Interaction of Cyperus rotundus Compounds and Curcumin with
Agents Involved in Auto Immune Beta-Cell Destruction: An In-Silico
Perspective
1.0 Introduction
Diabetes mellitus is broadly classified as Type 1 and Type 2. The Type 1 Diabetes
(T1D) mellitus appears to result from an insidious immunologic destruction of pancreatic beta
cells also known as Insulin Dependent 1 Diabetes mellitus. Type 2 is mostly due to insulin
resistance and associated factors, and is also termed as Non-Insulin Dependent 1 Diabetes
mellitus .T1D is usually a progressive autoimmune disease, as the beta cells are destroyed by
the body's own immune system. It is notknown as to how the cascade starts in the immune
system, but evidence suggests that both a genetic predisposition and environmental factors,
including a viral infection, are involved (Simon, H., 2010).
The cause for β cell destruction remained an enigma for years, but two discoveries in
the 1970s provided the basis for our current thinking about the disease (Gepts, 1965). First
was a strong linkage of Type 1 Diabetes to the highly polymorphic HLA class II immune
recognition molecules — DR and, later, DQ — located on chromosome 6. Extensive studies
have revealed a large number of high- and low-risk HLA alleles.The second discovery,
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providing direct evidence for autoimmunity, came by incubating sera from T1D patients with
frozen tissue sections of normal blood group (Notkins and Lernmark, 2001).
Certain immune events are important in this process that include destruction of beta
cells of the Islets of Langerhans by immune factors called cytokines which are produced by T
lymphocytes. Important cytokines involved in this process include Interleukin-1Beta, Tumour
Necrosis Factor-Alpha and Interferon-Gamma. Also, proteins like Glutamic Acid
Decarboxylase (GAD), insulin and Islet Cell Antigens contribute to the self-attack of the
body's own beta cells by serving as autoantigens.
Till date, there is no standardized cure or prevention for the autoimmune diabetes,
though various methods are being invented or discovered and are tried out.
Of late, the Bio-artificial pancreas, which is a cross section of bio-engineered tissue
with encapsulated islet cells delivering endocrinehormones in response to glucose is
designed.This enables the body to endogenously, in vivo, produce insulin in response to the
level of blood glucose. The idea behind this is to implant bioengineered tissue containing islet
cells, which would secrete the amounts of insulin, amylin and glucagon needed in response to
sensed glucose (Notkins and Lernmark, 2001).
The Islet cell regeneration approach, although appeared to be promising, theIslet
Neogenesis Associated Protein has had commercialization difficulties, and the actual
efficiency of this approach is yet to be established.
In the stem cells approach, islet cells are developed from the stem cells. Research in
this field is being done at several locations which include South Korea, Brazil, University of
North Carolina and many others.
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It is proposed that gene therapy, in which a viral vector is designed to deliberately
infect cells with DNA to carry on the viral production of insulin in response to the blood sugar
level, might eventually be also used to cure the cause of beta cell destruction, thereby curing
the new diabetes patient before the beta cell destruction is complete and irreversible.
Several groups of scientists are trying to cause the activation state of the immune
system to change from Th1 state (―attack‖ by killer T Cells) to Th2 state (development of new
antibodies). This constitutes the immunization approach, where biochemical mechanism is yet
to be found, that prevents the immune system from attacking beta cells, which may be used to
prevent the commencement of T1D.
1.1 Autoimmune Diabetes: Current Status of research and development for a cure
Gepts (1965), who studied medicine at the Université Libre de Bruxelles (ULB,
Brussels, Belgium) where he graduated as MD (in 1946) and specialized in pathology,
described the pathology of the endocrine pancreas in human diabetes and identified key
morphological differences between the types and stages of the disease. He is best known for
showing that insulitis, inflammatory infiltrates in and around pancreatic islets is characteristic
of recent-onset juvenile diabetes. There may be a partial overlap in etiology between T1D
(Type 1 Diabetes) and T2D (Type 2 Diabetes), which is masked by hyperglycemia in T2D
and autoimmune destruction of islets in T1D (Chaparro and Konigshofer, 2006). HLA
genotyping has become an important research tool for identifying subjects at risk of
developing T1D, because of the known role of HLA molecules in antigen presentation, the
HLA linkage and association supported the hypothesis that T1D has an autoimmune
component.
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Animal and clinical studies suggest that moderate immunosuppression in newly
diagnosed T1DM can prevent further loss of insulin production and can reduce insulin needs
(Voltarelliet al., 2007).This method of treatment has been chosen as the key background
support for the current research pursuit.
Herbal flavonoids are known to be potent antioxidants and thus prevent T1D in NOD
mice (Chaparro and Konigshofer, 2006). This research explores the effect of immune
modulators on the specific autoantigens and proteins that are involved in the pathway of the
destruction of the pancreatic beta cells. The interaction of curcumin from Turmeric(Curcuma
longa), belonging to the family, Zingiberaceae and other similar agents from Cyperus
rotundus), belonging to the family, Cyperaceaewith autoantigens and immune agents have
been studied using Docking experiments.
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