Sumathi, A (2015) Study of immunomodulators from various plant species. Doctoral thesis, (Synopsis) The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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Abstract
INTRODUCTION : An immune system is a system of biological structures and processes within an organism that protects against invading micro organisms by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. The immune mechanisms may vary from species to species. Unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. Jawed vertebrates, the Gnathostomes including humans, have even more sophisticated defence mechanisms which consists many types of proteins, cells, organs, and tissues that interact in an elaborate and dynamic network. Immune system is vulnerable to the free radical-induced oxidative stress. The cellular and humoral components of the immune system are particularly sensitive to increased levels of reactive oxygen species, which may cause premature immunosenescence. The immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy and transplant rejection and to stimulate protective responses against pathogens that largely elude the immune system. The modulation of immune response with the aid of various bioactives in order to alleviate certain diseases is an active area of interest. Immunomodulators are substances that have been shown to modify the immune systems response to a threat upon it. They modulate and potentiate the weapons of our immune system keeping them in a highly prepared state for any threat it may encounter. They increase the immune responsiveness of the body against pathogens by activating primarily the non-specific immune system. AIM : With the advancement of Science and Technology, the occurrence of diseases can be easily visualized by the health professionals. Our immune system detects a wide variety of agents, from viruses to parasitic worms, kills and disposes using various immune mechanisms. Disorders in the immune system can result in disease, including autoimmune diseases, inflammatory diseases and cancer. Although some studies have been successful, complete cure is still a major challenge. Herbal medicine has become an integral part of health care system, based on the combination of ayurvedic or traditional classics and ongoing scientific research. To address this challenge, certain medicinal plants with immunomodulant activity, will be selected and studied. The aim of this study was to validate the immunomodulant potential of two different plant species using in vitro experimental models and to provide scientific evidence to the ethnomedicinal use of the plant species. Finally, they were incorporated into a novel carrier called phytosome to promote its therapeutic action significantly. The principal goal was to conceptualize an ideal drug delivery system viz. phytosomes for the selected plant species using different types of phospholipids. The novel carriers loaded with bioactives not only deliver the drug(s) to specific organs within the body but also controls the delivery rate. Thus, using this novel drug delivery system, herbal drugs incorporated with phospholipids, it might be able to achieve constant and uniform concentration of the drug for longer period of time in the body. OBJECTIVES : To identify two different plant species which had been traditionally used to treat various ailments and extract the possible phytoconstituents using solvents of increasing polarity. • To perform systematic studies on the selected plants - Nymphaea nouchali (Nn) and Trichosanthes dioica (Td) for substantiating their therapeutic claims. • To investigate the immunomodulatory effects of different extracts of Nymphaea nouchali (Nn) and Trichosanthes dioica (Td) using in vitro assay methods. • To perform acute oral toxicity studies for the selected plant extracts of Nymphaea nouchali (Nn) and Trichosanthes dioica (Td) and thereby to identify the maximum tolerated dose (MTD). • To identify the selected plant extracts by spectroscopic methods (UV and IR). • To design and fabricate a novel drug delivery system using phytosomes, for effective delivery of herbal constituents. • To optimize the ratio of drug and phospholipids having an ideal spherical shape and an effective average particle size range. • To identify the best formulation which maintains steady state plasma drug concentration for prolonged period of time. • To summarize and finalize the obtained results by comparing with a standard using in vivo animal models for immunomodulant activity. MATERIALS AND METHODS : The selected plant species Nymphaea nauchali (Nn) and Trichosanthes dioica (Td) were extracted using soxhlet apparatus by successive solvent extraction technique. Five different solvents of increasing polarity (n-Hexane, Chloroform, Ethyl acetate, Methanol and Distilled water) were used for the extraction process. All the extracts were subjected to preliminary phytochemical investigations and in vitro immunomodulatory studies such as Nitroblue tetrazolium (NBT) assay and cellular lysosomal enzyme activity. Then the selected plant extracts were identified by means of UV-Visible and Infra Red spectroscopic methods. Acute toxicity studies were performed according to Organization for Economic Cooperation and Development (OECD) guidelines 425, received from CPCSEA, Ministry of Social Justice and Empowerment, Government of India30. Swiss albino mice weighing between 20-25 g in groups of six were used (n=6). The animals were fasted for 4 h with free access to water only. The both Nn and Td extracts were administered orally in doses of 2000 mg/kg to different groups of mice and observed for 14 days for mortality and physical/behavioural changes. The experiments were performed after the experimental protocols had been approved by the Institutional Animal Ethical Committee (183/SASTRA/IAEC/RPP). The phytosomes were prepared by combining the two methanolic extracts (Nn and Td) in an equimolar amount with various ratios of phospholipids using solvent evaporation technique31. The ratio of drug and phospholipid employed was 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10. Thereby four batches of formulations each containing six formulae, totally 24 formulations were made using four different types of phospholipids such as phosphatidic acid (PA), phosphatidyl choline (PC), phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS). Among the 24 phytosomal formulations, the one which produced better physicochemical characteristics, entrapment efficiency and sustained drug release for highest duration was selected for further in vivo studies. INFERENCE : From the preliminary phase of this research work, it was observed that alkaloids, flavonoids, proteins & free aminocids, saponins, tannins & phenolic compounds and terpenoids were the phytoconstituents present in the methanolic extract of Nymphaea nouchali and Trichosanthes dioica. These phytoconstituents might play an effective role to bring out electron-transferring system and intracellular killing in in vitro immunomodulatory assays which gives them an immuno modulation property. CONCLUSION : The methanolic extracts of two botanicals, Nymphaea nouchali and Trichosanthes dioica, were converted into phytosomes and evaluated for immunomodulatory activity. The therapeutic regimen of phytosomes containing both the plant extracts was able to produce significant synergistic immunostimulatory action. Phytosome formulations containing combined plant extracts have produced effective immunomodulant activity as compared to plain extracts and standard drug. These findings are very much promising that phytosome technology can be safely used to incorporate the phytoconstituents in various ratios using suitable phospholipids. The results of this research work provide a scientific evidence for the traditional use of Nymphaea nouchali and Trichosanthes dioica. Also the phytosome technology can offer an alternative therapy for the treatment of many ailments including AIDS, TB, etc and might be used in immunocompromised patients for boosting their immune system.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | synopsis, immunomodulators, plant species. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Subramani R |
| Date Deposited: | 20 Aug 2017 14:17 |
| Last Modified: | 24 Oct 2022 14:17 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/2751 |
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