INDEX

African Snake Root, Indian Snake Root (Rauwolfia vomitoria, R. serpentina)

Traditional Uses

Hypertension and arrhythmia.

Mechanism of Action

Rauwolfia’s effects on the heart include decreasing myocardial excitability, inhibiting atrial-ventricular conduction, and extending the refractory period of the heart rhythm.1

Much of the medicinal effects of Rauwolfia serpentina and Rauwolfia vomitoria have been attributed to the hypotensive indole alkaloid reserpine.2 Additional alkaloids found in Rauwolfia roots include the indoles ajmaline, ajmalicine, raubasine, imethylajmaline, methylisoajmaline, hydroxysarpagine, yohimbinic acid, and isorauhimbinic acid.3 The constituent ajmaline is thought to be antiarrhythmic.4

Before the advent of the current pharmaceutical options for hypertension (beta blockers, calcium channel blockers, and angiotensin-converting Inhibitors), reserpine was a mainstay in the management of hypertension. Reserpine acts via the CNS to reduce sympathetic tone, increase parasympathetic activity, and help normalize blood pressure, especially when symptoms result from stress and sympathetic nervous responses, as it may partially block adrenaline receptors.5 Reserpine’s ability to block adrenoreceptors on blood vessels can reduce stress-induced vasoconstriction that contributes to hypertension and heart palpitations.

Research suggests that reserpine may deplete peripheral catecholamine stores, contributing to hypotensive effects.6,7 Reserpine also seems to bind to vesicular monoamine transporters (VMATs) with high affinity, blocking neurotransmitter uptake into the vesicle and ultimately depleting catecholamines from storage vesicles. The actions of reserpine on the VMAT result in an acute catecholamine release, followed by chronic inhibition of catecholamine secretion, as a result of diminished releasable stores of vesicular catecholamine.8

Mechanisms involving cellular calcium influx and transport are also involved with the initiation and development of hypertension as a result of constrictive effects on vascular smooth muscle; thus, Rauwolfia may elicit vascular relaxation, reducing peripheral resistance and improving blood pressure.9

Although Rauwolfia can help reduce blood pressure, its effects are more pronounced on the CNS than the peripheral nervous system, through activity at the diencephalon, as reserpine decreases the release and accumulation of noradrenaline.8 Rauwolfia has a mildly sedating effect, making this herb especially indicated for those with concomitant tension, overwork, or poor sleep.

Evidence-Based Research

A review of the few randomized and placebo controlled trials that have been conducted on reserpine in the treatment of hypertension reported that reserpine is an effective tool in managing hypertension but that additional and larger trials are needed.10 One study that examined 108 elderly patients with II stage hypertensive disease reported that reserpine decreased arterial pressure and peripheral vascular resistance while increasing oxygen saturation in the tissues.11

A Rauwolfia product called Serpina was given to more than 100 patients for periods of 1 month to 1 year. In the study, a daily dose of one to three Serpina tablets was well tolerated. The product caused sedation and usually improved sleep, and it promoted moderate hypotension, particularly in labile patients with hypertension and tachycardia. It also seemed to have a sympatholytic effect, but did not produce postural hypotension.12

A Cochrane meta-analysis of randomized controlled trials of hypertension determined that Rauwolfia displayed similar efficacy to first-line antihypertensive drugs, without significant side effects.10 Much of the medicinal effects have been attributed to the alkaloids reserpine, ajmaline, and ajmalicine.13

Safety in Pregnancy and Breastfeeding

Animal studies have shown R. vomitoria to have teratogenic effects on rat fetal heart at the higher dosage range.14 Histological observations of the fetal heart showed marked distortion of the cardiac muscle nuclei and myocardial fibers in the treated groups, particularly those whose mothers received 250 mg/kg of the extracts. These effects were more pronounced in the groups whose mothers received the root extract compared with the control and the groups whose mothers received the leaf extract. Based on these findings, Rauwolfia would be best avoided during pregnancy.

General Safety

It is important to note that most Rauwolfia studies were conducted using isolated preparations of a single indole alkaloid constituent, reserpine, rather than extracts of the whole plant. This has given rise to a great deal of misinformation regarding the safety profile of Rauwolfia, as concerns about adverse effects that may have been observed with the reserpine isolate have been extrapolated, without any basis in evidence, to Rauwolfia, the whole plant. Unlike isolates of single extracts, which may have a greater potential to lead to negative effects, whole plant extracts generally act in balanced and synergistic ways. Furthermore, even the idea that reserpine may lead to depression by depleting dopamine from dopaminergic neurons turns out to be speculative. In fact, a systematic review found that both reserpine and Rauwolfia are associated with improvements in depression.15

Another serious misconception about Rauwolfia is that it is hepatotoxic. However, in an animal model of liver toxicity, Rauwolfia vomitoria was actually shown to be hepatoprotective.16

Dosage

The usual starting dose for Rauwolfia is about 10-25 mg of crude herb (which typically contains around 125 mcg of reserpine) once or twice a day. Based on extensive traditional use and current use in clinical practice, the main side effect to be on the lookout for with Rauwolfia in the therapeutic range is hypotension, which can be used as a gauge for monitoring dosage of this powerful plant ally in the management of high blood pressure.

Traditional Uses

Rauwolfia serpentina (Indian Snake Root) is an endangered species and illegal to import. Rauwolfia vomitoria (African Snake Root) is widely available and not endangered.

Rauwolfia is an herbaceous plant of Asian and South American tropical forests, and it is in a family known to contain powerful alkaloids and medicinal species. Native to India, Rauwolfia has been used as a traditional Ayurvedic medicine for many ailments, including anxiety, headaches, and snakebites and as a general sedative for more than a thousand years. It is reported that Gandhi regularly drank Rauwolfia tea for its calming effect.

Research emerged in the 1930s and 1940s describing the hypotensive effects of Rauwolfia and supporting its traditional use as a calming and relaxing agent. A Rauwolfia-based medicine for hypertension, Serpasil, was released in the United States in the 1950s.17 The use of isolated alkaloid preparations fell out of favor as other antihypertensive pharmaceuticals became available, but several medications for hypertension derived from reserpine are still used in other parts of the world today.

References

  1. J Pharmacol Exp Ther. 1958;124(4):324–32. The action of Rauwolfia alkaloids on the heart rate and on the functional refractory period of atrio-ventricular transmission in the heartlung preparation of the dog. Innes R, et al.
  2. J Chromatogr Sci. 2006;44(9):557–60. Quantitative determination of reserpine, ajmaline, and ajmalicine in Rauvolfia serpentina by reversed-phase high-performance liquid chromatography. Srivastava A, Tripathi AK, Pandey R, Verma RK, Gupta MM.
  3. J Nat Prod. 2005;68(6):848–52. Indole alkaloids and other constituents of Rauwolfia serpentina. Itoh A, Kumashiro T, Yamaguchi M, Nagakura N, Mizushina Y, Nishi T, Tanahashi T.
  4. Planta Med. 2002;68(10):906–11. A newly-detected reductase from Rauvolfia closes a gap in the biosynthesis of the antiarrhythmic alkaloid ajmaline. Gao S, von Schumann G, Stöckigt J.
  5. Neurosci Lett. 1986;63(1):96–100. Frequency- and reserpine-dependent chemical coding of sympathetic transmission: differential release of noradrenaline and neuropeptide Y from pig spleen. Lundberg JM, Rudehill A, Sollevi A, Theodorsson-Norheim E, Hamberger B.
  6. Can J Physiol Pharmacol. 2005;83(6):509–15. Reserpine-induced central effects: pharmacological evidence for the lack of central effects of reserpine methiodide. Nammi S, Boini KM, Koppula S, Sreemantula S.
  7. BMC Pharmacol. 2004;4:30. Reserpine methonitrate, a novel quaternary analogue of reserpine augments urinary excretion of VMA and 5-HIAA without affecting HVA in rats. Sreemantula S, Boini KM, Nammi S.
  8. Neurochem Int. 2010;56(6–7):760–7. Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles. Mandela P, et al. doi: 10.1016/j.neuint.2010.02.011. Epub 2010 Feb 20.
  9. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002;24(4):401–8. A forty-year study on hypertension. Liu LS, Chen MQ, Zeng GY, Zhou BF.
  10. Cochrane Database Syst Rev. 2009;(4):CD007655. Blood pressure lowering efficacy of reserpine for primary hypertension. Shamon SD, Perez MI.
  11. Kardiologiia. 1981;21(3):56–60. Effect of hypotensive therapy on oxygen metabolism in middle-aged and elderly hypertensive patients. Mart’ianova TA, Seryi EIa, Alekseev PA, Bykova LR.
  12. Br Heart J. 1949;11(4):350–5. A clinical trial of Rauwolfia serpentina in essential hypertension. Vakil R, et al.
  13. J Chromatogr Sci. 2006;44(9):557–60. Quantitative determination of reserpine, ajmaline, and ajmalicine in Rauvolfia serpentina by reversed-phase high-performance liquid chromatography. Srivastava A, Tripathi AK, Pandey R, Verma RK, Gupta MM.
  14. N Am J Med Sci. 2010;2(12):592–5. Comparative study of teratogenic potentials of crude ethanolic root bark and leaf extract of Rauwolfia vomitoria (apocynaceae) on the fetal heart. Eluwa MA, Udoaffah MT, Vulley MB, et al.
  15. IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS). e-ISSN: 2278-3008, p-ISSN:2319-7676. Volume 7, Issue 2 (Jul. – Aug. 2013), PP 18-22 www.iosrjournals.org
    16. The Effects of Rauwolfia Vomitoria Extract on the Liver Enzymes of Carbon Tetrachloride Induced Hepatotoxicity in Adult Wistar Rats. Ezejindu D.N, Okafor I. A, Anibeze C.I.P, Uloleme G.C.
  16. Cas Lek Cesk. 2007;146(7):573–7. Milestones of cardiovascular therapy. IV. Reserpine. Jerie P.
  17. J Psychopharmacol. 2023 Mar;37(3):248-260. doi: 10.1177/02698811221115762. Epub 2022 Aug 24. PMID: 36000248; PMCID: PMC10076328.The effects of reserpine on depression: A systematic review. Strawbridge R, Javed R.R, Cave J, Jauhar S, Young A.H.