • 3 Chen Weizhou, Wang Zhimin, Dong Yueli, Chen Lixin, Ting Guangs-heng. Studies on tolerance toward hypoxia and cardiac hemodynamics of Salvia Miltiorrhiza Composita in animals. Acta Pharm Sinica 1979; 14: 322-330
    PubMedGoogle Scholar
  • 4 Zhong Shan Hospital. The effect fo Injectio Salvial Compostus on experimental myocardial infarction in dog by electron microscopy. I. The observations on the course of regeneration. Acta Shanghai First Med Coll 1976; 1: 42-52
    PubMedGoogle Scholar
  • 5 White AM, Heptinstall S. Contribution of platelets to thrombus formation. Br Med Bull 1978; 34: 123-128
    CrossrefPubMedGoogle Scholar
  • 6 Xi-Yuan Hospital, Academy of Traditional Chinese Medicine. A study on the anti-thrombotic and thrombolytic effect of Coronary Heart II, in symposium: “Some research work on the cardiovascular diseases by the traditional Chinese medicine”?. 1979; 5: 11-22
    PubMedGoogle Scholar
  • 7 Wang Zhengsheng, Chen Chaoshi, Yang Zucai, Lou Fuging. The effect of Salvia Miltiorrhiza on anticoagulation and fibrin lysis in vitro. Chin J Int Med 1976; 6: 341-344
    PubMedGoogle Scholar
  • 8 Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929
    PubMedGoogle Scholar
  • 9 Tangen O, Berman HJ, Marfey P. Gel filtration: a new technique for separation of blood platelets from plasma. Thrombos Diathes Haemorrh 1971; 25: 268-278
    PubMedGoogle Scholar
  • 10 Jerushalmy Z, Zucker MB. Some effects of fibrinogen degradation products (FDP) on blood platelets. Thrombos Diathes Haemorrh 1966; 15: 413-419
    PubMedGoogle Scholar
  • 11 Mills DCB, Smith JB. The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3’25’-cyclic monophosphate in platelets. Biochem. J 1971; 121: 185-196
    CrossrefPubMedGoogle Scholar
  • 12 Makheja AN, Baily JM. Identification of the antiplatelet substance in Chinese Black Tree Fungus. N Engl J Med 1981; 304: 175
    PubMedGoogle Scholar
  • 13 Kaywin P, McDonough M, Insel PA, Shattil SJ. Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet α-adrenergic receptors. N Engl J Med 1978; 299: 505-509
    CrossrefPubMedGoogle Scholar
  • 14 Newman KD, Williams LT, Bishopric NH, Lefkowitz RJ. Identification of α-adrenergic receptors in human platelets by 3H-dihydroergocryptine binding. J Clin Invest 1978; 61: 395-402
    CrossrefPubMedGoogle Scholar
  • 15 Siegl AM. Identification of prostaglandin receptors on human platelets: Measurements of ligand binding, stimulation of adenyl cyclase and inhibition of platelet aggregation. Thomas Jefferson University; Doctoral Thesis 1980
    Google Scholar
  • 16 New England Nuclear. Instruction manual for the determination of cyclic AMP. Cyclic AMP 125I RIA kit. 1978
    PubMedGoogle Scholar
  • 17 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
    CrossrefPubMedGoogle Scholar
  • 18 Salomon Y, Londos C, Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem 1974; 58: 541-548
    CrossrefPubMedGoogle Scholar
  • 19 Mustard JF. Platelets and thrombosis in acute myocardial infarction. Hosp Pract 1972; 7: 115-128
    PubMedGoogle Scholar
  • 20 Born GVR. Platelet pharmacology in relation to thrombosis. Adv Cardiol 1970; 4: 161-174
    PubMedGoogle Scholar
  • 21 Szczeklik A, Gryglewski RJ, Musial J, Grodzińska L, Serwońska M, Marcinkiewicz E. Thromboxane generation and platelet aggregation in survivals of myocardial infarction. Thromb Haemostas 1978; 40: 66-74
    PubMedGoogle Scholar
  • 22 Sano T, Boxer MGJ, Boxer LA, Yokoyama M. Platelet sensitivity to aggregation in normal and diseased groups: a method for assessment of platelet aggregability. Thrombos Diathes Haemorrh 1971; 25: 524-531
    PubMedGoogle Scholar
  • 23 Frishman WH, Weksler B, Christopoulous JP, Smithen C, Killip T. Reversal of abnormal platelet aggregability and change in exercise tolerance in patients with angina pectoris following oral Propranolol. Circulation 1974; 50: 887-896
    CrossrefPubMedGoogle Scholar
  • 24 Salky N, Dugdale M. Platelet abnormalities in ischemic heart disease. Am J Cardiol 1973; 32: 612-617
    CrossrefPubMedGoogle Scholar
  • 25 Steele PP, Weily HS, Davies H, Genton E. Platelet function studies in coronary artery disease. Circulation 1973; 48: 1194-1200
    CrossrefPubMedGoogle Scholar
  • 26 Heptinstall S, Mulley GP, Taylor PM, Mitchell JRA. Platelet-release reaction in myocardial infarction. Br Med J 1980; 12: 80-81
    PubMedGoogle Scholar
  • 27 Hampton JR, Harrison MJG, Honour AJ, Mitchell JRA. Platelet behaviour and drugs used in cardiovascular disease. Cardiovasc Res 1967; 1: 101-107
    CrossrefPubMedGoogle Scholar
  • 28 Phillips C, Poyser N. Inhibition of platelet aggregation by onion extracts. Lancet 1978; 1: 1051-1052
    PubMedGoogle Scholar
  • 29 Makheja AN, Vanderhoek JY, Bailey JM. Inhibition of platelet aggregation and thromboxane synthesis by onion and garlic. Lancet 1979; 1: 781
    PubMedGoogle Scholar
  • 30 Hammerschmidt DE. Szechwan Purpura. N Engl J Med 1980; 302: 1191-1193
    CrossrefPubMedGoogle Scholar
  • 31 Fan Shihfang, Wang Wenping, Wang Zhihua, Huang Shikai, Qu Fujin, Sun Yaoshong. The effect of Salvia Miltiorrhiza on the ischemia injury of the heart in rabbits. Acta Pharm Sinica 1979; 14: 416-420
    PubMedGoogle Scholar
  • 32 Xi-Yuan Hospital, Academy of Traditional Chinese Medicine. Treatment of acute myocardial infarction with AMI mixture combined with western medicine (1974-1977); Effect of anti-myocardial infarction mixture on experimental myocardial infarction, in symposium “Some research work on the cardiovascular diseases by the traditional Chinese Medicine”?. 1979; 5: 4-23
    PubMedGoogle Scholar
  • 33 Shanghai First Med. Coll.. A preliminary study on the therapeutic effect and the mechanism of preparation of Salvia Miltiorrhizae, infused intravenously, on coronary heart disease. Chin J Int Med 1977; 4: 203-208
    PubMedGoogle Scholar
  • 34 Salzman EW. Cyclic AMP, and platelet function. N Engl J Med 1972; 286: 358-363
    CrossrefPubMedGoogle Scholar
  • 35 Marquis NR, Becker JA, Vigdahi RL. Platelet aggregation III. An epinephrine induced decrease in cyclic AMP synthesis. Biochem. Biophys Res Commun 1970; 39: 783-789
    CrossrefPubMedGoogle Scholar
  • 36 Malmsten C, Granstrom E, Samuelsson B. Cyclic AMP inhibits synthesis of prostaglandin endoperoxide (PGG2) in human platelets. Biochem Biophys Res Commun 1976; 68: 569-576
    CrossrefPubMedGoogle Scholar
  • 37 Salzman EW, Levine L. Cyclic 3’ 5’-adenosine monophosphate in human blood platelets. II. Effect of N-2’-0-Dibutyryl cyclic 3’5’-adenosine monophosphate on platelet function. J Clin Invest 1971; 50: 131-141
    CrossrefPubMedGoogle Scholar
  • 38 Steer ML, Salzman EW. Cyclic nucleotides in hemostasis and thrombosis. Adv Cyclic Nucleotide Res 1980; 12: 71-90
    PubMedGoogle Scholar
  • 39 Cole B, Robison A, Hartmann RC. Studies on the role fo cyclic AMP in platelet function. Ann Ny Acad Sci 1971; 185: 477
    CrossrefPubMedGoogle Scholar
  • 40 Colman RW, Kuchibhotla J, Schreiber AD. Effect of heterologous antiplatelet antibody on human platelets. Blood 1977; 50: 575-585
    PubMedGoogle Scholar
  • 41 Sinha AK, Shattil SJ, Colman RW. Cyclic AMP metabolism in cholesterolrich platelets. J Biol Chem 1977; 252: 3360-3314
    PubMedGoogle Scholar
  • 42 Hidaka H, Asano T. Human blood platelet 3’: 5’-cyclic nucleotide phosphodiesterase. Isolation of low-Km and high Km phosphodiesterase. Biochim Biophys Acta 1976; 429: 485-497
    CrossrefPubMedGoogle Scholar