Rauwolfia serpentina is very commonly used for treating hypertension in homeopathic & ayurvedic medicine. The genus Rauwolfia was named in the honor of 16th-century German physician Dr Leonhard Rauwolf, who studied plants while travelling in India & Rauwolfia serpentina was particularly selected for this study. The plant was mentioned in Indian manuscripts way back in 1000 bc.
Rauwolfia serpentina common name
Rauwolfia serpentina is more commonly known as Sarpagandha & also Indian snakeroot owing to its long, tapering, snake-like roots structure. It is an evergreen shrub native to tropical & subtropical regions of the world, including Europe, Africa, Asia, Australia & the Central & South America.
Rauwolfia serpentina ayurveda
R serpentina was used as Sarpagandha in ancient medicine in India for centuries to treat a wide variety of maladies, like snake & insect bites, fever, malaria, abdominal pain, and dysentery. It was also used as a uterine stimulant and as a cure for insanity.
This plant was used by many physicians throughout India in the 1940s. It was reported that Rauwolfia was the best hypertensive remedy used in India throughout the 1950s & it was reported to be used by 90% of all physicians or more than 60 000 doctors throughout the country. Besides the extensive domestic usage, it was exported to more than 17 countries. It was used throughout world in the 1950s, including the top countries, United States and Canada.
The Indian physician Rustom Jal Vakil introduced Rauwolfia to Western medicine. He continued to collect data on patients treated with Rauwolfia for 10 years, from 1939 to 1949. In 1949, he published his research paper on the antihypertensive properties of Rauwolfia serpentina in the British Medical Journal. He wrote about his detailed results from successfully treating 50 patients who had high blood pressure with the root of Rauwolfia. These results were ofcourse remarkable and significant. Consequently by 1949, more than 90% of Indian physicians were using Rauwolfia for the treatment of high blood pressure. After Dr Vakil’s research paper, more than 100 scientific articles were published on Rauwolfia serpentina & its wonders throughout the world.
However, later on it fell out of popularity when adverse side effects like depression and cancer became associated with it. Research in past has proved that Rauwolfia serpentina is a safe and natural treatment for hypertension. The plant provides clinicians with a safe and effective adjunct or even a replacement to allopathy in the treatment of high blood pressure. This article reviews the medical benefits of Rauwolfia serpentina & potential side effects if any.
Rauwolfia serpentina constituents
Rauwolfia contains many different phytochemicals like alcohols, sugars & glycosides, fatty acids, flavonoids, phytosterols, oleoresins, steroids, tannins, & the most important are alkaloids. The alkaloids found in this plant are indole alkaloids, & more than 50 of these alkaloids have been isolated. These indole alkaloids are derived from the amino acid tryptophan & alkaloids of Rauwolfia serpentina are responsible for all the wonders of this plant.
All parts of the Rauwolfia plant, including the stem and leaves, contain indole alkaloids, but they are highly concentrated in the bark of the root. The exact concentration of the alkaloids is variable.The identified indole alkaloids include ajmalidine, ajmaline, ajmalinine, ajmalicine, aricine, canescine, coryanthine, deserpidine, isoajmaline, isoserine, isoserpiline, lankanescine, neoajmaline, papaverine, raubasine, raucaffricine, rauhimbine, rauwolfinine, recanescine, rescinnamine, reserpiline, reserpine, reserpinine, sarpagine, serpentine, serpentinine, thebaine, yohimbine, and yohimbinine.
Reserpine, the major alkaloid of Rauwolfia serpentina
Reserpine is one of the major alkaloids of this plant. The reserpine content is highest in the root and lowest in the stems and leaves. Scientists have believed it to be the most prevalent indole alkaloid in the plant. The concentration of reserpine in the plant has been found to vary from 0.03% to 0.14% of the dry weight of the plant. Other alkaloids in the plant have also been identified to have biochemical medicinal actions, including canescine, deserpidine, recanescine, and rescinnamine.
Active constituent of Rauwolfia serpentina
Reserpine is the most widely studied alkaloid of Rauwolfia serpentina. It was first isolated & used by Robert Wallace Wiggins in 1950.
Further in 1952, isolated reserpine was introduced as the drug Serpasil for the treatment of hypertension, tachycardia, and thyrotoxicosis.
Reserpine is a white-to-yellow powder that becomes darker when exposed to light. It is odorless, water insoluble and has a bitter taste.
After oral ingestion, the bioavailability of reserpine has been determined to be between 50% and 70%. Absorption can be taken as fairly rapid, occurring between 1 and 2 hours after ingestion.
Reserpine is then widely distributed throughout the body to the brain, liver, spleen, kidney, and adipose tissue & also widely distributed to red blood cells and peripheral neurons. It has been found in breast milk and can cross the placenta and blood-brain barrier.
Rauwolfia serpentina mechanism of Action
The mechanism of action of reserpine is well researched. Reserpine binds to certain protein receptors called vesicular monamine transporters (VMATs) in the organelle membranes of specialized secretory vesicles of presynaptic neurons. Reserpine prevents intracellular neurotransmitters from binding to VMAT proteins and stops secretory vesicles from uptaking neurotransmitters.
Ultimately, use of reserpine ensures that no or few neurotransmitters are released from the presynaptic neuron. As a result, no or only slight transmission of the nerve impulse occurs in the postsynaptic neuron.
RAUWOLFIA SERPENTINA MEDICINAL USES
Rauwolfia and Blood pressure
In 1949, a study was conducted in India which involved 50 patients with hypertension & they were treated with Rauwolfia. In the results of this study, 85% of patients showed a drop in systolic blood pressure, and 81% of patients showed a drop in diastolic blood pressure.
In 1952, a study in Germany and Austria reported Rauwolfia to be effective in inducing a blood pressure drop in 25 patients with hypertension. In this study systolic pressure dropped an average of 30 mm Hg and diastolic pressure dropped 15 mm Hg. In 1953, Rauwolfia was found to be effective in 90% of a study’s participants, with a lowering of systolic blood pressure between 15 and 40 mm Hg. In same year, a study in Switzerland reported a lowering of blood pressure in 51 patients with hypertension. In 1954, a Japanese study reported lower blood pressure in 12 of 15 patients with hypertension. In 1954, a study in NewZealand reported that reserpine produced a striking fall in blood pressure within 4 to 6 hours of administration.
In 1952, a purified, standardized, isolated alkaloid extract called alseroxylon was introduced in the United States. The active ingredients of the purified extract were a mixture of reserpine and rescinnamine. In this study, 346 patients with hypertension were treated on an outpatient basis in public and private hospitals. Participants’ original blood pressures were greater than 150/100 mm Hg on admission. A consistent decrease in blood pressure readings of greater than 20 mm Hg was observed in patients treated with the alseroxylon extract.
A Rauwolfia product called serpina was given to more than 100 patients for periods of 1 month to 1 year. In this study, a daily dose of 1 to 3 Serpina tablets was well tolerated. Its action was slow to appear, ranging from 3 to 6 days, and it disappeared 7 to 21 days after stopping the drug. It did not produce any serious side effects.
The product caused sedation and usually improved sleep, however it was found to have a tendency to cause bradycardia and nasal congestion in some patients. It apparently was not habit forming. It appeared to be more effective in young, neurotic hypertensive patients with tachycardia than in those with long-established, fixed hypertension with vascular disease. Thirty-nine patients with an average blood pressure reading of 192/122 mm Hg and a pulse of 82 were treated with Serpina alone. The average blood pressure dropped to 165/95 mm Hg and the average pulse was 70. In 13 of 39 patients, blood pressure was controlled, returning to a normal reading of lower than 150/90 mm Hg.
Another study was designed to evaluate various effects of oral reserpine on a group of hypertensive individuals in an outpatient clinic. Reserpine from CIBA Pharmaceuticals was given in a dosage of 20 mg twice per day to 15 individuals who had initial blood pressures between 160/98 and 240/150 mm Hg. For those patients, systolic blood pressure dropped an average of 30.7 mm Hg and diastolic blood pressure dropped an average of 19 mm Hg. Some patients reported transient nausea, fainting, and dyspnea. The researchers concluded that the drug was a useful and potent agent in some patients with severe as well as mild hypertension.
Another study was undertaken to investigate the dose-related effects of reserpine on blood pressure, heart rate, and withdrawals due to adverse effects. None of the trials reported any withdrawals due to adverse effects. This helped to conclude that reserpine was effective in reducing systolic blood pressure to the same degree as other first-line antihypertensive drugs.
Rauwolfia serpentina: a potential plant to treat insomnia disorder
The primary effect of the alkaloids is the blockage of vesicular storage of monoamines, which finally leads to greater degradation of these neurotransmitters by the MAO enzyme & an overall decrease in neuronal activity in monoamine pathways. Thus, the overall effect produced is inhibitory & sedative.
Rauwolfia is best supported as an antipsychotic. In eastern medicine it continues to be used as a tranquilizer. The compound is approved for the treatment of hypertension & insomnia. However, the actual utility of Rauwolfia for insomnia is limited by its wide-ranging effects. When administered, rauwolfia causes a drop in blood pressure & may result in dizziness. Since Rauwolfia exerts a significant antagonistic effect on dopamine, it can promote sedation & sleep. It may sometimes cause unpleasant side effects commonly associated with antipsychotic medications, including problems with coordination & stereotypic movements. If utilized, rauwolfia should be carefully monitored for adverse effects. The typical safe dose is 600 mg/day, taken about 1 hour before bedtime.
Rauwolfia serpentina Other medical Uses
Rauwolfia has been studied for the treatment of mental diseases, including schizophrenia and bipolar disorder, epilepsy and seizures.
One study found Rauwolfia to be very effective in the treatment of anxiety. All forms of Rauwolfia were used in this study, including reserpine, alseroxylon, and the whole root, and all gave similar results in the control of overt anxiety in ambulatory patients.
Rauwolfia has been studied as a treatment for autistic children between the ages of 3.5 to 9 years. Another study found it to be effective in treatment of delirium tremens in alcohol & drug addicted patients. The researchers in that study observed a noted decrease in agitation, excitement, and acute hallucination episodes.
One study found that Rauwolfia treated migraine headaches effectively, providing a noted improvement in quality of life and a decrease in pain.
Another study used Rauwolfia to treat angina pectoris in patients with coronary artery disease & it showed a decrease in angina symptoms with a prolonged therapeutic effect. One-half of the patients in that study went on to develop normal electrocardiograms.
In another study, Rauwolfia was studied to examine its benefits in improving dermatosis. It has also been reported to improve psoriatic outbreaks.
Rauwolfia serpentina side Effects
Mild side effects with a good dose may include lethargy, sedation, depression, hypotension, nausea, vomiting, abdominal cramping, gastric ulceration, nightmares, bradycardia, angina-like symptoms, bronchospasm, skin rash, itching, galactorrhea, breast enlargement, sexual dysfunction, and withdrawal psychosis in 1 case.
The most common side effect noted in patients was nasal congestion, occurring in 5% to 15% of all patients. Another common side effect was that Rauwolfia serpentina causes gas & bloating. After several months of prolonged use, mental depression can occur and may persist. With extremely larger doses, Parkinson-like symptoms, extrapyramidal reactions, and convulsions can occur. Allergic reactions to Rauwolfia, including asthma, are rare.
Adequate doses of reserpine to decrease blood pressure do not cause reserpine-induced gastric ulcerations. Reserpine has been observed to cause a slight edema in some patients. Possible interactions with other drugs include cardiac glycosides, ephedra, alcohol, antipsychotic drugs, barbiturates, digoxin, diuretics, ephedrine, levodopa, monamine oxidase inhibitors, propranolol, stimulant drugs, and tricyclic antidepressants. Rauwolfia may interact with the some lab tests, including tests for corticosteroids, bilirubin, catecholamines, gastric acidity, norepinephrine, prolactin, thyroxine, and vanillylmandelic acid.
An association does not appear to exist between reserpine and the development of cancer. No increased risk of birth defects has been shown in women who consumed reserpine at any time during their pregnancy. There were no mutagenic, genotoxic, or recombinogenic effects of reserpine reported.
Rauwolfia and Breast Cancer
The use of Rauwolfia and reserpine products was sharply reduced in the late 1960s and early 1970s when an alleged relationship to the development of breast cancer was raised in the medical literature in 3 research studies. However a re-evaluation of the original studies showed that those conclusions were erroneous.
Subsequent research and analysis which was more accurately done & avoided the previous errors showed that no increase in the rate of breast cancer occurred in the patients using Rauwolfia or reserpine products. The study compared 257 women with breast cancer with 257 women that had no breast cancer and they were matched for age, date, admission diagnosis, and race. The odds ratio of developing breast cancer was 1:1 when comparing those who used Rauwolfia products with those who did not.
In that study, 109 patients were treated with Rauwolfia products, and 109 patients were treated with other pharmacologic drugs. The relative risk of developing breast cancer was 0.9 to 1.11 when comparing Rauwolfia to the other agents. The researchers concluded that it is unlikely that the use of Rauwolfia increases the risk of breast cancer.
Reserpine has been observed to increase prolactin levels. Prolactin levels were compared in 15 females who used reserpine for at least 5 years to 15 females who used a non reserpine antihypertensive. Mean prolactin levels were 50% higher in the females who consumed reserpine compared to those who did not. The researchers concluded that such an increase in postmenopausal women would likely cause only a very small increase in breast cancer, as has been shown in epidemiological studies. They also pointed out that prolactin does not have a role in breast carcinogenesis in humans.
Rauwolfia and Depression
The incidence of depression in patients taking Rauwolfia and reserpine was studied in an outpatient hypertensive clinic based in Montreal between June 1954 and December 1956. In that study, 296 patients were involved & they were observed and compared for the whole period of the study; out of total 296, 195 patients took Rauwolfia products alone or in combination with other drugs and 101 patients took no Rauwolfia products. In the group that took Rauwolfia products, 134 of 195 took reserpine alone, and 61 of 195 took a whole-root preparation or the purified alseroxylon.
Of the 101 patients in that study who took no Rauwolfia or reserpine, none reported depression. Of the group that took Rauwolfia products, 30 of 195 patients reported developing depression. Of those 30 patients, 24 were female and 6 were male, with ages ranging between 33 & 70 years with an average age of 52 years. The total incidence of depression in that study was calculated to be 10% but was found to be 15% of Rauwolfia or reserpine patients. Of these patients, the ones who reported the development of depression, 25 took reserpine products, and 5 took Rauwolfia or the alseroxylon fraction. Of those 5 patients, 2 took alseroxylon extract, and 3 took whole-root preparation. Of the patients who developed depression, 83% took reserpine and 17% took the whole-root or purified alkaloidal fraction.
In this study, the lapse time between administration of the drug and the appearance of mental symptoms was between 2 weeks and 14 months for reserpine, with an average of 4.5 months; from 2.5 to 3 months with the whole-root preparation; and 5 months with the alseroxylon fraction. The daily dose used in those patients was 0.75 to 4 mg of reserpine, with an average of 1.36 mg; 8 to 12 mg of alseroxylon, with an average of 10 mg; and 150 to 200 mg of the whole-root preparation, with an average 183 mg.
In the study, the severity of depression was also keenly observed & was graded from 1 to 4. Of the patients experiencing depression, 19 of 30 patients recovered completely when the drug was stopped. Of those patients, 11 of 19 showed total recovery & remaining showed marked improvement. A reduction of dosage in 6 cases provided faster complete recovery for 4 of those patients, marked improvement in 1 patient, and improvement in 1 patient. This helped to conclude that dosage is an important factor in development of depression. It was advised that a complete history of mental disease and depression was recommended before starting a patient on Rauwolfia therapy with a further recommendation that the daily dosage should be lower than 0.75 mg of reserpine.
Rauwolfia serpentina dosage
Rauwolfia serpentina is sometimes prescribed as combinations of herbal and mineral supplements to treat hypertension, using Rauwolfia and reserpine products alone or in combination with herbs and minerals. Rauwolfia combined with hawthorn and some form of magnesium gives good results.
The ideal dosage should not exceed 500 mg of Rauwolfia per day and ideally 100 mg of Rauwolfia twice a day to be on safe side. Some patients receive 300 to 400 mg per day if needed after careful analysis.
A continuous low dose of Rauwolfia is more safe to totally avoid any side effects & it gives good results too. It combines well with diuretics, angiotensin-converting enzyme (ACE) inhibitors, & angiotensin 2 receptor blockers (ARBs). Caution should be taken when the patient is on a β-blocker or calcium channel blocker.
It must not be given to patients who are already depressed no matter even if it’s very light.
It should not be prescribed to patients with congestive heart failure or cardiac decompensation, bradycardia or with a heartbeat of fewer than 60 beats per minute & weak, elderly patients as Rauwolfia can lower pulse rates by approximately 10 beats per minute in some patients & those patients may not benefit from adrenergic blockade. The risks of adverse events could potentially outweigh the benefits attained.
Conclusion
Rauwolfia appears to be a safe and effective treatment for hypertension when used in appropriate low doses. An equivalent dose of pure Rauwolfia alkaloids, also known as alseroxylon extract or pure reserpine, can also be used to treat hypertension. It has been noted that low dose reserpine can be safely recommended to patients who have been screened to be of benefit from the treatment. The total daily dose of Rauwolfia should be lower than 500 mg of root extract & ideally can be less than 250 mg per day. The dosage of purified alkaloid-alseroxylon extract should be lower than 5 mg per day and, can be less than 2.5 mg per day. The reserpine dose should be lower than 500 μg per day and can be lower than 250 μg per day.
