Authors :
Ramesh Bharadwaj MN; Mythreyi R; Dhanu AS; Poojith N Rajendran; Vinitha Sivasubramaniyan; Karthikeyan Muthusamy; Kanthesh M Basalingappa
Volume/Issue :
Volume 8 - 2023, Issue 9 - September
Google Scholar :
https://bit.ly/3TmGbDi
Scribd :
https://tinyurl.com/473bu77z
DOI :
https://doi.org/10.5281/zenodo.8357890
Abstract :
Background
Gymnema sylvestre, a member of the Asclepiadaceae
family and commonly known as Gurmar, thrives in the
tropical woodlands of southern and central India as well
as Sri Lanka. Celebrated for its manifold medicinal
attributes, Gymnema sylvestre leaves have earned
recognition for their roles as anti-diabetic,
hypolipidemic, stomachic, diuretic, refrigerant,
astringent, and tonic agents. The primary bioactive
components found in G. sylvestre are a complex array of
triterpenoid glycosides collectively referred to as
gymnemic acids, with gymnemagenin as the shared
aglycone. Refined gymnemic acids have demonstrated
their effectiveness in combating hyperglycaemia,
maintaining normal blood glucose levels, and reducing
hyperlipidemia in various in-vitro experiments. The
mechanism of action of gymnemic acids involves
stimulating the regeneration of pancreatic cells,
promoting insulin secretion, and inhibiting the
absorption of glucose. Gymnemic acid, a well-known
constituent sourced from Gymnema Sylvestre leaves,
plays an integral role in numerous polyherbal
formulations designed to manage Diabetes Mellitus. It is
important to note that gymnemagenin does not exist
independently but serves as a common aglycone within
gymnemic acids, attainable through processes involving
both acidic and basic hydrolysis. Accurate determination
of gymnemic acids poses a formidable challenge due to
their intricate composition, comprising closely related
compounds, and their scarcity as commercially available
reference substances. The ongoing research endeavor is
dedicated to devising and validating a rapid and
exquisitely sensitive methodology for precisely
quantifying this constituent.Method
Gymnemagenin, a bioactive compound, possesses
the unique capability of triggering the secretion of
insulin by the beta-cells of Langerhans within the human
body. This intriguing phenomenon has been
substantiated through meticulous in-silico analysis. We
retrieved the Dipeptidyl peptidases (1NU6) protein
structure from the Protein Data Bank website and
meticulously identified the active site residues of thisprotein based on an extensive review of the existing
scientific literature [1]. Furthermore, our investigation
led us to select gymnemagenin as the bioactive
compound, which we sourced from G. sylvestre via the
PubChem website. Following this, we meticulously
prepared the lead molecule for docking studies using the
powerful Open Babel software.
The extracted gymnemagenin product is evaluated
and formed into tablets in further study, and aimed to
study the G. sylvestre extracts in the pharmacy field
either treating the product with the cell lines or the
animal models.Results
The extracted phytochemicals have shown the
presence of several secondary metabolites obtained by
phytochemical screening Gymnema sylvestre leaves
shown positive results for tannins, saponin, terpenoids,
flavonoids. The interaction between the protein and
ligands were analysed using docking score. Therefore,
the protein-ligand complex was further subjected to
optimization by MD simulations using WebGRO from
simlabs, also MD simulation trajectories have also been
adopted as inputs for MMPBSA calculations of ligand
binding free energies and analysis of their binding
process.Conclusion
Utilizing gymnemagenin as a therapeutic approach
for diabetes mellitus presents an exciting opportunity to
enhance insulin production effectively. This potential
stems from its ability to modulate multiple signalling
transduction pathways that play pivotal roles in diabetes
management. The core objective of this study is to gauge
the effectiveness of phytochemicals in the treatment of
diabetes mellitus through rigorous in-silico analysis.
Furthermore, these bioactive compounds can be
subjected to in-depth examinations in both laboratory
and living systems to comprehensively assess their
collective impact.
Keywords :
In Silico, Molecular Docking, Molecular Dynamics, Diabetes Mellitus.
Background
Gymnema sylvestre, a member of the Asclepiadaceae
family and commonly known as Gurmar, thrives in the
tropical woodlands of southern and central India as well
as Sri Lanka. Celebrated for its manifold medicinal
attributes, Gymnema sylvestre leaves have earned
recognition for their roles as anti-diabetic,
hypolipidemic, stomachic, diuretic, refrigerant,
astringent, and tonic agents. The primary bioactive
components found in G. sylvestre are a complex array of
triterpenoid glycosides collectively referred to as
gymnemic acids, with gymnemagenin as the shared
aglycone. Refined gymnemic acids have demonstrated
their effectiveness in combating hyperglycaemia,
maintaining normal blood glucose levels, and reducing
hyperlipidemia in various in-vitro experiments. The
mechanism of action of gymnemic acids involves
stimulating the regeneration of pancreatic cells,
promoting insulin secretion, and inhibiting the
absorption of glucose. Gymnemic acid, a well-known
constituent sourced from Gymnema Sylvestre leaves,
plays an integral role in numerous polyherbal
formulations designed to manage Diabetes Mellitus. It is
important to note that gymnemagenin does not exist
independently but serves as a common aglycone within
gymnemic acids, attainable through processes involving
both acidic and basic hydrolysis. Accurate determination
of gymnemic acids poses a formidable challenge due to
their intricate composition, comprising closely related
compounds, and their scarcity as commercially available
reference substances. The ongoing research endeavor is
dedicated to devising and validating a rapid and
exquisitely sensitive methodology for precisely
quantifying this constituent.Method
Gymnemagenin, a bioactive compound, possesses
the unique capability of triggering the secretion of
insulin by the beta-cells of Langerhans within the human
body. This intriguing phenomenon has been
substantiated through meticulous in-silico analysis. We
retrieved the Dipeptidyl peptidases (1NU6) protein
structure from the Protein Data Bank website and
meticulously identified the active site residues of thisprotein based on an extensive review of the existing
scientific literature [1]. Furthermore, our investigation
led us to select gymnemagenin as the bioactive
compound, which we sourced from G. sylvestre via the
PubChem website. Following this, we meticulously
prepared the lead molecule for docking studies using the
powerful Open Babel software.
The extracted gymnemagenin product is evaluated
and formed into tablets in further study, and aimed to
study the G. sylvestre extracts in the pharmacy field
either treating the product with the cell lines or the
animal models.Results
The extracted phytochemicals have shown the
presence of several secondary metabolites obtained by
phytochemical screening Gymnema sylvestre leaves
shown positive results for tannins, saponin, terpenoids,
flavonoids. The interaction between the protein and
ligands were analysed using docking score. Therefore,
the protein-ligand complex was further subjected to
optimization by MD simulations using WebGRO from
simlabs, also MD simulation trajectories have also been
adopted as inputs for MMPBSA calculations of ligand
binding free energies and analysis of their binding
process.Conclusion
Utilizing gymnemagenin as a therapeutic approach
for diabetes mellitus presents an exciting opportunity to
enhance insulin production effectively. This potential
stems from its ability to modulate multiple signalling
transduction pathways that play pivotal roles in diabetes
management. The core objective of this study is to gauge
the effectiveness of phytochemicals in the treatment of
diabetes mellitus through rigorous in-silico analysis.
Furthermore, these bioactive compounds can be
subjected to in-depth examinations in both laboratory
and living systems to comprehensively assess their
collective impact.
Keywords :
In Silico, Molecular Docking, Molecular Dynamics, Diabetes Mellitus.
