Assessment of the in vitro anti-diabetic activity with molecular dynamic simulations of limonoids isolated from Adalia lemon peels.
Adalia lemon
Anti-diabetic activity
Limonoids
Molecular dynamic simulation
Scavenging activity
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 Sep 2024
14 Sep 2024
Historique:
received:
11
05
2024
accepted:
26
08
2024
medline:
15
9
2024
pubmed:
15
9
2024
entrez:
14
9
2024
Statut:
epublish
Résumé
Limonoids are important constituents of citrus that have a significant impact on promoting human health. Therefore, the primary focus of this research was to assess the overall limonoid content and isolate limonoids from Adalia lemon (Citrus limon L.) peels for their potential use as antioxidants and anti-diabetic agents. The levels of limonoid aglycones in the C. limon peel extract were quantified through a colorimetric assay, revealing a concentration of 16.53 ± 0.93 mg/L limonin equivalent. Furthermore, the total concentration of limonoid glucosides was determined to be 54.38 ± 1.02 mg/L. The study successfully identified five isolated limonoids, namely limonin, deacetylnomilin, nomilin, obacunone 17-O-β-D-glucopyranoside, and limonin 17-O-β-D-glucopyranoside, along with their respective yields. The efficacy of the limonoids-rich extract and the five isolated compounds was evaluated at three different concentrations (50, 100, and 200 µg/mL). It was found that both obacunone 17-O-β-D-glucopyranoside and limonin 17-O-β-D-glucopyranoside possessed the highest antioxidant, free radical scavenging, and anti-diabetic activities, followed by deacetylnomilin, and then the limonoids-rich extract. The molecular dynamic simulations were conducted to predict the behavior of the isolated compounds upon binding to the protein's active site, as well as their interaction and stability. The results revealed that limonin 17-O-β-D-glucopyranoside bound to the protein complex system exhibited a relatively more stable conformation than the Apo system. The analysis of Solvent Accessible Surface Area (SASA), in conjunction with the data obtained from Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and Radius of Gyration (ROG) computations, provided further evidence that the limonin 17-O-β-D-glucopyranoside complex system remained stable within the catalytic domain binding site of the human pancreatic alpha-amylase (HPA)-receptor. The research findings suggest that the limonoids found in Adalia lemon peels have the potential to be used as effective natural substances in creating innovative therapeutic treatments for conditions related to oxidative stress and disorders in carbohydrate metabolism.
Identifiants
pubmed: 39277638
doi: 10.1038/s41598-024-71198-5
pii: 10.1038/s41598-024-71198-5
doi:
Substances chimiques
Limonins
0
Hypoglycemic Agents
0
Plant Extracts
0
Antioxidants
0
nomilin
DRM0753K4T
limonin
L0F260866S
obacunone
751-03-1
alpha-Amylases
EC 3.2.1.1
Benzoxepins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21478Informations de copyright
© 2024. The Author(s).
Références
El-Feky, A. M. & Aboulthana, W. M. Chemical composition of lipoidal and flavonoidal extracts from Egyptian olive leaves with in Vitro biological activities. Egy. J. Chem. 66(13), 1903–1913 (2023).
Maqbool, Z. et al. Citrus waste as source of bioactive compounds: Extraction and utilization in health and food industry. Molecules 28(4), 1636 (2023).
pubmed: 36838623
pmcid: 9960763
doi: 10.3390/molecules28041636
Kholaf, G. M., Gomaa, E. G. & Ziena, H. M. Antimicrobial activity of some Egyptian citrus peels extracts. Alex. Sci. Exch. J. 38, 872–883 (2017).
Elsawi, S. A., Radwan, R. R., Elbatanony, M. M., El-Feky, A. M. & Sherif, N. H. Prophylactic effect of Opuntia ficusindica fruit peel extract against irradiation-induced colon injury in rats. Plantamedica 86(01), 61–69 (2020).
John, S., Monica, S. J., Priyadarshini, S., Sivaraj, C. & Arumugam, P. Antioxidant and antimicrobial efficacy of lemon (Citrus limonum L.) peel. Int. J. Pharm. Sci. Rev. Res. 46(1), 115–118 (2017).
El Sawi, S. A., Elbatanony, M. M., El-Feky, A. M. & Farghaly, A. A. Antimutagenic and cytotoxic potential of Punica granatum L. and Opuntia ficusindica L. peels. Egy. J. Chem. 67(1), 267–283 (2024).
Ceramella, J. et al. Exploring the anticancer and antioxidant properties of Vicia faba L. pods extracts, a promising source of nutraceuticals. PeerJ 10, e13683 (2022).
pubmed: 35996664
pmcid: 9392456
doi: 10.7717/peerj.13683
El-Feky, A. M. & El-Rashedy, A. A. Sterols and flavonoids in strawberry calyx with free radical scavenging, anti-inflammatory, and molecular dynamic study. Beni-Suef Univ. J. Bas. Appl. Sci. 12(1), 108 (2023).
doi: 10.1186/s43088-023-00445-x
Salem, M. A. et al. Investigation of the phytochemical composition, antioxidant, antibacterial, anti-osteoarthritis, and wound healing activities of selected vegetable waste. Sci. Rep. 13(1), 13034 (2023).
pubmed: 37563154
pmcid: 10415269
doi: 10.1038/s41598-023-38591-y
Klimek-Szczykutowicz, M., Szopa, A. & Ekiert, H. Citrus limon (Lemon) phenomenon—a review of the chemistry, pharmacological properties, applications in the modern pharmaceutical, food, and cosmetics industries, and biotechnological studies. Plants 9(1), 119 (2020).
pubmed: 31963590
pmcid: 7020168
doi: 10.3390/plants9010119
Ahmed, H. A., Nassrallah, A. A., Abdel-Raheem, M. A. & Elbehery, H. H. Lemon peel essential oil and its nano-formulation as green alternatives bioinsecticides to control Agrotis ipsilon (Lepidoptera: Noctuidae). Sci. Rep. 13, 17922 (2023).
pubmed: 37863942
pmcid: 10589301
doi: 10.1038/s41598-023-44670-x
Hamed, M. et al. Therapeutic potential of Citrus sinensis peels against rotenone induced Parkinsonism in rats. Curr. Bioact. Comp. 17(6), 22–39 (2021).
doi: 10.2174/1573407216999200918182514
Abou Baker, D. H. et al. Biochemical and pharmacological prospects of Citrus sinensis peel. Heliyon 8(8), e09979 (2022).
pubmed: 36039135
pmcid: 9418229
doi: 10.1016/j.heliyon.2022.e09979
Sridharan, B. et al. Beneficial effect of Citrus limon peel aqueous methanol extract on experimentally induced urolithic rats. Pharm. Biol. 54(5), 759–769 (2016).
pubmed: 26452728
doi: 10.3109/13880209.2015.1079724
Ali, J., Das, B. & Saikia, T. R. Antimicrobial activity of lemon peel (Citrus limon) extract. Int. J. Curr. Pharm. Res. 9(4), 79–82 (2017).
doi: 10.22159/ijcpr.2017v9i4.20962
Lu, X. et al. Nutrients and bioactives in citrus fruits: Different citrus varieties, fruit parts, and growth stages. Crit. Rev. Food Sci. Nutr. 63(14), 2018–2041 (2023).
pubmed: 34609268
doi: 10.1080/10408398.2021.1969891
Rather, J. A. et al. Fruit peel valorization, phytochemical profile, biological activity, and applications in food and packaging industries: Comprehensive review. Curr. Food Sci. Technol. Rep. 1, 63–79 (2023).
doi: 10.1007/s43555-023-00007-3
Mandadi KK, Jayaprakasha GK, Bhat NG, Patil BS (2007) Red Mexican grapefruit: a novel source for bioactive limonoids and their antioxidant activity. ZeitschriftfürNaturforschung C 62: 179–188.
Kelley, D. S. et al. Citrus limonin glucoside supplementation decreased biomarkers of liver disease and inflammation in overweight human adults. J. Funct. Foods 12, 271–281 (2015).
doi: 10.1016/j.jff.2014.11.026
Matsumoto, T. et al. Structures of antimutagenic constituents in the peels of Citrus limon. J. Nat. Med. 71, 735–744 (2017).
pubmed: 28699128
doi: 10.1007/s11418-017-1108-3
Olatunji, T. L., Odebunmi, C. A. & Ademola, A. E. Biological activities of limonoids in the Genus Khaya (Meliaceae): A review. Fut. J. Pharm. Sci. 7, 74 (2021).
doi: 10.1186/s43094-021-00197-4
Zahr, S., Zahr, R., El Hajj, R. & Khalil, M. Phytochemistry and biological activities of Citrus sinensis and Citrus limon: An update. J. Herbal Med. 41, 100737 (2023).
doi: 10.1016/j.hermed.2023.100737
Gualdani, R., Cavalluzzi, M. M., Lentini, G. & Habtemariam, S. The chemistry and pharmacology of citrus limonoids. Molecules 21(11), 1530 (2016).
pubmed: 27845763
pmcid: 6273274
doi: 10.3390/molecules21111530
Shi, Y. S. et al. Limonoids from Citrus: Chemistry, anti-tumor potential, and other bioactivities. J. Funct. Foods 75, 104213 (2020).
doi: 10.1016/j.jff.2020.104213
Nada, H., Elkamhawy, A. & Lee, K. Identification of 1H-purine-2,6-dione derivative as a potential SARS-CoV-2 main protease inhibitor: molecular docking, dynamic simulations, and energy calculations. PeerJ 10, e14120 (2022).
pubmed: 36225900
pmcid: 9549888
doi: 10.7717/peerj.14120
Šponer, J. et al. RNA structural dynamics as captured by molecular simulations: A comprehensive overview. Chem. Rev. 118(8), 4177–4338 (2018).
pubmed: 29297679
pmcid: 5920944
doi: 10.1021/acs.chemrev.7b00427
Lai, Y. et al. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development. Acta Pharm. Sin. B 12(6), 2751–2777 (2022).
pubmed: 35755285
pmcid: 9214059
doi: 10.1016/j.apsb.2022.03.009
Magurano, F. et al. Antioxidant activity of citrus limonoids and investigation of their virucidal potential against SARS-CoV-2 in cellular models. Antioxidants 10(11), 1794 (2021).
pubmed: 34829666
pmcid: 8615075
doi: 10.3390/antiox10111794
Breksa, A. P. 3rd. & Ibarra, P. Jr. Colorimetric method for the estimation of total limonoid aglycones and glucoside contents in citrus juices. J. Agric. Food Chem. 55(13), 5013–5017 (2007).
pubmed: 17542603
doi: 10.1021/jf063731c
Prieto, P., Pineda, M. & Aguilar, M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal. Biochem. 269, 337–341 (1999).
pubmed: 10222007
doi: 10.1006/abio.1999.4019
Oyaizu, M. Studies on product of browning reaction prepared from glucose amine. Jap. J. Nutr. 44, 307–315 (1986).
doi: 10.5264/eiyogakuzashi.44.307
Rahman, M. M., Islam, M. B., Biswas, M. & Alam, A. K. In vitro antioxidant and free radical scavenging activity of different parts of Tabebuia pallida growing in Bangladesh. BMC Res. Notes 8(1), 621–628 (2015).
pubmed: 26518275
pmcid: 4627625
doi: 10.1186/s13104-015-1618-6
Arnao, M. B., Cano, A. & Acosta, M. The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem. 73, 239–244 (2001).
doi: 10.1016/S0308-8146(00)00324-1
Chakraborthy, G. S. Free radical scavenging activity of Costus speciosus leaves. Indian J. Pharm. Educ. Res. 43, 96–98 (2009).
Wickramaratne, M. N., Punchihewa, J. & Wickramaratne, D. In-vitro alpha amylase inhibitory activity of the leaf extracts of Adenanthera pavonina. BMC Complem. Altern. Med. 16(1), 466 (2016).
doi: 10.1186/s12906-016-1452-y
Pistia-Brueggeman, G. & Hollingsworth, R. I. A preparation and screening strategy for glycosidase inhibitors. Tetrahedron 57, 8773–8778 (2001).
doi: 10.1016/S0040-4020(01)00877-8
Rammesmayer, G. & Praznik, W. Fast and sensitive simultaneous staining method of Q-enzyme, α-amylase, R-enzyme, phosphorylase and soluble starch synthase separated by starch: Polyacrylamide gel electrophoresis. J. Chromatogr. 623(2), 399–402 (1992).
doi: 10.1016/0021-9673(92)80384-7
Laemmli, U. K. Cleavage of structural proteins during the assembly of the head of Bacteriophage T4. Nature 227(5259), 680–685 (1970).
pubmed: 5432063
doi: 10.1038/227680a0
Nei, M. & Li, W. S. Mathematical model for studing genetic variation in terms of restriction endonuclease. Proc. Natl. Acad. Sci. USA 76, 5269–5273 (1979).
pubmed: 291943
pmcid: 413122
doi: 10.1073/pnas.76.10.5269
Nahoum, V. et al. Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors. Biochem J. 346(1), 201–208 (2000).
pubmed: 10657258
pmcid: 1220841
doi: 10.1042/bj3460201
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25(13), 1605–1612 (2004).
pubmed: 15264254
doi: 10.1002/jcc.20084
Li, H., Robertson, A. D. & Jensen, J. H. Very fast empirical prediction and rationalization of protein pKa values. Proteins 61(4), 704–721 (2005).
pubmed: 16231289
doi: 10.1002/prot.20660
Reflections, H. B. & ChemDraw, On. Chem. Eng. News Arch. 92(33), 26–27 (2014).
doi: 10.1021/cen-09233-scitech1
Hanwell, M. D. et al. Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform. 4(1), 17 (2012).
pubmed: 22889332
pmcid: 3542060
doi: 10.1186/1758-2946-4-17
Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31(2), 455–461 (2010).
pubmed: 19499576
pmcid: 3041641
doi: 10.1002/jcc.21334
Bikadi, Z. & Hazai, E. Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J. Cheminform. 1(1), 1–16 (2009).
doi: 10.1186/1758-2946-1-15
Morris, G. M. et al. Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 19(14), 1639–1662 (1998).
doi: 10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B
Hospital, A., Goñi, J. R., Orozco, M. & Gelpí, J. L. Molecular dynamics simulations: advances and applications. Adv. Appl. Bioinform. Chem. 8, 37–47 (2015).
pubmed: 26604800
pmcid: 4655909
Lee, T. S. et al. GPU-accelerated molecular dynamics and free energy methods in Amber18: Performance enhancements and new features. J. Chem. Inf. Model. 58(10), 2043–2050 (2018).
pubmed: 30199633
pmcid: 6226240
doi: 10.1021/acs.jcim.8b00462
Roe, D. R. & Cheatham, T. E. PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9(7), 3084–3095 (2013).
pubmed: 26583988
doi: 10.1021/ct400341p
Seifert, E. OriginPro 9.1: Scientific data analysis and graphing software-Software review. J. Chem. Inf. Model. 54(5), 1552–1552 (2014).
pubmed: 24702057
doi: 10.1021/ci500161d
Kollman, P. A. et al. Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Acc. Chem. Res. 33(12), 889–897 (2000).
pubmed: 11123888
doi: 10.1021/ar000033j
Ylilauri, M. & Pentikäinen, O. T. MMGBSA as a tool to understand the binding affinities of filamin-peptide interactions. J. Chem. Inf. Model. 53(10), 2626–2633 (2013).
pubmed: 23988151
doi: 10.1021/ci4002475
Hou, T., Wang, J., Li, Y. & Wang, W. Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J. Chem. Inf. Model. 51(1), 69–82 (2011).
pubmed: 21117705
doi: 10.1021/ci100275a
Greenidge, P. A., Kramer, C., Mozziconacci, J. C. & Wolf, R. M. MM/GBSA binding energy prediction on the PDBbind data set: Successes, failures, and directions for further improvement. J. Chem. Inf. Model. 53(1), 201–209 (2013).
pubmed: 23268595
doi: 10.1021/ci300425v
David, C. C. & Jacobs, D. J. Principal Component Analysis: A Method for Determining the Essential Dynamics of Proteins 193–226 (In Humana Press, 2014).
Kasahara, K., Fukuda, I. & Nakamura, H. A novel approach of dynamic cross correlation analysis on molecular dynamics simulations and its application to Ets1 dimer-DNA complex. PLoSOne 9(11), e112419 (2014).
doi: 10.1371/journal.pone.0112419
Yan, F. et al. Effect of double mutations T790M/L858R on conformation and drug-resistant mechanism of epidermal growth factor receptor explored by molecular dynamics simulations. RSC Adv. 8(70), 39797–39810 (2018).
pubmed: 35558225
pmcid: 9091310
doi: 10.1039/C8RA06844E
Tundis, R., Loizzo, M. R. & Menichini, F. An overview on chemical aspects and potential health benefits of limonoids and their derivatives. Crit. Rev. Food Sci. Nutr. 54(2), 225–250 (2014).
pubmed: 24188270
doi: 10.1080/10408398.2011.581400
Saini, R. K. et al. Bioactive compounds of citrus fruits: A review of composition and health benefits of carotenoids, flavonoids, limonoids, and terpenes. Antioxidants 11(2), 239 (2022).
pubmed: 35204122
pmcid: 8868476
doi: 10.3390/antiox11020239
Pichaiyongvongdee, S. & Haruenkit, R. Comparative studies of limonin and naringin distribution in different parts of pummelo [Citrus grandis (L.) Osbeck] cultivars grown in Thailand. Kasetsart J. Nat. Sci. 43, 28–36 (2009).
Sun, C., Chen, K., Chen, Y. & Chen, Q. Contents and antioxidant capacity of limonin and nomilin in different tissues of citrus fruit of four cultivars during fruit growth and maturation. Food Chem. 93(4), 599–605 (2005).
doi: 10.1016/j.foodchem.2004.10.037
Ozaki, Y. et al. Limonoid glucosides of satsuma mandarin (Citrus unshiu Marcov.) and its processing products. ACS Symp. Ser. 758, 107–119 (2000).
doi: 10.1021/bk-2000-0758.ch008
Hasegawa, S. Biochemistry of limonoids in Citrus. ACS Symp. Ser. 758, 9–30 (2000).
doi: 10.1021/bk-2000-0758.ch002
Tian, Q., Li, D., Barbacci, D., Schwartz, S. J. & Patil, B. S. Electron ionization mass spectrometry of citrus limonoids. Rapid. Commun. Mass Spectr. 17(22), 2517–2522 (2003).
doi: 10.1002/rcm.1218
El-Sayed, M. A., Al-Gendy, A. A., Hamdan, D. I. & El-Shazly, A. M. Phytoconstituents, LC-ESI-MS profile, antioxidant and antimicrobial activities of Citrus x limon L. Burm. F. cultivar variegated pink lemon. J. Pharm. Sci. Res. 9(4), 375 (2017).
Khalil, A. T., Maatooq, G. T. & El Sayed, K. A. Limonoids from Citrus reticulata. ZeitschriftFür Naturforschung C 58(3–4), 165–170 (2003).
doi: 10.1515/znc-2003-3-403
Sawabe, A. et al. Isolation and characterization of new limonoid glycosides from Citrus unshiu peels. Carbohydr. Res. 315(1–2), 142–147 (1999).
pubmed: 10385977
doi: 10.1016/S0008-6215(98)00328-0
Raman, G., Cho, M., Brodbelt, J. S. & Patil, B. S. Isolation and purification of closely related Citrus limonoid glucosides by flash chromatography. Phytochem. Anal. 16(3), 155–160 (2005).
pubmed: 15997847
doi: 10.1002/pca.835
Glabasnia, A. & Hofmann, T. On the non-enzymatic liberation of limonin and C 17-epilimonin from limonin-17-β-d-glucopyranoside in orange juice. Eur. Food Res. Technol. 228, 55–63 (2008).
doi: 10.1007/s00217-008-0906-y
Samanta S, Banerjee J, Ahmed R, Dash SK. Potential Benefits of Bioactive Functional Components of Citrus Fruits for Health Promotion and Disease Prevention. In Recent Advances in Citrus Fruits 451–499. (Springer International Publishing, 2023).
B’chir, F. & Arnaud, M. J. Chemical profile and extraction yield of essential oils from peel of Citrus limon, Citrus aurantium, and Citrus limetta: A review. Stud. Nat. Prod. Chem. 79, 135–204 (2023).
doi: 10.1016/B978-0-443-18961-6.00009-3
Janati, S. S., Beheshti, H. R., Feizy, J. & Fahim, N. K. Chemical composition of lemon (Citrus limon) and peels its considerations as animal food. Gida 37(5), 267–271 (2012).
Loganayaki, N., Siddhuraju, P. & Manian, S. Antioxidant activity and free radical scavenging capacity of phenolic extracts from Helicteres isora L. and Ceiba pentandra L.. J. Food Sci. Technol. 50(4), 687–695 (2013).
pubmed: 24425970
doi: 10.1007/s13197-011-0389-x
Ayeleso, A. O., Joseph, J. S., Oguntibeju, O. O. & Mukwevho, E. Evaluation of free radical scavenging capacity of methoxy containing-hybrids of thiosemicarbazone-triazole and their influence on glucose transport. BMC Pharmacol. Toxicol. 19, 84 (2018).
pubmed: 30522526
pmcid: 6282370
doi: 10.1186/s40360-018-0266-6
Sánchez-Marzo, N. et al. Relationships between chemical structure and antioxidant activity of isolated phytocompounds from lemon verbena. Antioxidants 8, 324 (2019).
pubmed: 31434276
pmcid: 6719922
doi: 10.3390/antiox8080324
Breksa, A. P. & Manners, G. D. Evaluation of the antioxidant capacity of limonin, nomilin, and limonin glucoside. J. Agric. Food Chem. 54, 3827–3831 (2006).
pubmed: 16719503
doi: 10.1021/jf060901c
Zou, Z., Xi, W., Hu, Y., Nie, C. & Zhou, Z. Antioxidant activity of citrus fruits. Food Chem. 196, 885–896 (2016).
pubmed: 26593569
doi: 10.1016/j.foodchem.2015.09.072
Kumar, S., Kumar, R., Dwivedi, A. & Pandey, A. K. In vitro antioxidant, antibacterial, and cytotoxic activity and in vivo effect of Syngonium podophyllum and Eichhornia crassipes leaf extracts on isoniazid induced oxidative stress and hepatic markers. Biomed. Res. Int. 2014, 459452 (2014).
pubmed: 25162013
pmcid: 4137625
doi: 10.1155/2014/459452
Akinloye, D. I., Osatuyi, O. A., Musibau, O. G., Yusuf, A. A. & Adewuyi, S. J. In vitro antioxidant activities, elemental analysis and some Bio-active Constituents of Acalypha wilkesiana muellarg and Acalypha wilkesiana java white leaf extracts. Chem. Soc. Nigeria 41(2), 150–157 (2016).
Yu, J. et al. Antioxidant activity of citrus limonoids, flavonoids, and coumarins. J. Agric. Food Chem. 53, 2009–2014 (2005).
pubmed: 15769128
doi: 10.1021/jf0484632
Najafian, M., Ebrahim-Habibi, A., Yaghmaei, P., Parivar, K. & Larijani, B. Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: An in vivo study in rats. Acta Biochimica Polonica 57(4), 553–560 (2010).
pubmed: 21060897
doi: 10.18388/abp.2010_2443
El-Shora, H. M., Metwally, A. M. & Salwa, A. K. Essential groups and stability of α-glucosidase of Penicillium notatum. Ann. Microbiol. 59, 285–291 (2009).
doi: 10.1007/BF03178330
Alqahtani, A. S. et al. Alpha-amylase and alpha-glucosidase enzyme inhibition and antioxidant potential of 3-oxolupenal and katononic acid isolated from Nuxia oppositifolia. Biomolecules 10, 61 (2019).
pubmed: 31905962
pmcid: 7022278
doi: 10.3390/biom10010061
Sarian, M. N. et al. Antioxidant and antidiabetic effects of flavonoids: A structure-activity relationship based study. Biomed. Res. Int. 2017, 8386065 (2017).
pubmed: 29318154
pmcid: 5727842
doi: 10.1155/2017/8386065
Miroslava, S. et al. Flavonoids target human herpesviruses that infect the nervous system: Mechanisms of action and therapeutic insights. Viruses 14, 592 (2022).
doi: 10.3390/v14030592
Shamsudin, N. F. et al. Flavonoids as antidiabetic and anti-inflammatory agents: A review on structural activity relationship-based studies and meta-analysis. Int. J. Mol. Sci. 23(20), 12605 (2022).
pubmed: 36293459
pmcid: 9604264
doi: 10.3390/ijms232012605
Sekhon-Loodu, S. & Rupasinghe, H. P. V. Evaluation of antioxidant, antidiabetic and antiobesity potential of selected traditional medicinal plants. Front. Nutr. 6, 53 (2019).
pubmed: 31106207
pmcid: 6494929
doi: 10.3389/fnut.2019.00053
Dedvisitsakul, P. & Watla-Iad, K. Antioxidant activity and antidiabetic activities of Northern Thai indigenous edible plant extracts and their phytochemical constituents. Heliyon 8(9), e10740 (2022).
pubmed: 36185148
pmcid: 9519484
doi: 10.1016/j.heliyon.2022.e10740
Anh, V. T. T. et al. Phytochemicals, antioxidant and antidiabetic activities of extracts from Miliusa velutina flowers. Horticulturae 7(12), 555 (2021).
doi: 10.3390/horticulturae7120555
El-Shamarka, M. E. A., Aboulthana, W. M., Omar, N. I. & Mahfouz, M. M. Evaluation of the biological efficiency of Terminalia chebula fruit extract against neurochemical changes induced in brain of diabetic rats: An epigenetic study. Inflammopharmacology 32, 1439–1460 (2024).
pubmed: 38329710
pmcid: 11006788
doi: 10.1007/s10787-024-01428-9
El-Sayed, A. F., Aboulthana, W. M., Sherief, M. A., El-Bassyouni, G. T. & Mousa, S. M. Synthesis, structural, molecular docking, and in vitro biological activities of Cu-doped ZnO nanomaterials. Sci. Rep. 14(1), 9027 (2024).
pubmed: 38641640
pmcid: 11031592
doi: 10.1038/s41598-024-59088-2
Almehizia, A. A., Aboulthana, W. M., Naglah, A. M. & Hassan, A. S. In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives. RSC Adv. 14(12), 8397–8408 (2024).
pubmed: 38476172
pmcid: 10928850
doi: 10.1039/D4RA00423J
Aboulthana, W. M. et al. The hepato- and neuroprotective effect of gold Casuarina equisetifolia bark nano-extract against Chlorpyrifos-induced toxicity in rats. J. Genetic Eng. Biotechnol. 21, 158 (2023).
doi: 10.1186/s43141-023-00595-6
El-Shora, H. M., Ibrahim, M. E. & Alfakharany, M. W. Activators and Inhibitors of α-glucosidase from Penicillium chrysogenum. Annu. Res. Rev. Biol. 24, 1–9 (2018).
doi: 10.9734/ARRB/2018/38408
El-Shora, H., Messgo, S. M., Ibrahim, M. E. & Alfakharany, M. W. Purification and characterization of α-glucosidase from Penicillium chrysogenum. Int. J. Phytomed. 10(4), 175–180 (2018).
Mirzaei, S. et al. Design, synthesis and biological evaluation of novel 5,6,7-trimethoxy-N-aryl-2-styrylquinolin-4-amines as potential anticancer agents and tubulin polymerization inhibitors. Bioorg. Chem. 98, 103711 (2020).
pubmed: 32179282
doi: 10.1016/j.bioorg.2020.103711
Hasanin, M., Hashem, A. H., El-Rashedy, A. A. & Kamel, S. Synthesis of novel heterocyclic compounds based on dialdehyde cellulose: Characterization, antimicrobial, antitumor activity, molecular dynamics simulation and target identification. Cellulose 28(13), 8355–8374 (2021).
doi: 10.1007/s10570-021-04063-7
Machaba, K. E., Mhlongo, N. N. & Soliman, M. E. S. Induced mutation proves a potential target for TB therapy: A molecular dynamics study on LprG. Cell Biochem Biophys 76(3), 345–356 (2018).
pubmed: 30073572
doi: 10.1007/s12013-018-0852-7
Wijffels, G., Dalrymple, B., Kongsuwan, K. & Dixon, N. Conservation of eubacterial replicases. IUBMB Life 57(6), 413–419 (2005).
pubmed: 16012050
doi: 10.1080/15216540500138246
Pan, L., Patterson, J. C., Deshpande, A., Cole, G. & Frautschy, S. Molecular dynamics study of Zn(Aβ) and Zn(Aβ)2. PLoS One 8(9), 70681–70688 (2013).
doi: 10.1371/journal.pone.0070681
Richmond, T. J. Solvent accessible surface area and excluded volume in proteins: Analytical equations for overlapping spheres and implications for the hydrophobic effect. J. Mol. Biol. 178(1), 63–89 (1984).
pubmed: 6548264
doi: 10.1016/0022-2836(84)90231-6
Cournia, Z., Allen, B. & Sherman, W. Relative binding free energy calculations in drug discovery: Recent advances and practical considerations. J. Chem. Inf. Model. 57, 2911–2937 (2017).
pubmed: 29243483
doi: 10.1021/acs.jcim.7b00564
Nassar, A. E. F., Kamel, A. M. & Clarimont, C. Improving the decision-making process in the structural modification of drug candidates: Enhancing metabolic stability. Drug Discov. Today 9(23), 1020–1028 (2004).
pubmed: 15574318
doi: 10.1016/S1359-6446(04)03280-5
Basnet, S., Ghimire, M. P., Lamichhane, T. R., Adhikari, R. & Adhikari, A. Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis. PLoSOne 18(3), e0275765 (2023).
doi: 10.1371/journal.pone.0275765