{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:36:58Z","timestamp":1789547818070,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this work, a green extraction technique, subcritical water extraction (SBWE), was employed to extract active pharmaceutical ingredients (APIs) from an important Chinese medicinal herb, Salvia miltiorrhiza (danshen), at various temperatures. The APIs included tanshinone I, tanshinone IIA, protocatechualdehyde, caffeic acid, and ferulic acid. Traditional herbal decoction (THD) of Salvia miltiorrhiza was also carried out for comparison purposes. Reproduction assay of herbal extracts obtained by both SBWE and THD were then conducted on Caenorhabditis elegans so that SBWE conditions could be optimized for the purpose of developing efficacious herbal medicine from Salvia miltiorrhiza. The extraction efficiency was mostly enhanced with increasing extraction temperature. The quantity of tanshinone I in the herbal extract obtained by SBWE at 150 \u00b0C was 370-fold higher than that achieved by THD extraction. Reproduction evaluation revealed that the worm reproduction rate decreased and the reproduction inhibition rate increased with elevated SBWE temperatures. Most importantly, the reproduction inhibition rate of the SBWE herbal extracts obtained at all four temperatures investigated was higher than that of traditional herbal decoction extracts. The results of this work show that there are several benefits of subcritical water extraction of medicinal herbs over other existing herbal medicine preparation techniques. Compared to THD, the thousand-year-old and yet still popular herbal preparation method used in herbal medicine, subcritical water extraction is conducted in a closed system where no loss of volatile active pharmaceutical ingredients occurs, although analyte degradation may happen at higher temperatures. Temperature optimization in SBWE makes it possible to be more efficient in extracting APIs from medicinal herbs than the THD method. Compared to other industrial processes of producing herbal medicine, subcritical water extraction eliminates toxic organic solvents. Thus, subcritical water extraction is not only environmentally friendly but also produces safer herbal medicine for patients.<\/jats:p>","DOI":"10.3390\/molecules26061634","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T11:38:58Z","timestamp":1615808338000},"page":"1634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Subcritical Water Extraction of Salvia miltiorrhiza"],"prefix":"10.3390","volume":"26","author":[{"given":"Brahmam","family":"Kapalavavi","sequence":"first","affiliation":[{"name":"Department of Chemistry, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninad","family":"Doctor","sequence":"additional","affiliation":[{"name":"Department of Chemistry, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biology, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1124\/jpet.105.085712","article-title":"Can claims, misleading information, and manufacturing issues regarding dietary supplements be improved in the United States of America?","volume":"314","author":"Gibson","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jada.2004.11.002","article-title":"Increasing trends in elderly persons use of nonvitamin, nonmineral dietary supplements and concurrent use of medicines","volume":"105","author":"Wold","year":"2005","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Huang, K.C. (1999). The Pharmacology of Chinese Herbs, CRC Press.","DOI":"10.4324\/9780367801892"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"A750","DOI":"10.1289\/ehp.112-a750","article-title":"Botanical Supplements: Weeding out the health risks","volume":"112","author":"Taylor","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_5","unstructured":"Committee on the Framework for Evaluating the Safety of Dietary Supplements, Food and Nutrition Board, Board on Life Sciences, Institute of Medicine, and National Research Council of the National Academies of Science (2004). Dietary Supplements: A Framework for Evaluating Safety, National Academies Press."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S1570-0232(04)00647-6","article-title":"Extraction methods and chemical standardization of botanicals and herbal preparations","volume":"812","author":"Ong","year":"2004","journal-title":"J. Chromatogr. B"},{"key":"ref_7","first-page":"76","article-title":"Total phenolics, antioxidant, antitumor, and enzyme inhibitory activity of Indian medicinal and aromatic plants extracted with different extraction methods","volume":"7","author":"Nile","year":"2017","journal-title":"Biotech"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/jssc.201600711","article-title":"Rapid and sensitive determination of phytosterols in functional foods and medicinal herbs by using UHPLC\u2013MS\/MS with microwave-assisted derivatization combined with dual ultrasound-assisted dispersive liquid\u2013liquid microextraction","volume":"40","author":"Sun","year":"2017","journal-title":"J. Sep. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.supflu.2016.11.019","article-title":"Supercritical fluid extraction of Rumex Acetosa L. roots: Yield, composition, kinetics, bioactive evaluation and comparison with conventional techniques","volume":"122","author":"Santos","year":"2017","journal-title":"J. Supercrit. Fluids"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Camargo, A.P., Ib\u00e1\u00f1ez, E., Cifuentes, A., and Herrero, M. (2017). Bioactives Obtained from Plants, Seaweeds, Microalgae and Food By-Products Using Pressurized Liquid Extraction and Supercritical Fluid Extraction. Compr. Anal. Chem.","DOI":"10.1016\/bs.coac.2017.01.001"},{"key":"ref_11","unstructured":"Mukherjee, P.K. (2002). Extraction of herbal drugs. Quality Control of Herbal Drugs, An Approach to Evaluation of Botanicals, Business Horizons Pharmaceutical Publishers. [1st ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0021-9673(98)00222-2","article-title":"Elution of organic solutes from different polarity sorbents using subcritical water conditions","volume":"810","author":"Yang","year":"1998","journal-title":"J. Chromatogr. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/jssc.200700008","article-title":"Subcritical water chromatography: A green approach to high-temperature liquid chromatography","volume":"30","author":"Yang","year":"2007","journal-title":"J. Sep. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1021\/ac960729j","article-title":"Subcritical water chromatography with flame ionization detection","volume":"69","author":"Miller","year":"1997","journal-title":"Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.chroma.2007.07.002","article-title":"Superheated water chromatography\u2014A green technology for the future","volume":"1184","author":"Smith","year":"2008","journal-title":"J. Chromatogr. A."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Doctor, N., and Yang, Y. (2018). Separation and Analysis of Aspirin and Metformin HCl Using Green Subcritical Water Chromatography. Molecules, 23.","DOI":"10.3390\/molecules23092258"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Doctor, N., Parker, G., Vang, V., Smith, M., Kayan, B., and Yang, Y. (2020). Stability and Extraction of Vanillin and Coumarin under Subcritical Water Conditions. Molecules, 25.","DOI":"10.3390\/molecules25051061"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1021\/es960242s","article-title":"Class-selective extraction of polar, moderately-, and nonpolar organic pollutants from solid waste using subcritical water","volume":"31","author":"Yang","year":"1997","journal-title":"Environ. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.tifs.2020.01.014","article-title":"Recent advances in subcritical water and supercritical carbon dioxide extraction of bioactive compounds from plant materials","volume":"97","author":"Essien","year":"2020","journal-title":"Trends Food Sci. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.chroma.2006.11.037","article-title":"Terpene degradation and extraction from basil and oregano leaves using subcritical water","volume":"1152","author":"Yang","year":"2007","journal-title":"J. Chromatogr. A"},{"key":"ref_21","first-page":"191","article-title":"Subcritical water extraction of polyphenols from endemic Algerian plants with medicinal properties","volume":"51","author":"Abdelmoumen","year":"2020","journal-title":"Acta Period. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jchromb.2016.04.021","article-title":"High performance curcumin subcritical water extraction from turmeric (Curcuma longa L.)","volume":"1022","author":"Kiamahalleha","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.foodchem.2016.05.006","article-title":"Superheated water extraction of glycyrrhizic acid from licorice root","volume":"210","author":"Shabkhiz","year":"2016","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1097\/00007691-200210000-00010","article-title":"Effect of Chinese medicines Chan Su and Danshen on EMIT 2000 and Randox digoxin immunoassays: Wide variation in digoxin-like immunoreactivity and magnitude of interference in digoxin measurement by different brands of the same product","volume":"24","author":"Datta","year":"2002","journal-title":"Ther. Drug Monit."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/rcm.2447","article-title":"Characterization of tanshinones in the roots of Salvia miltiorrhiza (Dan-shen) by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry","volume":"20","author":"Yang","year":"2006","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_26","first-page":"2813","article-title":"Salvia miltiorrhiza: Chemical and pharmacological review of a medicinal plant","volume":"4","author":"Wang","year":"2010","journal-title":"J. Med. Plants Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/j.chroma.2008.12.032","article-title":"Advancement in analysis of Salviae miltiorrhizae Radix et Rhizoma (Danshen)","volume":"1216","author":"Li","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_28","first-page":"485","article-title":"Tanshinone I effectively induces apoptosis in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells","volume":"33","author":"Nizamutdinova","year":"2008","journal-title":"Int. J. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.bbrc.2012.11.018","article-title":"Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells","volume":"430","author":"Jeong","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/carcin\/14.7.1321","article-title":"Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids","volume":"14","author":"Tanaka","year":"1993","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/ijc.20880","article-title":"Potential anticancer activity of tanshinone IIA against human breast cancer","volume":"116","author":"Wang","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/dvdy.22247","article-title":"Cancer models in Caenorhabditis elegans","volume":"239","author":"Kirienko","year":"2010","journal-title":"Dev. Dyn."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1159\/000354772","article-title":"Space flight and ageing: Reflecting on Caenorhabditis elegans in space","volume":"60","author":"Honda","year":"2014","journal-title":"Gerontology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-1-4614-4015-4_5","article-title":"Physiological control of germline development","volume":"757","author":"Hubbard","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.cell.2006.09.035","article-title":"A C. elegans model of nicotine-dependent behavior: Regulation by TRP-family channels","volume":"127","author":"Feng","year":"2006","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00429-009-0235-3","article-title":"Understanding the molecular basis of Alzheimer\u2019s disease using a Caenorhabditis elegans model system","volume":"214","author":"Ewald","year":"2009","journal-title":"Brain Struct. Funct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.trac.2012.03.013","article-title":"Analytical Eco-Scale for assessing the greenness of analytical procedures","volume":"37","author":"Migaszewski","year":"2012","journal-title":"Trends Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.talanta.2018.01.013","article-title":"A new tool for the evaluation of the analytical procedure: Green Analytical Procedure Index","volume":"181","year":"2018","journal-title":"Talanta"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/6\/1634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:58Z","timestamp":1760160958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/6\/1634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["molecules26061634"],"URL":"https:\/\/doi.org\/10.3390\/molecules26061634","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,15]]}}}