{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:20:58Z","timestamp":1784884858977,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T00:00:00Z","timestamp":1480982400000},"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>Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the quality and quantity of an herbal formulation (Chinese name: Yin-Chen-Hao-Tang) using physical and chemical examinations. Physical examination of Yin-Chen-Hao-Tang in pharmaceutical herbal products, raw fiber powders, and decoction preparations was performed using Congo red and iodine-potassium staining. A sensitive and validated method employing ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS\/MS) was developed to simultaneously quantify the bioactive compounds scoparone, geniposide, and rhein in the Yin-Chen-Hao-Tang formulation in different preparations. Physical examination indicated that cellulose fibers with irregular round shapes were present in the pharmaceutical herbal products. The developed UHPLC-MS\/MS method showed good linearity and was well validated. The quantification results revealed that the decoction preparations had the highest amounts of geniposide and rhein. Scoparone appeared in pharmaceutical herbal products from two manufacturers. This experiment provides a qualitative and quantitative method using physical and chemical examinations to test different preparations of herbal products. The results provide a reference for clinical herbal product preparations and further pharmacokinetic research.<\/jats:p>","DOI":"10.3390\/molecules21121673","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T10:07:17Z","timestamp":1481018837000},"page":"1673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Using Light Microscopy and Liquid Chromatography Tandem Mass Spectrometry for Qualitative and Quantitative Control of a Combined Three-Herb Formulation in Different Preparations"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-7961","authenticated-orcid":false,"given":"Tun-Pin","family":"Hsueh","sequence":"first","affiliation":[{"name":"Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Department of Traditional Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, E-DA Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9007-2547","authenticated-orcid":false,"given":"Tung-Hu","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan"},{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1093\/chromsci\/bmu226","article-title":"Subzero-temperature liquid-liquid extraction coupled with UPLC-MS-MS for the simultaneous determination of 12 bioactive components in traditional Chinese medicine gegen-qinlian decoction","volume":"53","author":"Shi","year":"2015","journal-title":"J. Chromatogr. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jpba.2013.10.002","article-title":"Quantitative analysis of flavonoids, alkaloids and saponins of Banxia Xiexin decoction using ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry","volume":"88","author":"Wang","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.3390\/molecules19044058","article-title":"Determination of bioactive components in Chinese herbal formulae and pharmacokinetics of rhein in rats by UPLC-MS\/MS","volume":"19","author":"Hou","year":"2014","journal-title":"Molecules"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/chromsci\/bmu051","article-title":"Detection and chemical profiling of Ling-Gui-Zhu-Gan decoction by ultra performance liquid chromatography-hybrid linear ion trap-orbitrap mass spectrometry","volume":"53","author":"Wang","year":"2015","journal-title":"J. Chromatogr. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/BF02977716","article-title":"Scoparone from artemisia capillaris inhibits the release of inflammatory mediators in RAW 264.7 cells upon stimulation cells by interferon-gamma Plus LPS","volume":"28","author":"Jang","year":"2005","journal-title":"Arch. Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kim, K.S., Yang, H.J., Lee, J.Y., Na, Y.C., Kwon, S.Y., Kim, Y.C., Lee, J.H., and Jang, H.J. (2014). Effects of beta-sitosterol derived from artemisia capillaris on the activated human hepatic stellate cells and dimethylnitrosamine-induced mouse liver fibrosis. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-363"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1055\/s-2004-818978","article-title":"Geniposide, an anti-angiogenic compound from the fruits of Gardenia jasminoides","volume":"70","author":"Koo","year":"2004","journal-title":"Planta Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.jep.2005.08.011","article-title":"Anti-inflammatory evaluation of gardenia extract, geniposide and genipin","volume":"103","author":"Koo","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4062\/biomolther.2013.005","article-title":"Protective effects of geniposide and genipin against hepatic ischemia\/reperfusion injury in mice","volume":"21","author":"Kim","year":"2013","journal-title":"Biomol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/ptr.2572","article-title":"Inhibition of cytochrome p450 enzymes by rhein in rat liver microsomes","volume":"23","author":"Tang","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_11","first-page":"1113","article-title":"Emodin, aloe-emodin and rhein inhibit migration and invasion in human tongue cancer SCC-4 cells through the inhibition of gene expression of matrix metalloproteinase-9","volume":"36","author":"Chen","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.3748\/wjg.v19.i26.4137","article-title":"Effects of rhein on intestinal epithelial tight junction in IgA nephropathy","volume":"19","author":"Peng","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s10753-011-9407-4","article-title":"ER stress, P66shc, and p-Akt\/Akt mediate adjuvant-induced inflammation, which is blunted by argirein, a supermolecule and rhein in rats","volume":"35","author":"Cong","year":"2012","journal-title":"Inflammation"},{"key":"ref_14","first-page":"1261","article-title":"Protective effect of rhein against oxidative stress-related endothelial cell injury","volume":"5","author":"Zhong","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jbiotec.2008.04.010","article-title":"Global transcriptional response of Staphylococcus aureus to rhein, a natural plant product","volume":"135","author":"Yu","year":"2008","journal-title":"J. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jpba.2008.07.028","article-title":"Metabolic urinary profiling of alcohol hepatotoxicity and intervention effects of Yin Chen Hao Tang in rats using ultra-performance liquid chromatography\/electrospray ionization quadruple time-of-flight mass spectrometry","volume":"48","author":"Wang","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jpba.2007.11.014","article-title":"Analysis of the constituents in the rat plasma after oral administration of Yin Chen Hao Tang by UPLC\/Q-TOF-MS\/MS","volume":"46","author":"Wang","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jep.2006.07.042","article-title":"Herb medicine Yin-Chen-Hao-Tang ameliorates hepatic fibrosis in bile duct ligation rats","volume":"109","author":"Lee","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1211\/jpp.59.4.0014","article-title":"Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in rats","volume":"59","author":"Lee","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3892\/ijmm_00000412","article-title":"Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis","volume":"25","author":"Lee","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.antiviral.2007.08.012","article-title":"Yin Chen Hao Tang, a Chinese prescription, inhibits both herpes simplex virus type-1 and type-2 infections in vitro","volume":"77","author":"Cheng","year":"2008","journal-title":"Antiviral. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3390\/molecules21010126","article-title":"Serum metabolomic characterization of liver fibrosis in rats and anti-fibrotic effects of Yin-Chen-Hao-Tang","volume":"21","author":"Zhang","year":"2016","journal-title":"Molecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18520","DOI":"10.3390\/ijms140918520","article-title":"Differential polarization nonlinear optical microscopy with adaptive optics controlled multiplexed beams","volume":"14","author":"Samim","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S0021-9258(18)64226-7","article-title":"Physical properties of starch. I. Relationship between iodine stain and chain length","volume":"236","author":"Bailey","year":"1961","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1002\/rcm.3296","article-title":"Development of a rapid and validated method for investigating the metabolism of scoparone in rat using ultra-performance liquid chromatography\/electrospray ionization quadruple time-of-flight mass spectrometry","volume":"21","author":"Wang","year":"2007","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.microc.2007.02.005","article-title":"Determinations of geniposide using LC\/MS\/MS methods via forming ammonium and acetate adducts","volume":"86","author":"Wang","year":"2007","journal-title":"Microchem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1002\/jssc.201401197","article-title":"An ultra high performance liquid chromatography with tandem mass spectrometry method for plasma and cerebrospinal fluid pharmacokinetics of rhein in patients with traumatic brain injury after administration of rhubarb decoction","volume":"38","author":"Wang","year":"2015","journal-title":"J. Sep. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0021-9673(02)01385-7","article-title":"Aqueous two-phase extraction as an effective tool for isolation of geniposide from gardenia fruit","volume":"977","author":"Pan","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0021-9673(02)00365-5","article-title":"Identification and determination of geniposide contained in Gardenia jasminoides and in two preparations of mixed traditional Chinese medicines","volume":"961","author":"Tsai","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jep.2013.07.022","article-title":"A novel concept for detoxification: complexation between aconitine and liquiritin in a Chinese herbal formula (\u2018Sini Tang\u2019)","volume":"149","author":"Peter","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.fitote.2011.07.014","article-title":"An in vivo analysis of the therapeutic and synergistic properties of Chinese medicinal formula Yin-Chen-Hao-Tang based on its active constituents","volume":"82","author":"Zhang","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/ptr.5266","article-title":"Anti-fibrotic and anti-tumorigenic effects of rhein, a natural anthraquinone derivative, in mammalian stellate and carcinoma cells","volume":"29","author":"Tsang","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/jssc.200700376","article-title":"Quality evaluation of Yin Chen Hao Tang extract based on fingerprint chromatogram and simultaneous determination of five bioactive constituents","volume":"31","author":"Wang","year":"2008","journal-title":"J. Sep. Sci."},{"key":"ref_34","unstructured":"Food and Drug Administration Center for Drug Evaluation and Research (2001). Guidance for Industry: Bioanalytical Method Validation, Available online: http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm368107.pdf2007."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/12\/1673\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:05Z","timestamp":1760210885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/12\/1673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,6]]},"references-count":34,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["molecules21121673"],"URL":"https:\/\/doi.org\/10.3390\/molecules21121673","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,6]]}}}