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Applications and uses of active ingredients from medicinal plants

Indian Journal of Novel Drug delivery 6(2), Apr-Jun, 2014, 106-111
Indian Journal of Novel Drug Delivery
An Official Publication of
Karnataka Education and
Scientific Society
Review Article
Applications and Uses of Active Ingredients from Medicinal Plants
Vidya Pratishthan’s School of Biotechnology (VSBT) Vidyanagari Baramati 413133, Pune, India
Article history:
Received on 14 February 2014
Modified on 24 March 2014
Accepted on 03 April 2014
The immune System is the most complex biological systems in the body. At the time
of infection related to viruses, bacteria and fungi only the immune system is able to
detect the pathogen by using a specific receptor to produce immediate response by
the activation of immune components such as cytokines, chemokines and release of
inflammatory mediators to modulate and potentiate the immune system.
Modulation of immune response, as a possible prophylactic or therapeutic
measure, by using various medicinal plant products has become a subject of
scientific investigation. According to Ayurveda, most of the commonly used active
ingredients i.e. plant derived materials (alkaloids, glycosides, proteins, lectins,
polysaccharides, etc.) are extracted from Indian medicinal plants for the treatment
of various ailments and have so many advantages over the conventionally used
drugs, which are so expensive and known to have harmful side effects.
© KESS All rights reserved
Medicinal Plant
Immunomodulation means that one can
modulate the immune response using various
substances either of natural or synthetic origin.
Several types of immunomodulators have been
identified, including substances isolated and
purified from natural sources such as plants
including microorganisms. Medicinal plants
which are used for many activities and provides
various alternative potential to conventional
chemotherapy for a variety of diseases especially
in reference to host defense mechanism.
According to literature, a large number of
medicinal plant products like polysaccharides,
lectins, peptides and flavonoids which are used
in the immune system for various in-vitro and in
vivo models
. Now a day, the importance of
medicinal plants has been increasing both for
pharmaceutical industry and traditional users.
Most of the countries believed or rely on
traditional medicines either it is developing or
under developing country. This traditional
medicine involves the use of different type of
organic extracts or the bioactive pure chemical
constituents as shown below-
A) Flavonoids
Flavonoids are a large family of polyphenolic
compounds synthesized by plants that have a
common chemical structure
. It is one of the
largest groups of phenols and played a major role
in plants i.e. color, pathogens, light and stress
and also very often in epidermis of leaves and
fruit skin. Several flavonoids isolated from
various medicinal plants and showed some
several beneficial properties. The number of
flavonoids isolated from various plants is
currently under investigation:-
The leaves of Orthosiphon stamineus, (Family
Lamiaceae) (Fig. 1) are commonly used as herbal
tea for diuresis, to treat rheumatoid arthritis,
diabetes, oedema, eruptive fever, influenza,
hepatitis, jaundice and hypertension
Figure 1: Orthosiphon stamineus
uthor for Correspondence:
Amit Gupta
et al / Indian Journal of Novel Drug Delivery 6(2), Apr-Jun, 2014, 106-111
O. stamineus contains several chemically active
constituents such as terpenoids (diterpenes and
triterpenes), polyphenols (lipophilic flavonoids
and phenolic acids), and sterols
. Recently, six
flavonoid compounds were isolated from the
leaves of the medicinal plant Orthosiphon
Several prenylated flavonoids isolated from the
leaves and stems of Dodonaea polyandra (Fig. 2).
This plant is generally used in the traditional
medicine system of Northern Kaanju people of
Cape York Peninsula, Queensland, Australia. The
extracts of leaves and stem studied have already
been studied and possess anti-inflammatory
Figure 2: Dodonaea polyandra.
Dorstenia mannii (Fig. 3) is a plant species in the
genus Dorstenia. The prenylated flavonoids
from Dorstenia mannii (6,8-diprenyleriodictyol,
dorsmanin C and dorsmanin F) were found to be
potent scavengers of the stable free radical 1,1-
diphenyl-2-picrylhydrazyl (DPPH), and are more
potent than butylated hydroxy toluene (BHT), a
common antioxidant used as a food additive and
these prenylated flavonoids showed potent anti-
oxidant activity as compared to the non-
prenylated flavonoids, quercetin
Figure 3: Dorstenia mannii
The number of flavonoids extracted
from Dryoathyrium boryanum (Fig.4) were
reported and considered as excellent
antioxidants and also showed anticancer activity
because of high flavonoids content in the fern
Figure 4: Dryoathyrium boryanum
Plant phenolics, especially dietary flavonoids, are
currently of major interest related to their
functional properties in promoting human
health. One of the medicinal plant where 13
phenolic substances and 29 extracts were
prepared from finnish plant materials against
number of microbes e.g. Aspergillus
niger, Bacillus subtilis, Candida
albicans, Escherichia coli, etc were studied and
showed that . flavone, quercetin and naringenin
were effective in inhibiting the growth of the
Thymus vulgaris (Family Lamiaceae) is a species
of flowering plant in the mint, native to southern
Europe from the western Mediterranean to
southern Italy. The crude extracts from locally
grown Thymus vulgaris showed high
concentration of flavonoids and it could be used
as antibiotics for different curable and uncurable
Figure 5: Thymus vulgaris
B) Polysaccharides
Polysaccharides isolated from various medicinal
plants, mushrooms, lichens, algae etc and
contained a number of prophylactic and
therapeutic properties which is beneficial for
anti-tumour activity, immunomodulation, wound
healing and other therapeutic effects. The
number of polysaccharides isolated from various
medicinal plants is still under investigation:-
Polysaccharides contains galactose, galacturonic
acid, and mannose isolated from Porana volubilis,
(Fig. 6) and reported as the first natural
Amit Gupta
et al / Indian Journal of Novel Drug Delivery 6(2), Apr-Jun, 2014, 106-111
nonsulfated polysaccharide from higher plants
with anticoagulant activity, which may be
considered as a new source of compounds with
action on coagulation and thrombosis
Figure 6: Porana volubilis
Water and water–ethanol soluble polysaccharide
materials were isolated from the leaves of
popular Malian medicinal plants Trichilia
emetica (Fig.7) and Opilia celtidifolia and fruits
of Crossopteryx febrifuga and showed significant
antitussive activity
. Some of the. pectic
polysaccharides strain i.e. BP-II, Oc50A1.I.A and
CC1P1 isolated from the Malian medicinal plants
like Biophytum petersianum, Cola cordifolia and
Opilia celtidifolia, respectively, are able to protect
against Streptococcus pneumoniae infection in
Figure 7: Trichilia emetica
Maytenus ilicifolia (Fig. 8) is one of the important
medicinal plants which played an important role
in the anti-ulcer effect. Its leaves are used in
homemade and industrial medicines for effective
treatment of stomach ulcers e.g. Significantly
inhibited ethanol-induced gastric lesions in rats,
and suggest that it has a protective anti-ulcer
An α-d-glucan novel polysaccharide, non toxic
which is isolated and characterized from the
medicinal plant Tinospora cordifolia (Fig. 9) and
it is composed of (14) linked back bone and
(16) linked branches with a molecular mass of
> 550 kDa and exhibiting unique immune
stimulating properties.
Figure 8: Maytenus ilicifolia
The cytokine profile of this novel polysaccharide
increased the Th1 pathway of T helper cell
differentiation essential for cell mediated
immunity. The water solubility, high molecular
mass, activation of B and T lymphocytes
including NK cells, complement activation, Th1
pathway-associated cytokine profile and absence
of oxidative stress confer important
immunoprotective potential to this novel α-d-
Figure 9: Tinospora cardifolia
Several polysaccharides have been isolated from
the leaves of Arctium lappa (Fig. 10), Aloe-
barbadensis, Althaea-officinalis var.
robusta, Plantago lanceolata, aerial parts and
roots of Rudbeckia fulgida, stems of Mahonia
aquifolium, and peach-tree (Prunus persica) gum
exudates. Out of these, these polysaccharides has
the ability to inhibit peroxidation of soyabean
lecithin liposomes by OH radicals
Figure 10: Arctium lappa
Amit Gupta
et al / Indian Journal of Novel Drug Delivery 6(2), Apr-Jun, 2014, 106-111
C) Alkaloids
Alkaloids are derived from various plant sources,
these are generally basic and contained one or
more nitrogen atoms and have a marked
physiological action on man or other animals.
The first structure of alkaloid Coniine was
established and in the twentieth century,
alkaloids featured strongly in the search for plant
drugs with anticancer activity. One of the
example of alkaloid e.g. Catharanthus which has
given both the activities i.e. anti-cancer and anti-
viral activity. Due to these activities, researchers
focused on alkaloids are currently under
Cissampelos sympodialis (Menispermaceae), plant
used in Brazilian folk medicine for the treatment
of respiratory allergies. In this plant, there is a
tendency to decrease antigen specific IgE levels
and enhanced CD4 and CD8 T cell population in
mice. These properties showed the
immunoregulatory effect of the plant
Diterpenoid alkaloid i.e. Bullatine A of the genus
Aconitum, possesses antirheumatic,
antiinflammatory and antinociceptive effects
alkaloid i.e. Cepharanthine
isolated from Stephania cepharantha Hayata and
has been shown to have anti-inflammatory, anti-
allergic, and immunomodulatory activities in
D) Lectins
These cell-agglutinating and sugar-specific
proteins have been named lectins. These are
widely distributed in plants and to some extent
also in invertebrates. In 1970s, few lectins have
been isolated and are extremely useful tools for
the detection of carbohydrates on cell surfaces,
in particular for the isolation and
characterization of glycoproteins. In recent
years, number of lectins have been isolated from
plants, animals as well as micro-organisms and
also established the hundreds of structures.
Consequently, it is considered that lectins
function as recognition molecules in cell–
molecule and cell–cell interactions in a variety of
biological systems.
On the basis of recent studies in biochemistry,
molecular cloning and related to structural
analysis, mostly all known plant lectins can be
classified into seven families of structurally and
evolutionarily-related proteins
, and most of
these divided into four groups of evolutionarily
related proteins: legume lectins, chitin-binding
lectins, monocot mannose-binding lectins and
type 2 ribosome inactivating proteins, among
which monocot mannose-binding lectins is more
popular and attracted to most of the
pharmaceutical companies because of their great
application values in biological and biomedical
research; such as in the isolation of mannose
containing glyconjugates, and their potent
inhibitory effect on animal and human
retroviruses, including HIV
. In addition, most
monocot mannose binding lectins which played
an important role in the plant’s defense against
different kinds of plant-eating organisms; which
is due to their recognition of high-mannose type
glycans of plant predators
. Up to now,
monocot mannose binding lectins have been
cloned from seven families of angiosperms
including Amaryllidaceae, Alliaceae, Orchidaceae,
Liliaceae, Iridaceae and Bromeliaceae
among which lectins from Amaryllidaceae
species have been extensively studied
However, little is known about the possible
origin and molecular evolution of the
carbohydrate-binding domains of plant lectins
from modern flowering plants with little gene
sequence information about plant lectins outside
higher flowering plants
. Until now, there have
been no reports on molecular cloning of lectin
genes from gymnosperms, including family
Taxaceae, therefore the molecular evolution
relationship of the plant lectins between
flowering plants and gymnosperms is unclear.
E) Therapeutic proteins
Now a days, pharmaceutical industries is largely
dependent on the production of relatively small
organic molecules i.e. antibiotics, analgesics etc
for the treatment of bacterial or viral diseases.
Recently, researchers focused on larger and
complex proteins as therapeutic agents. Since
proteins played an important role in
immunology and there are so many therapeutic
uses in preventing and curing diseases. One of
the examples of therapeutic protein i.e. Insulin a
small peptide is used for the treatment of
diabetes. In addition, the antigens are proteins
used in vaccination to induce the immune
response. On the other hand, the use of proteins
from plants means a lower cost of production
and easier expansion for large-volume
production than cell culture systems [33]. Inspite
of large investment in cell culture facilities, plant
protein production systems can be expanded
simply by growing and harvesting additional
plants. However, about 50 percent of the total
cost of production is in extraction and
purification of the proteins, which is required in
cell culture facilities.
Amit Gupta
et al / Indian Journal of Novel Drug Delivery 6(2), Apr-Jun, 2014, 106-111
Protein antigens isolated from various pathogens
have been expressed in plants and is able to
induce the immune responses resulting in
protection against intracellular or extracellular
diseases in humans. Plant derived protein as
antigen used as vaccines have been produced
against Vibrio cholerae, E. coli, hepatitis B virus,
rabies virus, rotavirus and respiratory syncytial
In plant virus particles expressing multiple
antigens from various pathogens have been
useful as vaccines against pulmonary infections
of Pseudomonas aeruginosa, opportunistic
infections of Staphylococcus aureus, malaria, HIV
and hepatitis B virus.. A company in California
has developed a virus-based system in tobacco to
produce personalized vaccines against cancer.
Plants have been used and tested as production
systems for different range of therapeutic
proteins to be used either directly in foods or
after purification
. Expression in plants of milk
proteins such as lactoferrin and beta-casein may
contribute the therapeutic values of these
proteins to other food products. Expression of
thioredoxin in most of the foods such as cereal
grains would increase the digestibility of
proteins and thereby reduce their allergenicity.
There are a number of medicinal plants which is
generally used for the enhancement of the body’s
immune response to fight against intracellular or
extracellular pathogens. In contrast, a large
number of proteins, polysaccharides, lectins and
flavonoids extracted from the plants are coming
in to the market by proper clinical trials.
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... According to Ayurveda, medicinal plant products are continuously used in the form of traditional medicine especially in Asian countries including India. These medicinal plant products are generally very effective for various ailments and their activities could be due to phytochemicals that are present in the forms of primary and secondary metabolites (1,2). These metabolites extracted from medicinal plants play important roles especially in the fields of immunology and virology for the treatment and prevention of animal and human diseases (3,4). ...
... These metabolites extracted from medicinal plants play important roles especially in the fields of immunology and virology for the treatment and prevention of animal and human diseases (3,4). Natural compounds in the forms of extract or fraction or pure molecules isolated from medicinal plants represent a major source of molecules with traditional medicinal properties (1,2,5). Therefore, researchers should have sufficient knowledge regarding primary and secondary metabolites extracted or isolated from medicinal plants because of their widespread uses and properties (1,2). ...
... Natural compounds in the forms of extract or fraction or pure molecules isolated from medicinal plants represent a major source of molecules with traditional medicinal properties (1,2,5). Therefore, researchers should have sufficient knowledge regarding primary and secondary metabolites extracted or isolated from medicinal plants because of their widespread uses and properties (1,2). In India, every year thousands of people are died because of dengue disease. ...
Full-text available
Introduction: Medicinal plants are considered to be safer, non-toxic and less harmful as compared to synthetic based drugs that are available. In this study, we focused on aqueous leaves extract of Calotropis gigantea for determining its antimicrobial activity in infected (dengue) human whole blood samples using flow cytometry. Methods: Infected dengue human blood samples (n = 5; confirmed on the basis of NS1 antigen to dengue virus;) were collected from pathology lab and evaluated its blood counts (lymphocytes, monocytes and granulocytes count); forward scatter (FSC) and side scatter (SSC) including CD14 monocyte surface marker following the use of variable doses of aqueous leaves extract of C. gigantea. Results: In this study, the results showed that aqueous leaves extract of C. gigantea caused enhancement in case of granulocytes FSC (shape and size) and SSC (granularity) counts but this aqueous extract inhibited CD14 monocyte surface marker population at higher doses. In contrast, dengue infected human blood samples used as control showed sudden decline in granulocytes count but there was enhancement in CD14 monocyte surface marker as compared to control group. Conclusion: Overall, C. gigantea in the form of aqueous leaves extract showed anti-dengue activity in infected human whole blood samples.
... According to the literature, flavonoids are considered them as polyphenolic compounds and are normally found in vegetables, fruits, flowers etc. Generally, flavonoids extracted from various medicinal plant products and showing various medicinal properties [5,6] e.g. anti-inflammatory, antiarthritic etc. ...
... In other words, flavonoids (crude form or its derivatives) have been used for curing different types of ailments or diseases. So, usage of these flavonoid based study was carried out by many researchers and claimed its antimicrobial, anti-inflammatory and antioxidant properties [3][4][5][6]. In contrast, these flavonoids may show various biological activities reported in plants, animals and microbes. ...
... Flavonoids (fifteen-carbon skeleton, incorporating two benzene rings linked via heterocyclic pyrane ring), firstly proposed by Geisman and Heinseiner which depicts all pigments related to plant having C6-C3-C6 skeleton [3]. These flavonoids are ubiquitous in nature and these are of plant origin and reported in the higher concentration of human and animal diet [3][4][5][6]. These flavonoids are not synthesized within the body (animals including human).The major role of flavonoids i.e. obstruction (oxidation of fats) along with protection ( i.e. vitamins and enzymes) [2][3][4][5][6]. ...
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In literature, various medicinal plants are reported and showing various immunobiologically activities in the form of primary and secondary metabolites. So, these metabolites especially flavonoids extracted from medicinal plant products and considered them as more crucial and valuable with respect to human health care. In short, these flavonoids exploited them as effective therapeutic agents and may play an effective as well as key role in drug discovery including development. Recently, government agencies (DST, DBT etc.) will be more aware about medicinal plant product conservation and sponsored various projects related to utilize them as new and more effective prophylactic and therapeutic agents. So, these studies may belong to the category of traditional healthcare system. In addition, medicinal plants also contained significant amount of trace metals and these may be contaminated from soil, water or air because of the existence of heavy metals e.g. Zn, Fe, Cu, Cr and Co. Other major sources of heavy metal contamination with respect to medicinal plants are dust, rainfall and fertilizers. The existence of these medicinal plant products containing flavonoids used as traditional medicine for human and these may be reported and undergoing various clinical test for determining its safety and efficacy parameters. In view of this, we collect the information about flavonoids extracted from medicinal plant products and tried to correlate with human healthcare. Key words: Medicinal Plants, Secondary Metabolites, Flavonoids and Healthcare.
... bacteria, fungi). The most familiar examples of secondary metabolites are alkaloids, antibiotics, terpenoids, flavonoids and peptides along with growth factors [1,2] . Most of the secondary metabolites are toxic or repellant to herbivores including microbes and also help them pertaining to defend these endophytic bacteria producing plants [3,4] . ...
... Most of the secondary metabolites are toxic or repellant to herbivores including microbes and also help them pertaining to defend these endophytic bacteria producing plants [3,4] . In other words, secondary metabolites are mainly classified into four major classes i.e. terpenoids/flavonoids/phenolic compounds/alkaloids and sulphur-containing compounds [1][2][3][4] . ...
Most of the microorganisms are reported in various medicinal plant products which played a major role with respect to plant’s health and development including human nutrition. In general, single plant species could possess and reported thousands of microbes recognized as epiphytes (near on plant tissue; rhizosphere and phyllosphere) or endophytes (residing microbes with in plant tissue). These microbes may totally depend on the colonization area of plant species. In this paper, we focused on various endophytic microorganisms and its correlation with various medicinal plants. As per the literature, endophytes reported on various medicinal plant products and its major role is to protect the plants from insects and animals. These endophytes are able to produce secondary metabolites that are beneficial in terms of human health nutrition or toxic against various pathogenic microorganisms. Now a day, endophytes are of great medicinal value in terms of protection that protects valuable crops from invasive insects. In this study, we highlighted the current and future strategies of endophytes (fungi and bacteria) with their host plants, which mainly contribute for production of desirable natural products along with bioactive secondary metabolites. This review aims to discuss about the contribution of secondary metabolites produced by various endophytic microbes and showing various immunopharmacological properties. KEYWORDS: Endophytes; medicinal plants; natural products; secondary metabolites
... In this regard, there is an increasing trend in the field of immunopharmacology for discovering novel drugs based on various herbal formulations. Plants synthesize a variety of phytochemicals most of which are extractable with various immunopharmacological activities (3,4). So, medicinal plant products proved to be a major resort for the treatment of animal and human diseases (3,4). ...
... Plants synthesize a variety of phytochemicals most of which are extractable with various immunopharmacological activities (3,4). So, medicinal plant products proved to be a major resort for the treatment of animal and human diseases (3,4). Mangifera indica (Mango; family Anacardiaceae) and Prosopis spicigera (Shami, family Fabaceae) showed number of medicinal properties e.g. ...
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Introduction: The treatment of viral infections with the available antiviral drugs is not free of side effects. Therefore, in the present study, our group focused on antiviral activity against Newcastle disease (NDV) and IBD viruses using medicinal plants especially leaves of Prosopis spicigera and Mangifera indica. Methods: Different medicinal plant products especially leaves of P. spicigera and M. indica were tested in the form of aqueous leaves extracts (0.5- 30 mg/mL; 50 μL) for anti-microbial activities on human peripheral blood mononuclear cells (PBMC) pertaining to determine their proliferation rate (cytotoxicity assay), tumor necrosis factor alpha (TNFα) production and CD14 monocyte surface marker. Results: Three medicinal plant aqueous extracts showed significant antimicrobial activity against PBMC at higher doses with respect to decline in proliferation assay, TNFα production and CD14 monocyte surface marker as compared to control. Conclusion: Aqueous leaves extract of P. spicigera and M. indica showed antimicrobial activities and might be useful for the treatment of various viral diseases.
... As per the literature, more than 400 medicinal plant species have anti-diabetic activity. There are numerous medicinal plants with antidiabetic activity belonging to families like Leguminosae, Liliaceae, Cucurbitaceae, Lamiaceae, Rosaceae, etc. (Gupta et al. 2014). The toxic effects exerted by the plants should be investigated to evaluate their safety index as most of the medicinal plants are associated with toxic potential (Ng'uni et al. 2018). ...
The current research was aimed to evaluate the antidiabetic activity of Terminalia citrina methanolic extract (TCME) by streptozotocin-induced diabetes in male Wistar rats. TCME exhibited better in-vitro antioxidant and alpha-amylase inhibitory activity as compared to other tested extracts. TCME at 250, 500, and 750 mg/kg showed notable (p < .05) antidiabetic potential by lowering fasting blood glucose level, restoring lipid level, serum amylase, HbA1c, kidney, and liver function tests as coevidenced from histological findings of the liver, pancreas, and kidney. TCME remarkably reinstated the antioxidant enzymatic activities (CAT: 0.181 ± 0.011 IU/mg protein, SOD: 21.45 ± 1.53 IU/mg protein) and reduced lipid peroxidation level (40.60 ± 2.41 µM/mg protein) in the liver and kidney tissue of diabetic rats at 750 mg/kg dose. The acute and subacute oral toxicity study of TCME exhibited no clinical toxicity signs and mortality. Its GC-MS spectrum unveiled the existence of 10-octadecenoic acid and other compounds which might have contributed to antidiabetic potential.
... In recent years, immunomodulatory properties of plants have drawn keen interest in among the researchers. Phytochemicals such as flavonoids, polysaccharides, lactones, alkaloids, terpenoids and glycosides are presented in several plants [12] which are responsible for their immunomodulatory properties. The natural immunomodulatory (derived from plants) agents are used worldwide to treat a wide number of infectious diseases. ...
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According to the World Health Organization, more than 80 % of the world's population totally relies on traditional forms of medicine, largely plant based to meet the primary health care needs of the people. In India, collection of medicinal plants from different regions, i.e. Western Ghats, Himalayan region etc. and processing these plant products like leaf, stem, and root and separates its primary as well as secondary metabolites and contributes a major part in Immunopharmacology especially for immunomodulatory activities. These immunomodulatory activities are so important for human beings pertaining to safe from various types of diseases. Currently, researchers more focused on medicinal plant products and considered as modulators of the complex immune system. Various studies were conducted and explored the metabolites chemicals in the form of saponins, flavonoids, terpenoids, glycoside, etc. These metabolites are mainly responsible to cause alterations or changes in the immunomodulatory properties. In this article, we collect some information about immunomodulatory activity of medicinal plant products. The major aim is too focused on plant based immunomodulators and capable for determining and modifying the immune response. Now a day, these immunomodulators may be required to speed up the process, development and maturation of specific and non-specific immunity in young susceptible animals, and also maintain immune surveillance.
... The immune system has two definite and imbricate mechanisms with which to fight conquering organisms, the antibody-mediated defense system (humoral immunity) and the cell-mediated defense system (cellular immunity) [2] . The term therapeutic plants which include varied types of plants used in analgesics and some of these plants including its fruit, seed etc. have a number of medicinal activities or properties [3,5] . There are many adjuvants having familiar use worldwide, including aluminum salts, oils and virosomes [6] . ...
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The role for vaccine adjuvants in case of veterinary and human vaccines has been a matter of great interest for the last so many years. Till now, only one adjuvant i.e. alum that are approved by Food and drug administration (FDA) for human use as well as for research purpose. Now a day, researchers worked with some plant based immunostimulators pertaining to determined humoral and cell mediated immune response against specific protein antigen. The only drawback for alum which enhanced only humoral response and poorly elicited cell mediated immunity. In an effort to search for those adjuvants that are derived from various medicinal plants and showed minimal side effects including toxicity. In this review, we focused on plant derived molecules or candidate used as adjuvant against specific protein antigen.
... According to Xie et al. (2015), there is an increasing interest of pharmaceutical sectors and researchers toward polysaccharides isolated from medicinal plants because of their biological activities including antioxidant (inhibition of lipid peroxidation, free radicals scavenging activities, protection of DNA from breaks induced by ROS), anti-inflammatory, anticancer activity (Xiaojuan et al., 2012;Amit et al., 2014;Tabarsa et al., 2017) and stimulation of Peripheral Blood Mononuclear Cells (PBMCs) proliferation and INFy cytokines production (Boudjeko et al., 2015). ...
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Antioxidant and immune modulatory activities of polysaccharides fractions isolated from Khaya grandifoliola stem bark and Cryptolepis sanguinolenta leaves were analyzed. Water-soluble total polysaccharides (TP) were extracted and precipitated in alcohol. Pectic (PF) and hemicellulosic fractions (HF) of cell walls were obtained using ammonium oxalate and potassium hydroxide. TP of K. grandifoliola and C. sanguinolenta pectins are mostly linked to proteins (86.39 ± 1.13 and 67.66 ±2.05 μg eqBSA/mg DW). Polysaccharide fractions of C. sanguinolenta are rich in phenolic compounds. Gas chromatography analyses showed that TP of C. sanguinolenta is an arabinoglucan type, consisting mainly of glucose (60.51%) and arabinose (10.36%), while TP of K. grandifoliola is constituted of glucose (30.53%), galactose (28.89%), arabinose (17.57%) and rhamnose (10.74%). Pectic fractions of the two plants would be a rhamnogalacturonan type constituted of galacturonic acid, rhamnose and arabinose; while HF fractions might be xyloglucan as they were mainly constituted of glucose, xylose and arabinose. The polysaccharide fractions (50 to 300 µg/mL) exhibited antioxidant activity on both DPPH and ABTS radicals, with TP showing the highest activities. Polysaccharides were assessed to be non-toxics at 200 µg/mL to Peripheral Blood Mononuclear Cells (PBMCs) and strongly inhibited MSP1 (Malaria antigen)-induced overproduction of IL-1β, IL-6 and TNF-α by PBMCs in the in vitro immunological assays.
... According to Xie et al. [12], there is an increasing interest of pharmaceutical sectors and researchers in polysaccharides isolated from medicinal plants because of their biological activities that are antioxidant (inhibition of lipid peroxidation, free radicals scavenging activities, protection of DNA from breaks induced by ROS), anti-inflammatory, anticancer [13][14][15], as well as the stimulation of PBMC proliferation and INFγ cytokine production [16,17]. Moreover, most polysaccharides derived from higher plants are relatively non-toxic and do not cause significant side effects as compared to immunomodulatory bacterial polysaccharides and synthetic compounds [18]. ...
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Background: Khaya grandifoliola (C.D.C.) stem bark, Cymbopogon citratus (Stapf) and Cryptolepis sanguinolenta (Lindl.) Schltr leaves are used in Cameroonian traditional medicine for the treatment of inflammatory diseases. Several studies have been performed on the biological activities of secondary metabolites extracted from these plants. However, to the best of our knowledge, the anti-neuro inflammatory and protective roles of the polysaccharides of these three plants have not yet been elucidated. This study aimed at investigating potential use of K. grandifoliola, C. sanguinolenta and C. citratus polysaccharides in the prevention of chronic inflammation. Methods: Firstly, the composition of polysaccharide fractions isolated from K. grandifoliola stem bark (KGF), C. sanguinolenta (CSF) and C. citratus (CCF) leaves was assessed. Secondly, the cytotoxicity was evaluated on Raw 264.7 macrophages and U87-MG glioblastoma cell lines by the MTT assay. This was followed by the in vitro evaluation of the ability of KGF, CSF and CCF to inhibit lipopolysaccharides (LPS) induced overproduction of various pro-inflammatory mediators (NO, ROS and IL1β, TNFα, IL6, NF-kB cytokines). This was done in Raw 264.7 and U87-MG cells. Finally, the in vitro protective effect of KGF, CSF and CCF against LPS-induced toxicity in the U87-MG cells was evaluated. Results: CCF was shown to mostly contain sugar and no polyphenol while KGP and CSP contained very few amounts of these metabolites (≤ 2%). The three polysaccharide fractions were non-toxic up to 100 μg.mL- 1. All the polysaccharides at 10 μg/mL inhibited NO production, but only KGF and CCF at 12.5 μg/mL down-regulated LPS-induced ROS overproduction. Finally, 100 μg/mL LPS reduced 50% of U87 cell viability, and pre-treatment with the three polysaccharides significantly increased the proliferation. Conclusion: These results suggest that the polysaccharides of K. grandifoliola, C. citratus and C. sanguinolenta could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.
... In this regard, researchers have focused on various medicinal plants to control the burden of this disease. Immunological exploration of these medicinal plants is totally based on phytochemical screening of primary and secondary metabolites (6). These metabolites of medicinal plants were examined for their immunopharmacological activities and approaches which lead to drug discovery and commonly referred as screening of natural products. ...
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Introduction: In general, primary or secondary metabolites derived from medicinal plant products might be responsible for stimulating or suppressing the immune system against specific protein antigens. The objective of this study was to evaluate the adjuvant potential of aqueous leaves extract of Azadirachta indica, Butea frondosa and Ficus religiosa against Swine flu vaccine antigen. Methods: In this study, our group evaluated the antibody (IgG) titre of Swine flu vaccine antigen (2 pg/mL) using variable doses (0.625-5 mg) of aqueous leaves extract of A. Indica, B. Frondosa and F. Religiosa. In addition, Swiss mice were immunized subcutaneously (100 pL) on day 0 with Swine flu vaccine antigen (1:1000 dilution). Splenocytes were collected on day 7 and cultured with variable doses of aqueous leaves extract of A. Indica, B. Frondosa and F. Religiosa pertaining to determine the total cellular content and splenocyte proliferation (Swine flu vaccine, Ovalbumin, OVA and Con A) assay. In addition, estimation of Th1 (IFN-gamma and TNF alpha) cytokines in cell culture supernatant containing swine flu vaccine antigen along with aqueous leaves extract were measured. Results: Aqueous leaves extract of A. Indica, B. Frondosa and F. Religiosa showed anti-Swine flu titre at higher doses. In ex vivo animal model studies these three medicinal plants in the form of aqueous leaves extract enhanced total cellular content at higher doses but increased in splenocyte proliferation (Swine flu vaccine, OVA and Con A) assay at lower doses. Similarly, there was enhancement in Th1 cytokines (IFN-gamma, TNF alpha) with respect to swine flu vaccine antigen containing aqueous extract at lower doses as compared to control group. Conclusion: Aqueous leaves extract of A. Indica, B. Frondosa and F. Religiosa showed adjuvant activity against Swine flu vaccine antigen and might be used in manufacturing active adjuvant for vaccine antigen.
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Many plants contain carbohydrate-binding proteins that are commonly designated as lectins, agglutinins, or hemagglutinins. Due to the obvious differences in molecular structure, biochemical properties, and carbohydrate-binding specificity, plant lectins are usually considered a complex and heterogeneous group of proteins. Recent advances in the structural analysis of lectins and molecular cloning of lectin genes enable subdividision of plant lectins in a limited number of subgroups of structurally and evolutionary related proteins. Four major lectin families, namely, the legume lectins, the chitin-binding lectins composed of hevein domains, the type 2 ribosome-inactivating proteins, and the monocot mannose-binding lectins comprise the majority of all currently known plant lectins. In addition to these four large families the jacalin-related lectins, the amaranthin family, and the Cucurbitaceae phloem lectins are now recognized as separate subgroups. Each of the above-mentioned lectin families is discussed in detail. The description of the individual lectin families includes (1) a brief historical note, (2) an overview of the occurrence, molecular structure, and primary structure of the lectins, (3) a detailed discussion of the structure of the gene(s) and the biosynthesis and posttranslational processing of the primary translation products, (4) a summary of carbohydrate-binding specificity, (5) if relevant a note on the occurrence of lectin-related proteins, (6) a description of the three-dimensional structure of the lectins and the protomers, (7) a detailed discussion of the molecular evolution, and (8) a critical assessment of the physiological role of each group of lectins. Lectins that cannot be classified into one of the seven groups are discussed separately. General conclusions about the structure, evolution, and function of plant lectins are summarized in the concluding remarks.
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Many plant species contain carbohydrate-binding pro- teins, which are commonly referred to as either lectins or agglutinins. Generally speaking, lectins are proteins that bind reversibly to specific mono- or oligosaccharidcs. Since the initial discovery of a hemagglutinating factor in castor bean extracts by Stillmark in 1888, several hundred of these proteins have been isolated and characterized in some detail with respect to their carbohydrate-binding specific- ity, molecular structure, and biochemical properties. Lec- tins from different plant species often differ with respect to their molecular structure and specificity. It is important, therefore, to realize that a11 plant lectins are artificially classified together solely on the basis of their ability to recognize and bind carbohydrates. Moreover, the question arises whether proteins with a completely different struc- ture and sugar-binding specificity fulfill the same physio- logical role. No conclusive answer can be given to this question as yet, for the simple reason that the role of most plant lectins is not known with certainty. There is, how- ever, growing evidence that most lectins play a role in the plant's defense against different kinds of plant-eating or- ganisms. The idea that lectins may be involved in plant defense is not new. In an earlier review, Chrispeels and Raikhel (1991) critically assessed the defensive role of the phytohemagglutinin family and a number of chitin-bind- ing proteins. During the last few years important progress has been made in the study of plant lectins in general and in the understanding of their effects on other organisms in particular. In this Update we summarize the recent devel- opments that support the defensive role of plant lectins and, in addition, discuss earlier work in this field against the background of our present knowledge of this group of plant proteins.
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The monocot mannose-binding lectins are an extended superfamily of structurally and evolutionarily related proteins, which until now have been isolated from species of the Amaryllidaceae, Alliaceae, Araceae, Orchidaceae, and Liliaceae. To explain the obvious differences in biological activities, the structure-function relationships of the monocot mannose-binding lectins were studied by a combination of glycan-binding studies and molecular modeling using the deduced amino acid sequences of the currently known lectins. Molecular modeling indicated that the number of active mannose-binding sites per monomer varies between three and zero. Since the number of binding sites is fairly well correlated with the binding activity measured by surface plasmon resonance, and is also in good agreement with the results of previous studies of the biological activities of the mannose-binding lectins, molecular modeling is of great value for predicting which lectins are best suited for a particular application.
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A mannose (Man)-binding lectin has been isolated and characterized from the thallus of the liverwort Marchantia polymorpha. N-terminal sequencing indicated that the M. polymorpha agglutinin (Marpola) shares sequence similarity with the superfamily of monocot Man-binding lectins. Searches in the databases yielded expressed sequence tags encoding Marpola. Sequence analysis, molecular modeling, and docking experiments revealed striking structural similarities between Marpola and the monocot Man-binding lectins. Activity and specificity studies further indicated that Marpola is a much stronger agglutinin than the Galanthus nivalis agglutinin and exhibits a preference for methylated Man and glucose, which is unprecedented within the family of monocot Man-binding lectins. The discovery of Marpola allows us, for the first time, to corroborate the evolutionary relationship between a lectin from a lower plant and a well-established lectin family from flowering plants. In addition, the identification of Marpola sheds a new light on the molecular evolution of the superfamily of monocot Man-binding lectins. Beside evolutionary considerations, the occurrence of a G. nivalis agglutinin homolog in a lower plant necessitates the rethinking of the physiological role of the whole family of monocot Man-binding lectins.
Transgenic rice lines containing the snowdrop (Galanthus nivalis) lectin gene (GNA) were investigated for the stability of expression of the GNA gene in the sixth (R6) generation. Western blot analysis revealed that GNA was stably expressed among the R6 individual plants at comparable levels with those from their parental lines. Insect bioassay tests of two independent transgenic rice homozygous R6 lines (Nos. 1 and 2) showed that both lines caused significant inhibition to the rice small brown planthopper (Laodelphax striatellus, SBPH) by decreasing SBPH survival, overall fecundity and retarding its development. These SBPH-resistant lines have been incorporated into a rice insect resistance breeding program for the control of SBPH. This is the first report that transgenic rice lines expressing GNA conferred enhanced resistance to SBPH.
Insect feeding trials were carried out to determine the effects of incorporating a range of plant derived proteins into artificial diets fed to leafhopper and planthopper pests of rice. The lectins Galanthus nivalis agglutinin (GNA) and wheat germ agglutinin (WGA), and the enzyme soy bean lipoxygenase (LPO) were shown to exhibit significant antimetabolic effects towards first and third instar nymphs of rice brown planthopper (Nilaparvata lugens Stål) when incorporated into artificial diet at 0.1% (w/v), 0.1% (w/v) and 0.08% (w/v) levels respectively. The lectin GNA was also shown to exhibit a significant antimetabolic effect towards third instar nymphs of the rice green leafhopper (Nephotettix cinciteps Uhler). A number of inert proteins, lectins, protein inhibitors and enzymes also tested showed relatively little or no effect towards both insects.
Mature seed-derived callus from an elite Chinese japonica rice (Oryza sativa L.) cv. Eyi 105 was cotransformed with two plasmids, pWRG1515 and pRSSGNA1,containing the selectable marker hygromycin phosphotransferase gene (hpt), the reporter β-glucuronidase gene (gusA) and the snow-drop (Galanthus nivalis) lectin gene (gna) via particle bombardment. After two rounds of selection on hygromycin-containing medium, resistant callus was transferred to hygromycin-containing regeneration medium for plant regeneration. Twenty-six independent transgenic rice plants were regenerated from 152 bombarded calli with a transformation frequency of 17%. Seventy-three percent of transgenic plants contained all three genes, which was revealed by PCR/Southern blot analysis. Thirteen out of 19 transgenic plants containing the gna gene expressed GNA (68%) at various levels with the highest expression being approximately 0.5% of total soluble protein. Genetic analysis confirmed Mendelian segregation of transgenes in progeny. From R2 generations with their R1 parentplants showing 3:1 Mendelian segregation patterns, we identified three independent homozygous lines containing and expressing all three transgenes.Insect bioassay and feeding tests showed that these homozygous lines had significant inhibition to the rice brown planthopper (Nilaparvata lugens, BPH) by decreasing BPH survival and overall fecundity, retarding BPH development and reducing BPH feeding.This is the first report that homozygous transgenic rice lines expressing GNA, developed by genetic transformation and through genetic analysis-based selection, conferred enhanced resistance to BPH, one of the most damaging insect pests in rice.
The molecular structure and carbohydrate-binding activity of the lectin from bulbs of spring crocus (Crocus vernus) has been determined unambiguously using a combination of protein analysis and cDNA cloning. Molecular cloning revealed that the lectin called C. vernus agglutinin (CVA) is encoded by a precursor consisting of two tandemly arrayed lectin domains with a reasonable sequence similarity to the monocot mannose-binding lectins. Post-translational cleavage of the precursor yields two equally sized polypeptides. Mature CVA consists of two pairs of polypeptides and hence is a heterotetrameric protein. Surface plasmon resonance studies of the interaction of the crocus lectin with high mannose-type glycans showed that the lectin interacts specifically with exposed alpha-1,3-dimannosyl motifs. Molecular modelling studies confirmed further the close relationships in overall fold and three-dimensional structure of the mannose-binding sites of the crocus lectin and other monocot mannose-binding lectins. However, docking experiments indicate that only one of the six putative mannose-binding sites of the CVA protomer is active. These results can explain the weak carbohydrate-binding activity and low specific agglutination activity of the lectin. As the cloning and characterization of the spring crocus lectin demonstrate that the monocot mannose-binding lectins occur also within the family Iridaceae a refined model of the molecular evolution of this lectin family is proposed.
The requirement for large quantities of therapeutic proteins has fueled interest in the production of recombinant proteins in plants and animals. The first commercial products to be made in this way have experienced much success, and it is predicted that in the future a plethora of protein products will be made using these 'natural' bioreactors.
Full-length cDNA of a mannose-binding lectin or agglutinin gene was cloned from a traditional Chinese medicinal herb Crinum asiaticum var. sinicum through RACE-PCR cloning. The full-length cDNA of C. asiaticum agglutinin (caa) was 820 bp and contained a 528 bp open reading frame encoding a lectin precursor (preproprotein) of 175 amino acid residues with a 22 aa signal peptide. The coding region of the caa gene was high in G/C content. The first 20 bp of the 5' UTR had a dC content of 50%, which was a typical feature of the leader sequence. By cutting away the signal peptide, the CAA proprotein was 15.79 kDa with a pl of 9.27 and contained 3 mannose-binding sites (QDNY). Random coil and extended strand constituted interlaced domination of the main part of the secondary structure. B-lectin conserved domain existed within N24 to G130. Predicted three-dimensional structure of CAA proprotein was very similar to that of GNA (Galanthus nivalis agglutinin). It is significant that besides certain homologies to known monocot mannose-binding lectins from Amaryllidaceae, Orchidaceae, Alliaceae and Liliaceae, caa also showed high similarity to gastrodianin type antifungal proteins. No intron was detected within the region of genomic sequence corresponding to the caa full-length cDNA. Southern blot analysis indicated that the caa gene belonged to a low-copy gene family. Northern blot analysis demonstrated that caa mRNA was constitutively expressed in all the tested tissue types including the root, bulb, leaf, rachise, flower and fruit tissues.