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Review Article
Year : 2020   |  Volume : 12   |  Issue : 2   |  Page : 44-49  

Exploring phytochemicals as novel immunomodulators

Mandeep Kaur, Jayshree Mahanty, Sudhir Kumar, Alok Sharma

Correspondence Address:Department of Pharmacognosy, ISF College of Pharmacy, Moga, Punjab, India

Source of Support: Nil, Conflict of Interest: None Declared


DOI: 10.4103/2231-4040.197331

Abstract  

Although synthetic and biological immunodrugs acting on single or, multiple targets have been used to treat immunity-related disorders and ailments, therapy is somehow irrational while treating the infection and presently most of immunostimulants and immunosuppressants in clinical use possess adverse side effects. There is a strong urge to use herbal medicines and natural products as multi-component agents in existing immunotherapy with a view to modulate the complex immune system in treating infection. Therapeutic efficacy of plant extracts has been suggested due to their wide array of immunomodulatory effects and influences on the immune system of the human body. Phytochemicals such as alkaloids, flavonoids, polysaccharides, lactones, diterpenoids, and glycosides have been reported to be responsible for the immunomodulating properties of medicinal plants. Thus, the search for natural products of plant origin as new leads for the development of potent and safe immunosuppressant and immunostimulant agents is gaining attention in today’s research and need. The present review will give an overview of secondary metabolites (alkaloids, polysaccharides, phenolics, terpenoids, flavonoids, saponins, and sterols) derived from natural origin exhibiting potent effects on cellular and humoral immune functions in preclinical investigations along with their clinical potential.

Keywords: Immunomodulators, phytochemicals, secondary metabolites, immunodrugs, medicinal plants

How to cite this article:
Kaur M, Mahanty J, Kumar S, Sharma A. Exploring phytochemicals as novel immunomodulators. Pharmaspire 2020;12(2):44-49.

INTRODUCTION

The immune system safeguards the human body against various infectious diseases and also deals with a previous microbial infection, immunization, and various external stimuli which trigger immunity. Besides, this immune response is capable of discrimination among body’s own protein or cells and foreign entities whether a pathogen or antigen.[1] As soon as the foreign pathogen is identified, the collective and coordinated biological reaction of specific immune cells and mediators against unknown strange substances activates the defense mechanism and even produce cidal effect against a foreign substance, thereby producing the immune response. The immune system has been categorized based on the function, namely, innate immune system (non-specific immune system) and adaptive immune system (specific immune system).[2] Biologicals barriers or chemical agents are also sometimes involved in innate immunity; however, the main mediators of the immune system which deliver instant defense include cytokines, acute phase proteins, macrophages, monocytes, complement, and neutrophils.[3] Distinct moieties expressed by pathogens, specifically known as pathogen-associated molecular patterns (PAMPs), are recognized by the host to detect the presence of a pathogen.[4] The present review will describe phytochemicals utilized as immunomodulators exhibiting potent effects on cellular and humoral immune functions in pre-clinical and clinical investigations.

MECHANISM OF IMMUNOMODULATORS

Natural immunomodulators act through germline-encoded and evolutionarily conserved host sensors known as pattern recognition receptors (PRRs), which further recognize the PAMPs. Once the PRRs recognize the PAMPs, an array of immune responses is quickly triggered through induction of different type I interferons, chemokines, and cytokines.[5] Secondary metabolites also play a pivotal role in all phases of non-specific immunity including antigen-presenting cells and macrophages which are further engaged in antibody-dependent cell-mediated cytotoxicity, secretion of cytokines, nitric oxide production, antigen presentation, processing, and phagocytosis.[6] Dendritic cells are responsible for the activation of basic and memory B and T cells. Phytochemicals affect various phases of dendritic cells’ differentiation, the effectors of innate immunity including natural killer cells are regulated, which govern specific and natural immune responses by producing tumor necrosis factor-α, interferon-γ, and granulocyte–macrophage colony-stimulating factor.[7]

PHYTOCHEMICALS AS IMMUNOADJUVANTS

Plant-based immune adjuvants are used to enhance the efficacy of vaccines and therefore could be considered specific immune stimulants. Immunoadjuvants hold the promise of being the true modulators of the immune response.[8] It has been proposed that they may be exploited as selectors between cellular and humoral helper T1 (Th1) and helper T2 cells (Th2), immunoprotective, immunodestructive, and reagenic (immunoglobulin E [IgE]) versus IgG type immune responses are posing a real challenge to vaccine designers.[9]

PHYTOCHEMICALS AS IMMUNOSTIMULANTS

Plant-based immunostimulants are inherently non-specific as they are envisaged as enhancements to a body’s resistance to microbial infection. They can act through innate as well as adaptive immune responses or by potentiating immune response in healthy individuals.[10] The immunostimulants are expected to serve as prophylactic and promoter agents, thereby enhancing the basic level of host immune response. However, in individuals with impairment of immune response, they are expected to act as immunotherapeutic agents treating disorders caused by pathogens.[11]

PHYTOCHEMICALS AS IMMUNOSUPPRESSANTS

Phyto based immunosuppressant are structurally and functionally heterogeneous group of drugs [Figure 1], often concomitantly administered in combination regimens with conventional immunity boosters to treat various types of organ transplant rejection and autoimmune diseases.[12,13]

NATURAL IMMUNOMODULATORS

At present, majority of research and development still focuses on biochemicals, biologicals, or single compounds as leads that aim at particular targets linked with a disease. Countless single compound and chemical entity isolated from a natural source with marked selectivity, potency, and low toxicity for targeted molecular/cellular targets and diseases have been explored by researchers in the past decade.[14] Hence, the design and development of drug candidates from numerous conventional, complementary, and alternative medicines are gaining interest in the formulation and development of novel immunomodulators.[15] The prevention and treatment of disease using plant-based medicines have been reported in mankind history, saving human lives during the pandemic in the past. In all cultures and through all ages, different parts of a huge number of medicinal plant species were used in therapy while treating various ailments.[16] Vinblastine, vincristine, and their semi-synthetic derivatives isolated from the Madagascar periwinkle (Catharanthus roseus), capsaicin from chili peppers (Capsicum species), paclitaxel from Pacific yew (Taxus brevifolia), and galantamine from the Caucasian snowdrop (Galanthus caucasicus) are examples of medicines based plant compounds as natural immunomodulators.The plant-based compounds which were chemically altered are included as warfarin, artemether, topotecan and irinotecan, morphine (scores of derivatives), and acetylsalicylic acid.[17] Immunomodulatory characteristics of plantbased therapeutics have made them potential candidate for research community and innovative technologies and the extensive research on immunomodulatory herbal drugs, plants, their extracts, and active compounds with immunomodulatory potential, may provide the valuable entities to develop as the novel immunomodulatory product.[18] Phytochemicals including alkaloids, glycosides, steroids, terpenoids, phenolics, pigments, flavonoids, and alkaloids possessing immunomodulatory properties and claiming potential secondary metabolites for promising immunomodulatory agents are discussed in the present review [Table 1].

ALKALOIDS AS IMMUNOMODULATORY AGENTS

Alkaloids represent a large group of potent secondary metabolites exhibit marked physiological activity on innate immunity and adaptive immunity, regulating the immune system in humans and animals.[33] Plant-based alkaloids have been consumed as potent therapeutics and improve immune function, demonstrating possible immunomodulatory roles of alkaloids.[19,20]

POLYSACCHARIDES AS IMMUNOMODULATORY AGENTS

Polysaccharides exhibit numerous therapeutic benefits and being investigated for their immune-boosting activity, inducing modulation of macrophage function. Scientific validation of polysaccharides fraction had explored discovery zones of novel therapeutic agents as a beneficial immunomodulatory agent.[21]

FLAVONOIDS AS IMMUNOMODULATORY AGENTS

Water-soluble flavonoids, composed of C6-C3-C6 skeleton possessing chemoprotective property, have attracted the attention of researchers to explore potentially important dietary supplements for enhancing immunity in disorders caused by microbes.[22]

GLYCOSIDES AS IMMUNOMODULATORY AGENTS

These organic compounds from plant and animal sources, on enzymatic or acid hydrolysis, yield one, or more sugar moieties. A wide range of polar compounds consisting of at least one sugar molecule linked to another non-sugar moiety possesses immunomodulatory action. Moreover, another glycosides such as glycosides and anthraquinone glycosides sesquiterpene glycosides are also reported as immunomodulator.[23]

TERPENOIDS AS IMMUNOMODULATORY AGENTS

Optically active terpenoids having a high melting point are reported to possess anti-arthritic activity, and their therapeutic role appears to be mediated by modulating immunological processes. Terpenoids also reported to enhance antibody production and suppress T-cell response; therefore, it can be bioevaluated for immunomodulatory activity.[24]

TANNINS ASIMMUNOMODULATORYAGENTS

Water-soluble complex phenolic substances classified under tannins occur widely in vascular plants and angiosperms, induce marked physiological activities such as stimulation of phagocytic cells, hostmediated tumor activity, and a wide range of anti-infective action.[25]

SAPONINS AS IMMUNOMODULATORY AGENTS

Triterpenoids and steroidal saponins possess an antitumor effect on cancer cells and inhibit tumor growth by cell cycle arrest and apoptosis. Saponins, in combination with conventional tumor treatment strategies, can be evaluated for improved immune response and claim promising therapeutic success rate.[26]

PHENOLIC COMPOUNDS AS IMMUNOMODULATORY AGENTS

Water-soluble secondary metabolites possessing aromatic ring and bearing one or more hydroxyl substituents are considered potentially toxic to the pathogens and can be well explored for bioevaluating immunomodulatory activities.[27,28]

STEROLS AS IMMUNOMODULATORY AGENTS

Sterols and sterolins such as phytosterols and β-sitosterol enhanced in vitro proliferative response of T-cells possessing immunomodulatory activities.[29]


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CONCLUSION

The relationship between the beneficial effects of phytochemicals and diseases is required to research long-term multidisciplinary studies. People are searching for herbal drugs and want to benefit medicinal values and live healthily. For this reason, the herbal market is growing day by day. The present paper can support to validate the bioactive compounds as for immunomodulator. The research result can be recognized as a global patent, and it may increase the economy of the country after commercialization. A number of phytochemicals have been isolated with the potential immunomodulatory activity that can explain and justify their use in traditional medicine in the past and could be helpful in the future as well. The aim of this review was to highlight the results of research done on immunomodulators of classified phytochemicals. Many plants and some phytoconstituents responsible for immunomodulation have been explained. The review also discussed the pharmacodynamics of various plant drugs that focus on revealing the mechanism involved in immunomodulation. This work could encourage researchers to undertake further work on medicinal plants with potential immunomodulatory activity.

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