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Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 163  

Review Article 

Natural Immunomodulators: Promising Therapy for Disease Management 

Muskan Altaf Tamboli, Rutuja Ramdas Bhosale, Naziya Ashpak Tamboli 

From, Professor & Amp, Department of Pharmacology, Sahydri College of Pharmacy, Methwade, Maharashtra, India 

ABSTRACT 

The immune system comprises a complex group of processes that provide defense against diverse pathogens. These defenses can 

be divided into innate and adaptive immunity, in which specific immune components converge to limit infections. We reviewed 

currently available experimental and clinical evidence to prove the efficiency, safety, and feasibility of immunomodulation in-vitro 

and in-vivo. We also reviewed the advantages and limitations of the described techniques. Despite its limitations, 

immunomodulation is considered as the therapy itself or as an adjunct with promising results and developing potential. Many 

plants and some phytoconstituents responsible for immunomodulation have been explained. The study also discusses biological 

screening methods for various plant drugs that focus on revealing the mechanism involved in immunomodulation. Nutraceuticals 

are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to 

the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. 

Key words:  Immune system, Immunomodulation, Nutraceutical plants, Anti-inflammatory 

utraceuticals which have also been called medical 

foods, designer foods, phytochemicals, functional 

foods and nutritional supplements, include such 

everyday products as “bio” yoghurts and fortified breakfast 

cereals, as well as vitamins, herbal remedies, and even 

genetically modified foods and supplements. Nutraceuticals 

may be used to improve health, delay the aging process, 

prevent chronic diseases, increase life expectancy, or support 

the structure or function of the body [1]. Immunomodulation 

is an alteration of the immune system and interfering with its 

functions; if it results in an enhancement of immune 

reaction, it is named an immune stimulation which primarily 

implies stimulation of non-specific system, that is, 

granulocytes, macrophages, complement, certain T-

lymphocytes and different effector substances. 

Immunosuppression implies mainly to reduce resistance  

Access this article online 

Received – 08th Nov 2023 

Initial Review – 27th Nov 2023 

Accepted – 14th Dec 2023 
 

Quick Response Code 

against infections, and stress and may occur on account of 

environmental or chemotherapeutic factors. 

Immunostimulation and Immunosuppression both need to be 

tackled to regulate normal immunological functioning. 

Hence, both immunostimulating and immunosuppressing 

agents have their standing, and the search for better agents 

exerting these activities is becoming a field of major interest 

all over the world [2].  

Many immunomodulators in clinical use are cytotoxic 

drugs with significant adverse effects. To overcome toxicity 

and existing available cytotoxic drugs there is a need for new 

immunomodulatory medications. Traditional medicines are 

the oldest approach for treating and managing any illness 

without causing severe or minor adverse effects. Further, the 

search for chemicals of plant origin as fresh lead for the 

creation of potent and safe immunomodulators is receiving a 

lot of attention [3]. 

_________________________________________________ 

Correspondence to: Muskan Altaf Tamboli, Department of 

Pharmacology, Sahydri College of Pharmacy, Methwade, 

Maharashtra, India. Email: muskanatamboli17@gmail.com 

Tel.: +91 7387963031 

N 

mailto:muskanatamboli17@gmail.com


Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 164  

IMMUNITY 

The resistance offered by the host to the harmful effect of 

pathogenic microbial infection is called immunity [4]. 

Types of Immunity: Broadly speaking, immunity or body 

defense mechanism is divided into two types, each with 

humoral and cellular components [5]. 

Natural or innate immunity is non-specific and is 

considered the first line of defense without antigenic 

specificity. It has two major components: a) Humoral: 

comprised by complement. b) Cellular: consists of 

neutrophils, macrophages, and natural killer (NK) cells. 

Specific or adaptive immunity is specific and is 

characterized by antigenic specificity. It too has two main 

components: a) Humoral: consisting of antibodies formed 

by B cells. b) Cellular: mediated by T cells. 

The various components of both types of immunity are 

interdependent and interlinked for their function. The 

mechanisms of innate and adaptive immunity are 

demonstrated in (Figure 1) [6]. 

 

Figure 1 - Mechanism of Innate Immunity and Adaptive Immunity 

Structure of Immune System [5] 

Organs of Immune System: Although functioning as a 

system, the organs of the immune system are distributed at 

different places in the body. These are as under:  

a) Primary lymphoid organs: i) Thymus ii) Bone marrow  

b) Secondary lymphoid organs: i) Lymph nodes ii) Spleen 

iii) MALT (Mucosa-Associated Lymphoid Tissue) located in 

the respiratory tract and GIT. 

Cells of Immune System [5] 

The cells comprising the immune system are as follows:  

Lymphocytes: Lymphocyte is the master of the human 

immune system. Morphologically, lymphocytes appear as a 

homogeneous group but functionally two major lymphocyte 

populations, T and B lymphocytes are identified; while a 

third type, NK cells, comprises a small percentage of 

circulating lymphocytes having the distinct appearance of 

large granular lymphocytes [5]. 

Monocytes and Macrophage: The role of macrophages in 

inflammation consists of circulating monocytes, organ-

specific macrophages, and histiocytic. Circulating 

monocytes are immature macrophages and constitute about 

5% of peripheral leucocytes. They remain in circulation for 

about 3 days before they enter tissues to become 

macrophages. The macrophage subpopulations like the 

dendritic cells found in the lymphoid tissue and Langerhans 

cells seen in the epidermis, are characterized by the presence 

of dendritic cytoplasmic processes and are active in the 

immune system [5]. 

Mast cells and Basophil: Basophils are a type of circulating 

granulocytes (0-1%) while mast cells are their counterparts 

seen in tissues, especially in connective tissue around blood 



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 165  

vessels and in submucosal locations. Basophils and mast 

cells have IgE surface receptors; thus, on coming in contact 

with antigen binding to IgE (e.g. allergic reaction to 

parasites), these cells get activated and release granules i.e. 

degranulate. These granules contain substances such as 

histamine platelet-activating factor, heparin, and certain 

chemical mediators (e.g. prostaglandins, leukotrienes). Mast 

cells and basophils are thus involved in mediating inflamma-

tion in allergic reactions and have a role in wound healing [5]. 

Neutrophils: Polymorphonuclear neutrophils (PMNs) are 

normally the most numerous of the circulating leucocytes 

(40-75%). The cytoplasm of PMNs contains lysosomal 

granules of three types: primary (azurophilic), secondary, 

and tertiary. PMNs have similar functions to those of 

macrophages and are therefore appropriately referred to as 

‘macrophages’ owing to their role as the first line of defense 

against an invading foreign organism in the body. However, 

these cells have limitations in size and type of organisms to 

be engulfed e.g. while they are capable of acting against 

bacteria and small foreign Particulate material but not 

against viruses and large particles [5]. 

Eosinophils: Eosinophils are also circulating granulocytes 

(1-6%). These cells play a role in allergic reactions and 

intestinal helminthiasis. The granules of eosinophils contain 

lysosomal enzymes, peroxidases, and chemical mediators of 

inflammation (e.g. prostaglandins, leukotrienes). On coming 

in contact with IgE opsonized antigen (e.g. helminths), 

eosinophils degranulate and release the chemicals stored in 

granules and incite inflammation [5]. 

Diseases of Immunity 

The diseases of the immune system are broadly classified 

into the following four groups: 

Immunodeficiency Disorder: Failure or deficiency of the 

immune system, which normally plays a protective role 

against infections, manifests in the occurrence of repeated 

infections in an individual having immunodeficiency 

disease. Traditionally, immunodeficiency diseases are 

classified into two types:  

a. Primary immunodeficiencies: are usually the result of 

genetic or developmental abnormality of the immune 

system.  

b. Secondary immunodeficiencies: arise from acquired 

suppression of the immune system. Since the first 

description of primary immunodeficiency by Bruton in 1952, 

an increasing number of primary and secondary 

immunodeficiency syndromes have been added to the list, 

the latest addition being the acquired immunodeficiency 

syndrome (AIDS) in 1981 [5]. 

Hypersensitivity Reactions: Hypersensitivity is defined as 

an exaggerated or inappropriate state of normal immune 

response with the onset of adverse effects on the body. The 

lesions of hypersensitivity are a form of antigen-antibody 

reaction. These lesions are termed hypersensitivity reactions 

or immunologic tissue injury, of which 4 types I, II, III, and 

IV. Depending upon   the rapidity, duration, and type of the 

immune response, these 4 types of hypersensitivity reactions 

are grouped into immediate and delayed types [5].  

a. Immediate type in which on the administration of 

antigen, the reaction occurs immediately (within seconds to 

minutes). Immune response in this type is mediated largely 

by humoral antibodies (B cell-mediated). Immediate type of 

hypersensitivity reactions includes type I, II and III.  

b. Delayed type in which the reaction is slower in onset and 

develops within 24-48 hours and the effect is prolonged. It is 

mediated by the cellular response (T cell-mediated) and it 

includes Type IV reaction [5]. 

Mechanisms of Hypersensitivity Reaction: Humans live in 

an environment teeming with substances capable of 

producing immunologic responses. Contact with antigens 

leads not only to the induction of a protective immune 

response, but also to reaction that can be damaging to tissue 

Exogenous antigen occur in the dust, pollens, foods, drugs 

microbiologic agent, chemicals and many blood product 

used in clinical practice the immune responses that may 

result from such exogenous antigen take a variety of from 

ranging from annoying but trivial discomforts, such as 

itching of skin, to potentially fatal diseases, such as 

bronchial asthma. The various reactions produced are called 

hypersensitivity reactions, a tissue injury in the reaction may 

be caused by humoral or cell-mediated immune mechanisms.  

Injurious immune reactions may be evoked not only by 

exogenous environmental antigens, but also by endogenous 

environmental antigens, but also by endogenous tissue 

antigens. Some of these immune reactions are triggered by 

homologous antigens that differ among individuals with 

different genetic backgrounds. Transfusion reactions and 

graft rejection are examples of immunologic disorders 

evoked by homologous antigens. Another category of 

disorders, those incited by self -, or autologous, antigens, 



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 166  

constitutes the important group of autoimmune diseases 

(discussed later). These diseases arise because of the 

emergence of immune responses against self–antigens [6]. 

Table 1 - Comparative Features of 4 Types of Hypersensitivity Reactions [5] 

Feature Type I 

[Anaphylactic, atopic] 

Type II 

[Cytotoxic] 

Type III  

[Immune-complex, 

Arthus reaction] 

Type IV 

[Delayed 

hypersensitivity] 

Definition  Rapidly developing immune 

response in a previously 

sensitized person 

Reaction of humoral antibodies 

that attack cell surface antigen 

and cause cell lysis 

Result from deposition of 

antigen-antibody 

complexes on tissues 

Cell-mediated slow and 

prolonged response  

Peak action time  15-30 minutes  15-30 minutes Within 6 hours  After 24 hours  

Mediated by  IgE antibodies IgG or IgM antibodies IgG or IgM antibodies Cell-mediated 

Examples i. Systemic anaphylaxis. ii. 

Local anaphylaxis [hay fever, 

bronchial asthma, food 

allergy]. 

i. Cytotoxic antibodies to blood 

cells [autoimmune haemolytic 

anaemia, transfusion reactions]. 

ii. Cytotoxic antibodies to tissue 

components [Graves’ disease, 

myasthenia gravis].  

i. immune complex 

glomerulonephritis. ii. 

Goodpastures syndrome. 

iii. Collagen diseases 

[SLE, rheumataoid 

arthritis]. iv. PAN. v. 

Drug-induced vasculitis. 

i. Reaction against 

microbacterial antigen 

[tuberculin reaction, 

tuberculosis]. ii. Reaction 

against virus-infected 

cells. iii. Reaction against 

tumour cells. 

 

Autoimmune Diseases: Autoimmunity is a state in which 

the body’s immune system fails to distinguish between ‘self’ 

and ‘non-self’ and reacts by formation of auto-antibodies 

against one’s tissue antigens. In other words, there is a loss 

of tolerance to one’s tissues; autoimmunity is the opposite of 

immune tolerance [5]. Depending upon the type of 

autoantibody formation, autoimmune diseases are broadly 

classified into two groups:  

a. Organ-specific diseases: In these, the autoantibodies 

formed react specifically against an organ or target tissue 

component and cause its chronic inflammatory destruction. 

The tissues affected are endocrine glands (e.g. thyroid, 

pancreatic islets of Langerhans, and adrenal cortex), 

alimentary tract, blood cells, and various other tissues and 

organs.  

b. Organ non-specific (Systemic) diseases: These are 

diseases in which several auto-antibodies are formed that 

react with antigens in many tissues and thus cause systemic 

lesions e.g. various systemic collagen diseases [5]. 

Possible immune disorders: These are the disorders in 

which the immunologic mechanisms are suspected in their 

etiopathogenesis. A classic example of this group is 

amyloidosis. 

Immunomodulators 

Immunomodulators: are natural or synthetic components 

that regulate the immune system and induce innate and 

adaptive defense mechanisms. Immunomodulators are drugs 

or components that suppress the immune system 

(immunosuppressants) or stimulate the immune system 

(immunostimulants) [4]. 

Classification of Immunomodulators 

Immunostimulants: immunostimulants are substances that 

stimulate the immune response or enhance body resistance 

against various infections by increasing the basal level of 

immune responses. Immunostimulants are used for the 

treatment of autoimmune diseases, chronic infections, viral 

infection, and cancer-like diseases. 

There are two types of Immunostimulants 

a. Specific Immunostimulant: It provides antigenic 

specificity in immune response e.g. antigen, vaccines. 

b. Non-Specific Immunostimulants: It act irrespective of 

antigenic specificity to augments immune response of 

other antigen or stimulate components of the immune 

system without antigenic specificity e.g. Adjuvants. 

 

Figure 2 - Examples of Immunostimulants  



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 167  

Immunosuppression: Immunosuppression is a reduction of 

the activation or efficacy of the immune system. It is a 

phenomenon wherein the ability of an organism to form 

antibodies in response to an antigenic stimulus is reduced or 

suppressed. This suppression may be the result of a disease 

that targets the immune system, such as HIV infection or a 

consequence of pharmaceutical agents used to fight cancer. 

In some cases, immunosuppression may be deliberately 

induced. Induction may be required for therapeutic 

interventions of tissue or organ transplantation to reduce the 

risk of organ rejection. It is also used for treating graft-

versus-host disease after a bone marrow transplant or for 

treatment of auto-immune diseases such as systemic lupus 

erythematosus, rheumatoid arthritis, Sjogrens syndrome or 

Crohn’s disease [4]. 

Two types of immunosuppression 

1. Non-specific immunosuppression: This 

immunosuppression invariably takes places, particularly in 

the natural instances related to immune deficiency disorders, 

or may even be induced by the gradual depletion of 

lymphoid tissue or by the administration of 

immunosuppressive drugs. It has been observed adequately 

that undue radiation exposure gives rise to significant 

depletion of lymphocytes. 

2. Specific immunosuppression: - Specific 

immunosuppression is usually induced either by antigen or 

antibody. Azathiopurine and corticosteroid combination 

therapy is commonly used in tissue transplantation to inhibit 

cell-mediated immunity [CMI]. Cyclosporine is commonly 

used in immunosuppressive therapy. The monoclonal 

antibody [OKT3] is also used as an immunosuppressive 

agent after organ transplantation in humans [4]. 

Nutraceuticals: Nutraceuticals is defined as substances that 

can be considered food or its part which, in addition to their 

normal nutritional value provide health benefits including 

prevention of disease or promotion of health. The knowledge 

about the nutritive value of various food items and their 

basic chemical roles has increased [4]. 

Classification of Nutraceuticals 

1. Nutraceuticals from food source: Nutraceuticals are 

obtained from plants, animals and microbial resources and 

are restricted to them only. Linolenic acid is found in animal 

flesh and is also synthesized in plants. Choline and 

aphosphatidyl choline are available in plants, animals, and 

also in microbes. 

2. Nutraceuticals indicating their action of mechanism: 

Nutraceuticals indicate their pharmacological activities i.e. 

Anti-oxidants, Anti-inflammatory, Anti-cancer, Anti-

bacterial, and Bone Protectives. 

3. Nutraceuticals according to their chemical nature:  

The chemical nature of nutraceuticals is Phenolic 

compounds, Protein-based Isoprenoids, Carbohydrate 

derivatives, Fatty acids and structural lipids, microbial, 

minerals, etc. 

4. Nutraceuticals according to their higher contents in 

specific food items: The food substances used as 

nutraceuticals contain antioxidants, prebiotics, probiotics 

omega-3-fatty acids, certains phytochemicals and dietary 

fibers. Expect probiotics, all these components are present in 

fruits, vegetables and different types of foods. [4] 

Advantages of Nutraceuticals 

a. They are substances like food and not considered drugs 

so have fewer side effects. 

b. They are mainly used as preventive are prophylactic to 

improve medical conditions. 

c. They have natural ingredients and dietary supplements to 

balance diet discrepancies. 

d. They enhance overall health and well-being. 

e. They are available without prescription means accessible 

and affordable [9]. 

Disadvantages of Nutraceuticals 

a. Quality and Regulation Issues: As compared to 

pharmaceuticals, nutraceuticals are not regulated very 

strictly and directly. Some of the health claims made for 

nutraceuticals may not be scientifically validated. There 

is a lack of proper regulation for nutraceuticals. 

b. Bioavailability: Nutraceuticals may have poor 

bioavailability and data related to pharmacokinetics and 

pharmacodynamics may not be available in some cases. 

c. Placebo effect: The body has a mechanism to recover on 

its own. In such cases, consumers may not use 

nutraceuticals to treat ailments and have a placebo effect. 

d. Safety and Interactions: Rarely, nutraceuticals may 

have some side effects. As there is a lack of appropriate 

regulations, there may be possible side effects, 

interaction with other drugs, or maybe in effectiveness in 

treating disorders [9].    



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 168  

Table 2 - A brief description of Immunomodulators derived from Nutraceuticals  

Common Name  Botanical name (Family) Part used  Chemical constituents  Other Biological 

Activity  

 Ref. 

no. 

Tea Camellia sinensis L. 

(Theaceae) 

Leaves Epigallocatechin gallate, 

Quercetin, Gallic acid 

Anti-Oxidant    25 

Tulsi Ocimum sanctum 

L.(Labiateae) 

Entire 

plant 

Essential Oil such as 

eugenol,Cavacrol 

Immunomodulator     8 

(14.14) 

Ginger Zingiber officinale roscoe 

(Zingiberaceae) 

Dried 

Rhizome 

Camphene, Citral, Borneol, 

Cineolc 

Anti-Oxidant    9 

(4.39-

4.42) 

Garlic Allium sativum (Liliaceae) Bulbs Diallyl disulfide, Diallyl 

trisulfide, Zinc, Vit-A 

Anti-Oxidant 

Immunomodulator 

   9 

(4.45-

4.46) 

Turmeric  Curcuma  langa 

(Zingiberaceae) 

Rhizome Curcumin Hydrophobic  Anti-Oxidants Anti-

Inflammatory 

    9 

(7.6) 

Amla Emblica officinalis gaetan 

(Euphorbiaceae) 

Fruit Tannins, Punigluconin, 

pedunculagin 

Anti-Oxidant    9 

(4.50-

4.51) 

Pepper Piper nigrum 

(Piperaceae) 

Fruit Volatile Oil, Guineensine, 

Limonenecamphene, 

Eugenol 

Anti-Oxidant    9 

(5.21) 

Tomato Solanum lycopersicum 

(Solanaceae) 

Fruit Lycopen, Lipophilic Anti-Oxidant     9 

(6.15) 

Thyme Thymus vulgaris L. 

(Labiateae) 

Leaves Flavonoids, Caffeic acid, 

Labiatic acid 

Anti-Oxidant     8 

(14.66-

14.67) 

Spirulina Spirulina plantensis 

(Oscillatoriceae) 

Algae Proteinous nitrogen, lipid, 

Protein, Oleic 

Immunostimulant    8 

(18.9-

18.10) 

Echinacea Echinacea purpurea 

(Compositae) 

Leaf, 

flower 

Arabinogalactan Immunostimulant    8 

(8.5) 

Alfalfa Medicago sativa Linn. 

(Leguminosae) 

Herb Vit.K, Vit.C, Thiamin, 

Riboflavin 

Immunomodulator     9 

(4.34-

4.35) 

Chicory Cichorium intybus L. 

(Asteraceae) 

Root Sucrose, Cellulose, Protein, 

Volatile oil, Chicoric acid 

Anti-Oxidant, 

Immunomodulator 

   9 

(4.36-

4.39) 

Fenugreek 

(Methi) 

Trigonella 

foenumgraceum L 

(Fabaceae) 

Herb  Ascorbic acid, B Carotene, 

Fibers, Graicunins 

Immunomodulator    9 

(4.42-

4.44) 

Amra (mango) Mangifera indica Linn. 

(Anacardiaceae) 

Bark Tannin, Catechin, 

Mangiferin 

Anti- Oxidant    8 

(10.3) 

Ashoka Saraca indica Linn. 

(Leguminosae) 

Dried Stem 

Bark 

Tannin, Haematoxylin, 

Ketosterol, Saponin 

Immunostimulant    8 

(10.14-

10.16) 

Ginseng Panax ginseng 

(Araliaceae) 

Root Ginsenosides, Ginsenine, β-

sitosterol 

Anti-Oxidant, 

Immnomodulator 

   8 

(9.50-

9.52) 



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 169  

Ashvagandha Withania somnifera dunal 

(Solanceae) 

Root Withanolides, Withaferin-A, 

Amino acids 

Immunomodulator    9 

(4.56-

4.58) 

Ginkgo Biloba Ginkgo biloba L. 

(Ginkgoaceae) 

Leaves Quercitrin, Rutin, 

Kaempferol, Ginkgolide-A 

Anti-Oxidant   9 

(5.13-

5.14) 

Shatavari Aspargus racemosus wild 

(Liliaceae) 

Root Shathavarin I-IV, Quercetin, 

Rutin 

Anti-Oxidant    8 

(9.62-

9.63) 

Milk-Thistle Milk thistle silybum 

marrianum gaerth 

(Compositae) 

Seed Silymarin, Silybin, 

Silycrystin 

Anti-Oxidant     8 

(9.77-

9.78) 

Guduchi Tinospora cordifolia , 

Miers (Menispermaceae) 

Leave And 

Stem 

Tinosporine, Tinosporic 

acid, Berberine 

Immunostimulant    8 

(9.101-

9.103) 

Rice Bran Oil Oryza sativa (gramineae) Seed .Fatty acid, Palmitic Acid  Anti-Oxidant     8 

(11.33-

11.34) 

Teel (Sesame) Sesamum indicum Linn. 

(Pedaliaceae) 

Seed Mucilage, HCl, Fixed oil. Anti-Oxidant, Anti-

Inflammatory 

  7 

(220) 

Wormwood Artemisia annua Linn. 

(Compositea) 

Herb Artemisinin Immunosuppressive   10 

Beggar-tricks Bidens pilosa L. 

(Asteraceae) 

Flower, 

Leave 

Polyacetylenes Anti-inflammatory , 

Immunosuppressive 

11 

Japanese 

Summer Grape 

Fruit 

Citrus nastudaidai hayata  

(Rutaceae) 

Fruit Auraptene, Flavonoids Antioxidant 12 

Fig Marigold Carpobrotus edulis L. 

(Aizoaceae) 

Flower, 

Fruit 

Alkaloids Immunomodulator 13 

Cone flower Echinacea angustifolia 

(Asteraceae) 

Flower Polysaccharides Immunomodulator 14 

Bringraja Eclipta alba L. 

(Compositae) 

Leaves Triterpenoids, Glucoside Antioxidant 15 

Sahijan Moringa oleifera L. 

(Moringaceae) 

Leaves Vit.A, Carotenoids, 

Saponins 

Antioxidant 16 

Paarijaata Anti Nyctanthes arbortr tristis 

L. (Oleaceae) 

Leaf, seed  Iridoid glicoside Inflammatory, 

Antispasmodic 

17 

Kutki Picrorhiza 

scrophulariiflora benth 

(Scrophulariaceae) 

Root Iridoid glycoside, 

Amphicoside 

Antioxidant 18 

Roseroot Rhodiola imbricate gray 

(Crassulaceae) 

Rhizomes Phenolics Immunostimulating 

Property 

19 

Glasswort Salicornia herbacea 

(Chenopodiaceae) 

Herb Polysaccharides Immunomodulator 20 

White cedar Thuja occidentalis L. 

(Arborvitae) 

leaves Polysaccharide Immunomodulator 21 

Haussknechtia Haussknechtia elymatica 

(Apioideae) 

Herb Phenolics Immunomodulator 22 



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 170  

Cispanche Cistanche desertisola 

(Orobalachaceae) 

Herb Polysaccharide Immunomodulator 23 

Brahmi Centella asiatica Linn. 

(Umbelliferae) 

Herb Triterpenoids, Saponins Immunomodulator 24 

Dragon Head Dracocephalum kotschyi      

(Lamiaceae) 

Herb Essential oil Immunomodulator 25 

Bay leaves 

(Tejpata) 

Cinnomomum tamala 

(Lauraceae) 

Leaves Eucalyptol, Terpineol, 

Eugenol 

Immunosuppressant 27 

Cumin (jira) Cuminum cyminum L. 

(Apiaceae) 

Seeds Cymol, Cuminol Immunostimulant, 

Immunosuppressant 

28 

Tamarind ( 

Imali) 

Tamarindus indica L.  

(Leguminosae) 

fruits Compesterol, seven 

hydrocarbon, acetic acid, 

tartaric acid 

Antioxidant, 

Immunomodulator 

29, 30 

Black Cumin  Nigella sativa L. 

(Ranunculaceae) 

Seeds Thymoquinone, 

Dithymoquinone 

Immunomodulator 31 

Bitter Melon 

(karela) 

Momordica charantia L. 

(Cucurbitaceae) 

Fruits , 

Seeds 

Triterpene, proteid, steroid  Antioxidant, 

Immunostimunt 

32 

Key lime (lemon) Citrus aurantiifolia 

Swingle (Rutaceae) 

Fruits, 

Leaves 

Limonene, Linalool, 

Citronellal 

Antioxidant 33 

Red Spiderling Boerhaavia diffusa L. 

(Nyctaginaceae) 

Roots Boerhavia acid , 

Boeravinone, Palmitic acid  

Antioxidant 34 

Sea buckthorn Hippophae rhamnoides L. 

(Elaeagnaceae) 

Leaves, 

fruits 

Quercetin derivatives, 

Hydrocinnamic acid  

Antioxidant 35 

Physic nut  Jatropha curcas L. 

(Euphorbiaceae) 

Leaves Phenolic acid, Lignans, 

Coumarins 

Antioxidant, 

Immunomodulator 

36 

Sweet flag Acorus calamus L. 

(Araceae) 

Rhizome Asarone, Monoterpene, 

Acorenone 

Antioxidant, 

Immunosuppressive 

37 

 

Chemistry of plant-derived immunomodulators 

1. Glycosides: These organic compounds from plant and 

animal sources, upon enzymatic or acid hydrolysis, yield 

one or more sugar moieties. Chemically, they are the 

acetals or sugar ethers, formed by the interaction of the 

hydroxyl groups of the sugar and non-sugar moieties, 

with the loss of a water molecule. Numerous glycosides 

have been shown to exert the desired immunomodulatory 

action [38]. 

2. Flavonoids: Chemically, flavonoids have a fifteen-

carbon skeleton (C6-C3-C6) which consists of two 

phenyl rings connected by a three-carbon bridge. Several 

types of flavonoids exert immunomodulatory activities, 

including apigenin (3), oligomeric proanthocyanidins (4), 

isoflavonoids, flavones, and anthocyanidins. Such 

flavonoids are found in Terminalia Arjuna [38]. 

3. Coumarins: These glycosides are derivatives of benzo-

a-pyrone (5); the furanocoumarins (6) are formed by 

fusion of furan ring to a coumarin at either the 6 and 7 

position or the 7 and 8 position. These glycosides also 

exert immunomodulatory activities. These glycosides 

also exert immunomodulatory activites [39]. 

4. Alkaloids: These organic compounds are of natural or 

synthetic origin, basic in nature, containing one or more 

nitrogen atoms, normally heterocyclic, of limited 

distribution and have specific physiological actions on 

the human or animal body [39]. 

 

Figure 3 - Flavonoids showing immunomodulatory 

activity 



Tamboli et al.                                                                                                                       Natural Immunomodulators 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 171  

 

Figure 4 – Coumarin 

 

Figure 5 - Plant alkaloids with immunomodulatory 

activity 

Concept of Rasayana  

The word Rasayana, a combination of two words (rasa and 

ayana), refers to nutrition and its transportation throughout 

the body. Rasayana therapy enhances the qualities of rasa, 

enriching it with nutrients so one can attain longevity, 

improved memory and intelligence, freedom from disorder, 

youthfulness, excellence of hair, complexion and voice, 

optimum development of physique and sense organs, 

mastery over phonetics and brilliance. As a dedicated stream 

of medication for immune promotion, anti-degenerative and 

rejuvenating health care, the Rasayana therapy of Ayurveda 

is known to prevent the effects of ageing and improve the 

quality of life for healthy as well as diseased individuals. 

Rasayana is helpful to improve immunity and is normally 

advised during the degenerative phase of life, which starts 

from around 45 years in both male and female  

Pharmacology of immunomodulatory activities from 

putative medicinal plants 

Mechanism of action of the Rasayanas/ 

immunomodulators 

It has been reported that the “Rasayanas” are rejuvenators, 

and nutritional supplements and possess strong antioxidant 

activities. They also exert antagonistic action on oxidative 

stressors, giving rise to the formation of different free 

radicals. They are used mainly to combat the effects of 

aging, atherosclerosis, cancer, diabetes, rheumatoid arthritis, 

autoimmune disease and Parkinson’s disease. The Rasayana 

herbs seem to operate through immunostimulant, 

immunoadjuvant, and immunosuppressant activities or by 

affecting the effector arm of the immune response. [40] 

Modulation of the immune responses through the stimulatory 

or suppressive activity of a phyto-extract may help maintain 

a disease-free state in normal or unhealthy people. Agents 

that activate host defense mechanisms in the presence of an 

impaired immune response can provide supportive therapy to 

conventional chemotherapy. [41]  

A high degree of cell proliferation renders bone marrow 

a sensitive target, especially to various cytotoxic drugs. Bone 

marrow is the organ most affected during any 

immunosuppression therapy with this class of drugs. Loss of 

stem cells and the inability of the bone marrow to regenerate 

new blood cells results in thrombocytopenia and leucopenia. 

[42] Many studies have reported the identification of 

immunomodulatory compounds with pharmacological 

activity and limited toxicity. In this context, 

ethnopharmacology represents the most important way 

possible to uncover interesting and therapeutically helpful 

molecules. The phytochemical analysis of Rasayana plants 

has revealed a large number of compounds including tannic 

acid, flavonoids, tocopherol, curcumin, ascorbate, 

carotenoids, polyphenols, etc., which have been shown to 

have potent immunomodulatory properties. The herbal 

mixture preparations of Indian traditional medicine may 

stimulate immunomodulation due to the content of plants 

with immunomodulatory properties that probably act 

synergistically. This hypothesis along with the lack of 

toxicity can be important to understand their use in the past 

as well as currently. [43] 

CONCLUSION 

The immune system is a complex organ with highly 

specialized cells and even a circulatory separate from blood 

vessels. Immunodeficiencies occur when one or more of the 

components of the immune system are inactive. 

Immunomodulation is the ruling of immune responses by 

stimulating them to prevent transmittable diseases or by 

suppressing them in undesired circumstances. Many 

proteins, amino acids, and natural compounds have shown a 

significant ability to regulate immune responses, including 

interferon-γ (IFN-γ), steroids, and DMG. Several medicinal 



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Vol 2 | Issue 4 | Oct – Dec 2023                                                                                Indian J Pharm Drug Studies | 172  

plants exhibit not only immunomodulatory activity but also a 

wide range of antioxidant, anti-inflammatory, and other 

medicinal activities. New immunomodulatory plants are 

important for the discovery of drugs with fewer side effects, 

less costly, more potent, and effective treatments developed 

for immune and related diseases.  

ACKNOWLEDGEMENTS 

I would like to thank Dr. Tamboli N.A, Dr. Tamboli A.M 

Sir, for providing the necessary facilities during my entire 

work. I would also like to thank Principal Dr. M.S Patil Sir, 

for continuous support and encouragement.  

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How to cite this article: Muskan Altaf Tamboli, Rutuja 

Ramdas Bhosale, Naziya Ashpak Tamboli. Natural 

Immunomodulators: Promising Therapy for Disease 

Management. Indian J Pharm Drug Studies. 2023; 

2(4):163-173. 

Funding: None                Conflict of Interest: None Stated 

 


