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Physicochemical interactions between the compounds may occur in the process of decoction, by which Kampo prescriptions are usually prepared for ingestion, and the interactions may change the extraction yields of the constituents. Berberine and baicalin have been reported to form precipitates. Orengedokuto, which consist of Coptis Rhizome, Gardenia Fruit, Phellodendron Bark and Scutellaria Root, has been a representative Kampo prescription used to treat inflammatory diseases. In our previous papers, we revealed that the precipitates formed in the decoction of orengedokuto without Gardenia Fruit mainly consists of berberine\u2013baicalin complex and that Gardenia Fruit reduced the amount of the precipitates in orengedokuto decoction. In this report, through solubility-enhancement assay based on HPLC, we identified crocins as the constituents of Gardenia Fruits, which enhanced the solubility of berberine\u2013baicalin complex. All-<jats:italic>trans<\/jats:italic> crocin-1 (<jats:bold>1<\/jats:bold>) and 13-<jats:italic>cis<\/jats:italic> crocin-1 (<jats:bold>5<\/jats:bold>) showed high activities among the isolated crocins, and the number of glucosyl groups in the molecule seemed correlated with the activity. As berberine and baicalin were reported as the anti-inflammatory constituents of Coptis Rhizome and Phellodendron Bark, and Scutellaria Root, respectively, Gardenia Fruit contributes anti-inflammatory activity of orengedokuto by increasing solubilities of anti-inflammatory constituents of the other component crude drugs in the prescription. Our result will add a scientific basis to the understanding of the effectiveness of orengedokuto as a whole.<\/jats:p>","DOI":"10.1007\/s11418-020-01446-1","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T10:04:41Z","timestamp":1598609081000},"page":"76-83","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Solubility enhancement of berberine\u2013baicalin complex by the constituents of Gardenia Fruit"],"prefix":"10.1007","volume":"75","author":[{"given":"Kazuki","family":"Okoshi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Uekusa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Narukawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9338-5047","authenticated-orcid":false,"given":"Fumiyuki","family":"Kiuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,28]]},"reference":[{"key":"1446_CR1","first-page":"138","volume":"34","author":"T Tomimori","year":"1980","unstructured":"Tomimori T, Yoshimoto M (1980) Quantitative variation of glycyrrhizin in the decoction of Glycyrrhizae Radix mixed with other crude drugs. 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