Platelet Interactor Herbs

Summary

Platelet Interactor Herbs (PAF Interactors)

introduction:
A number of herbs have inhibitory effects on Platelet Aggregation Factor (PAF) or are anti-aggregant due to other mechanisms. These mechanisms include collagen-receptor antagonists, thromboxane-receptor antagonists, ADP-receptor agonists, inhibitors of phosphoinositide breakdown, inhibitors of thromboxane formation, agents increasing cyclic nucleotides, and protein kinase C activators. PAF is a membrane-bound phospholipid inflammatory mediator, and PAF inhibitor plants are commonly used in the treatment of inflammatory conditions.

The majority of studies have been in vitro and on isolated constituents. Invariably, these herbs have several other activities, not only cardiovascular, some of which may also affect hemodynamics; see, for example, Allium sativum (garlic), which combines cholesterolemic, rheostatic blood thinning, antiaggregant and fibrinolytic activities and Ginkgo biloba which is antioxidant, vasodilatory and neuroprotective.
(Bordia A, et al.1998 Apr;58(4):257-63; Guh JH, et al. J Pharm Pharmacol 1995 Apr;47(4):329-32; Steiner M, Lin RS. J Cardiovasc Pharmacol 1998 Jun;31(6):904-908; Teng CM, Ko FN.Res Commun Mol Pathol Pharmacol 1998 Dec;102(3):211-225.)

interactions overview:
• herb group affecting drug performance: Heparin and Warfarin

• herb group affecting drug performance and toxicity: Aspirin and Ticlopidine

• herbal synergy: Edible Plants with High Levels of Vitamin K



Herbs

herb group affecting drug performance: Heparin and Warfarin

• mechanism: Herbs that inhibit platelet aggregation may potentiate the anticoagulant activity of warfarin or similar drugs. Ginkgo inhibits platelet adhesion and can increase any tendency toward bleeding. Three case reports of warfarin and Ginkgo interactions include one incident each of hyphema, subdural hemorrhage, and subarachnoid hemorrhage.
(Rosenblatt M, Mindel J. 1997; Rowin J, Lewis SL.1996; Vale S. 1998.)

• herbal concern: Vigilant monitoring of PT/INR values with warfarin-using patients who consume Ginkgo extracts is essential.

herb group affecting drug performance and toxicity: Aspirin and Ticlopidine

• research: A recent animal study has shown also Ginkgo synergises with the PAF inhibitor drug, ticlopidine. Generally, adverse effects are not likely to appear unless relatively large doses of these herbs or their combinations were consumed for an extended period of time.
(Kim YS, et al.Thromb Res 1998.Jul 1;91(1):33-38; Matthews MK Jr.Neurology 1998 Jun;50(6):1933-1934; Rosenblatt M, Mindel J. New Engl J Med 1997.336:1108; Rowin J, Lewis SL. Neurology 1996 Jun;46(6):1775-1776; Skogh M. Lancet. 1998 Oct 3;352(9134):1145-1146; Vale S, Lancet. 1998 Jul 4;352(9121):36.)

• herbal concern: Caution is also advised prior to surgical procedure, when failure of fibrinogenesis can be be potentially life-threatening. Patients scheduled for surgical procedures should advise their physicians if they are consuming PAF interactor herbs.

• herbal synergy: Indirect interaction with other herbs from the following groups may take place through various synergistic physiologic mechanisms including High Vitamin K herbs.

herbs with PAF agonism activity:

• herbal concern: PAF agonism has not been found in many herbs; the hemostatic effects of antihemorrhagic and styptic herbs being due to other mechanisms such as tannin astringency rather than enhancement of coagulation. However, a few hemostatic herbs have been shown to reduce clotting times, e.g., Panax notoginseng (Tienchi Ginseng).

Common herbs with PAF inhibitory activity:
• Allium cepa (Onion plant)
Allium sativum (Garlic)
• Ananas comosus (Bromelain, from fruit and stem)
• Andrographis paniculata (Chiretta, Andrographis)
• Angelica sinensis (Dong Quai)
Capsicum frutescens (Cayenne fruit)
• Carica papaya (Papain, from leaves and unripe fruit)
• Coleus forskohlii (Coleus root)
• Commiphora mukul (Guggul)
• Coptis spp. (generic Goldenthread)
• Curcuma longa, Curcuma aromatica (Turmeric root)
• Ganoderma lucidum (Reishi mushroom fruiting bodies)
Ginkgo biloba (Ginkgo leaves)
Panax ginseng (Chinese Ginseng)
• Paeonia lactiflora (White peony root)
• Salvia miltiorrhiza (Dan Shen root)
• Scutellaria baicalensis (Baical Skullcap root)
Zingiber officinale (Ginger rhizome)

restricted or unusual herbs with PAF inhibitory activity:
• Cinchona spp. (Cinchona) toxic
• Podophyllum peltatum (Mayapple) toxic

herbs with proaggregatory activity:
• Panax notoginseng (Tien Qi, Tienchi Ginseng)
• Mahonia spp. (Oregon Grape root) - isolated berberine studies.
Hydrastis canadensis (Goldenseal rhizome) - isolated berberine studies.




Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.



References

Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998 Apr;58(4):257-263.
Abstract: Thirty patients with coronary artery disease (CAD) were administered garlic (study group) while another 30 patients received the placebo (control group). Various risk parameters were determined at 1.5 and 3 months of garlic administration. Garlic, administered in a daily dose of 2 x 2 capsules (each capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic), reduced significantly total serum cholesterol and triglycerides, and increased significantly HDL-cholesterol and fibrinolytic activity. There was no effect on the fibrinogen and glucose levels. In vitro effects of the garlic oil on platelet aggregation (PAg) and eicosanoid metabolism were examined; it inhibited Pag induced by several platelet agonists, and also platelet thromboxane formation. Two important paraffinic polysulphides - diallyl disulphide (DADS) and diallyl trisulphide (DATS) - derived from garlic and are usual constituents of garlic oil, showed antiplatelet activity, and also inhibited platelet thromboxane formation. In this respect DATS was more potent than DADS. The nature of inhibition of PAg by DATS was found to be reversible.

Guh JH, Ko FN, Jong TT, Teng CM. Antiplatelet effect of gingerol isolated from Zingiber officinale. J Pharm Pharmacol 1995 Apr;47(4):329-332.
Abstract: The purpose of this investigation was to determine the antiplatelet mechanism of gingerol. Gingerol concentration-dependently (0.5-20 microM) inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 (9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha) and thrombin. Gingerol also concentration-dependently (0.5-10 microM) inhibited thromboxane B2 and prostaglandin D2 formation caused by arachidonic acid, and completely abolished phosphoinositide breakdown induced by arachidonic acid but had no effect on that of collagen, PAF or thrombin even at concentrations as high as 300 microM. In human platelet-rich plasma, gingerol and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5'-diphosphate (ADP, 5 microM) and adrenaline (5 microM) but had no influence on the primary aggregation. The maximal antiplatelet effect was obtained when platelets were incubated with gingerol for 30 min and this inhibition was reversible. It is concluded that the antiplatelet action of gingerol is mainly due to the inhibition of thromboxane formation.

Kim YS, et al. Antiplatelet and antithrombotic effects of a combination of ticlopidine and Ginkgo biloba extract. Thromb Res 1998;Jul 1;91(1):33-38.
Abstract: The antiplatelet and antithrombotic effects of the oral combination treatment of ticlopidine and Ginkgo biloba extract (EGb 761) were studied in normal and thrombosis-induced rats. The ex vivo inhibitory effect on ADP-induced platelet aggregation of a small dose of ticlopidine (50 mg/kg/day) in combination with EGb 761 (40 mg/kg/day) was comparable to a larger dose of only ticlopidine (200 mg/kg/day). Bleeding time was also prolonged by 150%. Thrombus weight was also consistently decreased by a combination of ticlopidine and EGb 761 in an arterio-venous shunt model at two doses of ticlopidine (50 mg/kg) plus EGb 761 (20 mg/kg) and ticlopidine (50 mg/kg) plus EGb 761 (40 mg/kg). A combinatory treatment in acute thrombosis model in mice also showed a higher recovery than a single treatment.

Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998 Jun;50(6):1933-1934. (Letter)

Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996Jun;46(6):1775-1776.

Skogh M. Extracts of Ginkgo biloba and bleeding or haemorrhage. Lancet 1998 Oct; 3, 352 (9134):1145-1146.

Steiner M, Lin RS. Changes in platelet function and susceptibility of lipoproteins to oxidation associated with administration of aged garlic extract. J Cardiovasc Pharmacol 1998 Jun;31(6):904-908.
Abstract: Garlic and some of its organosulfur components have been found to be potent inhibitors of platelet aggregation in vitro. Demonstration of their efficacy in vivo, however, especially when administered over extended periods, is sparse. We recently performed a 10-month study comparing the effect of aged garlic extract (AGE) with placebo on the lipid profiles of moderately hypercholesterolemic men. In the course of the intervention trial, we examined platelet functions and susceptibility of lipoproteins to oxidation in a subgroup of this study population. Study subjects supplemented with 7.2 AGE per day showed a significant reduction of epinephrine- and, to a lesser degree, collagen-induced platelet aggregation but failed to demonstrate an inhibition of adenosine diphosphate (ADP)-induced aggregation. Platelet adhesion to fibrinogen, measured in a laminar flow chamber at moderately high shear rate, was reduced by approximately 30% in subjects taking AGE compared with placebo supplement. A trend toward decreased susceptibility of lipoproteins to oxidation also was noted during AGE administration compared with the placebo period. We conclude that the beneficial effect of garlic preparations on lipids and blood pressure extends also to platelet function, thus providing a wider potential protection of the cardiovascular system.

Teng CM, Ko FN. Antiplatelet agents isolated from medicinal plants. Res Commun Mol Pathol Pharmacol 1998 Dec;102(3):211-225.
Abstract: Platelet-vessel wall interaction is an important process in physiological hemostasis and pathological thrombosis. In oriental countries, some medicinal plants have been claimed for uses to improve circulation, induce fibrinolysis or prevent thrombosis. In cooperation with chemists using bioassay-based step-by-step purification, some antiplatelet agents were isolated from plant sources. According to their effects on platelet aggregation, release reaction and signal transductions involved, these antiplatelet agents can be classified into eight groups: 1. platelet-activating factor (PAF) antagonists, 2. collagen-receptor antagonists, 3. thromboxane-receptor antagonists, 4. ADP-receptor agonists, 5. inhibitors of phosphoinositide breakdown, 6. inhibitors of thromboxane formation, 7. agents increasing cyclic nucleotides, and 8. protein kinase C activators. These new pharmacological agents derived from medicinal plant sources may be useful as leads to develop as effective cardiovascular drugs.

Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998 Jul4;352(9121):36.