PDF

Reversing Hypertension with Rauwolfia, Viscum and Piscidia

Abstract

Rauwolfia, Viscum, and Psicidia are well known herbs used in the treatment of hypertension. These herbs contain several different bioactive constituents including alkaloids, lectins, rotenones, flavonoids and isoflavones, among others, which research indicates as being cardioprotective, promote vascular health and reduce blood pressure. As the mechanisms of action are different for each herb, due to the varying bioactive compounds present, they can be used alone or in combination for these indications.

Patients being treated with the above-described herbs need to be carefully monitored, particularly for interactions with any concomitant antihypertensive medication—and herbal doses individually tailored.

AARM REFERENCE REVIEWS:

These are AARM reference reviews in which clinicians can obtain a quick overview of understanding with respect to how herbs, nutrients, and hormones can be used effectively in clinical practice. The dosages recommended are based on therapeutic results. Side effects that have not been seen in clinical experience or found in clinical studies but only been theorized have been identified and depicted as Unsubstantiated Theoretical Concerns.

Since many nutrients and herbs on the market have not gone through double-blind studies but have been used extensively in clinical settings for hundreds, and for some thousands of years, these reference reviews have attempted to give a unified opinion on how to use these herbs effectively. The opinions expressed are from different professors and experts in the field of nutritional and botanical medicine. Some information is based on personal opinions and can not be quantified as fact. However, if clinicians only restricted themselves to what is fully proven by double-blind studies, the art of healing and restoring health with nutrients and herbs would be lost.

CLINICAL IMPLICATIONS

The use of herbal medicines can be effective in the treatment of hypertension African snake root (Rauwolfia vomitoria), European Mistletoe (Viscum album) and Jamaican Dogwood (Piscidia erythrina) can normalize blood pressure via different mechanisms, and can synergistically support and tone the cardiovascular system. Rauwolfia, Viscum and Piscidia (alone or in combination with other herbs) support vascular tone, blood flow and viscosity, stress response, adrenaline and sympathetic nervous tone, and other mechanisms that enhance overall circulatory health and control blood pressure. In some subset of hypertensive patients, herbal medicines can be weaned off totally while patients remain normotensive.

KEY HERBS DISCUSSED:

African Snake Root (Rauwolfia vomitoria), European Mistletoe (Viscum album) and Jamaican Dogwood (Piscidia erythrina)

PRIMARY INDICATIONS:

Hypertension

ADJUNCTIVE OR STAND-ALONE TREATMENT:

Adjunctive or Stand-Alone

BIOACTIVE CONSTITUENTS:

Rauwolfia: Diverse alkaloids including ajmaline, chandrine, deserpidine, reserpine, rescinnamine, sarpagine, serpentinine, and yohimbine

Viscum: Lectins, phenylpropanoids

Piscidia: Isoflavones, rotenoids, piscidin

Rauwolfia whole plant root 200 mg daily containing 300mcg reserpine a day, European Mistletoe up to 2.5 grams daily, Jamaican Dogwood whole plant 50-400 mg a day

SYNERGISTIC HERBAL FORMULA:

African Snake Root (Rauwolfia), Mistletoe (Viscum), Jamaican Dogwood (Piscidia), Hawthorn (Craaegus), and Motherwort (Leonorus)

SIDE EFFECTS (AND CAUTIONS):

This herbal synergistic formula may interact with anti-hypertensive medications in some patients to cause hypotension and bradycardia. While treating patients with the above herbs, it is important to determine any concomitant anti-hypertensive prescriptions, and to closely monitor blood pressure. Because Rauwolfia contains reserpine, at high doses it can promote or exacerbate Parkinson’s disease. Nasal congestion and diarrhea may occur in patients taking more than 200 mg of Rauwolfia daily. While findings are inconclusive, one study found reserpine to cause depression in 10% of the study patients; however, this percentage is not higher than found in the general population. Some researchers cites Reserpine induced depression as a myth. Rauwolfia, Viscum and Piscidia are not recommended in pregnancy. At higher doses than 2.5 grams a day, there is some evidence that Viscum is contraindicated in Tuberculosis and Aids.

UNSUBSTANTIATED THEORETICAL CONCERNS:

Rauwolfia: There is some theoretical evidence that Rauwolfia should not be taken with alcohol, antipsychotics, antidepressants barbiturates, digoxin, monoamine oxidase inhibitors, propranolol, and stimulant drugs.

Viscum: There is some theoretical evidence that Viscum may decrease effectiveness of immune suppressant drugs.

Piscidia: There is some theoretical evidence this herb should not be taken with central nervous system (CNS) depressant medications.

Editors Note: The first drug studied to be effective in treating depression in a randomized placebo-blind controlled study was reserpine. This study was published in the Lancet in 1955.

DISCUSSION

Hypertension is a very common medical problem commonly treated with prescription antihypertensive drugs; however, these medications are not without side effects. Additionally, the patients over time often require increased dosage to control blood pressure and/or additional antihypertensive medications. It is recommended that herbal therapy for hypertension be combined with a healthy lifestyle, low-sodium diet, and reduced stress. Lifestyle modifications and herbal treatments can control blood pressure or be added to an antihypertensive protocol. Some herbs can also support, restore and protect cardiac and vascular health.

RAUWOLFIA AND ITS BIOACTIVE CONSTITUENTS

Rauwolfia (in the Apocynaceae family) grows mainly in the tropical forests of Asia and India. The Apocynaceae family is rich in alkaloids and other constituents with important medicinal effects. Rauwolfia contains a large number of bioactive constituents, though most attention has been directed towards the indole alkaloids. These alkaloids are generally classified as either reserpine-like or yohimbine-like. R. serpentina and R. vomitoria contain relatively high concentrations of reserpine. Rauwolfia serpentina is currently considered an endangered herb; it being replaced with the non-endangeredRauwolifa vomitoria in synergistic herbal formulas.

Yohimbine is well known as a selective alpha-adrenergic antagonist in the peripheral blood vessels. Antagonism at these receptors relaxes smooth muscle and lowers blood pressure. Examples of prescription alpha-adrenergic blockers are doxazosin (Cardura) and prazosin (Minipress). Reserpine, on the other hand, acts primarily in the central nervous system at the level of monoamines in the neuronal synapses. Reserpine reduces sympathetic nervous system tone and increases parasympathetic activity via effects on neurotransmittors.

Another principle reserpine-like alkaloid is rescinnamine, which has an antihypertensive effect similar to reserpine. While rescinnamine has a greater hypotensive effect in dogs than reserpine, in humans, it is slightly less potent per gram than reserpine. Deserpidine is structurally related to reserpine (11-demethoxyreserpine) and also has anti-hypertensive effects. Most clinical trials have used deserpidine in combination with a thiazide drug.

Ajmaline (derived from R. serpentine) is a class I antiarrhythmic drug that is highly useful in diagnosing Brugada Syndrome (hereditary cardiac disorder), and differentiating between subtypes of patients with this disease. In fact, administration of the Rauwolfia alkaloid to patients with this type of arrhythmia is known as the “Ajmaline Test”; EKG results of this test are considered to be the best predictor of patients at risk for sudden death from the condition. Ajmaline is a sodium channel blocker that has a short duration of action when given intravenously, which makes it ideal for diagnostic purposes.

jrm-2012-2012010_fig1

Rauwolfia serpentina

© Steven Foster Group, Inc. All rights reserved.

THE MEDICINAL EFFECTS OF RAUWOLFIA

Reserpine has been shown to normalize blood pressure, especially in cases of hypertension exacerbated by stress and sympathetic nervous system activity. In fact, prior to the development of beta-blockers, calcium channel blockers, ACE inhibitors, and diuretics, reserpine was a leading therapeutic agent utilized by physicians in the management of hypertension.

Rauwolfia has a mild sedating effect and possible anti-depressant effect; therefore, this herb is especially indicated for those with known concomitant tension or insomnia. However, it is not typically used for exhausted and lethargic patients because it may worsen their fatigue. It is essential to start with a small dose of Rauwolfia to determine if the herb is well-tolerated. Due to its significant side effects, the use of isolated alkaloid reserpine was generally abandoned as other antihypertensive medications became available.

Research in the 1930s and 1940s described the hypotensive effects of Rauwolfia, and its traditional use as a calming and relaxing agent. A Rauwolfia-based medicine for hypertension (Serpasil) was released in the 1950s; several derivatives remain on the market today, and reserpine-based antihypertensive medications are currently used in Russia. A review of randomized, placebo-controlled trials with reserpine concluded that it was an effective tool in the management of hypertension but that additional and larger clinical trials were needed.

Rauwolfia reduces peripheral resistance, thereby lowering blood pressure, and decreases arterial pressure and increases tissue oxygen saturation. The isolated Rauwolfia component (called Ajmaloon in India, from the Sanskrit name for the plant), has a positive effect on blood pressure through its effect on vascular baroreceptors The reserpine alkaloid may also partially block adrenaline receptors.

THE USE OF VISCUM

The Loranthaceae family contains several plant genera including Viscum or ‘Mistletoe’. Several species of Viscum are used worldwide as herbal medicines. Viscum album contains lectins, phenylpropanoids and flavonoids that inhibit cAMP by inducing phosphodiasterase to break down cAMP. The flavonoids include syringin and conferin which may contract the aorta, while kalopanaxin has a relaxing effect. When used in tandem, they have tonifying effects on vascular muscle tone.

An ethanol extract of Viscum album was shown to reduce vascular tension when placed in contact with endothelial tissue. Viscum stimulates both the synthesis and release of nitric oxide to enable vasodilation. Nitric oxide is released from the vascular endothelium, and plays a role in local inflammatory processes; it helps to regulate the degree of vasodilation versus vasoconstriction via a mechanism independent of nerve regulation (such as adrenergic innervation).

Viscum album has been used as a blood pressure-regulating agent in Nigeria. Nigerian researchers reported that Viscum interfered with calcium ion-driven vascular contraction; both the influx of calcium and mobilization of calcium in intracellular stores were believed to be affected. Researchers in Serbia reported that hydroethanol extracts of Viscum album were capable of lowering blood pressure in rats, and that the use of muscarinic receptor blockers diminished or totally abolished the hypotensive effects of Viscum. This suggests that Viscum may act via muscarinic nerve transmission.Likewise, Viscum album has been shown to prevent changes in blood viscosity in a manner that is supportive to maintaining healthy blood pressure.Lectins found in Viscum may affect glycoprotein receptors, erythrocytes, lymphocytes and platelets, and contribute to its positive effects on blood viscosity and blood flow.

Besides blood pressure regulation, Viscum flavonoids may have other cardio-protective effects; it has been shown to reduce tissue damage by inhibiting platelet activating factor (PAF) response and reducing free intracellular calcium ions. Herbal practitioners usually prescribe Viscum as a tincture or tea; few encapsulated products are available on the market. When Viscum is used to treat cancer it is prepared by a different extraction method and given by subcutaneous injection.

THE USE OF PISCIDIA

The physicians in the early 1900’s researched and described Piscidia’s effects on the cardiovascular system; they stated that Piscidia could slow the pulse and briefly increase arterial tension followed by a long reduction in arterial tension. Piscidia was sometimes prescribed as a morphine-substitute to promote restful sleep, because it did not have the numerous side effects associated with morphine.

Piscidia erythrina is a flowering tree in the Fabaceae (legume) family, found in Central America, the West Indies and the Caribbean. It is historically used for pain, tension, insomnia, and to control high blood pressure. Its common name is ‘Jamaican Dogwood’. The linguistic derivation of Piscidia is related to its indigenous historical use as a toxin to stun fish. In fact, the isoflavonoid, sumatrol, and a variety of rotenones are credited with causing fish toxicity and are being investigated as potential chemotherapeutic agents.

Piscidia has powerful effects on the heart, vascular system, respiratory centers and nerve conduction, and is traditionally prescribed in small, doses.Its chemical constituents have not been well-studied; however, it is known to contain the resins, piscidin, jamaicin, and ichthynone. The sum of its chemical constituents are credited with muscle-relaxing effects which could account for its traditional use to treat pain and muscle spasms. Animal studies have also shown an anxiolytic effect that may contribute to its hypotensive actions.

DISCLOSURE OF INTERESTS

Dr. Saunders reports personal fees related to employment or seeing patients from CCNM, the Dundas Naturopathic Centre, and from Beaumont Health Systems, Troy Hospital, MI, outside the submitted work. Dr. Winston reports personal fees from Herbalist & Alchemist, Inc, outside the submitted work. Dr. Stansbury and Dr. Zampieron have nothing to disclose.

REFERENCES

  1. Baumeister AA, Hawkins MF, Uzelac SM. The myth of reserpine-induced depression: role in the historical development of the monoamine hypothesis. J Hist Neurosci 2003; 12(2):207–20.
  2. Fraser HS. Reserpine: A tragic victim of myths, marketing, and fashionable prescribing. Clin Pharmacol Ther 1996; 60(4):368–73.
  3. Kearney PM, Whelton M, Reynolds K, Whelton PK, He J. Worldwide prevalence of hypertension: a systematic review. J Hypertens 2004; 22(1):11–9.
  4. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365(9455):217–23.
  5. Dransfield MT, Rowe SM, Johnson JE, Bailey WC, Gerald LB. Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD. Thorax 2008; 63(4):301–5.
  6. Huen SC, Goldfarb DS. Adverse metabolic side effects of thiazides: implications for patients with calcium nephrolithiasis. J Urol 2007; 177(4):1238–43.
  7. Steckelings UM, Artuc M, Wollschlager T, Wiehstutz S, Henz BM. Angiotensin-converting enzyme inhibitors as inducers of adverse cutaneous reactions. Acta Derm Venereol 2001; 81(5):321–5.
  8. Takishita S. [Antihypertensive drug therapy: adverse effects and drug interactions]. Nippon Rinsho 2001; 59(5):992–7.
  9. Savory B, Turnbull JH. Luminescence spectra of yohimbine, reserpine and related alkaloids. Journal of Photochemistry 1983; 23(2):171–81.
  10. Smirk FH, McQueen EG. Comparison of rescinnamine and reserpine as hypotensive agents. Lancet 1955; 269(6881):115–16.
  11. Cronheim G, Brown W, Cawthrone J, Toekes MI, Ungari J. Pharmacological studies with rescinnamine, a new alkaloid isolated from Rauwolfia serpentina. Proc Soc Exp Biol Med 1954; 86(1):120–4.
  12. Fife R, MacLaurin JC, Wright JH. Rescinnamine in treatment of hypertension in hospital clinic and in general practice. Br Med J 1960; 2(5216):1848–50.
  13. Moyer JH, Dennis E, Ford R. Drug therapy (Rauwolfia) of hypertension. II. A comparative study of different extracts of Rauwolfia when each is used alone (orally) for therapy of ambulatory patients with hypertension. AMA Arch Intern Med 1955; 96(4):530–43.
  14. Billow BW, Spector R, Martorella FJ, Paley SS, Harris SB. The effect of a new Rauwolfia derivative, deserpidine, in hypertension. N Y State J Med 1958; 58(22):3641–2.
  15. Moyer JH, Kinard SA, Herschberger R, Dennis EW. Deserpidine (canescine) for the treatment of hypertension. South Med J 1957; 50(4):499–502.
  16. Cromwell HA. Control of hypertension with hydrochlorothiazide and deserpidine. Med Times 1961; 89:801–6.
  17. Kossover MF, Goldman AM. A combination of methyclothiazide and deserpidine in the treatment of essential hypertension. Dis Chest 1962; 42:170–5.
  18. Brugada R, Brugada J, Antzelevitch C et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101(5):510–5.
  19. Rolf S, Bruns HJ, Wichter T et al. The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol. Eur Heart J 2003; 24(12):1104–12.
  20. Jerie P. [Milestones of cardiovascular therapy. IV. Reserpine]. Cas Lek Cesk 2007; 146(7):573–7.
  21. Shamon SD, Perez MI. Blood pressure lowering efficacy of reserpine for primary hypertension. Cochrane Database Syst Rev 2009;(4):CD007655.
  22. Liu LS, Chen MQ, Zeng GY, Zhou BF. [A forty-year study on hypertension]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2002; 24(4):401–8.
  23. Mart’ianova TA, Seryi EI, Alekseev PA, Bykova LR. [Effect of hypotensive therapy on oxygen metabolism in middle-aged and elderly hypertensive patients]. Kardiologiia 1981; 21(3):56–60.
  24. Fahim M, Khan MS, Hameed HA. Effect of Ajmaloon on the baroreceptor-heart rate reflex in anaesthetized rabbits and monkeys. Indian J Physiol Pharmacol 1995; 39(2):101–5.
  25. Lundberg JM, Rudehill A, Sollevi A, Theodorsson-Norheim E, Hamberger B. Frequency- and reserpine-dependent chemical coding of sympathetic transmission: differential release of noradrenaline and neuropeptide Y from pig spleen. Neurosci Lett 1986; 63(1):96–100.
  26. Deliorman D, Calis I, Ergun F, Dogan BS, Buharalioglu CK, Kanzik I. Studies on the vascular effects of the fractions and phenolic compounds isolated from Viscum album ssp album. J Ethnopharmacol 2000; 72(1-2):323–9.
  27. Rodriguez-Cruz ME, Perez-Ordaz L, Serrato-Barajas BE, Juarez-Oropeza MA, Mascher D, Paredes-Carbajal MC. Endothelium-dependent effects of the ethanolic extract of the mistletoe Psittacanthus calyculatus on the vasomotor responses of rat aortic rings. J Ethnopharmacol2003; 86(2-3):213–8.
  28. Mojiminiyi FB, Owolabi ME, Igbokwe UV, Ajagbonna OP. The vasorelaxant effect of Viscum album leaf extract is mediated by calcium-dependent mechanism. Niger J Physiol Sci 2008; 23(1-2):115–20.
  29. Radenkovic M, Ivetic V, Popovic M, Brankovic S, Gvozdenovic L. Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. Clin Exp Hypertens 2009; 31(1):11–9.
  30. Ofem OE, Eno AE, Nku CO, Antai AB. Viscum album (mistletoe) extract prevents changes in levels of red blood cells, PCV, Hb, serum proteins and ESR in high salt-fed rats. J Ethnopharmacol 2009; 126(3):421–6.
  31. Gorudko IV, Buko IV, Cherenkevich SN, Polonetsky LZ, Timoshenko AV. Lectin-induced aggregates of blood cells from patients with acute coronary syndromes. Arch Med Res 2008; 39(7):674–81.
  32. Chu W, Qiao G, Bai Y et al. Flavonoids from Chinese Viscum coloratum produce cytoprotective effects against ischemic myocardial injuries: inhibitory effect of flavonoids on PAF-induced Ca2+ overload. Phytother Res 2008; 22(1):134–7.
  33. Ellingwood F. The American Materia Medica, Therapeutics and Pharmacognosy. 1919.
  34. Blatt CT, Chavez D, Chai H et al. Cytotoxic flavonoids from the stem bark of Lonchocarpus aff. fluvialis. Phytother Res 2002; 16(4):320–5.
  35. Jang DS, Park EJ, Kang YH et al. Potential cncer chemopreventive flavonoids from the stems of Tephrosia toxicaria. J Nat Prod 2003; 66(9):1166–70.
  36. Della LR, Zilli C, Del NP, Redaelli C, Tubaro A. Isoflavones as spasmolytic principles of Piscidia erythrina. Prog Clin Biol Res 1988; 280:365–8.
  37. Della LR, Tubaro A, Redaelli C. [Evaluation of the activity on the mouse CNS of several plant extracts and a combination of them]. Riv Neurol1981; 51(5):297–310.