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Immunomodulatory leads from medicinal plants

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Indian Journal of Traditional Knowledge
Vol. 13 (2), April 2014, pp. 235-256

Immunomodulatory leads from medicinal plants

Pulok K Mukherjee1,*, Neelesh K Nema1, Santanu Bhadra1, D Mukherjee1, Fernão C Braga2 & Motlalepula G Matsabisa3
1
School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata - 700 032, India; 2 Faculty
of Pharmacy, Universidade Federal de Minas Gerais, Av. Olegário Maciel, 2360, Belo Horizonte, Brazil; 3 South African Medical
Research Council, Francie van Zijl Drive, Parow Valley, Cape Town, South Africa
E-mail: naturalproductm@gmail.com
Received 19.03.13, revised 23.08.13

Immunomodulation is the alteration of immune response which may increase or decrease the immune responsiveness.
Medicinal plants, since times immemorial, have been used virtually in all cultures as a source of medicine for altering the
immune systems. Several medicinal plants have been investigated for immunomodulatory potentials and they are proved to
have beneficial effect on alteration of immune system by diverse mechanisms in animals. The present review will provide an
up to date knowledge about the medicinal plants used as immunomodulators and their phytoconstituents. This article
highlights on the phytochemistry, pharmacology, therapeutic usage and related aspects of 55 medicinal plants, such as
Allium sativum, Aloe vera, Andrographis paniculata, Azadirachta indica, Boerhaavia diffusa, Boswellia serrata, Curcuma
longa, Centella asiatica, Carica papaya, Datura quercifolia, Emblica officinalis, Hydrastis Canadensis, Hypericum
perforatum, Ocimum sanctum, Panax ginseng, Plantago major, Plantago asiatica, Piper longum, Tinospora cordifolia,
Mangifera indica, Momordica charantia, Withania somnifera, etc. which have been investigated for their
immunomodulatory potentials, and they are proved to acquire beneficial effect on alteration of immune system by diverse
mechanisms. Thus an approach for integration of the available information on several species of medicinal plants used as
immunomodulators along with the metabolites responsible for the same has been made in this article.

Keywords: Immunomodulation, Medicinal plants, Natural immunomodulators

IPC Int. Cl.8: A61K 36/00, A01C 1/08, A61K 39/00

The term "immunomodulation" means the alteration
of immune response which may increase or decrease
the immune responsiveness. Enhancement in the
immune responsiveness is called immunostimulation
and reduction in the immune responsiveness is called
immunosuppression. An immunomodulators may be
defined as a substance, biological of synthetic, which
can stimulate, suppress or modulate any of the
components of the immune system including both
innate and adaptive arms of the immune response.
The essence of immunomodulation is that a
pharmacological agent acting under various dose and
time regimens displays an immunomodulating
effect1,2. Possible mechanism of immunomodulation
has been summarized in Fig. 1.
The extreme manifestations of immunomodulating
action of biologically active substances are
immunosuppression and immunostimulation, hence
both immunostimulating agents and
immunosuppressing agents have their own standing
and search for better agents exerting these activities is
______________
*Corresponding author
becoming the field of major interest all over the world3.
Natural adjuvants, synthetic agents, antibody reagents
are used as immunosuppressive and immunostimulative
agents. But there are major limitation to the general use
of these agents such as increased risk of infection and
generalized effect throughout the immune system4. To
overcome these problems a number of drugs from
natural source either herbal or mineral have been used as
to alter the human immune system5. There are several
medicinal plants are employed in different system of
medicine throughout the world to improve the
immunological disorders. In India use of plants as
remedy can be traced back to 6000 BC. Ayurveda –
ancient science of life is believed to be prevalent for last
5000 yrs in India6, 7. In recent times modulation of
immune response to cure various diseases has been a
very interesting concept and the concept of rasayana in
ayurveda deals with the same. Ayurvedic system of
medicine describes this concept of rasayana under
which plants with rejuvenating activity have been
described by the emphasis on promotion of health by
strengthening host defenses against different diseases.
They have been categorized by ayurveda as ‘Rasayan’
236 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014

literally meaning a house or place of ‘Ras’, i.e.

essential vehicle of life. These plants have been found
to have role in the promotion of health by
strengthening host defences against different diseases.
Beside that these rasayana plants also have other
properties like delaying the onset of senescence and
improving mental functions by strengthening the
psycho-neuro-immune axis8. Therefore a number of
plants with their extracts, active fractions have been
investigated for immune response modifying activity
(Table 1). In addition, biologically active compounds
from natural sources have always been of great interest
to scientists working on infectious diseases9 or to
improve immune function. Hence, in this review
attempt has been made to highlight the experimental
work on immunomodulation of various Indian Fig. 1Mechanism of immunomodulation
medicinal plants along with their possible mechanism
of action with possible constituenrts. wound rats compared to rats in the control group. It was
also observed that the levels of TNF-α and IL-6 reduce
Medicinal plants and their constituents with significantly12. Dihydrocoumarin derivatives (1, 2) were
immunomodulatory potentials isolated from Aloe vera which exhibited
Structures of some important phytoconstituents immunomodulatory activity in relation to increasing the
have given separately in the text from serial No. 1-32 phagocytic activity and stimulating the production of
Acorus calamus L. (Araceae)
superoxide anions in the oxygen respiratory burst of rat
Acorus calamus commonly known as “Bach or peritoneal macrophages13.
Vacha or Sweet Flag” is a semi-aquatic herb with
Allium sativum L. (Alliaceae)
creeping rhizomes and sword shaped long leaves found
Allium sativum (Garlic) is an essential dietary component
throughout India near marshy places, river banks and
cultivated throughout India, and familiar worldwide as
lakes. The plant showed diverse pharmacological
garlic. There is some evidence for immunomodulatory
potentials including antibacterial, sedative, spasmolytic,
effect of garlic or selected garlic constituents showing
hypocholesterolaemic, insecticide, antiulcer, etc.10.
increased T-lymphocyte blastogenesis and phagocytosis,
Ethanolic extract of rhizome of the plant proved to
as well as modulation of cytokine production in vitro and
possesses anti-cellular and immunomodulatory
in vivo. Kyo et al. (2001) have found that aged garlic
properties. This extract inhibited proliferation of
extract showed variety of anti allergic and antitumor
mitogen and antigen stimulated human peripheral blood
through tumor cell growth inhibition and
mononuclear cells (PBMCs). Further rhizome extract
chemopreventative effects14. They demonstated that
also inhibited growth of several cell lines of mouse and
histamine release in the rat basophil cell line RBL-2H3
human origin, production of nitric oxide, interleukin-2
was induced by mouse anti-trinitrophenyl (TNP)
(IL-2) and tumor necrosis factor-a (TNF-α)11.
monoclonal antibody and the TNP-bovine serum albumin
Aloe vera (L.) Burm.f. (Asphodelaceae) (BSA) hapten carrier complex. The extract at doses of
Aloe vera is a very well known medicinal plant, 1.25, 2.5 and 5.0 gm/100 gm significantly inhibited the
grows in arid climates and widely distributed in antigen specific histamine release by 50, 80 and 90%,
Africa and other arid areas. It is claimed that Aloe respectively. Oral administration of extract (10 ml/kg)
vera has wound and burn healing properties and also also decreased 25–45% of the ear swelling, used as an
posses a strong anti-inflammatory and index of immunoglobulin IgE mediated skin reaction. In
immunomodulatory effects. The effects of Aloe vera the psychological stress model, the extract significantly
on microcirculation and levels of TNF-α and IL-6 prevented the decrease in spleen weight and restored the
were investigated in rats after inducing burn. It was reduction of anti-SRBC hemolytic plaque-forming
found that the amount of leukocyte adhesion was cells caused by the electrical stress20. It is
significantly reduced in the Aloe vera treated burn- also reported that at low concentration garlic extract
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR 237

Table 1Medicinal plants possessing immunomodulatory properties(Cond.)

Sl No. Plant name Parts used Immunomodulatory mechanism References
1. Eclipta prostrata (L.) L. Whole plant Induces phagocytic index, antibody titer of mice 41
(Asteraceae) Increase non-specific immune response and lysosomal
activity of the humoral responses
2. Phyllanthus emblica L. Fruits Imunosuppressive effects on lymphocyte proliferation 43
(Euphorbiaceae) Restoration of IL-2 and IFN- γ production
3. Evolvulus alsinoides (L.) L. Whole plant Decreases the level of nitric oxide synthase (NOS) 44
(Convolvulaceae) Exert adaptogenic properties
4. Ficus benghalensis L. Whole plant Enhance the phagocytosis of the human 45
(Moraceae) neutrophils in vitro
Increase the antibody titer value
5. Glycyrrhiza glabra L. Bark & root Enhanced immune and antioxidant enzyme activities 46, 47
(Leguminosae) Stimulates immune cells by CD69 expression on CD4
and CD8 T cells and macrophages function
6. Hippophae rhamnoides L Leaves & fruits Inhibits chromium-induced free radical production, 48
. (Elaeagnaceae) apoptosis, DNA fragmentation
Stimulates IL-2 and IFN-γ production
7. Hydrastis canadensis L. Root Reduces plasma TNF-α, IFN- γ and NO levels 49
(Ranunculaceae) Inhibits the T helper -type 2 cytokine profile
8. Hypericum perforatum L. Aerial parts Increase candidacidal activity of neutrophils and 50
(Hypericaceae) decreased adhesion function of epithelial cells
Alter the function of NF-kB
9. Jatropha curcas L. Leaves Increase the antibody titers, lymphocyte and 51
(Euphorbiaceae) macrophage cells
10. Mangifera indica L. Fruits Increase in humoral antibody (HA) titre and DTH 52
(Anacardiaceae) Enhance production of IgG1 and IgG2b
11. Matricaria chamomilla L. Flowers Activation of immune cells of peripheral blood, and 53
(Asteraceae) increased sensitivity of effector cells to helper signals
12. Mollugo verticillata L. Leaves Inhibits the production of NO 54
(Molluginaceae)
13. Momordica charantia L. Fruits & seeds Inhibits the release of TNF-α, NO and proliferation of 55
(Cucurbitaceae) spleen cells induced by PHA and Con A
14. Morinda citrifolia L. Fruits Stimulating the release TNF-α, IL-β, IL-10, IL-12, 56
(Rubiaceae) IFN-γ
15. Nelumbo nucifera Rhizome & seed Reduce NO production, protects mast cells 59,60
Gaertn.(Nymphaeceae) degranulation
Express CD40, CD80, CD86
16. Nerium oleander L. Leaves Inhibited haemaglutination antibodies, DTH reaction, 61
(Apocynaceae) phagocytic index etc in mice
17. Nigella sativa L. Seeds Reduces pancreatic ductal adenocarcinoma cell (PDA) 62
(Ranunculaceae) synthesis of monocyte chemoattractant protein-1 (MCP-1),
TNF- α , IL-1β and cyclooxigenase (COX) -2
Inhibits the polymorpho nuclear leukocytes functions
18. Ocimum tenuiflorum L. Aerial parts Inhibits antigen induced histamine release from the 63
(Labiatae) peritoneal mast cells, foot pad thickness and leucocyte
migration
19. Plantago species (Plantago major L. Seed It expressed higher levels of MHC class II molecules 64
& P. asiatica L. (Plantaginaceae) and costimulatory molecules such as CD80 and CD86
It acts on human peripheral blood mononuclear cells
(PBMC) through lymphocyte transformation; enhance
the secretion of IFN-γ.
20. Piper longum L. Fruits & leaves Increase the total WBC count, bone marrow 65
(Piperaceae) cellularity, α- esterase positive cells, enhance the total
antibody production
(Table 1-Contd.)
238 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014

Table 1Medicinal plants possessing immunomodulatory properties

Sl No. Plant name Parts used Immunomodulatory mechanism References
21. Acorus calamus L. (Araceae) Rhizome Increase the production of IL-2, tumor necrosis factor 11
(TNF)-α
22. Aloe vera (L.) Burm.f. Leaves Increases phagocytosis and stimulating the production 12, 13
(Asphodelaceae) of superoxide
23. Allium sativum L. (Alliaceae) Fruits Suppress leukocyte inflammatory cytokine production 14,15
24. Andrographis paniculata Wall. ex Aerial parts Increase the production of IL-2, Inhibits of NO 17
Nees (Acanthaceae) production
25. Azadirachta indica A. Juss. Leaves Increase IgM and IgG production 18
(Meliaceae) Inhibits of NO synthesis, degranulation of neutrophils
26. Asparagus racemosus Willd Root Increase the production of leucocytosis 20
(Liliaceae) Enhances the phagocytic activity of the macrophages
27. Argyreia speciosa (L. f.) Sweet Root & seeds Enhance the production of circulating antibody titre 21
(Convolvulaceae) Increase in DTH reaction
28. Baliospermum montanum (Willd.) Root & leaves Enhances neutrophil phagocytic function such as 22
Müll.Arg. (Euphorbiaceae) neutrophil locomotion, chemotaxis
Stabilized mast cell degranulation induced by
compound 48/80.
29. Bidens pilosa L. (Asteraceae) Whole plant Enhances the cytokine production and white blood 23
cells population
Increases IFN-γ promoter activity
30. Boerhaavia diffusa L. Root Inhibits human NK cell cytotoxicity in vitro 24
(Nyctaginaceae) Inhibits production of NO, IL-2 and TNF-α
31. Boswellia serrata Roxb. ex Colebr. Bark Inhibits passive paw anaphylaxis reaction and mast 26
(Burseraceae) cells protection
32. Calendula officinalis L. Leaves & flowers Inhibits tumor cell proliferation 28
(Asteraceae)
33. Camellia sinensis (L.) Kuntze Leaves Enhances the neopterin production in peripheral 29
(Theaaceae) mononuclear cells
34. Capparis zeylanica L Leaves Prevents myelosupression in mice with 30
(Capparidaceae) cyclophosphamide and potentiats DTH reaction
35. Carica papaya L. Leaves & seeds It enhances the phytohemagglutinin responsiveness of 31
(Caricaceae) lymphocytes
It inhibits the classical complement-mediated
hemolytic pathway
36. Centella asiatica (L.) Leaves It increases the phagocytic index, total WBC count and 32
Urban. (Umbelliferae) Inhibited human peripheral blood mononuclear cell
(PBMC) mitogenesis and production of IL-2 and TNF-α
37. Chelidonium majus L. Aerial parts Exert antitumor immunostimulatory effect 33
(Papaveraceae)
38. Chrysanthemum indicum L. Aerial parts Increases DTH reaction, antibody generation, 34
(Compositae) Potentiates the mononuclear phagocytosis function
39. Cichorium intybus L. Root Increases DTH reaction, phagocytic activity and 35
(Asteraceae) natural killer (NK) cell activity and IFN-γ secretion
40. Citrus aurantiifolia (Christm.) Fruits & leaves Inhibits proliferation of PHA activated mononuclear 36
Swingle (Rutaceae) cells, staphylococcal protein
41. Cryptolepis dubia (Burm.f.) Root It stimulates the DTH reaction and also increases the 37
M.R.Almeida. (Apocynaceae) humoral antibody production
42. Curcuma longa L. Rhizome It shows immunomodulation through inhibition of 38,39
(Zingiberaceae) proliferation induced by PMA and anti-CD28
antibody. Also it inhibits the T lymphocytes isolated
from healthy donors induced by PHA
43. Desmodium gangeticum (L.) DC. Whole plant Enhance NO production and provided resistance 40
(Fabaceae) against infection established in peritoneal macrophages
by the protozoan parasite Leishmania donovani
(Table 1-Contd.)
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR 239

Table 1Medicinal plants possessing immunomodulatory properties

Sl No. Plant name Parts used Immunomodulatory mechanism References
44. Acorus calamus L. (Araceae) Rhizome Increase the production of IL-2, tumor necrosis factor 11
(TNF)-α
45. Aloe vera (L.) Burm.f. Leaves Increases phagocytosis and stimulating the production 12, 13
(Asphodelaceae) of superoxide
46. Allium sativum L. (Alliaceae) Fruits Suppress leukocyte inflammatory cytokine production 14,15
47. Andrographis paniculata Wall. ex Aerial parts Increase the production of IL-2, Inhibits of NO 17
Nees (Acanthaceae) production
48. Azadirachta indica A. Juss. Leaves Increase IgM and IgG production 18
(Meliaceae) Inhibits of NO synthesis, degranulation of neutrophils
49. Asparagus racemosus Willd Root Increase the production of leucocytosis 20
(Liliaceae) Enhances the phagocytic activity of the macrophages
50. Argyreia speciosa (L. f.) Sweet Root & seeds Enhance the production of circulating antibody titre 21
(Convolvulaceae) Increase in DTH reaction
51. Baliospermum montanum (Willd.) Root & leaves Enhances neutrophil phagocytic function such as 22
Müll.Arg. (Euphorbiaceae) neutrophil locomotion, chemotaxis
Stabilized mast cell degranulation induced by
compound 48/80.
52. Bidens pilosa L. (Asteraceae) Whole plant Enhances the cytokine production and white blood 23
cells population
Increases IFN-γ promoter activity
53. Boerhaavia diffusa L. Root Inhibits human NK cell cytotoxicity in vitro 24
(Nyctaginaceae) Inhibits production of NO, IL-2 and TNF-α
54. Boswellia serrata Roxb. ex Colebr. Bark Inhibits passive paw anaphylaxis reaction and mast 26
(Burseraceae) cells protection
55. Calendula officinalis L. Leaves & flowers Inhibits tumor cell proliferation 28
(Asteraceae)
56. Camellia sinensis (L.) Kuntze Leaves Enhances the neopterin production in peripheral 29
(Theaaceae) mononuclear cells
57. Capparis zeylanica L Leaves Prevents myelosupression in mice with 30
(Capparidaceae) cyclophosphamide and potentiats DTH reaction
58. Carica papaya L. Leaves & seeds It enhances the phytohemagglutinin responsiveness of 31
(Caricaceae) lymphocytes
It inhibits the classical complement-mediated
hemolytic pathway
59. Centella asiatica (L.) Leaves It increases the phagocytic index, total WBC count and 32
Urban. (Umbelliferae) Inhibited human peripheral blood mononuclear cell
(PBMC) mitogenesis and production of IL-2 and TNF-α
60. Chelidonium majus L. Aerial parts Exert antitumor immunostimulatory effect 33
(Papaveraceae)
61. Chrysanthemum indicum L. Aerial parts Increases DTH reaction, antibody generation, 34
(Compositae) Potentiates the mononuclear phagocytosis function
62. Cichorium intybus L. Root Increases DTH reaction, phagocytic activity and 35
(Asteraceae) natural killer (NK) cell activity and IFN-γ secretion
63. Citrus aurantiifolia (Christm.) Fruits & leaves Inhibits proliferation of PHA activated mononuclear 36
Swingle (Rutaceae) cells, staphylococcal protein
64. Cryptolepis dubia (Burm.f.) Root It stimulates the DTH reaction and also increases the 37
M.R.Almeida. (Apocynaceae) humoral antibody production
65. Curcuma longa L. Rhizome It shows immunomodulation through inhibition of 38,39
(Zingiberaceae) proliferation induced by PMA and anti-CD28
antibody. Also it inhibits the T lymphocytes isolated
from healthy donors induced by PHA
66. Desmodium gangeticum (L.) DC. Whole plant Enhance NO production and provided resistance 40
(Fabaceae) against infection established in peritoneal macrophages
by the protozoan parasite Leishmania donovani
(Table 1-Contd.)
240 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014

Table 1Medicinal plants possessing immunomodulatory properties(Cond.)

Sl No. Plant name Parts used Immunomodulatory mechanism References
67. Eclipta prostrata (L.) L. Whole plant Induces phagocytic index, antibody titer of mice 41
(Asteraceae) Increase non-specific immune response and lysosomal
activity of the humoral responses
68. Phyllanthus emblica L. Fruits Imunosuppressive effects on lymphocyte proliferation 43
(Euphorbiaceae) Restoration of IL-2 and IFN- γ production
69. Evolvulus alsinoides (L.) L. Whole plant Decreases the level of nitric oxide synthase (NOS) 44
(Convolvulaceae) Exert adaptogenic properties
70. Ficus benghalensis L. Whole plant Enhance the phagocytosis of the human 45
(Moraceae) neutrophils in vitro
Increase the antibody titer value
71. Glycyrrhiza glabra L. Bark & root Enhanced immune and antioxidant enzyme activities 46, 47
(Leguminosae) Stimulates immune cells by CD69 expression on CD4
and CD8 T cells and macrophages function
72. Hippophae rhamnoides L Leaves & fruits Inhibits chromium-induced free radical production, 48
. (Elaeagnaceae) apoptosis, DNA fragmentation
Stimulates IL-2 and IFN-γ production
73. Hydrastis canadensis L. Root Reduces plasma TNF-α, IFN- γ and NO levels 49
(Ranunculaceae) Inhibits the T helper -type 2 cytokine profile
74. Hypericum perforatum L. Aerial parts Increase candidacidal activity of neutrophils and 50
(Hypericaceae) decreased adhesion function of epithelial cells
Alter the function of NF-kB
75. Jatropha curcas L. Leaves Increase the antibody titers, lymphocyte and 51
(Euphorbiaceae) macrophage cells
76. Mangifera indica L. Fruits Increase in humoral antibody (HA) titre and DTH 52
(Anacardiaceae) Enhance production of IgG1 and IgG2b
77. Matricaria chamomilla L. Flowers Activation of immune cells of peripheral blood, and 53
(Asteraceae) increased sensitivity of effector cells to helper signals
78. Mollugo verticillata L. Leaves Inhibits the production of NO 54
(Molluginaceae)
79. Momordica charantia L. Fruits & seeds Inhibits the release of TNF-α, NO and proliferation of 55
(Cucurbitaceae) spleen cells induced by PHA and Con A
80. Morinda citrifolia L. Fruits Stimulating the release TNF-α, IL-β, IL-10, IL-12, 56
(Rubiaceae) IFN-γ
81. Nelumbo nucifera Rhizome & seed Reduce NO production, protects mast cells 59,60
Gaertn.(Nymphaeceae) degranulation
Express CD40, CD80, CD86
82. Nerium oleander L. Leaves Inhibited haemaglutination antibodies, DTH reaction, 61
(Apocynaceae) phagocytic index etc in mice
83. Nigella sativa L. Seeds Reduces pancreatic ductal adenocarcinoma cell (PDA) 62
(Ranunculaceae) synthesis of monocyte chemoattractant protein-1 (MCP-1),
TNF- α , IL-1β and cyclooxigenase (COX) -2
Inhibits the polymorpho nuclear leukocytes functions
84. Ocimum tenuiflorum L. Aerial parts Inhibits antigen induced histamine release from the 63
(Labiatae) peritoneal mast cells, foot pad thickness and leucocyte
migration
85. Plantago species (Plantago major L. Seed It expressed higher levels of MHC class II molecules 64
& P. asiatica L. (Plantaginaceae) and costimulatory molecules such as CD80 and CD86
It acts on human peripheral blood mononuclear cells
(PBMC) through lymphocyte transformation; enhance
the secretion of IFN-γ.
86. Piper longum L. Fruits & leaves Increase the total WBC count, bone marrow 65
(Piperaceae) cellularity, α- esterase positive cells, enhance the total
antibody production
(Table 1-Contd.)
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR 241

Table 1Medicinal plants possessing immunomodulatory properties(Cond.)

Sl No. Plant name Parts used Immunomodulatory mechanism References
87. Premna tomentosa Willd. Stem bark Decrease the lymphocyte proliferation and antioxidant 66
(Verbanaceae) levels
88. Prunella vulgaris L. Fruits Stimulates the proliferation of T-lymphocytes and 67
(Lamiaceae) suppressed NO production in lipopolysaccharide-
stimulated macrophages
89. Psoralea corylifolia L. Leaves Up regulates the production of OVA-specific Th1 68
(Fabaceae) cytokine (IFN-γ) and down regulated OVA-specific
Th2 cytokine
90. Punica granatum L. Fruits Inhibits the leucocyte migration 69
(Punicaceae)
91. Rhinacanthus nasutus (L.) Kurz. Whole plant Increased the production of IL-2 and TNF-α 33
(Acanthaceae)
92. Salvia officinalis L. Aerial parts Induce rat thymocyte proliferation 70
(Lamiaceae)
93. Tamarindus indica L. (Leguminosae) Fruits Inhibits the phorbol myristate acetate (PMA) 71,72
stimulated neutrophil function, neutrophil NADPH
oxidase activity, and elastase activity
94. Terminalia chebula Retz. Fruits Increase in HA titer and DTH reaction 73
(Combretaceae)
95. Tinospora cordifolia (Willd.) Miers Stem & root Increase the total white blood cell count, bone marrow 74
(Menispermaceae) cellularity and α-esterase positive cells
Enhance the macrophage activation
96. Trigonella foenum-graecum L. Seeds Increases the phagocytic index and phagocytic 75
(Fabaceae) capacity of macrophages, enhancement of thymus and
bone marrow cellularities
97. Urtica dioica L. Aerial parts Reduce TNF-α and other inflammatory cytokines by 76
(Urticaceae) inhibiting the genetic transcription factor
98. Withania somnifera (L.) Dunal Root Increase total WBC count, bone marrow cellularity, 77
(cultivated var.) (Solanaceae) circulating antibody titer, plaque forming cells in the
spleen, phagocytic activity of macrophages

significantly reduced that IL-12 production, but IL-10
production was increased. The TNF-α (tumor necrosis
factor), IL-1α, IL-6, IL-8, Tcell interferon-gamma
(IFN-γ), IL-2, and TNF-α were observed to decreased
significantly with the extract15.
Andrographis paniculata (Burm.f.) Wall. ex. Nees. (Acanthaceae)
Andrographis paniculata is one of the Chinese and
Indian herbs reputed to be effective in the treatment of
cold, diarrhea, fever, and inflammation, etc.16.
Methanolic extract of A. paniculata has potential for
anticancer and immunomodulatory activities in
human cancer and immune cells. The extract and its
dichloromethane fraction significantly inhibited the
proliferation of HT-29 (colon cancer) cells and
augment the proliferation human peripheral blood
lymphocytes low concentrations. Three diterpene
compounds were isolated from the plant, viz.
andrographolide (3), 14-deoxyandrographolide and
14-deoxy-11, 12-didehydroandrographolide.These
molecules showed enhanced proliferation and
interleukin-2 (IL-2) induction in human peripheral
blood lymphocytes23. It was also reported that
andrographolide exhibits nitric oxide (NO) inhibitory
property in endotoxin-stimulated macrophages17.
Azadirachta indica A. Juss. (Meliaceae)
Azadirachta indica is well known in India and its
neighbouring countries for more than 2000 yrs as one
of the most versatile medicinal plants having a wide
spectrum of biological activity including anti-
inflammatory, anti-diabetic, antiviral, anticarcinogenic,
immunostimultory, etc. Aqueous extract of stem bark
has been shown to enhance the immune response of
Balb-c mice to sheep red blood cells in-vivo. The
aqueous extract showed strong anticomplementary
effects with dose, time-dependently, and most
pronounced in the classical complement pathway
assay. In addition, a dose-dependent decrease in the
chemiluminescence of polymorphonuclear leukocytes
and a dose-dependent increase in the production of
migration inhibition factor by lymphocytes were also
242 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014
observed. Neem oil has been shown to possess
immunostimulant activity by selectively activating the
cell-mediated immune mechanisms to elicit an
enhanced response to subsequent mitogenic or
antigenic challenge. Neem oil also possesses
immunomodulatory effects in mice. The intraperitoneal
(i.p.) injection of neem oil in mice showed increased in
leukocytic cells after 3 days of treatment. In addition,
the peritoneal macrophages of mice exhibited enhanced
phagocytic activity and expression of MHC class-II
antigens. Nimbidin is a mixture of tetranortriterpenes
and is the major active principle of the seed oil of A.
indica possessing potent antiinflammatory and
antiarthritic activities by inhibiting some of the
functions of macrophages and neutrophils relevant to
the inflammatory response following both in vivo and
in-itro exposure. Oral administration of 5-25 mg/kg
nimbidin to rats for 3 consecutive days significantly
inhibited the relocation of macrophages to their
peritoneal cavities in response to inflammatory stimuli
and also inhibited phagocytosis and phorbol-12-
myristate-13-acetate (PMA) stimulated respiratory
burst in these cells. Nimbidin also inhibited nitric oxide
(NO) and prostaglandin E2 (PGE2) production in
lipopolysaccharide (LPS) stimulated macrophages
following in-vitro exposure. Further observation
proved that nimbidin also attenuated degranulation in
neutrophils assessed in terms of release of
β-glucuronidase, myeloperoxidase and lysozyme18, 19.
Asparagus racemosus Willd (Liliaceae)
Asparagus racemosus (Shatavari) is recommended in
Ayurvedic texts for prevention and treatment of gastric
ulcers, dyspepsia and as a galactogogue. The Asparagus
genus is considered to be of medicinal importance
because of the presence of steroidal saponins and
sapogenins in various parts of the plant. A. racemosus is
commonly mentioned as a rasayana in the Ayurveda.
Immunomodulating property of A. racemosus has been
shown to protect the rat and mice against experimental
induced abdominal sepsis. Oral administration of
decoction of powdered root of A. racemosus has been
reported to produce leucocytosis and predominant
neutrophilia along with enhanced phagocytic activity of
the macrophages and polymorphs. Percentage mortality
of A. racemosus treated animals was found to be
significantly reduced while survival rate was comparable
to that of the group treated with a combination of
metronidazole and gentamicin. A. racemosus showed
anti-sepsis activity by altering function of macrophages,
indicates its possible immunomodulatory property.
Alcoholic extract of A. racemosus has been found to
enhance both, humoral and cell mediated immunity of
albino mice injected with sheep red blood cells as
particulate antigen20.
Argyreia speciosa (L. f.) Sweet (Convolvulaceae)
Argyreia speciosa Sweet of the family
convolvulaceae, commonly known as Vryddhadaru in
Sanskrit, is a woody climber found throughout in
India. It has been used as a ‘rasayana’ drug in the
traditional Ayurvedic system of medicine. The roots
of this plant have been regarded as alternative and
tonic, and are said to be useful in rheumatism and
diseases of the nervous system. The ethanolic extract
of the root of A. speciosa was showed
immunomodulatory activity via DTH reaction, effect
on humoral immune responses and phagocytic
function of the cells. The extract caused increase in
DTH reaction and significantly enhanced the
production of circulating antibody titre. This indicates
the enhanced responsiveness of macrophages and T
and B lymphocytes involved in antibody synthesis21.
Baliospermum montanum (Willd.) Müll.Arg. (Euphorbiaceae)
Baliospermum montanum of family Euphorbiaceae
is a stout under shrub with herbaceous branches from
the roots. It is found in tropical and subtropical
Himalaya from Kashmir eastwards to Arunachal
Pradesh. The immunomodulatory activity of
B. montanum has not been reported scientifically. The
different concentration (25, 50, 100 µg/ml) of aqueous
extract of roots of B. montanum has been shown
immunomodulatory activity through neutrophil
phagocytic function such as neutrophil locomotion,
chemotaxis, immunostimulant activity of
phagocytosis of killed Candida albicans and
qualitative nitroblue tetrazolium test by using human
neutrophils22.
Bidens pilosa L. (Asteraceae)
Bidens pilosa is the largest flowering plant family
in the world and it is used as an ethnical medicine for
bacterial infection or immune modulation in Asia,
America and Africa. Aqueous infusion of B. pilosa
has an immunolodulatory effect by enhancing the
cytokine production and white blood cells population.
Hot water extracts from B. pilosa and its butanol
fraction increased IFN-γ promoter activity by 2 to 6
folds. From its butanol fraction the responsible
molecules, centaurein (4) (EC50 =75µg/ml) and its
aglycone (centaureidin) were isolated which showed
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR
augmentation of IFN-γ promoter activity. Centaurein
induced the activity of NFAT and NFκB enhancers,
located within the IFN-γ promoter23.
Boerhaavia diffusa L. (Nyctaginaceae)
It is a common plant grows widely in the tropics in
both dry and rainy seasons in India, Nigeria and many
other countries. Ethanolic extract of B. diffusa root
significantly inhibited the human NK cell cytotoxicity
in vitro, IL-2 and TNF-α in human PBMCs the cell
proliferation production of NO in mouse macrophage
cells. It is also observed that intracytoplasmic IFN-γ
and cell surface markers such as CD16, CD25, and
HLA-DR did not get affected on treatment with B.
diffusa extract24. Solvent fraction of B.diffusa root
extract was studied for its effect on cellular and
humoral functions in mice. Oral administration of the
fraction (25–100 mg/kg) significantly inhibited
SRBC-induced delayed hypersensitivity reactions in
mice. A significant dose-related increase in antibody
titre was observed during pre- and post-immunisation
treatment. Eupalitin-3-O-β-D-galactopyranoside (5)
isolated from ethanolic extract of B.diffusa which
inhibited PHA-stimulated proliferation of peripheral
blood mononuclear cells, two-way MLR and NK cell
cytotoxicity as well as LPS induced NO production
by RAW 264.7. The compound also inhibited
production of PHA stimulated IL-2 at the protein and
mRNA transcript levels and LPS stimulated TNF-α
production in human PBMCs; it also blocked the
activation of DNA binding of nuclear factor-KB and
AP-1, two major transcription factors centrally
involved in expression of the IL-2 and IL-2R gene,
which are necessary for T cell activation and
proliferation25.
Boswellia serrata Roxb. ex Colebr. (Burseraceae)
Boswellia serrata, or Salai, is one of Ayurveda’s
most potent anti-inflammatory herbs. On its own or in
combination with other herbs, Boswellia is used both
externally and internally to treat rheumatoid arthritis,
back pain, fibrositis and osteoarthritis. Clinical trials
and animal studies with B. serrata have confirmed its
antiinflammatory and pain-relieving effects.
Boswellic acid (6), is a pentacyclic triterpene acid
present in the extract of gum resin of B. serrata. It has
been reported that boswellic acid effect on cell
mediated and humoral immunity. In concentrations
greater than 3.9µg/ml of boswellic acids produced
almost similar and dose related inhibition of
proliferative responsiveness of splenocytes to
243
mitogens and alloantigen. Preincubation of
macrophages with different concentrations of
boswellic acid enhanced the phagocytic function of
adherent macrophages. Sharma et al. (1998) has
reported that boswellic acid has antianaphylactic
activity and stabilized the mast cell from
degranulation against compound 48/80. A significant
inhibition in the compound 48/80 induced
degranulation of mast cells in dose-dependant manner
(20, 40 and 80 mg/kg, p.o.) was observed26.
Calendula officinalis L. (Asteraceae)
Calendula officinalis is an important plant in
Indian medicinal systems which have diverse
medicinal uses including anti-viral, anti-genotoxic,
anti-inflammatory properties27. Numbers of
immunomodulatory effects have also been attributed
to this plant. 70% ethanolic extract of C. officinalis
showed mitogenic activity on human peripheral blood
lymphocytes and thymocytes. The extract also
possesses a proliferative responsiveness activity of
human lymphocytes and mixed lymphocyte reaction.
The laser activated C. officinalis extract showed a
potent in vitro inhibition of tumor cell proliferation on
a wide variety of human and murine tumor cell lines.
The inhibition ranged from 70 to 100%. Mechanisms
of inhibition were identified as cell cycle arrest in
G0/G1 phase and Caspase-3-induced apoptosis28.
Camellia sinensis (L.) Kuntze (Theaaceae)
Camellia sinensis (green tea) is being used as a
traditional medicine in Vietnam and China for long
time for antitumor, antiviral and immunostimulative
properties. The extract of C. sinensis enhanced the
neopterin production in unstimulated peripheral
mononuclear cells, but an effective reduction of
neopterin formation in cells stimulated with
concanavalin A, phytohemagglutinin, or interferon-γ
was found. It was also reported that the extract of C.
sinensis in combination with low dose cyclosporine A
significantly prolongs graft survival as well as
increase the production of immunosuppressive
cytokine, IL-10. Further the extract decreases
cyclosporine A induced high TGF-β production,
which is implicated in cyclosporine A induced
nephrotoxicity. It was also reported that the extract
inhibited both nonspecific and antigen-specific
proliferation of T cells in vitro29.
Capparis zeylanica L. (Capparidaceae)
Capparis zeylanica commonly known as Indian
caper is a climbing shrub found throughout India and
244 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014
it has been used as a 'Rasayana' drug in the traditional
Ayurvedic system of medicine. The leaves of the
plant are extensively used as counter-irritant,
febrifuge, treatment in piles, etc. The
immunomodulatory activity of ethanolic and water
extracts of C. zeylanica leaves have been repoted by
Ghule et al. (2006) through several immunomologica
parameters including neutrophil adhesion test,
humoral response to sheep red blood cells, delayed-
type hypersensitivity reaction, phagocytic activity and
cyclophosphamide-induced myelosuppression. The
water extract of C. zeylanica leaves at 300 mg/kg, oral
dose evoke a significant increase in neutrophil
adhesion to nylon fibres. The ethanolic extract dose
dependenltly increased antibody titres in mice and
potentiated the delayed-type hypersensitivity reaction
induced by sheep red blood cells. The ethanolic
extract also prevented myelosuppression in mice
treated with cyclophosphamide drug30.
Carica papaya L. (Caricaceae)
Carica papaya has been traditionally used as
ethnomedicine for a number of disorders, including
cancer. Various parts including leaves, fruit, seeds,
etc. are being used to treat many diseases. Recently C.
papaya seed extract is currently being marketed as a
nutritional supplement with purported ability to
rejuvenate the body condition and to increase energy.
The product claims to improve immunity against
common infection and body functioning. The crude
seed extract and two other bioactive fractions
significantly enhanced the phytohemagglutinin
responsiveness of lymphocytes and significantly
inhibited the classical complement-mediated
hemolytic pathway. Otsuki et al. (2010) reported that
the aqueous extract of C. papaya leaves exhibits anti-
tumor activity with significant growth inhibition of
tumor cell lines. The production of IL-2 and IL-4 was
reduced following the addition of C. papaya leaves
extract, whereas that of IL-12p40, IL-12p70, IFN-γ
and sTNF-α was enhanced without growth inhibition.
The cytotoxicity of activated Peripheral blood
mononuclear cells (PBMC) against K562 was
enhanced by the addition of the extract31.
Centella asiatica (L.) Urb. (Umbelliferae)
Centella asiatica is commonly known as
‘mandukparni’. It grows mainly in wet areas in India,
upto an altitude of 650 m. The plant has several
medicinal uses, i.e. sedative, spasmolytic, anti-anxiety
and anti-stress action. It is also reported that C.
asiatica extract and its main constituent asiaticoside
(7) possesses immunomodulatory activity, acting by
increasing phagocytic index and total WBC count. In
human peripheral blood mononuclear cells (PBMCs),
Centella asiatica (water extract) significantly
increases proliferation and the production of IL-2 and
TNF-α In contrast, an ethanol extract of Centella
asiatica inhibited human PBMC mitogenesis and the
production of IL-2 and TNF-α32.
Chelidonium majus L. (Papaveraceae)
Chelidonium majus has multiple applications in
Korean traditional medicine because of its anti-
tumoral, cytotoxic, anti-inflammatory and anti-
microbial activities and has long been known to have
anti-inflammatory effects. C. majus has been
investigated for immunomodulatory potential and the
results proved that methanolic extract of the plant
having pronounced immunomodulatory effects. The
methanolic extract significantly suppressed the
progression of collagen-induced arthritis and inhibited
the production of TNF-α, IL-6 IFN-γ, B cells and γδ T
cells in spleen and lymph node. The erosion of
cartilage was vividly reduced in mouse knees after
treatment of the extract. It was also reported by the
author that the same extract increased proportion of
CD4+, CD25+ regulatory T cells in vivo. Te levels of
IgG and IgM rheumatoid arthritis factor were also
decreased with the extract33.
Chrysanthemum indicum L. (Compositae)
Chrysanthemum indicum has long been used in as a
traditional medicine in Korea, China, and Japan to
treat various immune-related diseases. Recently, it has
been reported that 70% ethanolic extract of C.
indicum inhibited skin inflammation in mice by
reducing topical edema. Administration of the ethanol
extract at 200 mg/kg (i.p.), is leading to substantial
reductions in skin thickness and tissue weight,
inflammatory cytokine production, neutrophil-
mediated myeloperoxidase activity, and various
histopathological indicators. In addition, the extract
was effective at reducing inflammatory damage
induced by chronic 12-O-tetradecanoyl-phorbol-13-
acetate (TPA) exposure34.
Cichorium intybus L. (Asteraceae)
Cichorium intybus has an extensive uses in folk
medicines in India for the treatment of liver disorders,
gallstones, and inflammation of the urinary tract, fever,
vomiting, diarrhea, and enlargement of the spleen. It
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR
has been investigated that 70% ethanol extract of the C.
intybus showed a complete inhibitory effect on the
proliferation of lymphocytes in the presence of
phytohaemaglutinin. Effects of the ethanol extract of C.
intybus on the immunotoxicity of ethanol were also
investigated in ICR strain mice. The results revealed
that the combination of C. intybus extract and ethanol
showed significant increases in the circulating
leukocytes and the relative weights of liver, spleen and
thymus, as compared with those in mice treated with
ethanol alone. In addition, the splenic plaque forming
cells and hemagglutination titers to sheep red blood
cells, and the secondary IgG antibody response to
bovine serum albumin were markedly enhanced by the
extract plus ethanol treatment compared to the
treatment of ethanol alone. The mice which received
the combination of C. intybus extract and ethanol, a
significant increase in delayed-type hypersensitivity
reaction, phagocytic activity, natural killer cell activity
and cell proliferation as well as IFN-γ secretion were
also observed35.
Citrus aurantiifolia (Christm.) Swingle (Rutaceae)
In vitro immunomodulatory effect of concentrated
juice of Citrus aurantifolia was investigated by
Gharagozloo and Ghaderi (2001) using the parameter
of production of specific polyclonal antibodies in
rabbits. The immunomodulatory effect of the extract
was tested in mitogen activated cultured mononuclear
cells. The culture results indicated that proliferation of
phytohemagglutinin activated mononuclear cells was
significantly inhibited by C. aurantifolia juice dose
dependently. At the dose of 500 µg/ml of the extract
could inhibit proliferation of staphylococcal protein A
activated mononuclear cells36.
Cryptolepis dubia (Burm.f.) M.R.Almeida. (Apocynaceae)
The ethanol extract of root of the plant Cryptolepis
dubia (Syn: C. buchanani) has been reported to
possesses immunomodulatory activity in mice and
rats. Oral administration of C. buchanani root extract
showed significant stimulation of the delayed type
hypersensitivity reaction and humoral antibody
production. The oral LD50 was found to be more than
3 gm/kg in both rats and mice37.
Curcuma longa L. (Zingiberaceae)
Curcuma longa, a perennial herb widely distributed
in India. The rhizome of C. longa has numerous
medicinl uses including analgesic, anti-inflammatory,
wound healing and immunomodulatory activities. The
chief constituent of C. longa is curcumin (8), which
245
palyed a major role for immunomodulatory activity.
Bone marrow cellularity, alpha-esterase positive cells
and macrophage phagocytic activity were enhanced by
Curcumin administration. Numerous evidences suggest
that curcumin can modulate both the proliferation and
the activation of T cells. It was reported that curcumin
inhibits the proliferation induced by PMA and anti-
CD28 antibody or that induced by PHA of T
lymphocytes isolated from healthy donors38. Yadav et
al. (2005) reported that curcumin can suppress the
phytohemagglutinin-induced proliferation of human
peripheral blood mononuclear cells and inhibit IL-2
expression and NF-κB39.
Desmodium gangeticum (L.) DC. (Fabaceae)
Desmodium gangeticum (L.) is a small shrub of
tropical regions that has been used as a bitter tonic,
febrifuge, digestive, anticatarrhal and antiemetic in
inflammatory conditions of the chest and other
organs. D. gangeticum has also been reported to
contain alkaloids, flavone and isoflavanoid
glycosides. Total alkaloids of this species showed
anticholinesterase, smooth muscle stimulant, CNS
stimulant and depressant responses. Mishra et al.
(2005) has been reported that aminoglucosyl
glycerolipid (9) of D. gangeticum possesses
immunomodulatory activities. This compound
exhibited in-vitro immunomodulatory activities, as it
enhanced nitric oxide (NO) production and provided
resistance against infection established in peritoneal
macrophages by the protozoan parasite Leishmania
donovani40.
Eclipta prostrata (L.) L. (Asteraceae)
The methanol extract of Eclipta prostrata (syn.
Eclipta alba) whole plant that contains 1.6% of
wedelolactone showed immunomodulating effect in
vivo. Administration of five doses (100 to 500 mg/kg
body wt) significantly increased phagocytic index,
antibody titer; F ratios of the phagocytic index and
WBC count. Heighest linearity patterns of the dose-
response relationship were found in case of
phagocytic index and lower in the case of antibody
titer. In-vivo study showed that the aqueous extract of
E. prostrata leaves significantly increased non-
specific immune response and lysozyme activity of
the humoral responses in Oreochromis mossambicus41
Phyllanthus emblica L. (Euphorbiaceae)
Phyllanthus emblica (syn. Emblica officinalis) or
‘Amla’ is a small or medium size tree found in all
246 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014
deciduous forests of India. Amla fruits are largely
used in Indian medicine. It is used as an acrid,
diuretic, refrigerant, laxative, diarrhea and
dysentery42. It is a popular ingredient of ‘Triphala’
and ‘Chyawanprash’. The anti-inflammatory response
of E. officinalis extract has been well established and
predicted mechanism for anti-inflammation is based
on its function to reduce lymphocyte proliferation and
histopathological severity of synovial hyperplasia43.
Evolvulus alsinoides (L.) L. (Convolvulaceae)
Evolvulus alsinoides is an important and very
popular plant in Ayurvedic system of medicine to
improve intelligence, memory and higher mental
fuctions. The immunomodulatory property of E.
alsinoides extract was investigated and the result
exposed that a remarkable reduction in inflammation
and edema was observed. The extract also induced
that nitric oxide synthase (NOS) significantly. At
cellular level immunosuppression occurred during the
early phase of the disease. There was mild synovial
hyperplasia and infiltration of few mononuclear cells
in the extract treated animals44.
Ficus benghalensis L. (Moraceae)
Ficus benghalensis has been used by ayurvedic
practitioners, in India to boost the immune system to
fight a number of diseases. Gabhe et al. (2006) was
investigate for immunomodulatory potential of
various extracts of F. Benghalensis. The successive
methanol and water extracts exhibited a significant
increase in the percentage phagocytic responses and
methanol extract was found to exhibit a dose related
increase in the hypersensitivity reaction, to the sheep
red blood cells antigen, at concentrations of 100 and
200 mg/kg. The methanol extract also significantly
increased the antibody titer value dose dependently45.
Glycyrrhiza glabra L. (Leguminosae)
The root extract of Glycyrrhiza glabra is used as a
medicine for various diseases including anti-
inflammatory as well as anti-allergy46. It was
investigated that crude polysaccharide fraction of the
shoot and hairy root of G. glabra induced nitric oxide
production by murine peritoneal macrophages in-
vitro. In addition, the polysaccharide of G. glabra
dose-dependently improved immune and antioxidant
enzyme activities in mice. Glycyrrhizin (10) and β-
glycyrrhetinic acid (11) are the major components of
G. glabra believed to have immunomodulatory
properties. β-glycyrrhetinic acid has a potent
inhibitory activity on the classical complement
pathway (IC50 = 35µM), but it has no inhibitory
activity towards the alternative pathway (IC50 >
2500µM) 47.
Hippophae rhamnoides L. (Elaeagnaceae)
Several reports have been made on
immunomodulation of Hippophae rhamnoides L.
(Seabuckthorn) using different types of
immunomodulatory models. Alcoholic extracts of
leaves and fruits of H. rhamnoides at 500 µg/ml
concentrations were found to inhibit chromium-
induced free radical production, apoptosis, DNA
fragmentation and restored the anti-oxidant status to
that of control cells. The extract of leaf of H.
rhamnoides also reported to possesses
immunomodulatory activity through cellular and
humoral immune response. Administration of leaf
extract at 100 mg/kg dose along with chromium (Cr)
significantly inhibited Cr-induced
immunosuppression. The extract significantly
inhibited Cr-induced reactive oxygen species
generation and maintained the cell size identical to
that of control cells. Cr treatment markedly inhibited
the mitochondrial transmembrane potential by larger
lymphocytes in particular, while the leaf extract
restored the same significantly. The leaf extract at
100µg/ml alone stimulated IL-2 and IFN-γ production
even in the absence of concanavalin A and also
inhibited Cr-induced decline in IL-2 and IFN-γ
production but it did not change IL-4 production. The
ethanolic extract and of H. rhamnoides fruit and its
flavones fraction have been reported to stimulate the
production of interleukin-6 and tumor necrosis factor-
alpha (TNF-α) in peripheral blood mononuclear cells
(PBMCs). The increased expressions of p-I κB, NF-
κB and p-p38 were observed with flavones fraction of
H. rhamnoides fruit extract in human PBMCs with
significantly suppressed expression of CD2548.
Hydrastis canadensis L. (Ranunculaceae)
Hydrastis canadensis (Goldenseal) is indigenous to
North America, and commonly used in conjunction
with echinacea for the treatment of colds and flu.
Sevaral reports have been published for its
immunomodulatory activity. Root extract of H.
canadensis showed antigen-specific in vivo
immunomodulatory potential on rats that were injected
with the novel antigen keyhole limpet hemocyanin.
Berberine (12) alkaloid is thought to be the potent
immunomodulator present in H. Canadensis. Berberine
suppressed experimental autoimmune tubulointerstitial
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR
nephritis in BALB/c mice at a daily dose of 10 mg/kg.
It causes a decrease in the number of CD3 (+), CD4
(+), CD8 (+), and sIg (+) lymphocytes in comparison
with tubulointerstitial nephritis mice. The same
tendency was noticed in the lymphocytes from kidney
infiltrates of treated animals. Berberine at 50 mg/kg for
5 days significantly decreased the mortality rate and
attenuated tissue injury of the lungs and small intestine
in mice challenged with lipopolysaccaride (LPS). The
berberine also significantly reduced the plasma TNF-α,
IFN-γ and NO levels, but did not suppress plasma IL-
12 levels in mice exposed to LPS49.
Hypericum perforatum L. (Hypericaceae)
Hypericum perforatum (St. John's wort) is an ancient
folk remedy, has been used as antiviral, antibacterial,
anti-inflammatory, bruises, dysentery, jaundice,
diarrhea, antidepressant and a wide range of other
complaints. H. perforatum extract also reported to have
immunomodulatory effect on cytokine-induced
tryptophan degradation in human peripheral blood
mononuclear cells and in the production of the immune
activation marker neopterin. The lipophilic fraction of H.
perforatum exerted immunosuppressing properties with
respect to cellular and humoral immune response.
Hyperforin (13) is the active component of H.
perforatum which can stimulate IL-8 expression in
human intestinal epithelia cells and primary hepatocytes.
Hyperforin is also able to induce expression of mRNA,
encoding another major inflammatory mediator--
intercellular adhesion molecule-1. Hyperforin induced
IL-8 mRNA through a xenobiotic receptor -independent
transcriptional activation pathway50.
Jatropha curcas L. (Euphorbiaceae)
The immunomodulatory effect of an 80% methanol
extract of Jatropha curcas has been reported by Abd-
Alla et al. (2009). The extract showed stimulation of
both humoral and cell-mediated seroresponse through
increases of the antibody titers, lymphocyte and
macrophage cells. Bioactivity guided activation of the
extract was established to find out five componenets
viz. di-C-glucoside, 6,6"-di-C-β-D-glucopyranoside-
methylene-(8,8")-biapigenin (14), apigenin 7-O-β-D-
neohesperidoside (15), apigenin 7-O-β-D-galactoside
(16), orientin (17), vitexin (18). These compounds at
0.25 mg/kg dose showed immunostimulatory activity
as a similar mechanism to that of the extract51.
Mangifera indica L. (Anacardiaceae)
Mangifera indica is a medicinal plant traditionally
used in tropical regions. M. indica is being used from
247
many years to treat several disorders including
anemia, hypotension, rheumatism gingivitis, diarrhea,
dysentery, diabetes, asthma, infertility, lupus,
prostatitis, prostatic hyperplasia, gastric disorders etc.
Alcoholic extract of stem bark of Mangifera indica
was studied for immunomodulatory activity on both
the cell mediated as well as humoral immunity.
Administration of the extract produced increase in
humoral antibody (HA) titre and delayed type
hypersensitivity (DTH) in mice. From these studies it
can be shown that Mangifera indica has
immunostimulatory activity. Mangiferin (19) is one of
the most impotant molecules present in almost all
parts of the plant viz. leaves, fruits, roots etc and it
has been reported that mangiferine possesses
immunomodulatory activity by increasing the
production of IgG1 and IgG2b52.
Matricaria chamomilla L. (Asteraceae)
Heteropolysaccharides of Matricaria chamomilla
has been reported to have immunomodulatory
activity. The immunomodulating activity of the
heteropolysaccharides of M. chamomilla during air
and immersion cooling was investigated by Uteshev
et al. (1999). The polysaccharide was found to
normalizd the developed the immune response upon
air cooling and enhanced but do not normalized this
process upon immersion cooling. The
immunomodulating effect of the
heteropolysaccharides upon cooling is attributed to
initiation of immunostimulating properties of heavy
erythrocytes, activization of immunoregulation cells
of peripheral blood, and increased sensitivity of
effector cells to helper signals. The effect of M.
chamomilla and vaccination frequency on cattle
immunization against rabies was reported by de Souza
et al., (2008). There was no effect observed on
treatment with M. chamomilla on cattle immunization
against rabies; however, antibody titers were
protective in cattle vaccinated twice, while 93.3% of
cattle vaccinated only once had titers under 0.5 UI/ml
after 60 days. The M. chamomilla did not alter the
humoral immune response in cattle, and two vaccine
doses are suggested for achieving protective antibody
titers53.
Mollugo verticillata L. (Molluginaceae)
Mollugo verticillata is a weed plant common in
warm and/or wet regions of the American continent.
The ethanolic extract of M. verticillata showed
immunostimulatory activity in mice; when the
248 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014
peritoneal cells of mice were stimulated with Bacillus
Calmette Guérin (BCG). But when mice peritoneal
cells treated with the extract along with BCG showed
a drastic reduction in NO production. The extract of
M. verticillata directly increased NO release by
peritoneal cells, but suppressed the immune response
of these cells when treated with BCG antigen and
Mycobacterium tuberculosis. Further analysis of the
extract revealed that quercetin and triterpenoid
glycosides are the probably responsible components
for the effect of this plant material on the immune
system54.
Momordica charantia L. (Cucurbitaceae)
Momordica charantia (bitter melon) is a very
popular plant in various systems of traditional
medicine for several uses including anti-diabetic,
anthelmintic, contraceptive, dysmenorrhea, eczema,
anti-malarial, anti-gout, jaundice, leucorrhea, piles,
pneumonia, psoriasis, cancer, immunomodulation,
etc. The immunomodulatory activity of various
components of bitter gourd, including peel, pulp, and
seed, was assessed by measuring different parameters
like IFN-γ, IL-4, etc. Two abortifacient proteins, α
and β momorcharin have been isolated from the seeds
of the M. charantia and it was found that non-
cytotoxic concentrations of these proteins
significantly inhibited the mitogenic responses of
mouse splenocytes to concanavalin A,
phytohaemagglutinin and lipopolysaccharide in a
dose-dependent manner. In addition, the alloantigen-
induced lymphoproliferation and the in vitro
generation of a primary cytotoxic lymphocyte
response were severely suppressed in the presence of
these proteins. Momorcharin is also able to decrease
the functional capacity of macrophages and delayed-
type hypersensitivity response as well as the humoral
antibody formation to sheep red blood cells55.
Morinda citrifolia L. (Rubiaceae)
Morinda citrifolia (Noni) has been used in folk
remedies by polynesians for over 2000 yrs, and is
reported to have a broad range of therapeutic effects,
including antibacterial, antiviral, antifungal,
antitumor, anthelmintic, analgesic, hypotensive, anti-
inflammatory, and immune enhancing effects. The
alcoholic extract of M. citrifolia fruit various
concentrations inhibited the production of tumor
necrosis factor-alpha, (TNF-α).The alcoholic extract
of M. citrifolia was found to contain a polysaccharide-
rich substance that inhibited tumor growth through
activation of the host immune system. The extract was
also capable of stimulating the release of several
mediators from murine effector cells, including TNF-
α, interleukin-1beta (IL-1β), IL-10, IL-12, interferon-
gamma (IFN-γ) and nitric oxide (NO) 56.
Nelumbo nucifera Gaertn. (Nymphaeceae)
Nelumbo nucifera is a very known aquatic medicinal
plant which has been used as a traditional medicine in
India, China, Korea, Japan etc. from ancient time57. All
most all parts of the plant have been reported for
various pharmacological properties including
hypoglycaemic, antidiarrhoeal, antimicrobial, diuretic,
antipyretic, psychopharmacological, anti-inflammatory,
anti-ischemic, antioxidant, hepatoprotective, etc. Very
recently, it has been reported that hydro-alcoholic
extract of N. nucifera rhizome and seed showed
immunomodulatory potentials through altering the
haematological parameters, enhanced phagocytosis,
potentiated delayed type hypersensitivity in mice. The
hydroalcoholic extract of seed and rhizome increased
the total and differential leukocyte count and dose-
dependently potentiatiated the DTH reaction in mice.
Furhter, in vitro study with both the extracts revealed
that they have capability to stabilize the mesenteric
mast ceels and erythrocytes membrane of Wister rats.
The extracts also decreased the LPS- induced metric
oxide production and expression of co-stimulatory
molecules like CD40, CD80 and CD8658, 59, 60.
Nerium oleander L. (Apocynaceae)
Nerium oleander is an ornamental plant and widely
cultivated in Mosul (Iraq). There are several records
are available of this plant that the plant can be used as
arodenticid, insecticide, for indigestion, fever,
leprosy, venereal diseases, etc. Al-Farwachi (2007)
has been reported that the aqueous extract of N.
oleander leaf exerts a prominent immunomodulatory
effect on the rabbit’s immune system. The inhibitory
and the stimulatory effect of the extract on the
production of haemagglutination antibodies in the
rabbits against SRBC have been observed with the
extract treated animals. At the doses of 25, 50 and 75
mg/kg, a dose dependent inhibition of
haemagglutination antibodies was observed from the
result. In addition, the extract also inhibits the delayed
type hypersensitivity reaction, phagocytic activity and
percentage of nitro-blue tetrazolium positive cells61.
Nigella sativa L. (Ranunculaceae)
The seeds and seed oil of Nigella sativa have been
employed for thousands of years in folk medicine
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR
throughout the world for the treatment and prevention
of a number of diseases and conditions that include
asthma, diarrhoea and dyslipidaemia, etc. The seed oil
has been reported to have effect on
immunomodulation. The oil showed significant
decrease in splenocytes and neutrophils counts, but a
rise in peripheral lymphocytes and monocytes in the
experimental animals. Further, active principle
components of seed oil of N. sativa was identified as
thymoquinone (20) which possesses potent anti-
inflammatory effects on several inflammation-based
models including experimental encephalomyelitis,
colitis, peritonitis, oedama, and arthritis through
suppression of the inflammatory mediators
prostaglandins and leukotriens. Thymoquinine
showed beneficial immunomodulatory properties
through augmenting the T cell- and natural killer cell-
mediated immune responses62.
Ocimum tenuiflorum L. (Labiatae)
Ocimum tenuiflorum (syn. O. sanctum) commonly
known as ‘Tulsi’ has been extensively used in
Ayurvedic system of medicine for various ailments
and has been shown to possess significant
adaptogenic/anti-stress properties. Different parts of
the plant are claimed to be effective in a number of
diseases. The fixed oil obtained from O. sanctum
seeds is reported to possess significant anti-
inflammatory, antipyretic, analgesic and antiarthritic
activities. A steam distilled extract of O. sanctum
leaves has been shown to enhance anti-sheep red
blood cells and IgE antibody titre. Alcoholic extract
of O. sanctum showed immunomodulatory activity in
both non-stressed as well as stressed animals. In non-
stressed animals it was found that O. sanctum seed oil
produced a significant increase in anti-SRBC
antibody titre and caused a significant inhibition of
antigen induced histamine release from the peritoneal
mast cells. The oil also produced a significant
reduction in foot pad thickness in mice and
percentage leucocyte migration inhibition. It also has
been repoted that hydroalcoholic extract of O.
sanctum leaf at 10 mg/kg/day produced
radioprotective activity in mice against 11Gy of Co-
60 γ- irradiation63.
Plantago species (Plantago major L. & P. asiatica L.
(Plantaginaceae)
A number of Plantago species especially Plantago
major and Plantago asiatica (Plantaginaceae)
have been used in the treatment of many ailments,
viz. inflammation, infection, cancer and
249
immunomodulation. The hot water extract of
P. asiatica possessed significant inhibitory effect on
the proliferation of lymphoma, carcinoma and on viral
infection. P. major and P asiatica both exhibited dual
effects of immunodulatory activity, enhancing
lymphocyte proliferation and secretion of IFN-γ at low
concentrations (< 50 µg/ml). These results indicated
that hot water extracts of P. major and P. asiatica
possess a broad-spectrum of antileukemia,
anticarcinoma and antiviral activities, as well as
activities which modulate cell-mediated immunity.
Further several pure phytomolecules have been isolated
from extract of P. major, i.e. aucubin (21), chlorgenic
acid (22), ferulic acid (23), p-coumaric acid (24),
vanilic acid (25), luteolin (26), baicalein (27). All these
molecules are reported to possess a strong
immunomodulatory activity on human peripheral blood
mononuclear cells (PBMC) through lymphocyte
transformation and secretion of IFN-γ using enzyme-
linked immunosorbent assay (ELISA) 64.
Piper longum L. (Piperaceae)
Piper longum is an important medicinal plant, and
is used in traditional medicine by many people in Asia
and Pacific islands especially in Indian medicine.
Piper longum is reported as good remedy for treating
gonorrhea, menstrual pain, tuberculosis, sleeping
problems, respiratory tract infections, chronic gut
related pain and arthritic conditions. Alcoholic extract
of the fruits of P. longum and its component piperine
(28) was studies for their immunomodulatory activity.
The report revealed that the extract as well as piperine
increase the total WBC count, bone marrow
cellularity. They also induce the number of α- esterase
positive cells, total antibody production, total number
of plaque forming cells. These effects may be due to
the combined action of humoral and cell-mediated
immune responses65.
Premna tomentosa Willd. (Verbanaceae)
Premna tomentosa is widely used traditional
medicinal plant. The leaves extract of this plant
reported to stimulate immune system in response to
Chromium (VI) induced immunosuppression in
splenic lymphocytes. The leaves extract at pre-treated
dose concentration of 500 µg/ml decreased
cytotoxicity and reactive oxygen species level
suppressed by Chromium treatment in lymphocyte
cells culture. Further treatment of extract restored the
antioxidant levels and lymphocyte proliferation
similar to control cells66.
250 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014
Prunella vulgaris L. (Lamiaceae)
Prunella vulgaris is medicinal plant used in the
traditional Chinese medicine for hundreds of years as
a variety of ailments. Phytochemicals of this plant
reported to modulate various immune factors like
histamine, TNF-α, IgG, IgG1, IgG2b, NO, LTB4,
IFN-γ, IL-2 and Src family protein kinase. Other
Prunella species, P. laciniata was also reported to
posse’s immunomodulating activity in vitro. The
aquoues extract of both species stimulated
T-lymphocytes proliferation and suppression of NO
production by LPS-stimulated macrophages67.
Psoralea corylifolia L. (Fabaceae)
P. corylifolia seed extract reported to shows
immune stimulating property in mice. Administration
of extract stimulates natural killer cell activity,
antibody-dependent cellular cytotoxicity, antibody-
forming cells and antibody complement-mediated
cytotoxicity during tumor development. Lee & Kim
(2008) was also reported that this plant extract
modulating Th1/Th2 cytokine balance via inhibiting
accumulation of eosinophils, upregulating the
expression of IFN-γ and downregulating the
expression of IL-4 in spleen cells culture medium68.
Punica granatum L. (Family: Punicaceae)
Punica granatum fruits powder reported to
stimulate cell-mediated immune response in rabbits.
Oral administration of aqueous suspension of P.
granatum fruits powder at a dose concentration of 100
mg/kg increased rabbit’s antibody titre against
typhoid-H antigen and inhibited the migration of
leucocytes69.
Rhinacanthus nasutus (L.) Kurz (Acanthaceae)
It was demonstated that Rhinacanthus nasutus
extract has immunomodulating property. Punturee et
al. (2005) reported that the aquous and ethanol extract
of R. nasutus significantly increased PBMC
proliferation and the production of IL-2 and TNF-α in
vitro. Whereas in vivo study revealed that the ethanol
extract significantly increased the secondary antibody
response in BALB/c mice. These results demonstared
that the R. nasutus extract has immunomodulating
activity with regards to non-specific cellular and
humoral immunity32.
Salvia officinalis L. (Lamiaceae)
Aerial parts of Salvia officinalis reported to rich
mainly with polysaccharides including
arabinogalactans, pectin and glucuronoxylan-related
polymers. The active fractions of these compounds
showed immunomodulatory effects in the in vitro
comitogenic thymocyte test. All the fractions
increased rat thymocyte proliferation in order to
glucuronoxylan-related polymers > pectin>
arabinogalactans fractions. The pectin and
arabinogalactans fractions also showed significant
comitogenic effect with SIcomit/SImit ratio 3-4
indicated that these fractions have potential adjuvant
properties70.
Tamarindus indica L. (Leguminosae)
The tamarind (Tamarindus indica) is indigenous to
Asian countries and widely cultivated in the American
continents. The fruit pulp extract of T. indica
traditionally used in spices, food components and
juices etc in all over world. The fruit of T. indica is
rich in polyphenols which have several potential uses
like anti-atherosclerotic, antioxidant and
immunomodulatory. A polysaccharide isolated from
T. indica which showed immunomodulatory activities
such as phagocytic enhancement, leukocyte migration
inhibition and inhibition of cell proliferation. It has
also been reported that hydro-alcoholic extract of fruit
of T. indica inhibited the neutrophil reactive oxygen
species generation, triggered by opsonized zymosan,
n-formyl-methionyl-leucyl-phenylalanine or phorbol
myristate acetate and assessed by luminol- and
lucigenin-enhanced chemiluminescence. The extract
showed more effective inhibition of the PMA-
stimulated neutrophil function the opsonized
zymosan. The extract also inhibited neutrophil
NADPH oxidase activity, degranulation and elastase
activity at concentrations higher than 200 µg/106 cells,
without being toxic to the cells71. Further it has also
been reported that the fruit pulp extract of T. indica
blocked the increase of complement activity caused
by the cholesterol-rich diet. The activity of 0.8 mg/ml
of the extract on the classical/lectin pathways
increased after 30 min of pre-incubation, while that of
the alternative pathway decreased after 15 min at
1 mg/ml concentration of the extract72.
Terminalia chebula Retz. (Combretaceae)
Terminalia chebula popularly known as
‘Myrobalan’ or ‘Haritaki’ is found mainly in the sub-
Himalayan tracks and in all deciduous forests of
India. Fruits are an important source of tannins. It is
mainly used as an astringent, laxative, stomachic and
tonic.it is an ingredient of ayurvedic preparation
‘Triphala’. The aqueous fruit extract of Terminalia
 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR
chebula has been investigated for its effect on cell-
mediated and humoral components of the immune
system in mice. Administration of Terminalia chebula
extract produced an increase in humoral antibody
(HA) titer and delayed-type hypersensitivity (DTH) in
mice. So it was concluded that the Terminalia chebula
extract is a promising drug with immunostimulant
properties73.
Tinospora cordifolia (Willd.) Miers (Menispermaceae)
Immunomodulatory and antitumor actions of
medicinal plant Tinospora cordifolia are mediated
through activation of tumor-associated macrophages.
Intraperitoneal administration of Tinospora cordifolia
extract in tumour-bearing mice not only augments the
basic function of macrophages such as phagocytosis
but also their antigen presenting ability and secretion
of IL-1, TNF-α and other cytokines. The aqueous
extract of T. cordifolia exhibited boosting of
phagocytic ability of macrophage in vitro at 5µg/ml.
At the dose of 10 mg/kg (in vivo) the aqueous and
ethanolic extracts of T. cordifolia significantly
increased the antibody production against SRBC in
animals when compared to control. The methanolic
extract of T. cordifolia stem extract showed to
increase the total WBC count, bone marrow
cellularity(18.16×106/femur) and α-esterase positive
cells (1423/4000 cells). The extract is also increased
humoral immune response, by increasing the plaque-
forming cells in the spleen and enhances macrophage
activation. T. cordifolia extract reduced solid tumour
growth and synergistically acted with
cyclophosphamide in reducing the animal tumours74.
Trigonella foenum-graecum L. (Fabaceae)
Trigonella foenum-graecum is a widely used
medicinal and dietary herb through out of the world.
Several biological potential of the plant has been
reported including hypo-glycaemic, anti-
inflammatory, anti-allergic, etc. The aqueous extract
of T. foenum has been evaluated for
immunomodulatory activity by Hafeez et al. (2003).
The result exposed that the extract at 50, 100 and 250
mg/kg doses significantly increased the relative organ
weight of thymus and liver. The cellularities of
thymus and bone marrow were also significantly
increased at the same doses of the extract. A
significant increase in the delayed type
hypersensitivity response was monitored at doses of
50 and 100 mg/kg of the extract. At the dose of 100
mg/kg the extract showed humoral immunity as
measured by plaque-forming cells. A significant
251
increase in phagocytic index, phagocytic capacity of
macrophages and lymphoproliferation assay was also
observed with the extract treated animals75.
Urtica dioica L. (Urticaceae)
Urtica dioica has been used as an adjuvant remedy
in the treatment of arthritis form long time in Germany.
The leaf and aerial parts of the plant extracts contains
active compounds that reduce TNF-α and other
inflammatory cytokines by inhibiting the genetic
transcription factor. The major compounds like
quercetin-3-O-rutinoside (29), kaempherol-3-O-
rutinoside (30) and isorhamnetin-3-O-glucoside (31)
were isolated from the methanolic extract of the aerial
parts of U. dioica and these components produced
immunomodulatory activities in vitro by chemotaxis
and intracellular killing activity (NBT reduction) tests.
All compounds were determined to have significant
chemotactic effects in 4, 8, 16 µg/ml doses. The results
supported that the extract as well as its fraction could
possibly be useful for treating patients suffering from
neutrophil function deficiency and chronic
granulomatous diseases76.
Withania somnifera (L.) Dunal (cultivated var.) (Solanaceae)
Withania somnifera, commonly known as Indian
ginseng, has been an important herb in the Ayurvedic
and indigenous medical systems for over 3000 yrs.
Different investigators have reported antiserotogenic,
adaptogenic, anticancer and anabolic activity, and
beneficial effects in the treatment of arthritis, geriatric
problems, and stress. Withania somnifera has been
revealed as immunostimulator and immunoregulator
in immune inflammation animal models. It has been
reported that administration of W. somnifera extract
reduced leucopenia induced by cyclophosphamide
(CP). This may be correlated as this extract could
reduce the CP-induced toxicity and its usefulness in
cancer therapy. There is an enhancement in the
circulating antibody titre and the number of plaque
forming cells in the spleen was observed after
administration of W. somnifera extract. It was also
found that Methanolic extract of W. somnifera
exhibited radioprotective effect in normal BALB/c
mice with increased bone marrow cellularity and
reduction in chromosomal damage caused by sub
lethal dose of gamma radiation. The level of IFN-γ,
IL-2, and granulocyte macrophage colony-stimulating
factor (GM-CSF) in normal BALB/c mice was found
to increase in mice by administration of W. somnifera
root extract. Withanolide (32) activated the murine
252 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014

Structures of some important phytoconstituents

 MUKHERJEE et al.: MEDICINAL PLANTS AS IMMUNOMODULATOR
macrophages, phagocytosis, and increased lysosomal
enzymatic activity secreted by the macrophages,
while also displaying anti-stress activity and positive
effects on learning and memory in rats.
Glycowithanolides and a mixture of sitoindosides IX
and X isolated from WS were evaluated for their
immunomodulatory and central nervous system
effects (antistress, memory, and learning) in Swiss
mice and Wistar strain albino rats77.
Discussion
The basic function of the immune system is to
protect the individual against infectious agents and
potential pathogens which puts the immune system in
a vital position between a healthy and diseased state
of a host. lmmunomodulators can be classified as
immunoadjuvants, immunostimulants and
immunosuppresants. lmmunoadjuvants are used to
increase the efficacy of vaccines and since specific
immunoadjuvants are used with specific vaccines,
therefore could be considered as specific
immunostimulants. lmmunostimulants by definition
are inherently non-specific in nature as they are
envisaged to enhances body's resistance against
infection. They can act through innate immune
response and through adaptive immune response.
Immunosuppressants could be used for control
pathological immune response and are active in
autoimmune diseases, immediate & delayed type of
hypersensitivity immune reactions and graft
rejection78. Naturally produced medicinal plant
products offer as an alternate immunomodulatory and
therapeutic agents so as to overcome some of these
hazards such as their non-availability in some
developing countries, risk of misuse leading to drug
resistance, environmental pollution and food residues
and subsequently may be sustainable and
environmentally acceptable. In clinical medicine, both
aspects of immunomodulation viz.
immunostimulation and immunosuppression are
equally important. In conventional chemotherapy
immunopotentiation is an ideal choice, when the host
defense mechanisms are to be activated under
conditions of impaired immune response79.
In this article 55 medicinal plants, reported for their
immunomodulatory activity have been reviewed.
Several commonly used plants used in therapy with
immunomodulatory activity included in this review
are Allium sativum, Aloe vera, Andrographis
paniculata, Azadirachta indica, Boerhaavia diffusa,
Boswellia serrata, Curcuma longa, Centella asiatica,
253
Carica papaya, Datura quercifolia, Emblica
officinalis, Hydrastis Canadensis, Hypericum
perforatum, Ocimum sanctum, Panax ginseng,
Plantago major, Plantago asiatica, Piper longum,
Tinospora cordifolia, Magnifera indica, Momordica
charantia, Withania somnifera etc. Thease plants
possess immunomodulatory effects through various
mechanisms including their effect concerned with
different cells like WBCs, macrophages, antigen
presenting cells, mast cells, natural killer cells etc and
co-stimulatory molecules in the body. The therapeutic
and phytochemical aspects of this review revealed
that the extracts of different plant species have
prospective immunomodulatory effects through
alteration of total and differential leukocyte count,
delayed type hypersensitivity reaction, phagocytosis,
mast cell protection, nitric oxide production,
expression of co-stimulatory molecules etc. In
addition, some extracts reduced the production of
nitric oxide and expressed the co-stimulatory
molecules (CD40, CD80 and CD86) significantly,
which supports their effectiveness as
immunomodulatory agents. The phytomolecules like
andrographolide, asiaticoside, curcumin, glycyrrhizin,
berberine, orientin, vitexin, mangiferin, piperine,
withanolide and others have also been highlighted.
Traditional significance of study to the society/researchers
The modulation of immune response through
concept of rasayana in ayurveda is popular, where
plants with rejuvenating activity have been described.
Several plants have been identified as rasayanas in the
Indian Ayurveda and other systems of medicine
possessing various immuno-pharmcological
properties such as immunostimulant,
immunoadjuvant, neurostimulant, antiageing,
antirheumatic, anticancer, adaptogenic, antistress, etc.
This traditional knowledge with its holistic and
systemetic approach supported by experimental
evidances can serve as an innovative and powerful
discovery engine for newer, safer and affordable
medicines. Immunomodulation using traditional
medicinal plants can provide an alternative to
conventional chemotherapy for a variety of diseases,
especially when host defence mechanism has to be
activated under the conditions of impaired immune
response or when a selective immunosuppression is
desired in situations like autoimmune disorders. The
concept of using rasayanas for health gets more
credibility, when we realized that herbal antioxidants
concurrently exhibit significant immunomodulatory
254 INDIAN J TRADITIONAL KNOWLEDGE, VOL. 13, NO. 2, APRIL 2014
activities. Thus this study represents perspective of
the medicinal plants effective as immunomodulatory
agents from natural resourses.
Conclusion
Major highlights of this review are on the
description about immunomodulators from plant
origin with phytochemical compounds and their
relevance mechanism of action. This may help to
recommend lead compounds from natural resources
for drug development and establishing their efficacy
from traditional resources. Several plants having
potential immunomodulatory property have been
discussed in this review, several other plants
possessing similar type of activities have also been
explored as natural immunomodulators. Thus, this
review will not only help the researcher to know
about natural immunostimulants but also will help to
exploit several traditional medicines for drug
discovery and development.
Acknowledgement
The authors are grateful to the Department of
Science and Technology for financial support through
India-Brazil-South Africa (IBSA) Trilateral
Cooperation Program File No. INT/IBSA/01-
04/2010(i); dated 18/05/2011), Government of India,
New Delhi.
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