{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:51Z","timestamp":1785437931292,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission of Pakistan, Islamabad","doi-asserted-by":"publisher","award":["15908"],"award-info":[{"award-number":["15908"]}],"id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]},{"award":["15908"],"award-info":[{"award-number":["15908"]}],"id":[{"id":"https:\/\/ror.org\/038y3sz68","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The global healthcare system faces a significant challenge due to the escalating prevalence of type 2 diabetes, affecting over 10% of the world\u2019s population. Suppression of postprandial hyperglycemia through inhibition of carbohydrate-hydrolyzing enzymes is an effective therapeutic strategy. Although curcumin effectively inhibits \u03b1-amylase and \u03b1-glucosidase activities, its lower solubility and bioavailability restrict its clinical application. In this study, five mono-carbonyl curcumin analogues (CA1\u2013CA5) were synthesized and evaluated for their antidiabetic potential following selective experimental methods both in vitro, and in vivo. Enhanced delivery for the most potent analogue was achieved through PEGylated graphene oxide (PEG-GO) to overcome the shortcomings of curcumin compounds. Methods: In silico ADME profiling was conducted using SwissADME, and molecular docking studies were performed with AutoDock Vina (v1.5.7) to assess enzyme binding interaction. The synthesized compounds were further evaluated using in vitro \u03b1-amylase and \u03b1-glucosidase inhibition assays, followed by in vivo blood profile analysis. The most active analogue CA3 (chloro derivative) was loaded onto PEG-GO and characterized using UV\u2013visible spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Results: Among all of the compounds, CA3 exhibits the strongest binding affinity and highest enzyme inhibitory activity, followed by CA2 and CA4. PEG-GO-CA3 demonstrated significantly enhanced biological activity compared to its free form. In vivo studies showed marked improvements in body weight and lipid profile, along with significant reductions in blood glucose, glycated hemoglobin, urea, creatinine, alanine aminotransferase, and aspartate aminotransferase levels over a 28-day treatment period as compared to a diabetic control. Spectroscopic and morphological analyses confirmed successful loading of CA3 onto PEG-GO (27.7\u201331.5%) with a release profile of 38\u201357% after 12 and 36 h in a controlled environment at pH 7. Conclusions: These findings suggest that PEG-GO-loaded mono-carbonyl curcumin analogues represent promising therapeutic candidates for the management of T2DM.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050568","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:06:21Z","timestamp":1777860381000},"page":"568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nano-Enabled Potentiation of a Lead Mono-Carbonyl Curcumin Analogue via PEGylated Graphene Oxide for Enhanced Glycemic Control"],"prefix":"10.3390","volume":"18","author":[{"given":"Babar","family":"Ayub","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6121-5441","authenticated-orcid":false,"given":"Haya","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-7730","authenticated-orcid":false,"given":"Farman Ali","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7347-1127","authenticated-orcid":false,"given":"Nasir Mehmood","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Agriculture, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1117-1246","authenticated-orcid":false,"given":"Abid","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kifayat","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8143-2363","authenticated-orcid":false,"given":"Syed Wadood Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Malakand, Chakdara, Dir (Lower), Khyber Pakhtunkhwa 18300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China"},{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-6525","authenticated-orcid":false,"given":"Shujaat","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Khyber Pakhtunkhwa 18000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/03007995.2024.2333440","article-title":"Diabetes: A review of its pathophysiology, and advanced methods of mitigation","volume":"40","author":"Gupta","year":"2024","journal-title":"Curr. 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