Immunodmodulation: herbal perspective and investigations-A review

Immunomodulation had been in application in medical systems and the traditional Indian systems like Ayurveda. It has various applications in medicine for altering the defence of the body that is immunity. A lot of conditions that require immunomodulation are supported by drugs for immune suppression and immune stimulation. They are often called as immune suppressants and immune stimulants. There are other class of drugs, immune adjuvants. Synthetic drugs are notorious for causing side effects and the herbal alternatives had been investigated for the activity. So the herbs stand as the alternatives for the synthetic drugs in better treating the disease that concern the immune system. The inconsistency of the in-vivo response of the immunity, with the phytochemicals, is also a limiting step for their effective usage as immunomodulatory agents when it comes to practical application. Overall, herbs had been supplying the chemical constituents that can be used directly or in the purified form as immunomodulatory agents. This review is the segregation of the various methods available to perform the screening of the drugs and extracts for immunomodulatory activity. This paper also enlists various herbs used for immunomodulation and had been proven for the same recently from 2010 to date.

Immunomodulation, Herbal Drugs, Immune Suppression, Immune Stimulation ABSTRACT Immunomodulation had been in application in medical systems and the traditional Indian systems like Ayurveda. It has various applications in medicine for altering the defence of the body that is immunity. A lot of conditions that require immunomodulation are supported by drugs for immune suppression and immune stimulation. They are often called as immune suppressants and immune stimulants. There are other class of drugs, immune adjuvants. Synthetic drugs are notorious for causing side effects and the herbal alternatives had been investigated for the activity. So the herbs stand as the alternatives for the synthetic drugs in better treating the disease that concern the immune system. The inconsistency of the in-vivo response of the immunity, with the phytochemicals, is also a limiting step for their effective usage as immunomodulatory agents when it comes to practical application. Overall, herbs had been supplying the chemical constituents that can be used directly or in the puriied form as immunomodulatory agents. This review is the segregation of the various methods available to perform the screening of the drugs and extracts for immunomodulatory activity. This paper also enlists various herbs used for immunomodulation and had been proven for the same recently from 2010 to date.

INTRODUCTION
Immunity is a signi icant and lexible defence mechanism in the body that protects from pathogens and microorganisms. It prevents disease-causing organisms from attacking and depleting the body's normal functions. The body's immunity has an ability to synthesize a wide range of molecules that can recognize and eliminate any foreign organisms (Richard et al., 2003). Immunomodulation is not a new term that is evolved recently in medicine. It had been in practice from late 1800 till today. The use of vaccines was the general method to modulate immunity in human beings. The term immunomodulation reminds few scientists names like Louis Pasteur, Jonas Salk, Edward Jenner and Emil von Behring. Vaccines involve the process of invoking the body's natural immune system. Arti icially generated antigens or weakened or attenuated disease causing microorganisms are used to target and provoke the synthesis of antibodies against a speci ic antigen. This provocation induces the needed defence mechanism in the body and is a huge milestone in immunomodulation. Immunomodulation is de ined as alteration (increase/decrease) of the immune response of the body to antigens. Any enhancement or stimulation in the immunity is called as immunestimulation, and lowering of the immune response of the sensitivity is termed as immune-suppression. The core concept of the immunomodulation lies in alteration of immunity by any agent that causes disease or toxicity but at a varied dose and time.

Need for Immunomodulation
Immune suppression is usually applied in the following cases.
1. To suppress the transplant rejection after organ or tissue transplantation (Heart, Kidney, Liver, Skin etc.).
2. To limit the GVHD (Graft v/s Host Disease) after bone marrow transplantation.
3. To suppress elevated immunity in autoimmune disorders like Myasthenia gravis, SLE, RA and Psoriasis.
4. To suppress selectively the Rh of the hemolytic disease of the newborn babies.
Immune-stimulation is needed when the immune system of the host is inactive or impaired. This is a therapeutically needed in the conditions with infections, disease and prophylactically need in the period post-surgery to prevent opportunistic infections.

Screening of immunomodulatory activity
There are various methods by which a herbal extract or a drug can be screened for the immunomodulatory activity. In general, there are two classes of screening methods. They are in vivo and in vitro evaluation. Usually, in vivo evaluation employs Rats or any other higher animals for screening. There are different methods to estimate the activity in animals by measuring various body tissues analysis. The analyses were made by inducing the hypersensitivity or allergens into the animal body, followed by the drug administration and examined for the activity.
The following are the induction methods and estimation types of immunomodulation.

Transplantation
Induction of the allogenic transplant rejection and GVHD (Graft v/s Host Disease) determination.

Thyroidal induction
Experimental induction of autoimmune thyroiditis and hypersensitivity in the thyroid.

Arthritis estimation
Induction of adjuvant arthritis, induction of reversed passive arthritis, progressive arthritis induced by proteoglycans and arthritis induced by collagen type II.

Skin and nerves related
Cutaneous passive anaphylaxis method, MRL/IPR strain mice to test SLE and experimentally induced myasthenia gravis.

Hypersensitivities
Systemic induction of anaphylaxis, immediate hypersensitivity of Arthus type, induction of delayed hypersensitivity and Schultz-Dale reactions.

Other Systems
Induction of glomerulonephritis by anti basement membrane antibody, induction of autoimmune myocarditis by porcine cardiac myosin and myocarditis induced by coxsackievirus.
As there is raising concern for the testing and treatment of animals in the laboratories, the use of animals is slowly replaced by simulation software and in vitro procedures. The following parameters are evaluated when doing in vitro evaluation. They are, 1. In vitro Plaque Forming Colonies (PFC test).
2. Estimation of the histamine inhibition release that occurs in mast cells.
4. Estimation of the proliferation of lymphocytes that is induced by Mitogen.
5. Determination of the chemiluminescence in the macrophages.
6. Estimation of Inhibition of the proliferation of T cells.

Herbal investigations
There are synthetic drugs that have potent immuno modulatory activity but are not devoid of side effects. Few of them include Alopecia, Lung toxicity, Lymphoma, Nephrotoxicity, Hepatic ibrosis, Seizures, Hirsutism, etc. (Kremer et al., 1994). Immunomodulation has been adopted in the traditional systems of medicine like Ayurveda, in which the concept of rasayana has most prominence. Various plants have been studied as rasayana drugs in Ayurveda and other Indian systems of medicines. Immunomodulatory activity of various plants had been used for their immunoadjuvant activity, antirheumatic activity, antiageing property, anticancer and adaptogenic activity. This folklore and scienti ic activity in this ield had a holistic and innovative approach for the discovery of powerful lead molecules and affordable drugs. The medicinal plants and herbs are known to be safer and better alternatives. Phytomedicine gained its importance  (Nidaullah et al., 2010) 2 Aloe vera (Linn) Pyrogallol induced immunosuppression in rats (Nidaullah et al., 2010) 3 Angelica sinensis (Oliv.) Diels lipopolysaccharide (LPS) stimulated RAW264.7 cells macrophages model (Nidaullah et al., 2010) 4 Apocynum cannabinum L.
TPA induced ear edema in rats.

Piper longum Linn
In vitro model of Rabbit platelets and murine macrophage RAW264.7 cells (Nidaullah et al., 2010) Continued on next page Cells Proliferation and differentiation of osteoblastic MC3T3-E1 cell in vitro. (Liu et al., 2010) recently in this arena and this article is one of the attempts to review the immunomodulatory plants that have been investigated for activity after 2010.

CONCLUSIONS
Medicinal plants and natural drugs are used as potent sources of immunomodulation and contributors for the derivation of the leads responsible for the development of immunomodulatory agents. The drug discovery and isolation of those leads from the herbal origin are more speci ic in the chemotherapy. Apart from the advantages of the herbal medicines in view of their safety and potency, the limitations for the use of herbs concerning their variations in the quantity of chemical constituents had to be addressed. The inconsistency of the in vivo response with the phytochemicals is also a limiting step for their effective usage as immunomodulatory agents. Overall, herbs had been supplying the chemical constituents that can be used directly or in the puri ied form as immunomodulatory agents.