Benzyl trisulphide, extract from Petiveria alliacea, to suppress SLE manifestations

By: Andrea Carolina Vincenti PérezRISE Program

Introduction

What is SLE?

• Systemic lupus erythematosus is an autoimmune disease in which organs, cells and tissues are affected by tissue-binding autoantibodies and immune complexes.

• SLE is caused by interactions between susceptible genes and environmental factors, resulting in abnormal autoimmune responses.

Why the abnormal immune responses do occurs?

• Multiples susceptible genes• Environmental agents• Activation of T and B lymphocytes.

Autoantibodies in SLE

• Autoantibodies are directed against DNA/protein or RNA/protein.

• During apoptosis, these antigens migrate to cell surfaces, where they are enclosed in blebs, and membrane phospholipids change orientation so that antigenic portions are near the surface.

Prevalence

• 90% of patients are women of child-bearing years.

• Prevalence of SLE in United States is 15 to 50 per 100,000.

What is Benzyl trisulphide?

• Is an extract from Petiveria Alliacea, Anamu, is a small molecule which plays a role in immune system suppression.

• Benzyl trisulphide down regulates proinflamatory cytokines.

• Cause the elevation in the production of granulocytes and erythrocytes in mice.

Why Petiveria Alliacea for SLE?

1. The treatments options for SLE are very limited and almost all of them consists of chemotherapy and/or steroids.

2. Evidence shows that benzyl trisulphide, extracted from Petiveria alliacea may be a therapeutic option for SLE.

3. Benzyl trisulfide may block the overactive immune system in SLE by down regulating IL-1, IL-6,IL-8

Why Petiveria Alliacea for SLE?

4. Benzyl trisulphide may stop the overactive immune system.

Hypothesis

“Benzyl trisulphide will suppress SLE disease activity in NZB/ W F1 mice model.”

Methods and Materials

Materials

• 40 Female Mice: NZB/ W F1. These mice will be obtain from Jackson Laboratories.

• Anamu plants• Materials for benzyl trisulphide extraction. • Laboratory for sample analysis. • Distilled water

Methods

Methods

Extraction Methods

Soxhlet extraction Sonification Maceration

Methods

• 20 mice will be assign to control group and 20 to experimental group.

• Baseline labs in both groups. • Control group will received IV distilled water

daily.• Experimental group will receive benzyl

trisulphide (30 gm/kg x day) via IV.

Methods

• After 4 weeks of treatment blood sampling for ANA, anti dsDNA, C-3 and C-4, and U/A.

• Lab sampling will be done on weeks 0,4,8,12.• Mean antibody titers and labs will be

compared .

Expected Results

• I expect that if the benzyl sulfite is able to down regulate the inflammatory prostaglandins the group of mice treated with the experimental drug will show a decrease in disease activity, and as a result suppression of lupus activity.

Potential Pitfalls

• Calculating the adequate dose of extract to be use.

• IV benzyl trisulfiphide has not been used.• Recurrent blood sampling is a limitation

because it makes the study more expensive.• Intravenous injection of material to mice

might be technically difficult and use of a restraining device might be use

Future Work

• If the Benzyl trisulphide have a positive effect on the NZB/W F1 mice, I will proceed to conduct the same experiment but with a larger number of mice.

References:1. Raintree Nutrition , tropical plant database. www.rain-tree.com/anamu.htm2. De Andrade, De Melo, et al . Potential Behaviour and prooxidant effects of Petiveria

Alliacae L extract in adults rats. J Ethnopharmacol. 2012 Sep 28;143(2):604-10. doi: 10.1016/j.jep.2012.07.020. Epub 2012 Aug 7.http://www.ncbi.nlm.nih.gov/pubmed/22890225

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4. LAD Williams, H Rosner,HG levy, EN Baron. A Critical Review of Dibenzy Trisulphide Isolated form Petiveria Alliacea L. West Indian Med J 2007;56 (1):17-21.

5. D Perry,A Sang, Y Yin, et al. Review Article: Murine Models of Systemic Lupus Erythematosus. Journal of biomedicine and biotechnology, vol 2011, article ID 271694

6. Williams LAD,Rosner h, et al. Antiproliferation /cytotoxic action of dibenzyl trisulphite, a secondary metabolite Petiveria Alliacea. Jam J Sci Tech 2004;15-60

7. R Segal,M Dayan, et al. Methotrexate treatment in Murine Experimental SLE; clinical benefits associated with cytokine manipulation. Clin Exp Immunology

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