{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:21:12Z","timestamp":1781954472333,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Turmeric (Curcuma longa L., Zingiberaceae) is a widely consumed spice and functional food valued for its bioactive constituents. Using an activity-guided strategy, this study identified the dichloromethane fraction as the most potent anti-inflammatory fraction, exhibiting markedly stronger inhibition of reactive oxygen species (ROS) production than ibuprofen (IC50\u00a0\u2264\u00a0 0.4 vs. 11.2 \u03bcg\/mL). Bioassay-guided purification yielded bisacurone (1), didemethoxycurcumin (2), and \u03b2-turmerone (3), with compounds 1 and 2 reported here for the first time in this fraction. Among them, \u03b2-turmerone displayed the strongest anti-inflammatory activity (IC50 = 4.7 \u03bcg\/mL), consistent with in silico docking and molecular dynamics analyses, revealing greater binding affinity and complex stability with myeloperoxidase (\u0394Gbind = \u221220.90 vs. \u221218.89 kcal\/mol for ibuprofen). Gas chromatography\u2013mass spectrometry (GC-MS) profiling revealed a phytochemical profile dominated by turmerones and curlone, correlating with the observed bioactivity. None of the fractions exhibited acute toxicity in brine shrimp lethality assays, indicating a favorable preliminary safety profile. Our findings demonstrate the value of activity-guided isolation combined with computational validation for identifying turmeric-derived bioactives with promising nutraceutical potential, warranting further in vivo evaluation.<\/jats:p>","DOI":"10.3390\/foods14244205","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T10:35:51Z","timestamp":1765190151000},"page":"4205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-Inflammatory Activity-Guided Isolation and In Silico Validation of Turmeric (Curcuma longa L.) Phytochemicals"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3719-4198","authenticated-orcid":false,"given":"Zhuldyz","family":"Uvaniskanova","sequence":"first","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5495-5556","authenticated-orcid":false,"given":"Salar","family":"Hafez-Ghoran","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Research Campus, North Carolina Agricultural and Technical State University, 500 Laureate Way, Kannapolis, NC 28081, USA"},{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0783-5791","authenticated-orcid":false,"given":"Muhammad","family":"Ikhlas Abdjan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Surabaya, Surabaya 60213, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-3358","authenticated-orcid":false,"given":"Bel Youssouf G.","family":"Mountessou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Higher Teacher Training College, University of Yaound\u00e9 I, Yaound\u00e9 P.O. Box 47, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6521-4478","authenticated-orcid":false,"given":"Fatemeh","family":"Taktaz","sequence":"additional","affiliation":[{"name":"Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Research Campus, North Carolina Agricultural and Technical State University, 500 Laureate Way, Kannapolis, NC 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-3747","authenticated-orcid":false,"given":"Fadjar","family":"Mulya","sequence":"additional","affiliation":[{"name":"Nanotechnology Engineering, Faculty of Advanced Technology and Multidiscipline, Airlangga University, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-1255","authenticated-orcid":false,"given":"Gulnaz A.","family":"Seitimova","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Iqbal Choudhary","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan"},{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"ref_1","unstructured":"Kuete, V. (2017). Chapter 19-Curcuma longa. Medicinal Spices and Vegetables from Africa, Academic Press."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dosoky, N.S., and Setzer, W.N. (2018). Chemical composition and biological activities of essential oils of Curcuma species. Nutrients, 10.","DOI":"10.3390\/nu10091196"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"871","DOI":"10.2174\/1381612825666190402163940","article-title":"Ethnobotany, phytochemistry and traditional uses of Curcuma spp. and pharmacological profile of two important species (C. longa and C. zedoaria): A review","volume":"25","author":"Ayati","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e202402443","DOI":"10.1002\/slct.202402443","article-title":"The ethonomedical profiles and pharmacological properties of phytochemicals from Curcuma longa Linn. -A decade update","volume":"9","author":"Saha","year":"2024","journal-title":"ChemistrySelect"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hafez Ghoran, S., Calcaterra, A., Abbasi, M., Taktaz, F., Nieselt, K., and Babaei, E. (2022). Curcumin-based nanoformulations: A promising adjuvant towards cancer treatment. Molecules, 27.","DOI":"10.3390\/molecules27165236"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1080\/10942912.2022.2082464","article-title":"A review on selected pharmacological activities of Curcuma longa L.","volume":"25","author":"Jyotirmayee","year":"2022","journal-title":"Int. J. Food Prop."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhu, X., Quan, Y.-Y., Yin, Z.-J., Li, M., Wang, T., Zheng, L.-Y., Feng, S.-Q., Zhao, J.-N., and Li, L. (2023). Sources, morphology, phytochemistry, pharmacology of Curcumae longae Rhizoma, Curcumae Radix, and Curcumae Rhizoma: A review of the literature. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1229963"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s42535-024-01038-4","article-title":"Turmeric (Curcuma longa): An insight into its food applications, phytochemistry and pharmacological properties","volume":"38","author":"Jikah","year":"2025","journal-title":"Vegetos"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fu, Y.-S., Chen, T.-H., Weng, L., Huang, L., Lai, D., and Weng, C.-F. (2021). Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed. Pharmacother., 141.","DOI":"10.1016\/j.biopha.2021.111888"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/nutrit\/nuae221","article-title":"Effects of the curcuminoid and non-curcuminoid compounds of turmeric on the gut microbiome and inflammation: Potential use in the treatment and prevention of disease","volume":"83","author":"Kacena","year":"2025","journal-title":"Nutr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101074","DOI":"10.1016\/j.focha.2025.101074","article-title":"Turmeric (Curcuma longa L.) extract in different solvents: A comparative study of curcuminoid content, volatile compounds, and antimicrobial activity with molecular docking insights","volume":"8","author":"Moulick","year":"2025","journal-title":"Food Chem. Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.intimp.2012.06.003","article-title":"Anti-inflammatory effects of aromatic-turmerone through blocking of NF-\u03baB, JNK, and p38 MAPK signaling pathways in amyloid \u03b2-stimulated microglia","volume":"14","author":"Park","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Streyczek, J., Apweiler, M., Sun, L., and Fiebich, B.L. (2022). Turmeric extract (Curcuma longa) mediates anti-oxidative effects by reduction of nitric oxide, iNOS protein-, and mRNA-synthesis in BV2 microglial cells. Molecules, 27.","DOI":"10.3390\/molecules27030784"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1002\/mnfr.201200838","article-title":"Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric","volume":"57","author":"Aggarwal","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Poudel, D.K., Ojha, P.K., Rokaya, A., Satyal, R., Satyal, P., and Setzer, W.N. (2022). Analysis of volatile constituents in Curcuma species, viz. C. aeruginosa, C. zedoaria, and C. longa, from Nepal. Plants, 11.","DOI":"10.3390\/plants11151932"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/vjch.202300062","article-title":"Chemical properties and inhibitory activities of tyrosinase, \u03b1-glucosidase, and urease from chloroform extract of Curcuma aromatica Salisb. rhizomes","volume":"61","author":"Le","year":"2023","journal-title":"Vietnam J. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Araya-Sibaja, A.M., Vargas-Huertas, F., Quesada, S., Azofeifa, G., Vega-Baudrit, J.R., and Navarro-Hoyos, M. (2024). Characterization, antioxidant and cytotoxic evaluation of demethoxycurcumin and bisdemethoxycurcumin from Curcuma longa cultivated in costa rica. Separations, 11.","DOI":"10.3390\/separations11010023"},{"key":"ref_18","first-page":"1934578X1300800633","article-title":"Biological studies of turmeric oil, Part 2: Isolation and characterization of turmeric oil components; Cytotoxic activity against pancreatic cancer cells","volume":"8","author":"Yan","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_19","unstructured":"Adams, R.P. (2017). Identification of Essential Oil Components by Gas Chromatography\/Mass Spectrometry, 4.1 ed., Allured Publ Crop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117053","DOI":"10.1016\/j.jep.2023.117053","article-title":"Oliveria decumbens Vent. (Apiaceae): Biological screening and chemical compositions","volume":"318","author":"Mirahmad","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13990","DOI":"10.1021\/bi0111808","article-title":"Human myeloperoxidase: Structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 \u00c5 resolution","volume":"40","author":"Fiedler","year":"2001","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1021\/cr200107z","article-title":"Challenges for density functional theory","volume":"112","author":"Cohen","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/jcc.27218","article-title":"DOCK 6: Incorporating hierarchical traversal through precomputed ligand conformations to enable large-scale docking","volume":"45","author":"Balius","year":"2024","journal-title":"J. Comput. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s10822-012-9565-y","article-title":"Evaluation of DOCK 6 as a pose generation and database enrichment tool","volume":"26","author":"Brozell","year":"2012","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1002\/jcc.23905","article-title":"DOCK 6: Impact of new features and current docking performance","volume":"36","author":"Allen","year":"2015","journal-title":"J. Comput. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J. Phys. Chem. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA. py: An efficient program for end-state free energy calculations","volume":"8","author":"McGee","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.phymed.2003.12.011","article-title":"The effect of turmeric extracts on inflammatory mediator production","volume":"12","author":"Lantz","year":"2005","journal-title":"Phytomedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6154","DOI":"10.1021\/acs.jafc.0c02607","article-title":"Mechanistic differences in the inhibition of NF-\u03baB by turmeric and its curcuminoid constituents","volume":"68","author":"Edwards","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/j.bcp.2010.01.033","article-title":"Bisdemethylcurcumin and structurally related hispolon analogues of curcumin exhibit enhanced prooxidant, anti-proliferative and anti-inflammatory activities in vitro","volume":"79","author":"Ravindran","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","first-page":"805756","article-title":"Comparative evaluation of anti-inflammatory activity of curcuminoids, turmerones, and aqueous extract of Curcuma longa","volume":"2013","author":"Bagad","year":"2013","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1871523014666150407150533","article-title":"Anti-inflammatory activity of polysaccharide fraction of Curcuma longa extract (NR-INF-02)","volume":"14","author":"Ramanaiah","year":"2015","journal-title":"Anti-Inflamm. Anti-Allergy Agents Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.47552\/ijam.v15i1.4188","article-title":"Incorporation of standardised extract of Curcuma longa Linn into phytosomes and its evaluation for in vitro anti-inflammatory potential and Brine shrimp lethality assay","volume":"15","author":"Marennavar","year":"2024","journal-title":"Int. J. Ayurvedic Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S2222-1808(16)61152-0","article-title":"Variability of curcuminoid content and lack of correlation with cytotoxicity in ethanolic extracts from 20 accessions of Curcuma aeruginosa RoxB","volume":"6","author":"Nurcholis","year":"2016","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.sajb.2023.11.042","article-title":"Phytochemical investigation and antibacterial activity of Curcuma longa against multi-drug resistant bacteria","volume":"164","author":"Kirmani","year":"2024","journal-title":"S. Afr. J. Bot."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.3390\/molecules19079535","article-title":"Secondary metabolite profiling of Curcuma species grown at different locations using GC\/TOF and UPLC\/Q-TOF MS","volume":"19","author":"Lee","year":"2014","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.4314\/swj.v19i4.41","article-title":"Antimicrobial activities, GC-Ms composition and proximate analysis of volatile oil extract from tumeric rhizomes (Curcuma longa)","volume":"19","author":"Micheal","year":"2024","journal-title":"Sci. World J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Brogi, S., Ramalho, T.C., Kuca, K., Medina-Franco, J.L., and Valko, M. (2020). In silico methods for drug design and discovery. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00612"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101570","DOI":"10.1016\/j.rechem.2024.101570","article-title":"Synthesis, molecular docking studies, and evaluation of antibacterial and antioxidant activities of pyrazoline derivatives","volume":"8","author":"Mohammed","year":"2024","journal-title":"Results Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Khan, A.A., Alsahli, M.A., and Rahmani, A.H. (2018). Myeloperoxidase as an active disease biomarker: Recent biochemical and pathological perspectives. Med. Sci., 6.","DOI":"10.20944\/preprints201802.0104.v1"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1134\/S0026893308040195","article-title":"Radius of gyration as an indicator of protein structure compactness","volume":"42","author":"Lobanov","year":"2008","journal-title":"Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/pro.2449","article-title":"Contribution of hydrogen bonds to protein stability","volume":"23","author":"Pace","year":"2014","journal-title":"Protein Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"116725","DOI":"10.1016\/j.ejmech.2024.116725","article-title":"PROTAC technology: From drug development to probe technology for target deconvolution","volume":"276","author":"Yan","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1080\/17568919.2025.2498875","article-title":"Key advances and application prospects of PROTAC technologies in the next 5 years","volume":"17","author":"Qin","year":"2025","journal-title":"Future Med. Chem."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/24\/4205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T11:04:06Z","timestamp":1765191846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/24\/4205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,7]]},"references-count":47,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["foods14244205"],"URL":"https:\/\/doi.org\/10.3390\/foods14244205","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,7]]}}}