Download immunomodulators from plant source: a review

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
Yasin et al.
World Journal of Pharmacy and Pharmaceutical Sciences
SJIF Impact Factor 5.210
Volume 4, Issue 08, 21-36.
Review Article
ISSN 2278 – 4357
IMMUNOMODULATORS FROM PLANT SOURCE: A REVIEW
Hina Yasin*1, Fakhsheena Anjum1, Hina Abrar2, Sana Ghayas1, Muhammad Ali
Masood1, Tamha Fatima1, Mariam Naz1, Wajiha Jabeen1
1
Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan.
2
Baqai Medical University, Karachi, Pakistan.
Article Received on
25 May 2015,
ABSTRACT
Revised on 16 June 2015,
Accepted on 07 July 2015
immune system against infections since centuries as these drug
The use of phytochemicals has been a supportive practice for our
substances enhance the immune response against infections. There are
abundant
plants
which
possess
immunomodulatory
and
*Correspondence for
immunostimulatory activities. The immunomodulatory activities of
Author
Dr. Hina Yasin
various substances existing in natural sources have been determined in
Dow College of
this article through literature review. Various techniques are also
Pharmacy, Dow
determined through which separation and isolation of such substances
University of Health
Sciences, Karachi,
could be done in Pakistan. The present review will focus on latest
developments regarding immunomodulatory activities of plants which
Pakistan.
have been reported from the year 2000 to early 2012.
KEYWORDS: Immunomodulatory agent, phytochemicals, plant source, Tinospora
cordifolia, Allium sativum, Curcuma longa.
INTRODUCTION
Immunomodulators can be broadly categorized as immunoadjuvants, immunostimulants and
immunosuppresants. Immunoadjuvants are used to escalate the effectiveness of vaccines and
since particular immunoadjuvants are used with particular vaccines, thus they could be
considered as specific immunostimulants. Non availability of an appropriate adjuvant for
human use has been one of the important tripping blocks in our skills to develop different
vaccines like malarial vaccines.[1]
Immunostimulants are integrally non-specific in nature as they are predicted to augment
body's resistance against infection. They can act via distinctive immune and adaptive immune
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response. In healthy persons, the immunostimulants are likely to function as prophylactic or
promoter agents i.e. as immunopotentiators by increasing the basic levels of immune
response, and in the persons with impairment of immune response as immunotherapeutic
agent. In literature, many plants are evident having immunomodulatory effect by using
modern scientific methodologies. The examples of such plants include Allium
sativum
(Lasun), Aloe vera (Gharita kumari), Andrographis paniculata (kirayat), Asparagus racemose
(Satawar), Azadirachta indica (neem), Curcuma longa (Haldi), Nyctanthus arbor-tristis
(Harsinghar), Ocimum sanctum (Tulsi), Panax ginseng (ginseng), Phyllanthus emblica
(amla), Picrorrhiza kurroa (kutali), Tinospora cordifolia (giloe), and Withania somnifera
(Ashwagandha).
The immune system commendably protects our body from invading agents and foreign
bodies. There are numerous cells and molecules which are proficient in distinguishing,
restraining and eradicating several harmful elements. Transition of the immune system
denotes any amendment in the immune response that may implicate stimulation, expression,
augmentation or inhibition of any part or stage of the immune response for extermination of
foreign antigen. Various phytochemicals are recognized for possessing natural products
containing anti-infective properties that work either by directly affecting the pathogen or
indirectly by stimulating inherent and acquired defense mechanisms of the host. [2,3]
Immunomodulating agents
An immunomodulator or adaptogenic agent is the drug substance that modifies the immune
system.[4] In general, immunomodulators are categorized as Immunosuppressants and
Immunostimulators due to their effects. They have the capability to augment an immune
response or guard against foreign bodies.[5] A new and budding branch of pharmacology is
Immunopharmacology which intends to search for immunomodulators. In clinical medicine,
immunodulator’s possible practices encompasses the improvement or reinstatement of
immune insufficiency so as to help against infections i.e. for the management of AIDS or the
suppression of regular or excessive immune function for the prevention of rejection or
reaction against transplanted organ or in autoimmune disease. [2,6]
Immunization is the process of introducing an antigen into the body to pledge shield against
pathogens without instigating disease. The substances which are introduced to institute a
defensive immune response are called vaccines which may be live, attenuated or killed. [7]
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COMMON PLANTS WITH IMMUNOMODULATORY AGENTS
Table: Some common plants with immunomudulatory agents with their specific parts
used. [8]
Some plant products with immunomodulatory and anthelmintic properties are discussed as
follows
1. Nyctanthus arbor-tristis (Harsinghar):
This plant is extensively used in traditional
medicinal system in India and has been reported to contain antileishmanial, hepatoprotective,
antiviral and antifungal activities. Strong stimulation of antigen specific and non-specific
immunity, thereby increasing humoral and DTH response to SRBC and macrophage
migration, has been established in mice and extreme activity was seen in the seeds. [9]
2. Picrorrhiza kurroa (kutali): P. kurroa is a favorable immunomodulatory agent.
[10]
It
enhanced antibody and DTH response to RBCs of sheep in mice. Picroliv is an iridoid
glycoside derived from this plant which significantly protected golden hamster against
challenge with Leishmania donovani promastigote; its lethal effects (77%) had been seen in
microfilariae of Litomosoides carinii in cotton rats.[11,12]
3. Cissampelos pareira (Akanadi): This plant is reported to have antiviral properties and is
also effective against urinary tract infections. Other species like C. mucromata also have
immunomodulatory and anthelmintic activities.[13]
4. Bauhinia variegate (Kachnar): This plant has been reported to have both
immunomodulatory and anthelmintic activities.
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5. Blechnum orientale (Rajhans): This plant also has both immunomodulatory and
anthelmintic activities.
6. Butea monosperma (Dhak): This native medicinal plant possesses immunostimulatory,
antihelminthic, antibacterial and antiasthamatic properties.
7. Capparis zeylanica, Linn.
Capparis zeylanica, Linn (family: Capparidaceae) is commonly called Indian caper, which is
found throughout India and has been used as a ‘Rasayana’ drug in the traditional Ayurvedic
system of medicine. ‘Rasayana’ plants are principally recommended for the treatment of
immune disorders.
[14]
In Northern India, the leaves are widely used as counter-irritant,
febrifuge and as a cataplasm in swellings, boils and piles. [15] Different species of Capparisare
are valuable in the treatment of cough, asthma, inflammation, fevers, cholera and also as
poultice in gout and rheumatism. [16]
8. Allium sativum: Garlic is acknowledged for the enhancement of the immune system since
long and most of the research is dedicated to its organo-sulfur compound. Latest outcomes
have shown that the antitumor effect of allyl sulfur compounds may be linked to their antiinflammatory and immunostimulatory actions.
[17]
While some immunomodulatory proteins
from garlic have been defined, their characteristics are still unidentified. [18]
9. Tinospora cordifolia
It
is
used
in
numerous
native
drug
preparations
for
general
health and other disease conditions, possessing anti-allergic, anti-hepatotxic, anti-diabetic and
anti-pyretic characteristics (all green). Its alcoholic extract showed immunomodulatory
activity on rats; produced substantial increase in the WBC count and bone marrow
cells demonstrating stimulatory effect on haeomopoetic system. More research is underway
soas to explore the cellular changes and other pharmacological and biotechnological investiga
tion in male wister rat. [19]
10. Curcuma longa
Turmeric has curcumin which reduces the proliferation and activation of T-cells. Curcumin
treatment also increases the number of B-cell. [20] Reports have established that the aqueous
extract of turmeric lessened the level of SGOT, SGPT and bilirubin in Carbon tetrachloride
(CCl4) intoxicated mice. Apart from damaging the liver system, CCl4 also lessened various
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non specific host response parameters like morphological alteration, phagocytosis, nitric
oxide release, etc. Administration of its aqueous extract presented noteworthy defense from
damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of
CCl4 intoxicated mice. [21]
11. Azadirachta indica
Azadirachta indica belongs to family meliaceae and is well known in the sub continent for
more than 2000 years as one of the most adaptable medicinal plants with wide spectrum of
biological
activity
i.e.
anti-inflammatory,
anti-diabetic,
antiviral,
anticarcinogenic,
immunostimultory, etc.[22-24] The immunomodulatory effect of Neem (Azadirachta indica)
seed’s aqueous, ethanolic extracts and Candida albicans cell wall mannoproteins on the
immune response of mice vaccinated with Brucella Rev-1 vaccine was studied. Aqueous and
ethanolic Neem seed’s extract exhibited the highest augmentation in all immunological
parameters engaged in comparison with mannoproteins of Candida albicans cell wall. [25]
METHODOLOGY FOR REVIEW
This is a review article composed after conducting a literature based survey from year 2000
to early 2014. More than 80 articles were carefully chosen and studied comprehensively,
selected from different sources.
[1-8, 11, 19, 24]
Only those natural sources containing
immunomodulatory effects/agents were selected that are native to Pakistan and their
separation and isolation could be done easily in Pakistan. Among them, Allium sativum,
Tinospora cordifolia, Curcuma longa, Capparis zeylania, etc. were studied in depth with the
methods for their separation and isolation.
DISCUSSION
Few plants in Pakistan having immunomodulatory activities that can be extracted & separated
with help of simple techniques.
1. Allium sativum
It belongs to the family Lilliacea and it is generally known as Garlic. It is well-known for it is
medicinal properties and originated in Central Asia. Garlic has been used in food and as
medicine worldwide since antiquity. Today it is a famous constituent in culinary herb as well
as has established antioxidant, anticancer and even immunomodulator. [26-31]
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Method for separation: The three major proteins i.e. QA-1, QA-2, and QA-3, that
demonstrate
immunomodulatory
properties
are
separated
by
using
Q-Sepharose
Chromatography technique from raw and aged garlic extracts.[8,32]
Importance and uses: Allium sativum has noteworthy effects in the situations like
Alzheimer’s
disease,
dermatologic
infections,
cardiovascular
diseases
(including
atherosclerosis, strokes, hypertension, thrombosis and hyperlipidemias), stress, and microbial
infections. It also holds anti-cancer activity. [28,31,33,34] Allicin is an active component which is
isolated from garlic. It shows 4 main activities: antibacterial activity against Escherichia coli,
antifungal activity against Candida albicans, antiparasitic activity against Entamoeba
histolytica and Giardia lamblia, and also antiviral activity.
[35]
The diallyl sulfide (DAS) and
thiacremonone in garlic have revealed having anti-arthritic properties and garlic extract has
shown anti inflammatory properties as well.
[33]
The 1, 2-Vinyldithiin has shown anti
adipogenic and anti inflammatory actions on human pre-adipocytes; hence considered as antiobesity nutraceutical. [36]
2. Tinospora cordifolia
It belongs to the family Meninspermaceae and is generally known as Guluchi, Giloy etc. It is
a widely used shrub in folk and ayurvedic systems of medicine. The chemical constituents of
T. cordifolia belong to different classes that include alkaloids, steroids, glycosides,
diterpenoid
lactones,
polysaccharides,
aliphatic
compounds,
phenolics,
and
sesquiterpenoids.[37]
Method for separation: The ripened T. cordifolia barks are freshly collected, cut, dried in
shade and then powdered coarsely. Then the powder is defatted with petroleum ether at
temperature 60 - 80°C and extracted through soxhlet extractor using hexane. The extract is
dried under reduced pressure by rotary vacuum evaporator with 7% w/w percent yield and the
extract is then stored in refrigerator.[38]
Importance and uses: T. cordifolia is expressed and recommended as a monoherbal as well
as polyherbal preparation. Although it is alcoholic but the aqueous extracts have been verified
positively for immuno-modulatory activity. It is reported to impede the immunosuppressive
effect of cyclophosphamide.
[39-46]
The shrub has been found to substantially reduce the
deaths from E. coli induced peritonitis and also showed defense in cholestatic patients against
E. coli infections. It is parallel to gentamicin and is also recognized for its hepato-protective
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effects.[37,44,47] Significant anti-inflammatory effects in both acute and subacute models of
inflammation have been reported for the dried stem of T. cordifolia.[37] Its herbal extract has
revealed radio-protective prospective from gamma-irradiation. Its use as an adjunct to therapy
for the following conditions has displayed substantial results: HIV, diabetic foot, free radical
mediated injury and stress; it also possesses significant anti-tumor activity.[6,48-52]
3. Curcuma longa
Curcuma longa belongs to the family Zingiberacea and is usually known as Saffron India,
Haldi (Hindi), turmeric, etc. It is an extensively used herb in the folk and ayurvedic
medicines. The chemical constituents contained in this herb are Essential oil (zingerberine)
and curcuminoids (curcumin1 and curcumin III) as major constituents while the others
include sesquiterpenes , ar-turmerone, ar-curcumene ,a-sabinene, borneol,cineole,myrcene
and b-pinene, a-terpine, nelimonene, p-cymene, perillyl alcohol, turmerone, eugenol, isoeugenol, eugenol methyl ether and iso-eugenol methyl ether, Stigmasterol, cholesterol, Bsitosterol and fatty acids.[53-55]
Method for separation: Curcumin is extracted from the dried root of the rhizome Curcuma
Longa by grinding it into powder and washing with a suitable solvent that selectively extracts
coloring material. After distillation, this procedure produces an oleoresin with coloring matter
content of 25-35 % along with volatile oils and additional resinous extractives. This oleoresin
is further subjected to washes with selective solvents to extract the Curcumin pigment. This
process yields a powdered, purified food color, known as Curcumin powder, having more
than 90% coloring matter and very diminutive amount of volatile oil and other dry stuff of
natural source. The solvents employed for extraction include acetone, methanol, isopropanol
and ethanol.[56-58]
Importance and uses: The immunomodulator Curcumin is used potentially for the
formulation of an adjunct therapy against cerebral malaria. Recent studies have validated
scientific confirmation regarding its prophylactic and therapeutic prospective, straightening
out its anti-inflammatory, anti-carcinogenic, and anti-infectious activities, and also its
spasmolytic, CNS stimulant, anti-parasitic, antispasmodic and anti-arthiritic properties. [59-65]
4. Capparis zeylania
Traditionaly Capparis zeylania L. was first time reported for use as a vegetable.[66] Its
contemporary phytochemical screening has revealed the occurrence of fatty acids and
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flavonoids in the leaves.[67,68] Flavonoids have been identified to have antioxidant,
antineoplastic, antiulcer, anti-inflammatory and antimicrobial actions.[69,70]
Method for separation
For the preparation of extract, 500gm of dried coarse powdered plant were charged into
soxhlet’s apparatus (hot extraction) and successively with petroleum ether (600- 800C),
chloroform, etyalcetate and methanol in order of their increasing polarity. The successive
methanolic extract deep brown colour) was filtered and dried under reduced pressure to get a
solid mass free from the solvent. The yield was 6.9% with respect to dry starting materials
with characteristic odour & greasy consistency.[83]
Importance and uses
Root bark is ground with water, boiled and taken orally to treat indigestion.[71] Traditionally it
is used as Antidote to snake bite, to cure swelling of testicle, small pox, boils, cholera, colic,
hemiplagia, neuralgia, sores, pneumonic and pleurisy.[72-75] Leaf and stem parts are as
spasmolyte.
[76]
Root bark preparation is used as a sedative.[77] Leaves extract of Capparis
zeylania L. with black pepper powder is taken twice daily for the treatment of dysentery. [78]
Leaves’ juice of Capparis zeylania L. is taken orally with cup of fresh goat milk for curing
cough and cold.
[79]
For the treatment of diabetes ripened fruits are consumed twice
fortnightly and during ingestion, stem bark extract is administered thrice daily.[80] Capparis
zeylania L. plant is also served as an appetizer prepared as a dipping paste with pepper,
tamarind and garlic.[81] Grind the stem bark by adding 10 seeds of black pepper, 2 bulbs of
garlic and mix it into 500ml water; given twice daily for two days to cure colic. Handful fresh
roots, 50g onions, 50g jaggery are ground all together and made into a bolus; feed Capparis
zeylania L. twice daily for 3 days to cure convulsive seizures.[82]
5. Azadirachta indica
The Neem (Azadirachta indica A. Juss) tree, belonging to the Meliaceae family, possesses
various insecticidal compounds against a range of agricultural insect pests. Neem contains
numerous biologically active chemicals called limonoids such as Azadirachtin A, nimbin,
salannin, azadirachtol, nimbidin, gedunin, etc. which are accountable for miscellaneous
activities such as insect anti-feedant, insect growth disruption, insecticidal, nematicidal,
fungicidal, bactericidal etc.[84,85]
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Method for separation: Cold Maceration Method was used for extraction in which the dried
leaves were blended into powder and one liter of ethanol was used as extracting substance.
Homogeneity of the mixture was confirmed by stirring the mixture regularly and the mixture
was allowed to stand for 3 days for maximum extraction prior to filtration. The filtrate was
heated in a round bottom flask balanced on a hot water bath, which made the extract
concentrated.[86]
Importance and uses: Neem tree yields are used for many medicinal and agricultural
purposes. It is largely used as herbal medicine in its native countries and is used in many
pharmaceutical and cosmetic products; also for pest control in homes. Their leaves’ paste is a
valuable management for skin injuries. Small parts of leaves mixed with regular feed may
affect intestinal parasites in livestock.[87]
CONCLUSION
Important herbal immunomodulators with minimal side effects need more exploration as
clinical potential to be used as medicine in future. Many plants with potential
immunomodulatory properties have been conferred in this review. Chief highlights of this
review are on the account of immunomodulators with phytochemical compounds and their
pertinent mechanism of action. This may aid in recommending principal compounds from
natural resources for drug development and instituting their effectiveness from customary
resources.
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