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Gene & Protein in Disease Effect of phytochemicals in diabetes

1. Introduction during ischemia insulin secretion , and transcriptional
[18]
activation of preproinsulin gene . Food-starved cells
[13]
Diabetes mellitus is a disorder of metabolism and is activate AMPK with sugar and the activated target
characterized by hyperglycemia in which impaired promotes glucose uptake by modulating insulin secretion
carbohydrate, fat, and protein metabolism takes place due and decreasing hepatic gluconeogenesis . Metformin
[1]
to insulin deficiency or insulin resistance [1,2] . The increased (N,N-dimethyl biguanide) is an oral antihyperglycemic
plasma glucose promotes glucotoxicity which leads to drug that stimulates AMPK [19,20] , despite having side effects
tissue injury, sclerosis of glomerular capillaries, retinopathy like late assimilation of hexoses (e.g., glucose), amino acids
and blindness, neuropathy and peripheral vascular (AA), and intestinal absorption of vitamin B12, abdominal
insufficiency, gangrene of limbs, and other pathological pain, vomiting, malnourishment, swelling, mild diarrhea,
changes and secondary complications in multiple organ and metallic taste, as well as tiredness .
[21]
systems such as hypertension, vascular complications, early
atherosclerosis, and heart attack [1-3] . The onset of diabetes Plants have a large number of biomolecules having a
cases is increasing and doubling every decade. The cases broad range of structure variation and medicative actions
have been magnified from 30 million to 463 million from with no or fewer side effects and toxicity in comparison to
1985 to 2019 and may become 578 million and 700 million synthetic drugs, and the ability to care for a wide variety of
by 2030 and 2045, respectively [3,4] . Diabetes is the second illnesses and infections [7,22,23] . Literature reported about 1200
most common disease in India, where approximately plants and their components having antihyperglycemic
1 million diabetic cases are found in Jharkhand . This properties [24-26] . Catharanthus roseus, formerly known as
[5]
disease is the ninth major cause of death worldwide, and the Vinca rosea, commonly known as Madagascar periwinkle
international expenses on diabetes and related health were and sadabahar in India, belongs to the Apocynaceae family
11% in 2013 , and about 12% (> $550 billion) in 2019 [6,7] . and has antitumor, antimicrobial, and antihyperglycemic
[3]
Diabetes mellitus is broadly categorized into two groups: effects due to the presence of a large number of secondary
Type I (5% of the diabetic population, genetic origin) and metabolites (eg; alkaloids, phenols, etc.). C. roseus alkaloids
Type II (95% of the diabetic population). The majority of can reduce blood glucose levels and glucotoxicity-induced
prevalent cases are related to Type II diabetes caused by secondary complications [27-34] . The pharmacodynamics of
environmental factors instead of genetic background [4,8] . C. roseus alkaloids at the molecular level is still unexplored.
Hence, this study aimed to address the AMPK1/2 targets
Adenosine monophosphate protein kinase (AMPK) and C. roseus alkaloids interaction concerning control
stimulation has a significant role in cellular energy through an in silico method. The exploration of the
homeostasis or metabolism. The target is present in appropriate structure of ligands and the mechanism of
several tissues including the liver, brain, cardiac muscle, action provided evidence of whether the compounds
and skeletal muscle [1,9] . AMPK is a member of the serine/ interact with the target and are able to reduce high blood
threonine protein kinase family and is turned on by the sugar levels better than metformin. Further wet lab and
stimuli that raise the cellular AMP: ATP ratio. AMPK is clinical validations (animal and human trials) will be
a heterotrimeric protein (αβγ). Its catalytic alpha subunit performed to examine the effectiveness and potency of
has two isoforms alpha-1 and alpha-2 which control individual C. roseus alkaloids in natural conditions against
the actions of several vital metabolic enzymes through Type II diabetes and other linked diseases.
phosphorylation [10,11] . Alpha-1 isoform of AMPK (AMPK1)
plays an important role in safeguarding cells from stresses 2. Methodology
that bring out ATP depletion by turning off ATP-consuming
biosynthetic pathways, regulating insulin release [12,13] , 2.1. Drug target selection
immune-suppression, differentiation of myeloid-derived With the help of the literature and human model criteria,
suppressor cells (MDSC) , prohibiting skeletal muscle AMPK (UniProt ID: Q13131, P54646) was chosen and
[14]
hypertrophy , regulation of mTOR signaling pathway, unloaded from UniProt . SWISS-MODEL servers were
[15]
[17]
and macrophage proliferation . Alpha-2 isoform of used for homology modeling of proteins .
[35]
[16]
AMPK (AMPK2) has a role in the invigilation of cellular
energy status, regulates insulin sensitivity, recycling of 2.2. Detection of physiochemical properties of the
insulin receptors, phosphorylation of metabolic enzymes, target protein
deactivates acetyl-CoA carboxylase (ACC) and beta- Online software ProtParam was used for target protein
hydroxyl beta-methylglutaryl-CoA reductase (HMGCR) sequence analysis and its physical and chemical parameters
[17]
enzymes , control the biosynthesis of fatty acid and determination . The self-optimized prediction method
[36]
cholesterol, sustain myocardial energy homeostasis (SOPMA) was used for the prediction of secondary structures
Volume 2 Issue 3 (2023) 2 https://doi.org/10.36922/gpd.0927