{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:12:33Z","timestamp":1773670353367,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The study aimed to investigate the anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-biofilm activity of 3-methoxy-5-hydroxy-2-(3-methyl-2-butenyl) bibenzyl (DELC) isolated from Cajanus cajan (L.) Millsp (pigeon pea) leaves, while evaluating its biocompatibility and exploring its potential as an antibiotic alternative.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>DELC exhibited potent anti-MRSA activity, with a minimum inhibitory concentration (MIC) of 3.12\u00a0\u03bcg\/mL and MBC of 6.25\u00a0\u03bcg\/mL. At 2\u00a0\u00d7\u00a0MIC, it achieved complete eradication of 106 CFU\/mL MRSA within 120 min, demonstrating faster bactericidal action than vancomycin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Antibiofilm studies<\/jats:title>\n                    <jats:p>2\u00a0\u00d7\u00a0MIC DELC inhibited biofilm formation as effectively as 4\u00a0\u00d7\u00a0MIC vancomycin. In mature biofilms, merely 1\/2\u00a0\u00d7\u00a0MIC DELC penetrated and eliminated a portion of embedded viable bacteria\u2014a feat unattainable even with 8\u00a0\u00d7\u00a0MIC vancomycin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Mechanistic studies<\/jats:title>\n                    <jats:p>DELC induced oxidative stress, generating ROS that damaged the bacterial membrane, causing nucleic acid leakage. It also suppressed \u03b1-hemolysin secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RNA-seq analysis revealed<\/jats:title>\n                    <jats:p>At 1\u00a0\u00d7\u00a0MIC, DELC blocked ATP synthesis and repair systems, leading to metabolic inhibition and virulence attenuation. At\u00a0\u22652\u00a0\u00d7\u00a0MIC, it directly lysed bacterial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Biocompatibility<\/jats:title>\n                    <jats:p>DELC showed no hemolysis or cytotoxicity, indicating excellent safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DELC demonstrates potent anti-MRSA activity characterized by rapid bactericidal effects, a concentration-dependent dual mechanism\u2014metabolic inhibition at low concentrations progressing to direct cellular lysis at higher concentrations, and superior antibiofilm capacity. Its outstanding biocompatibility strongly supports its clinical translation potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxaf290","type":"journal-article","created":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T12:51:47Z","timestamp":1763902307000},"source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic study of 3-Methoxy-5-hydroxy-2-(3-methyl-2-butenyl) bibenzyl from pigeon pea against MRSA and biofilms: a highly promising natural inhibitor"],"prefix":"10.1093","volume":"136","author":[{"given":"Guang-Ying","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu-Bi","family":"Xiong","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou South China Business School Department of Hygiene and Health, , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long-Feng","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Dan","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9049-2992","authenticated-orcid":false,"given":"Jie-Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangzhou University of Chinese Medicine , Guangzhou 510006 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"2025121803570027400_bib10","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1007\/s11418-023-01727-5","article-title":"Four new stilbenes and one new flavonoid with potential antibacterial and\u00a0anti-SARS-CoV-2 activity from Cajanus cajan","volume":"77","author":"Chen","year":"2023","journal-title":"J Nat Med"},{"key":"2025121803570027400_bib1","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1128\/mmbr.00024-06","article-title":"How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria","volume":"70","author":"Deutscher","year":"2006","journal-title":"Microbiol Mol Biol Rev"},{"key":"2025121803570027400_bib2","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1111\/j.1462-2920.2006.01143.x","article-title":"Temporal gene-expression in Escherichia coli K-12 biofilms","volume":"9","author":"Domka","year":"2007","journal-title":"Environ Microbiol"},{"key":"2025121803570027400_bib3","doi-asserted-by":"publisher","first-page":"22871","DOI":"10.1038\/srep22871","article-title":"Structure of ThiM from vitamin B1 biosynthetic pathway of Staphylococcus aureus\u2014insights into a novel pro-drug approach addressing MRSA infections","volume":"6","author":"Drebes","year":"2016","journal-title":"Sci Rep"},{"key":"2025121803570027400_bib4","doi-asserted-by":"publisher","first-page":"6877","DOI":"10.3390\/molecules27206877","article-title":"Revisiting the nutritional, chemical and biological potential of Cajanus cajan (L.) 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