{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:48:23Z","timestamp":1791420503855,"version":"4.3.3"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Plant Sci."],"abstract":"<jats:p><jats:italic>Salvia plebeia<\/jats:italic> (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in <jats:italic>S. plebeia.<\/jats:italic> We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in <jats:italic>S. plebeia<\/jats:italic>. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including <jats:italic>SpPAL<\/jats:italic>, <jats:italic>SpC4H<\/jats:italic>, <jats:italic>Sp4CL2<\/jats:italic>, <jats:italic>Sp4CL5<\/jats:italic>, <jats:italic>SpCHS1<\/jats:italic>, <jats:italic>SpCHI<\/jats:italic>, <jats:italic>SpFNS<\/jats:italic>, <jats:italic>SpF6H1<\/jats:italic>, <jats:italic>SpF6OMT1<\/jats:italic>, <jats:italic>SpF6OMT2<\/jats:italic>, <jats:italic>SpUGT1<\/jats:italic>, <jats:italic>SpUGT2<\/jats:italic>, and <jats:italic>SpUGT3<\/jats:italic>. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in <jats:italic>Escherichia coli<\/jats:italic>, and obtained a yield of 5.33 and 3.86 mg\/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of <jats:italic>S. plebeia<\/jats:italic> during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components.<\/jats:p>","DOI":"10.3389\/fpls.2023.1228356","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T03:45:51Z","timestamp":1692071151000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients"],"prefix":"10.3389","volume":"14","author":[{"given":"Yiqun","family":"Dai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjian","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116599","article-title":"Hispidulin exhibits neuroprotective activities against cerebral ischemia reperfusion injury through suppressing NLRP3-mediated pyroptosis","volume":"232","author":"An","year":"2019","journal-title":"Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.pbi.2005.03.007","article-title":"Glycosyltransferases: managers of small molecules","volume":"8","author":"Bowles","year":"2005","journal-title":"Curr. Opin. Plant Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e115149","DOI":"10.1371\/journal.pone.0115149","article-title":"Computational identification and systematic classification of novel cytochrome P450 genes in Salvia miltiorrhiza","volume":"9","author":"Chen","year":"2014","journal-title":"PloS One"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.598556","article-title":"Anticancer effect of Salvia plebeia and its active compound by improving T-cell activity via blockade of PD-1\/PD-L1 interaction in humanized PD-1 mouse model","volume":"11","author":"Choi","year":"2020","journal-title":"Front. Immunol."},{"key":"B5","volume-title":"Pharmacopoeia of the People\u2019s Republic of China","year":"1997"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1002\/ptr.7797","article-title":"Homoplantaginin attenuates high glucose-induced vascular endothelial cell apoptosis through promoting autophagy via the AMPK\/TFEB pathway","volume":"37","author":"Fan","year":"2023","journal-title":"Phytother. Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113156","article-title":"Glycorandomization: A promising diversification strategy for the drug development","volume":"213","author":"Goel","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.16438\/j.0513-4870.2021-0962","article-title":"Discovery and functional characterization of flavone O-glycosyltransferases in Scutellaria baicalensis","volume":"56","author":"Han","year":"2021","journal-title":"Acta Pharm. Sin."},{"key":"B9","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1097\/FJC.0000000000000318","article-title":"Homoplantaginin inhibits palmitic acid-induced endothelial cells inflammation by suppressing TLR4 and NLRP3 inflammasome","volume":"67","author":"He","year":"2016","journal-title":"J. Cardiovasc. Pharm."},{"key":"B10","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3892\/ol.2021.12892","article-title":"Rosmanol induces breast cancer cells apoptosis by regulating PI3K\/AKT and STAT3\/JAK2 signaling pathways","volume":"22","author":"Jiang","year":"2021","journal-title":"Oncol. Lett."},{"key":"B11","volume-title":"Jiang Su Chinese Materia Medica Standards","year":"2016"},{"key":"B12","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ymben.2018.11.008","article-title":"Production of plant-specific flavones baicalein and scutellarein in an engineered E. coli from available phenylalanine and tyrosine","volume":"52","author":"Li","year":"2019","journal-title":"Metab. Eng."},{"key":"B13","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/S1875-5364(10)60034-9","article-title":"Quantitative evaluation of 4-Coumarate: CoA Ligase (4CL) activity and correlated chemical constituents in four plant materials by chromatographic analysis","volume":"8","author":"Li","year":"2010","journal-title":"Chin. J. Nat. Med."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111843","article-title":"Salvia plebeia R. Br. polysaccharides (SPP) against RSV (respiratory syncytial virus) infection: Antiviral effect and mechanisms of action","volume":"141","author":"Liang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109589","article-title":"Salvia plebeia R. Br.: an overview about its traditional uses, chemical constituents, pharmacology and modern applications","volume":"121","author":"Liang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ejphar.2015.02.041","article-title":"Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats","volume":"755","author":"Lin","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"118359","DOI":"10.1016\/j.lfs.2020.118395","article-title":"Hispidulin: a promising flavonoid with diverse anti-cancer properties","volume":"259","author":"Liu","year":"2020","journal-title":"Life Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(T) (-Delta Delta C) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1104\/pp.17.01183","article-title":"Carnosic acid and carnosol, two major antioxidants of Rosemary, act through different mechanisms","volume":"175","author":"Loussouarn","year":"2017","journal-title":"Plant Physiol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/plants7020030","article-title":"Flavonoid functions in plants and their interactions with other organisms","volume":"7","author":"Mathesius","year":"2018","journal-title":"Plants-Basel"},{"key":"B21","doi-asserted-by":"publisher","first-page":"107316","DOI":"10.1016\/j.bioteChadv.2018.11.005","article-title":"Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering","volume":"38","author":"Nabavi","year":"2020","journal-title":"Biotechnol. Adv."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1105\/tpc.108.063826","article-title":"Local differentiation of sugar donor specificity of flavonoid glycosyltransferase in Lamiales","volume":"21","author":"Noguchi","year":"2009","journal-title":"Plant Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12864-022-08391-1","article-title":"Characterization of UDP-glycosyltransferase family members reveals how major flavonoid glycoside accumulates in the roots of Scutellaria baicalensis","volume":"23","author":"Pei","year":"2022","journal-title":"BMC Genomics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.plaphy.2013.02.001","article-title":"The flavonoid biosynthetic pathway in Arabidopsis: Structural and genetic diversity","volume":"72","author":"Saito","year":"2013","journal-title":"Plant Physiol. Biochem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.3390\/nu12082260","article-title":"Immunomodulatory effect of a Salvia plebeia R. aqueous extract in forced swimming exercise-induced mice","volume":"12","author":"Shin","year":"2020","journal-title":"Nutrients"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2021.712038","article-title":"Integrated metabolomics and transcriptome analysis of flavonoid biosynthesis in Safflower (Carthamus tinctorius L.) with different colors","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Plant Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3969\/j.issn.1006-9690.2010.04.009","article-title":"Study on the flavanoids in different collection period of Salvia plebeia R.Br. by HPLC","volume":"29","author":"Wang","year":"2010","journal-title":"Chin. Wild Plant Resour."},{"key":"B28","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.gpb.2020.06.002","article-title":"Comparative genome analysis of Scutellaria baicalensis and Scutellaria barbata reveals the evolution of active flavonoid biosynthesis","volume":"18","author":"Xu","year":"2020","journal-title":"Genomics Proteomics Bioinf."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1002\/1873-3468.12312","article-title":"Enzymatic production of oroxylin A and hispidulin using a liverwort flavone 6-O-methyltransferase","volume":"590","author":"Zhang","year":"2016","journal-title":"FEBS Lett."},{"key":"B30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.molp.2017.08.009","article-title":"Two CYP82D enzymes function as flavone hydroxylases in the biosynthesis of root-specific 4\u2019-Deoxyflavones in Scutellaria baicalensis","volume":"11","author":"Zhao","year":"2018","journal-title":"Mol. Plant"},{"key":"B31","doi-asserted-by":"publisher","first-page":"10440","DOI":"10.3390\/molecules190710440","article-title":"Dynamic changes of flavonoids contents in the different parts of rhizome of Belamcanda chinensis during the thermal drying process","volume":"19","author":"Zhu","year":"2014","journal-title":"Molecules"}],"container-title":["Frontiers in Plant Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2023.1228356\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T03:46:52Z","timestamp":1692071212000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2023.1228356\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,14]]},"references-count":31,"alternative-id":["10.3389\/fpls.2023.1228356"],"URL":"https:\/\/doi.org\/10.3389\/fpls.2023.1228356","relation":{},"ISSN":["1664-462X"],"issn-type":[{"value":"1664-462X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,14]]},"article-number":"1228356"}}