{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:54:21Z","timestamp":1777100061568,"version":"3.51.4"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A2040"],"award-info":[{"award-number":["U20A2040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Radix Scutellariae, a crucial botanical drug widely used in Asian countries, is derived from the roots of\n Scutellaria baicalensis<\/jats:italic>\n Georgi and exhibits diverse pharmacological activities, including antipyretic, analgesic, anti-inflammatory, antibacterial, antiviral, sedative, hypotensive, hypolipidemic, hepatoprotective, and choleretic effects. Owing to excessive market demand, the wild resources are insufficient, and cultivated Radix Scutellariae has thus become the primary source; however, this shift has resulted in a decline in medicinal quality. To address this quality issue, the present study proposes the hypothesis that exogenous nitric oxide (NO) enhances secondary metabolism in fresh roots of\n S. baicalensis<\/jats:italic>\n Georgi via reactive oxygen species (ROS)-mediated pathways, thereby improving its medicinal quality. Fresh roots of\n S. baicalensis<\/jats:italic>\n Georgi were treated with sodium nitroprusside (SNP) at concentrations of 0.0, 7.5, and 20 mmol\/L to induce ROS bursts. At the optimal concentration of 20 mmol\/L SNP, the levels of superoxide anion radicals (O\n 2<\/jats:sub>\n \u00b7\u207b), hydrogen peroxide (H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n ), and malondialdehyde (MDA) increased by 95.1%, 134.5%, and 211.5%, respectively (\n P<\/jats:italic>\n \u2009<\u20090.01). Correspondingly, the activities of antioxidant enzymes\u2014including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)\u2014rose by 87.2%, 47.5%, and 59.4%, respectively (\n P<\/jats:italic>\n \u2009<\u20090.01). The activity of phenylalanine ammonia-lyase (PAL), a key enzyme in flavonoid biosynthesis, increased by 70% (\n P<\/jats:italic>\n \u2009<\u20090.01). While the contents of major secondary metabolites (baicalin and wogonoside) remained stable, the levels of their high-activity derivatives (baicalein and wogonin) increased dramatically by 1603.2% and 1256.1%, respectively (\n P<\/jats:italic>\n \u2009<\u20090.01). Pharmacological assays revealed that 20 mmol\/L SNP treatment enhanced pharmacological activities: the inhibition rate of body temperature elevation in rats, the inhibition rate of writhing response in mice, and the inhibition rate of auricular swelling in mice increased by 11.7%, 14.9%, and 27.4% (\n P<\/jats:italic>\n \u2009<\u20090.01), respectively. This treatment also reduced serum interleukin-6 (IL-6) and tumor necrosis factor-\n \u03b1<\/jats:italic>\n (TNF-\n \u03b1<\/jats:italic>\n ) levels in mice by 13.5% and 16.8% (\n P<\/jats:italic>\n \u2009<\u20090.01), respectively. Collectively, this study confirms that exogenous NO induces ROS bursts in fresh\n S. baicalensis<\/jats:italic>\n Georgi roots and improves the quality of cultivated Radix Scutellariae via ROS-mediated enhancement of secondary metabolism, and clarifies the NO-ROS-secondary metabolism regulatory axis, providing valuable insights for quality improvement strategies of other medicinal plants.\n <\/jats:p>","DOI":"10.1371\/journal.pone.0339961","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:27:34Z","timestamp":1767205654000},"page":"e0339961","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biological studies on exogenous NO stress to improve the quality of Radix Scutellariae herbs"],"prefix":"10.1371","volume":"20","author":[{"given":"Kai","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafei","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jincai","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2911-8885","authenticated-orcid":true,"given":"Xiangcai","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"pone.0339961.ref001","doi-asserted-by":"crossref","first-page":"113198","DOI":"10.1016\/j.jep.2020.113198","article-title":"Traditional uses, ten-years research progress on phytochemistry and pharmacology, and clinical studies of the genus Scutellaria","volume":"265","author":"J Shen","year":"2021","journal-title":"J Ethnopharmacol"},{"issue":"9","key":"pone.0339961.ref002","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/jphp.13129","article-title":"Scutellaria baicalensis Georgi. 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metabolism","volume":"6","author":"G Huimin","year":"2016","journal-title":"Int J Pharm Investig"},{"issue":"2","key":"pone.0339961.ref016","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0304-4165(95)00158-1","article-title":"Generation of reactive oxygen species by the redox cycling of nitroprusside","volume":"1289","author":"DN Ramakrishna Rao","year":"1996","journal-title":"Biochim Biophys Acta"},{"issue":"10","key":"pone.0339961.ref017","first-page":"403","article-title":"Nitric Oxide Enhances Cytotoxicity of Lead by Modulating the Generation of Reactive Oxygen Species and Is Involved in the Regulation of Pb2+ and Ca2+ Fluxes in Tobacco BY-2 Cells","volume":"8","author":"J Wu","year":"2019","journal-title":"Plants (Basel)"},{"key":"pone.0339961.ref018","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0891-5849(98)00093-8","article-title":"The basic chemistry of nitrogen monoxide and peroxynitrite","volume":"25","author":"WH Koppenol","year":"1998","journal-title":"Free Radic Biol Med"},{"issue":"3","key":"pone.0339961.ref019","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/jxb\/eraa440","article-title":"Nitric oxide and hydrogen sulfide modulate the NADPH-generating enzymatic system in higher plants","volume":"72","author":"FJ Corpas","year":"2021","journal-title":"J Exp Bot"},{"issue":"3","key":"pone.0339961.ref020","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1023\/A:1020336626361","article-title":"Involvement and interaction of various signaling compounds on the plant metabolic events during defense response, resistance to stress factors, formation of secondary metabolites and their molecular aspects","volume":"71","author":"G Sudha","year":"2002","journal-title":"Plant Cell Tiss Org Cult"},{"key":"pone.0339961.ref021","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.foodchem.2019.04.010","article-title":"Effect of sodium nitroprusside treatment on 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Cao","year":"2022","journal-title":"PeerJ"},{"issue":"8","key":"pone.0339961.ref040","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.3390\/molecules28083599","article-title":"The Classification, Molecular Structure and Biological Biosynthesis of Flavonoids, and Their Roles in Biotic and Abiotic Stresses","volume":"28","author":"W-B Zhuang","year":"2023","journal-title":"Molecules"},{"issue":"19","key":"pone.0339961.ref041","first-page":"2519","article-title":"Antioxidant and Anti-Inflammatory Activities of Endemic Plants of the Australian Wet Tropics","volume":"11","author":"K Yeshi","year":"2022","journal-title":"Plants (Basel)"},{"issue":"3","key":"pone.0339961.ref042","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.jep.2006.09.036","article-title":"Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats","volume":"110","author":"T Lu","year":"2007","journal-title":"J Ethnopharmacol"},{"issue":"45","key":"pone.0339961.ref043","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-1296.176063","article-title":"H2O2 Improves Quality of Radix scutellariae Through Anti-oxidant Effect","volume":"12","author":"S Qi","year":"2016","journal-title":"Pharmacogn Mag"},{"issue":"11","key":"pone.0339961.ref044","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1007\/s11427-013-4562-5","article-title":"Effects of ecological factors on secondary metabolites and inorganic elements of Scutellaria baicalensis and analysis of geoherblism","volume":"56","author":"L Guo","year":"2013","journal-title":"Sci China Life Sci"},{"issue":"7","key":"pone.0339961.ref045","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/pca.3402","article-title":"Rapid and comprehensive quality evaluation of Huang-qin from different origins by FT-IR and NIR spectroscopy combined with chemometrics","volume":"35","author":"K Lv","year":"2024","journal-title":"Phytochem Anal"},{"issue":"1","key":"pone.0339961.ref046","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/13880209.2018.1492620","article-title":"A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis","volume":"56","author":"Z-L Wang","year":"2018","journal-title":"Pharm Biol"},{"issue":"6","key":"pone.0339961.ref047","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/jps.20593","article-title":"Investigation of the absorption mechanisms of baicalin and baicalein in rats","volume":"95","author":"L Taiming","year":"2006","journal-title":"J Pharm Sci"},{"issue":"26","key":"pone.0339961.ref048","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.3748\/wjg.v28.i26.3047","article-title":"Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review","volume":"28","author":"R Ganguly","year":"2022","journal-title":"World 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