<p>Diabetes is a long-lasting condition of glucose metabolism caused by abnormalities in insulin secretion and effectiveness. Type 2 diabetes with persistent hyperglycemia, managed with various hypoglycemic medications, has severe adverse effects and can harm vital organs. Anti-diabetic medication from Indian traditional medicinal plants has shown no such side effects. The current study aimed to explore and assess the antidiabetic potential of terpenoid phytocompounds from two types of <i>Gymnema sylvestre</i> extracts. The current study utilized various analytical methods to validate anti-diabetic phytocompounds from <i>Gymnema sylvestre</i>; further, it will be confirmed by studying its crucial interaction with diabetic target proteins. GCMS analysis of <i>Gymnema sylvestre</i> revealed compounds, most notably terpenoid compounds. In vitro anti-diabetic validation reveals that <i>Gymnema sylvestre</i> chloroform leaf extract possesses equipotent anti-diabetic potential (IC50 15.20 ± 0.92&#xa0;µg/ml and 12.20 ± 0.52&#xa0;µg/ml) when compared with the standard drug acarbose (IC50 11.20 ± 0.72&#xa0;µg/ml and 9.40 ± 0.42&#xa0;µg/ml) against alpha amylase and alpha glucosidase enzymes, respectively. Further in silico docking analysis of phytocompounds from <i>Gymnema sylvestre</i> against three diabetic target proteins (alpha amylase, aldose reductase, and alpha glucosidase) revealed that Gymnemic Acid I exhibits higher binding affinity with alpha amylase with a docking score of − 10.3&#xa0;kcal/mol than the standard drug acarbose (− 8.7&#xa0;kcal/mol). Top-scored terpenoid compounds from <i>Gymnema sylvestre were</i> screened for further ADMET and DFT analyses along with the standard drug acarbose, and their results revealed that terpenoid compounds showed good pharmacokinetic and DFT indices. Finally, four complexes, 1B2Y-gymnemic acids, 1B2Y-acarbose, 1US0-lupeol, and 1US0-acarbose, screened for MDS and MMGBSA analysis, revealed good number of hydrogen, hydrophobic, water bridges interaction and interaction fractions through their simulation trajectories of screened ligand with anti-hyperglycemic target proteins. The findings of this study reveal that terpenoid compounds from <i>Gymnema sylvestre</i> possess anti-diabetic potential and bring new improvements for alternative medicine in the treatment of diabetes.</p>

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Exploration and validation of anti-diabetic potential of terpenoid phytocompounds from Indian traditional medicinal plant Gymnema sylvestre

  • Nandu Baby,
  • Anu Mariam Kurian

摘要

Diabetes is a long-lasting condition of glucose metabolism caused by abnormalities in insulin secretion and effectiveness. Type 2 diabetes with persistent hyperglycemia, managed with various hypoglycemic medications, has severe adverse effects and can harm vital organs. Anti-diabetic medication from Indian traditional medicinal plants has shown no such side effects. The current study aimed to explore and assess the antidiabetic potential of terpenoid phytocompounds from two types of Gymnema sylvestre extracts. The current study utilized various analytical methods to validate anti-diabetic phytocompounds from Gymnema sylvestre; further, it will be confirmed by studying its crucial interaction with diabetic target proteins. GCMS analysis of Gymnema sylvestre revealed compounds, most notably terpenoid compounds. In vitro anti-diabetic validation reveals that Gymnema sylvestre chloroform leaf extract possesses equipotent anti-diabetic potential (IC50 15.20 ± 0.92 µg/ml and 12.20 ± 0.52 µg/ml) when compared with the standard drug acarbose (IC50 11.20 ± 0.72 µg/ml and 9.40 ± 0.42 µg/ml) against alpha amylase and alpha glucosidase enzymes, respectively. Further in silico docking analysis of phytocompounds from Gymnema sylvestre against three diabetic target proteins (alpha amylase, aldose reductase, and alpha glucosidase) revealed that Gymnemic Acid I exhibits higher binding affinity with alpha amylase with a docking score of − 10.3 kcal/mol than the standard drug acarbose (− 8.7 kcal/mol). Top-scored terpenoid compounds from Gymnema sylvestre were screened for further ADMET and DFT analyses along with the standard drug acarbose, and their results revealed that terpenoid compounds showed good pharmacokinetic and DFT indices. Finally, four complexes, 1B2Y-gymnemic acids, 1B2Y-acarbose, 1US0-lupeol, and 1US0-acarbose, screened for MDS and MMGBSA analysis, revealed good number of hydrogen, hydrophobic, water bridges interaction and interaction fractions through their simulation trajectories of screened ligand with anti-hyperglycemic target proteins. The findings of this study reveal that terpenoid compounds from Gymnema sylvestre possess anti-diabetic potential and bring new improvements for alternative medicine in the treatment of diabetes.