Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes
Type 2 diabetes mellitus and diabetic foot ulcers remain serious worldwide health problems. Caffeic acid is one of the natural products that has been experimentally proven to have diverse pharmacological properties. This study aimed to assess the inhibitory activity of caffeic acid and ethanolic ext...
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MDPI AG
2023-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/20/7182 |
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| author | Enade P. Istyastono Nunung Yuniarti Vivitri D. Prasasty Sudi Mungkasi Stephanus S. W. Waskitha Michael R. S. Yanuar Florentinus D. O. Riswanto |
| author_facet | Enade P. Istyastono Nunung Yuniarti Vivitri D. Prasasty Sudi Mungkasi Stephanus S. W. Waskitha Michael R. S. Yanuar Florentinus D. O. Riswanto |
| author_sort | Enade P. Istyastono |
| collection | DOAJ |
| description | Type 2 diabetes mellitus and diabetic foot ulcers remain serious worldwide health problems. Caffeic acid is one of the natural products that has been experimentally proven to have diverse pharmacological properties. This study aimed to assess the inhibitory activity of caffeic acid and ethanolic extract of spent coffee grounds targeting DPP-4 and MMP-9 enzymes and evaluate the molecular interactions through 50-ns molecular dynamics simulations. This study also introduced our new version of PyPLIF HIPPOS, PyPLIF HIPPOS 0.2.0, which allowed us to identify protein–ligand interaction fingerprints and interaction hotspots resulting from molecular dynamics simulations. Our findings revealed that caffeic acid inhibited the DPP-4 and MMP-9 activity with an IC<sub>50</sub> of 158.19 ± 11.30 µM and 88.99 ± 3.35 µM while ethanolic extract of spent coffee grounds exhibited an IC<sub>50</sub> of 227.87 ± 23.80 µg/100 µL and 81.24 ± 6.46 µg/100 µL, respectively. Molecular dynamics simulations showed that caffeic acid interacted in the plausible allosteric sites of DPP-4 and in the active site of MMP-9. PyPLIF HIPPOS 0.2.0 identified amino acid residues interacting more than 10% throughout the simulation, which were Lys463 and Trp62 in the plausible allosteric site of DPP-4 and His226 in the active site of MMP-9. |
| first_indexed | 2024-03-10T21:00:21Z |
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| id | doaj.art-1f263adadd4f496ab1758f2dce2c9bc6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T21:00:21Z |
| publishDate | 2023-10-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1f263adadd4f496ab1758f2dce2c9bc62023-11-19T17:33:56ZengMDPI AGMolecules1420-30492023-10-012820718210.3390/molecules28207182Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 EnzymesEnade P. Istyastono0Nunung Yuniarti1Vivitri D. Prasasty2Sudi Mungkasi3Stephanus S. W. Waskitha4Michael R. S. Yanuar5Florentinus D. O. Riswanto6Research Group of Computer-Aided Drug Design and Discovery of Bioactive Natural Products, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta 55282, IndonesiaDepartment of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaDepartment of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USADepartment of Mathematics, Faculty of Science and Technology, Sanata Dharma University, Yogyakarta 55282, IndonesiaResearch Group of Computer-Aided Drug Design and Discovery of Bioactive Natural Products, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta 55282, IndonesiaResearch Group of Computer-Aided Drug Design and Discovery of Bioactive Natural Products, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta 55282, IndonesiaResearch Group of Computer-Aided Drug Design and Discovery of Bioactive Natural Products, Faculty of Pharmacy, Sanata Dharma University, Yogyakarta 55282, IndonesiaType 2 diabetes mellitus and diabetic foot ulcers remain serious worldwide health problems. Caffeic acid is one of the natural products that has been experimentally proven to have diverse pharmacological properties. This study aimed to assess the inhibitory activity of caffeic acid and ethanolic extract of spent coffee grounds targeting DPP-4 and MMP-9 enzymes and evaluate the molecular interactions through 50-ns molecular dynamics simulations. This study also introduced our new version of PyPLIF HIPPOS, PyPLIF HIPPOS 0.2.0, which allowed us to identify protein–ligand interaction fingerprints and interaction hotspots resulting from molecular dynamics simulations. Our findings revealed that caffeic acid inhibited the DPP-4 and MMP-9 activity with an IC<sub>50</sub> of 158.19 ± 11.30 µM and 88.99 ± 3.35 µM while ethanolic extract of spent coffee grounds exhibited an IC<sub>50</sub> of 227.87 ± 23.80 µg/100 µL and 81.24 ± 6.46 µg/100 µL, respectively. Molecular dynamics simulations showed that caffeic acid interacted in the plausible allosteric sites of DPP-4 and in the active site of MMP-9. PyPLIF HIPPOS 0.2.0 identified amino acid residues interacting more than 10% throughout the simulation, which were Lys463 and Trp62 in the plausible allosteric site of DPP-4 and His226 in the active site of MMP-9.https://www.mdpi.com/1420-3049/28/20/7182type 2 diabetes mellitusdiabetic foot ulcerscaffeic acidmolecular dynamics simulationsPyPLIF HIPPOS 0.2.0 |
| spellingShingle | Enade P. Istyastono Nunung Yuniarti Vivitri D. Prasasty Sudi Mungkasi Stephanus S. W. Waskitha Michael R. S. Yanuar Florentinus D. O. Riswanto Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes Molecules type 2 diabetes mellitus diabetic foot ulcers caffeic acid molecular dynamics simulations PyPLIF HIPPOS 0.2.0 |
| title | Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes |
| title_full | Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes |
| title_fullStr | Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes |
| title_full_unstemmed | Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes |
| title_short | Caffeic Acid in Spent Coffee Grounds as a Dual Inhibitor for MMP-9 and DPP-4 Enzymes |
| title_sort | caffeic acid in spent coffee grounds as a dual inhibitor for mmp 9 and dpp 4 enzymes |
| topic | type 2 diabetes mellitus diabetic foot ulcers caffeic acid molecular dynamics simulations PyPLIF HIPPOS 0.2.0 |
| url | https://www.mdpi.com/1420-3049/28/20/7182 |
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