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STUDIES ON SOME NATURAL COMPOUNDS FOR THEIR IMMUNOMODULATORY ACTIVITY

Mesaik, Muhammad Ahmed Hassan Osman (2003) STUDIES ON SOME NATURAL COMPOUNDS FOR THEIR IMMUNOMODULATORY ACTIVITY. PhD thesis, University of Karachi, Karachi.

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Abstract

Immune system is a remarkably sophisticated defense system within vertebrates, to protect them from invading agents and cancers. It is able to generate varieties of cells and molecules capable of recognizing and eliminating limitless varieties of foreign and undesirable agents. Modulation of the immune system denotes to any change in the immune response that can involve induction, expression, amplification or inhibition of any part or phase of the immune response. Stimulation of the immune response is desired for certain people such as immunocompromised patient. Whereas, suppression of the immune response is thought for others, such as transplant recipient, allergic and inflammatory diseased patients. Autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and juvenile diabetes are defects of our immune system. On the other hand, rejection of transplanted organ by immune system is undesirable. Immunosuppressive drugs are given to control autoimmune diseases and rejection of transplanted organs. The present work was initiated to screen a large number of compounds, isolated and characterized at H.E.J. Research institute of Chemistry, for their immunomodulating potentials. This present work describes immunomodulatory activity of 28 (natural and few synthetic) compounds using the following immunological and biochemical assays and methods: Chemiluminescence, Chemotaxis, Lymphocyte Transformation Assay, Cytokine production and MTT assay. Ten compounds were found potent immunosuppressive in chemiluminescence assay. Among them chrysosplenetin, methyl-gallate and cheiradone had a very low IC50. These compounds also found to affect chemotaxis in a similar way. Fourteen compounds were found to suppress T cell proliferation. Chrysosplenetin compound was the most potent even up to 1ug/ml. Four of the tested compounds {Sericic-acid (methyl-ester), Methyl-gallate, Coagulin H and Chrysosplenetin} were found suppressing Th-1 as well as Th-2 Cytokines production, including IL-2, IL-4 & IFN-y. Their activity was well comparable to prednisolone on cytokine production. Sericic-acid and methyl-gallate had strong suppressive activity on IL-4 production but not on IFN-y production. Four compounds {Lupeol, Bellericagenin-b, Xylopic acid derivative and B Sitosterol} were found to boost the humoral response in Swiss Albino mice to Bovine Serum Albumin, compared with Freund's Complete Adjuvant. Compounds found significantly active, but non-toxic in our systems could be used as immunosuppressive or anti-inflammatory agents. However, the exact mechanism and the nature of their immunomodulatory activity need to be further investigated, before recommending these compounds to the list of therapeutic agents.

Item Type:Thesis (PhD)
Uncontrolled Keywords:Immunomodulatory, Immune system, Immunocompromised, Autoimmune, Chemiluminescene, Chemotaxis, Lymphocyte Transformation Assay, Cytokine production, MTT assay, Chrysosplenetin, methyl-gallate, Cheiradone, Chrysosplenetin, Sericic-acid (methyl-ester), Methyl-gallate, Coagulin H, Chrysosplenetin, Lupeol, Bellericagenin-b, Xylopic acid, B Sitosterol
Subjects:Biological & Medical Sciences (c) > Biological Sciences(c1) > Biology (c13)
ID Code:566
Deposited By:Mr. Muhammad Asif
Deposited On:18 Aug 2006
Last Modified:04 Oct 2007 21:01

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