Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation
Abstract This study investigates the inhibitory potential of four glucosinolates—glucoerucin, glucoiberin, gluconasturtiin, and glucotropaeolin—isolated from watercress (Nasturtium officinale) against Protein Tyrosine Phosphatase 1B (PTP1B), a key regulator of insulin signaling. Molecular docking, m...
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2025-06-01
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| Online Access: | https://doi.org/10.1186/s13065-025-01544-9 |
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| author | Noha A. Ahmed Ahmed A. Allam Hassan A. Rudayni Fahad M. Alshabrmi Faris F. Aba Alkhayl Doaa A. Abdelrheem Al Mokhtar Lamsabhi Sarah I. Othman Emadeldin M. Kamel |
| author_facet | Noha A. Ahmed Ahmed A. Allam Hassan A. Rudayni Fahad M. Alshabrmi Faris F. Aba Alkhayl Doaa A. Abdelrheem Al Mokhtar Lamsabhi Sarah I. Othman Emadeldin M. Kamel |
| author_sort | Noha A. Ahmed |
| collection | DOAJ |
| description | Abstract This study investigates the inhibitory potential of four glucosinolates—glucoerucin, glucoiberin, gluconasturtiin, and glucotropaeolin—isolated from watercress (Nasturtium officinale) against Protein Tyrosine Phosphatase 1B (PTP1B), a key regulator of insulin signaling. Molecular docking, molecular dynamics (MD) simulations, and MM/PBSA free energy calculations identified glucoerucin (−17.18 ± 3.51 kcal/mol) and gluconasturtiin (−13.54 ± 1.79 kcal/mol) as the strongest binders, with stable interactions involving Phe280 and Phe196 through π-π stacking. Potential Energy Landscape (PEL) analysis further confirmed that these two compounds occupied the most stable low-energy conformational states, reinforcing their favorable binding to PTP1B. In vitro enzyme inhibition assays provided experimental validation that glucoerucin (IC₅₀ = 6.07 ± 0.69 µM) and gluconasturtiin (IC₅₀ = 7.65 ± 0.45 µM) demonstrated the strongest inhibitory effects, comparable to ursolic acid (IC₅₀ = 7.11 ± 0.95 µM). Enzyme kinetics revealed a non-competitive inhibition mechanism, with K i values of 6.29 µM and 7.02 µM, suggesting allosteric regulation. ADMET analysis indicated good solubility and metabolic stability but limited oral bioavailability due to low gastrointestinal (GI) absorption. These findings highlight glucoerucin and gluconasturtiin as promising natural PTP1B inhibitors, warranting further optimization for therapeutic applications in type 2 diabetes management |
| format | Article |
| id | doaj-art-44cec59eee864343b5e7b5a826631aec |
| institution | Kabale University |
| issn | 2661-801X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj-art-44cec59eee864343b5e7b5a826631aec2025-08-20T03:47:24ZengBMCBMC Chemistry2661-801X2025-06-0119112410.1186/s13065-025-01544-9Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulationNoha A. Ahmed0Ahmed A. Allam1Hassan A. Rudayni2Fahad M. Alshabrmi3Faris F. Aba Alkhayl4Doaa A. Abdelrheem5Al Mokhtar Lamsabhi6Sarah I. Othman7Emadeldin M. Kamel8Physiology Division, Zoology Department, Faculty of Science, Beni-Suef UniversityDepartment of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU)Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU)Department of Medical Laboratories, College of Applied Medical Sciences, Qassim UniversityDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim UniversityDepartment of Biology, College of Science, Princess Nourah bint Abdulrahman UniversityDepartamento de Química and Institute for Advanced Research in Chemical Science (IAdChem), Facultad de Ciencias, Módulo 13, Universidad Autónoma de MadridDepartment of Biology, College of Science, Princess Nourah bint Abdulrahman UniversityChemistry Department, Faculty of Science, Beni-Suef UniversityAbstract This study investigates the inhibitory potential of four glucosinolates—glucoerucin, glucoiberin, gluconasturtiin, and glucotropaeolin—isolated from watercress (Nasturtium officinale) against Protein Tyrosine Phosphatase 1B (PTP1B), a key regulator of insulin signaling. Molecular docking, molecular dynamics (MD) simulations, and MM/PBSA free energy calculations identified glucoerucin (−17.18 ± 3.51 kcal/mol) and gluconasturtiin (−13.54 ± 1.79 kcal/mol) as the strongest binders, with stable interactions involving Phe280 and Phe196 through π-π stacking. Potential Energy Landscape (PEL) analysis further confirmed that these two compounds occupied the most stable low-energy conformational states, reinforcing their favorable binding to PTP1B. In vitro enzyme inhibition assays provided experimental validation that glucoerucin (IC₅₀ = 6.07 ± 0.69 µM) and gluconasturtiin (IC₅₀ = 7.65 ± 0.45 µM) demonstrated the strongest inhibitory effects, comparable to ursolic acid (IC₅₀ = 7.11 ± 0.95 µM). Enzyme kinetics revealed a non-competitive inhibition mechanism, with K i values of 6.29 µM and 7.02 µM, suggesting allosteric regulation. ADMET analysis indicated good solubility and metabolic stability but limited oral bioavailability due to low gastrointestinal (GI) absorption. These findings highlight glucoerucin and gluconasturtiin as promising natural PTP1B inhibitors, warranting further optimization for therapeutic applications in type 2 diabetes managementhttps://doi.org/10.1186/s13065-025-01544-9WatercressPTP1BGlucosinolatesIn silicoIn vitro |
| spellingShingle | Noha A. Ahmed Ahmed A. Allam Hassan A. Rudayni Fahad M. Alshabrmi Faris F. Aba Alkhayl Doaa A. Abdelrheem Al Mokhtar Lamsabhi Sarah I. Othman Emadeldin M. Kamel Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation BMC Chemistry Watercress PTP1B Glucosinolates In silico In vitro |
| title | Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation |
| title_full | Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation |
| title_fullStr | Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation |
| title_full_unstemmed | Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation |
| title_short | Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation |
| title_sort | watercress derived glucosinolates as potential allosteric ptp1b inhibitors a dual in silico and in vitro study on insulin signaling modulation |
| topic | Watercress PTP1B Glucosinolates In silico In vitro |
| url | https://doi.org/10.1186/s13065-025-01544-9 |
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