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Rauvolfia Serpentina L. Benth. Ex Kurz.: Phytochemical, Pharmacological and

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Int. J. Pharm. Sci. Rev. Res.

, 23(2), Nov – Dec 2013; nᵒ 56, 348-355 ISSN 0976 – 044X

Review Article

Rauvolfia serpentina L. Benth. ex Kurz.: Phytochemical, Pharmacological and


Therapeutic Aspects
a b c *d
Reeta Kumari , Brijesh Rathi , Anita Rani , Sonal Bhatnagar
a
Department of Botany, Sri Venkateswara College, University of Delhi, New Delhi- 110021, India.
b
Department of Chemistry, Sri Venkateswara College, University of Delhi, New Delhi- 110021, India.
c
Department of Botany, Dyal Singh College, University of Delhi, New Delhi- 110003, India.
d*
DDE, Kuvempu University, Shimoga – 577 451, Karnataka, India.
*Corresponding author’s E-mail: sbhatnagar.du@gmail.com

Accepted on: 16-10-2013; Finalized on: 30-11-2013.


ABSTRACT
Rauvolfia serpentina is an important medicinal plant in the pharmaceutical world due to the presence of its immense therapeutic
properties. The plant is known for curing various disorders because of the presence of alkaloids, carbohydrates, flavonoids,
glycosides, phlobatannins, phenols, resins, saponins sterols, tannins and terpenes. The plant parts, root and rhizome have been used
since centuries in Ayurvedic medicines for curing a large number of diseases such as high blood pressure, mental agitation, epilepsy,
traumas, anxiety, excitement, schizophrenia, sedative insomnia and insanity. The plant contains more than 50 different alkaloids
which belong to the monoterpenoid indole alkaloid family. The major alkaloids are ajmaline, ajmalicine, ajmalimine, deserpidine,
indobine, indobinine, reserpine, reserpiline, rescinnamine, rescinnamidine, serpentine, serpentinine and yohimbine. R. serpentina is
also known for its antimicrobial, antifungal, anti-inflammatory, antiproliferative, antidiuretic and anticholinergic activities. The
herbal medicine is still the basis of primary health care for 75–80% of the world population because of its cultural acceptability,
better compatibility with the human body and lesser side effects. Therefore, there is a need for us to search alternative, naturally
available remedies for curing million’s of people worldwide. Due to all these properties, the present review aims to evaluate the
various pharmacological, phytochemical and therapeutic properties of R. serpentina.
Keywords: Antihypertensive, Herbal remedy, Indole Alkaloids, Medicinal plant, Reserpine.

INTRODUCTION important plant used for the purposes of obtaining drugs


is Rauvolfia serpentina.

I ncrease in world population poses huge challenges to


satisfy the need for food, shelter and cloth. There is a
rise in demand for medicine, as millions of people are
suffering from various types of diseases worldwide. There
are several pharmaceutical formulations available
Rauvolfia serpentina L. Benth. Ex Kurz. is an evergreen,
woody, glabrous and perennial shrub with maximum
height upto 60 cm. The plant possess tuberous root with
pale brown cork and elliptic to lanceolate or obovate
commercially for the treatments of disorders but they are leaves in whorls of three.8 The plant belongs to the family
costly, not effective and show numerous toxic effects. Apocynaceae and occurs in habitats of tropical and
Therefore, there is an urgent need for us to use an subtropical regions. The family includes 50 species,
alternate, naturally available medications or herbal distributed worldwide in the region of the Himalayas,
remedies which do not show any side effects. Over 80 % Indian peninsula, Burma, Indonesia and Sri Lanka and is
of world population are dependent on herbal medicine indigenous to India, Bangladesh and other regions of
for its therapeutic effects and more than 800 plant Asia.9,10 The plant is commonly known as Sarpagandha,
1
species shows hypoglycaemic activity. In India, various Chandrabagha, Snake root plant, Chotachand, Chandrika
11
indigenous plants are used to cure disease, as nature has and Harkaya etc. The roots, leaves and juice are of
provided a perfect storehouse of remedies to cure all medicinal importance and have attracted the attention of
2
elements of humanity. The medicinal plants show the practitioners of indigenous system of medicine, as it
presence of various chemical substances such as contain a large number of secondary metabolites (N-
alkaloids, hydrogen, carbon, nitrogen, glycosides, volatile containing indole alkaloids) localized mainly in the roots
oils, fatty acids, resins, gums and tannins that are and rhizomes.5,12 It has been used in India as a part of the
responsible for treating various diseases.3-5. According to Ayurvedic medical system for the treatment of various
WHO (World Health Organization), any plant or its parts ailments.13 In Ayurvedic medicines, the roots of R.
containing substance that can be used therapeutically or serpentina is used as a remedy for curing hypertension,
can be used as raw material for chemical or insomnia, mental agitation, gastrointestinal disorders,
pharmaceutical synthesis is classified as a drug.6 Today excitement, epilepsy, traumas, anxiety, excitement,
about 300 species of medicinal and aromatic plants are schizophrenia, sedative insomnia and insanity.12,14 In
used worldwide in the pharmaceutical, food, cosmetics Siddha medicine, R. serpentina roots are used for curing
and fragrance industries.4,7,8 One of the medicinally hypertension-associated headache, dizziness,
amenorrhea, oligomenorrhea and dysmenorrhea like

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Int. J. Pharm. Sci. Rev. Res., 23(2), Nov – Dec 2013; nᵒ 56, 348-355 ISSN 0976 – 044X

abnormalities. According to Rajendran and Agarwal PHYTOCHEMICAL CONSTITUENTS


(2007)15, fruits and seeds have also been used for its
Rauvolfia serpentina has been a prevailing field of
medicinal or ethno botanical purposes by the ethnic
research for decades and several workers have explored
tribes of Virudhungar district Tamil Nadu, India. 5,10-12,29
this area due to its phytochemical properties. The
Scientists have been working on the phytochemical various phytochemical compounds or secondary
analysis of the plant due to its medicinal importance. It metabolites present in R. serpentina include alkaloids,
has been used as anthelmintic and anti-hypertensive phenols, tannins and flavonoids.
drugs. It is used as an antidote against snake bite and
Alkaloids
bites of other poisonous insects. In diarrhoea, dysentery,
cholera, fever, opacity of the cornea and central epilepsy Alkaloids are large group of organic molecules which
and ecbolic R. serpentina also played an important contain a heterocyclic nitrogen ring. These are brought
role.10,16 The plant is known to cure various circulatory about by different organisms such as animals and
17
disorders due to the presence of alkaloids. The root microbes, but a particularly diverse array of alkaloids is
juices or extract is used to treat liver and abdomen pain, produced by plants. Approximately 10 % of plant species
various gastrointestinal disorders and to expel intestinal are believed to produce alkaloids as secondary
18-20 21
worms from the childrens. Mao et al. (2009) have metabolites, where they work predominantly in providing
reported the plant as a function of the ethnobotanical defence against herbivores and pathogens. Pure isolated
wealth of north east India. The plant also shows the use alkaloids and their synthetic derivatives are used as
by local people of Eastern Ghats, Uttar Pradesh, medicinal agents for their analgesic, antispasmodic and
Karnataka and Bangladesh against snake bite.22 The roots bactericidal effects.37 The alkaloids obtained from the
and leaf buds are crushed with milk, made into a paste root extract acts directly on central nervous system and
23,24
and used externally on the affected areas. The other thereby reduces blood pressure as compared to other
diseases such as pneumonia, malaria, body aches, blood-pressure lowering agents. R. serpentina root is
eczema, burns, menstrual disorders, scabies, skin cancers, reported to contain 0.7 – 3.0 % of total alkaloids and
asthma, respiratory problems, eye inflammation, spleen about 0.1% of the active principle reserpine which is an
diseases and fever can also be cured using R. indole alkaloid, present in the root. Hence, root biomass
serpentina.19,20,25-30 The present review work emphasizes production of this plant could be of economic
on the potential of R. serpentina as antifungal, anti- importance. On the basis of the structure there are three
inflammatory, antioxidant, antiproliferative, types of alkaloids namely, weak basic indole alkaloids,
anticancerous, antidiuretic, antifibrillar, antiarrhythmic, alkaloids of intermediate basicity and strong
anticholinergic, antidysentry, antidiarrhoeal anhydronium bases.38 The various alkaloids identified in
antihypotensive, anticontractile, antidiuretic, Rauvolfia (Figure 1) include ajmaline, ajmalimine,
sympathomimetic, and tranquillizing agent.31-36 ajmalicine, deserpidine, indobine, indobinine, reserpine,
reserpiline, rescinnamine, rescinnamidine, serpentine,
serpentinine and yohimbine etc.39,40

Figure 1: Chemical structures of some alkaloids present in Rauvolfia serpentina.

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Available online at www.globalresearchonline.net 349
Int. J. Pharm. Sci. Rev. Res., 23(2), Nov – Dec 2013; nᵒ 56, 348-355 ISSN 0976 – 044X

Amongst all, resperine is the principle alkaloid which Ajmalicine


shows large number of clinical applications.41,42 Along
Alkaloid, ajmalicine have a large number of applications in
with resperine, yohimbine, serpentine, deserpidine,
the treatment of circulatory diseases, especially in
ajmalicine and ajmaline are used to treat hypertension
43,44 providing relief to normal cerebral blood flow. It affects
and breast cancer.
the function of smooth muscle, prevent strokes and helps
Reserpine in lowering blood pressure.39 An estimated 3500 kg of
ajmalicine is isolated annually from either Rauvolfia or
It is a pure crystalline single alkaloid, derived from the
Catharanthus spp. by pharmaceutical industries for the
roots of Rauvolfia and was first isolated in 1952.45 It is a
treatment of circulatory diseases. The synthetic pathway
relatively weak tertiary base occurring in the oleoresin
starts with geraniol through iridodial and irdotrial by the
fraction of the roots and is useful in the treatment of
synthesis of loganin, which on oxidation converts loganin
hypertension, cardiovascular diseases and neurological
into secoloanin. This helps the tryptamine to form
diseases.46,47 The antihypertensive properties of Rauvolfia
corynanthe type nucleus that results in the formation of
roots are attributed to reserpine (3,4,5-trimethyl benzoic
ajmalicine.41,59 The ajmalicine is derived from tryptophan
acid ester of reserpic acid, an indole derivative of 18-
which is converted to tryptamine via secologanin,
hydroxy yohimbine type). It is the most prominent of all
48,49 strictosidine and cathenamine. Reduction of cathenamine
alkaloids and used mainly as a natural tranquillizer.
to ajmalicine is facilitated by enzyme NADPH and
Reserpine is now being utilized as a tool in physiologic
tryptophan decarboxylase (TDC). Decarboxylase might be
studies of body functions and in pharmacological studies.
the key enzyme involved in the synthesis of ajmalicine in
The antihypertensive actions of reserpine are due to its Rauvolfia.60
depressant action on central nervous system (CNS) and
Serpentine
peripheral nervous system by binding to catecholamine
storage vesicles present in the nerve cell. This prevents Serpentine, a type II topoisomerase inhibitor, exhibits
the normal storage of catecholamines and serotonin in antipsychotic properties.61,62 The enzyme peroxidase
decline of catecholamine. It interferes with the function (PER) is responsible for oxidation of ajmalicine to
of autonomic nervous system by depleting the serpentine by catalyzing bisindole alkaloid localized in the
transmitter substance from the adrenergic neurons and vacuole.41
possibly by activating the central parasympathetic
Rescinnamine
system.50-52 These substances are mostly involved in
controlling heart rate, cardiac contraction and peripheral Rescinnamine, a purified ester alkaloid of alseroxylon
resistance. It also helps in sedation and lowering of blood fraction in species of Rauvolfia; related chemically and
pressure, especially in cases of hypertension exacerbated pharmacologically to reserpine with similar uses.
by stress and sympathetic nervous system activity. Investigated in 1950’s and used for the treatment of
Reserpine causes the release of 5-hydroxytryptamine (5- hypertension as an antihypertensive agent. It is clinically a
HT) from all tissues in which it is normally stored and less potent alkaloid than reserpine and not so effective in
results in increase of urinary metabolites.53 lowering blood pressure.63 Rescinnamine inhibits
angiotensin converting enzyme, peptidyl dipeptidase that
Ajmaline
catalyzes the conversion of angiotensin I to the
The compound was first isolated by Salimuzzaman vasoconstrictor substance, angiotensin II which stimulates
Siddiqui in 1931 from the roots of R. serpentine. He aldosterone secretion by the adrenal cortex. Firstly it
named it ajmaline, after Hakim Ajmal Khan, one of the inhibits the Angiotensin Converting Enzyme (ACE) and
most illustrious practitioners of Unani medicine in South then blocks the conversion of angiotensin I to angiotensin
54,55
Asia. Derived from roots of R. serpentina as a class I II. Inhibition of ACE results in decreased plasma
antiarrhythmic agent, it is highly useful in diagnosing angiotensin II. As angiotensin II is a vasoconstrictor and a
Brugada Syndrome (hereditary cardiac disorder), and negative-feedback mediator for renin activity, its lower
differentiating between subtypes of patients with this concentration results in a decreasing in blood pressure
disease.56 These agents are primarily classified into four and stimulation of baroreceptor reflex mechanisms,
major groups on the basis of their mechanism of action which ultimately results in decreased vasopressor activity
i.e. sodium channel blockade, beta-adrenergic blockade, and aldosterone secretion.64
repolarization prolongation and calcium channel
Deserpidine
blockade. Ajmaline is a sodium channel blocker that
shows instant action when given intravenously, which Deserpidine is an ester alkaloid isolated from Rauvolfia. It
makes it ideal for diagnostic purposes. The administration differs from reserpine only by means of absence of a
of Rauvolfia alkaloid to patients with this type of methoxy group at C-11, which is synthesized from
57,58
arrhythmia is known as the “Ajmaline Test”. It has reserpine. It is used mainly for its antipsychotic and
been reported to stimulate respiration and intestinal antihypertensive properties. It is capable of reducing high
movements. The action of ajmaline on systemic and blood pressure by controlling nerve impulses along
42
pulmonary blood pressure is similar as of serpentine. various nerve pathways. As a result, they act on the heart
and blood vessels to lower blood pressure and also for
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Available online at www.globalresearchonline.net 350
Int. J. Pharm. Sci. Rev. Res., 23(2), Nov – Dec 2013; nᵒ 56, 348-355 ISSN 0976 – 044X

the relief of psychotic behaviour. Deserpidine also binds Mineral composition


and inhibits the angiotensin converting enzyme and
Rauvolfia is also known to contain a large number of
competes with angiotensin I for binding at the
macro and micro-nutrients and the most abundant macro
angiotensin-converting enzyme. It also blocks the 76
65 nutrient is calcium. The potential of R. serpentina to
conversion of angiotensin I to angiotensin II.
stop bleeding and its use in treating wounds can be due
Yohimbine to its high calcium content, as it helps in blood
coagulation. R. serpentina contains low sodium content
A pharmacologically well characterized alkaloid
that can be an added advantage due to the direct
Yohimbine, is used as a selective alpha-adrenergic
relationship of sodium intake with hypertension in
antagonist or alpha-blocker in the blood vessels for the 82
human. The presence of zinc shows that plant can play
treatment of erectile dysfunction It dilates blood vessels
valuable roles in the management of diabetes, which
and increases blood flow in the penis, which helps in
result from insulin malfunction.76
improving erectile function.66-69 Yohimbine was also
explored as a remedy for diabetes in animal and human The plant R. serpentina is also an excellent source of
models carrying polymorphisms of the α2A-adrenergic ascorbic acids, riboflavin, thiamin and niacin.83 Ascorbic
receptor gene. Antagonism at these receptors relaxes acid is vital for body performance as it plays an important
79
smooth muscle and lowers blood pressure. It works by role in normal wound healing , and lack of it impairs the
increasing certain chemicals in the body, which dilates the normal formation of intercellular substances throughout
70
pupils of the eye. the body (including collagen, bone matrix and tooth
dentine). The R. serpentina is used in herbal medicine as a
Phenols
potential source of useful drugs for the treatment of
Phenols are the secondary plant metabolites widely many diseases as it is a rich source of phytochemicals,
distributed in the plant kingdom mainly herbs, shrubs, minerals and vitamins.5,33
vegetables and trees.71,72 The presence of phenols is
R. serpentina in pharmacology
considered toxic for the growth and development of
various pest and pathogens.73 Presence of high quantity R. serpentina holds an important position in the
of total polyphenolic compounds in R. serpentina shows pharmaceutical world due to the presence of various
significant antidiabetic and hypolipidemic properties.30,74 alkaloids in the oleoresin fraction of the roots. Alkaloids
In medicine, it is used as an expectorant and emulsifying of this plant have a great medicinal importance to
agent. The presence of phenolic compounds indicates treat cardiovascular diseases84, high blood pressure85,
that this can be used as anti-microbial agent. hypertension43, arrhythmia86, various psychiatric
diseases87, mental disorders88, breast cancer89, human
Tannins
promyelocytic leukemia29 like diseases. Reserpine is the
The oxidation inhibiting activity of tanni is due to the main alkaloid that shows highly complex pattern of
presence of gallic acid and diagallic acid.75 Tannins have activity mainly variation of amine concentration in brain.
stringent properties, they hasten the healing of wounds It is responsible for influencing the concentration of
and inflamed mucous membranes. Thus, explain the use glycogen, acetyl choline, g-amino butyric acid, nucleic
of R. serpentina in treating many disorders by traditional acids and anti-diuretic hormone. The effects of reserpine
medicine healers in South eastern India.33,76 include respiratory inhibition, stimulation of peristalsis,
myosis, relaxation of nictating membranes and also
Flavonoids
influences temperature regulating centre. It increases the
5
These are potent water-soluble antioxidants and free volume and free acidity of gastric secretion. The Pitkriya
radical scavengers, which prevent oxidative cell damage capsule (Unani formulation) contains arsol (R.
77,78 90
and have strong anticancerous activity. Flavonoids in serpentina) which acts as Musakkin-wo-Munawwim
intestinal tract also lower the risk of heart disease. As (sedative and hypnotic), Mudir (Diuretic), Musakkin-e-
antioxidants, flavonoids provide anti-inflammatory Asab (nervine sedative) and Mukhaddir (anesthetic). Its
activity used for the treatment of diseases in herbal various pharmacological activities include anticholinergic,
medicine.5,79 hypotensive, anticontractile, sedative, relaxant,
hyperthermic, antidiuretic, sympathomimetic, hypnotic,
Saponins
vasodialater, antiemetic, anti-fibrillar activity tranquilizing
Saponins are glycoside of both triterpenes and sterols and agent, anti-arrhythmic, antifungal and nematocidal.29,91 R.
have been detected in over 70 families of plants. Some of serpentina is believed to have following pharmacological
the characteristics of saponins include formation of foams attributes: (1) By the action on vasomotor centre, as it
in aqueous solutions, hemolytic activity, cholesterol leads to generalized vasodilatation by lowering blood
binding properties and bitterness.80 Saponin has the pressure. (2) By depressant action on the cerebral centres
property of coagulating red blood cells. The high saponin as it soothes the general nervous system. (3) It exerts a
content of Rauvolfia serpentina substantiates the use of sedative action on the gastric mucosa and shows
33,81
this extracts to stop bleeding and in treating wounds. stimulating action on the plain musculature of the

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Int. J. Pharm. Sci. Rev. Res., 23(2), Nov – Dec 2013; nᵒ 56, 348-355 ISSN 0976 – 044X

intestinal tract. (4) It also stimulates the bronchial Mental illness, schizophrenia, high blood pressure and
musculature.12 other diseases
R. serpentina as a medicinal herb and therapeutic agent The root of the plant is used in high blood pressure,
14,24
mental agitation, insomnia and sedative. The root
R. serpentina has an extensive spectrum of valuable
extract obtained is considered to be the best medicine for
therapeutic actions, mainly effective in the treatment of
high blood pressure and has been adapted by the medical
hypertension and psychotic disorders like schizophrenia,
fraternity in most countries. The derived alkaloids have a
anxiety, epilepsy, insomnia, insanity, and also used as a
direct effect on hypertension and are widely used in
sedative, a hypnotic drug.12,92 The plant is reported to
preparation of medicine. Extracts of R. serpentina is also
contain a large number of therapeutically useful indole 18 19
helpful in curing other diseases such as fever , malaria ,
alkaloids and these alkaloids are largely located in the
eye diseases , pneumonia , asthma , AIDS99,
19 25 98
roots. Fabricant and Fransworth (2001)17 has emphasized
headache99 skin disease100 and spleen disorder.101
the various ethnobotanical uses to cure various
circulatory disorders. Extracts of the roots are valued for CONCLUSION
the treatment of intestinal disorders, particularly
Worldwide large number of peoples are suffering from
diarrhoea and dysentery and also as anathematic. Mixed
several chronic diseases, due to significant variation in the
with other plant extracts, they have been used in the
climate and environment. To cure large number of people
treatment of cholera, colic and fever. The root was
there is an urgent need for an herbal drug that can be
believed to stimulate uterine contraction and
utilized to treat various diseases with better cultural
recommended for the use in childbirth. A study by Azmi
acceptability, compatibility with the physical body and
and Qureshi (2012)30 showed therapeutic effects of
lesser side effects. Thus, to fulfil this requirement R.
Rauvolfia with incomplete hypoglycemic action in diabetic
serpentina is a promising herbal option in the
hypertensive patients. The juice of the leaves has been
pharmaceutical world due to the presence of significant
used as a remedy for the opacity of the cornea.93
chemical compounds in roots. The present review work
Rauvolfia’s juice and extract obtained from the root can
will shed new insights on the potential of R. serpentina as
be used for treating gastrointestinal and circulatory
antioxidant, anticancerous, antidiuretic, antiarrhythmic,
diseases. The Juice of tender leaves and root extract is
antidysentry, antidiarrhoeal antihypotensive,
used to treat liver pain, stomach pain, dysentery and to
anticontractile, and tranquillizing agent.
expel intestinal worms.19 The extract is also utilized to
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