TY - JOUR
T1 - Assessment of the hypoglycemic and anti-hemostasis effects of Paederia foetida (L.) in controlling diabetes and thrombophilia combining in vivo and computational analysis
AU - Ferdous, Jannatul
AU - Rahman, Md Ekhtiar
AU - Sraboni, Farzana Sayed
AU - Dutta, Amit Kumar
AU - Rahman, Md Siddikur
AU - Ali, Md Roushan
AU - Sikdar, Biswanath
AU - Khan, Alam
AU - Hasan, Md Faruk
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/12
Y1 - 2023/12
N2 - Paederia foetida is valued for its folk medicinal properties. This research aimed to assess the acute toxicity, hypoglycemic and anti-hemostasis properties of the methanolic extract of P. foetida leaves (PFLE). Acute toxicity of PFLE was performed on a mice model. Hypoglycemic and anti-hemostasis properties of PFLE were investigated on normal and streptozotocin-induced mice models. Deep learning, molecular docking, density functional theory, and molecular simulation techniques were employed to understand the underlying mechanisms through in silico study. Oral administration of PFLE at a dosage of 300 µg/kg body weight (BW) showed no signs of toxicity. Treatment with PFLE (300 µg/kg/BW) for 14 days resulted in a hypoglycemic condition and a 30.47% increase in body weight. Additionally, PFLE mixed with blood exhibited a 44.6% anti-hemostasis effect. Deep learning predicted the inhibitory concentration (pIC50, nM) of Cleomiscosins against SGLT2 and FXa to be 7.478 and 6.017, respectively. Molecular docking analysis revealed strong binding interactions of Cleomiscosins with crucial residues of the target proteins, exhibiting binding energies of −8.2 kcal/mol and −7.1 kcal/mol, respectively. ADME/Tox predictions indicated favorable pharmacokinetic properties of Cleomiscosins, and DFT calculations of frontier molecular orbitals analyzed the stability and reactivity of these compounds. Molecular simulation dynamics, principal component analysis and MM-PBSA calculation demonstrated the stable, compact, and rigid nature of the protein-ligand complexes. The methanolic PFLE exhibited significant hypoglycemic and anti-hemostasis properties. Cleomiscosin may have inhibitory properties for the development of novel drugs to manage diabetes and thrombophilia in the near future.
AB - Paederia foetida is valued for its folk medicinal properties. This research aimed to assess the acute toxicity, hypoglycemic and anti-hemostasis properties of the methanolic extract of P. foetida leaves (PFLE). Acute toxicity of PFLE was performed on a mice model. Hypoglycemic and anti-hemostasis properties of PFLE were investigated on normal and streptozotocin-induced mice models. Deep learning, molecular docking, density functional theory, and molecular simulation techniques were employed to understand the underlying mechanisms through in silico study. Oral administration of PFLE at a dosage of 300 µg/kg body weight (BW) showed no signs of toxicity. Treatment with PFLE (300 µg/kg/BW) for 14 days resulted in a hypoglycemic condition and a 30.47% increase in body weight. Additionally, PFLE mixed with blood exhibited a 44.6% anti-hemostasis effect. Deep learning predicted the inhibitory concentration (pIC50, nM) of Cleomiscosins against SGLT2 and FXa to be 7.478 and 6.017, respectively. Molecular docking analysis revealed strong binding interactions of Cleomiscosins with crucial residues of the target proteins, exhibiting binding energies of −8.2 kcal/mol and −7.1 kcal/mol, respectively. ADME/Tox predictions indicated favorable pharmacokinetic properties of Cleomiscosins, and DFT calculations of frontier molecular orbitals analyzed the stability and reactivity of these compounds. Molecular simulation dynamics, principal component analysis and MM-PBSA calculation demonstrated the stable, compact, and rigid nature of the protein-ligand complexes. The methanolic PFLE exhibited significant hypoglycemic and anti-hemostasis properties. Cleomiscosin may have inhibitory properties for the development of novel drugs to manage diabetes and thrombophilia in the near future.
KW - Density-functional theory
KW - Hemostasis
KW - Hypoglycemia
KW - Molecular docking
KW - Molecular dynamics simulation
KW - Paederia foetida
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U2 - 10.1016/j.compbiolchem.2023.107954
DO - 10.1016/j.compbiolchem.2023.107954
M3 - Article
C2 - 37738820
AN - SCOPUS:85171451805
SN - 1476-9271
VL - 107
JO - Computational Biology and Chemistry
JF - Computational Biology and Chemistry
M1 - 107954
ER -