{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:53:24Z","timestamp":1784123604350,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asia-Japan Research Institute, Ritsumeikan Asia-Japan Research Organization, Ritsumeikan University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Traditional Japanese medicines, i.e., Kampo medicines, consist of crude drugs (mostly plants) that have empirical pharmacological functions (\u2018Yakuno\u2019 in Japanese), such as clearing heat. Crude drugs with cold properties, such as Phellodendron bark, have the empirical function of clearing heat as they cool the body. Because we found that anti-inflammatory compounds were present in several crude drugs for clearing heat, it is speculated that the empirical function of clearing heat may be linked to anti-inflammatory activities. When 10 typical crude drugs were selected from 22 herbal crude drugs for clearing heat, we identified anti-inflammatory compounds in five crude drugs, including Phellodendron bark. In this study, the other crude drugs were extracted and partitioned with ethyl acetate (EtOAc) and n-butanol to obtain three crude fractions. All the EtOAc-soluble fractions, except that from Forsythia fruits, inhibited interleukin (IL)-1\u03b2-induced nitric oxide (NO) production in primary-cultured rat hepatocytes. Anti-inflammatory compounds were identified from these EtOAc-soluble fractions: baicalein from Scutellaria roots, (\u2212)-nyasol from Anemarrhena rhizomes, and loniflavone from Lonicera leaves and stems. (+)-Phillygenin was purified from Forsythia fruits by removing cytotoxic oleanolic and betulinic acids. These compounds suppressed the production of NO and cytokines in hepatocytes. Anti-inflammatory compounds were not purified from the EtOAc-soluble fraction of Rehmannia roots because of their low abundance. Collectively, these findings indicate that anti-inflammatory compounds are present in all 10 crude drugs for clearing heat, confirming that these anti-inflammatory compounds in crude drugs provide the empirical functions for clearing heat. Other empirical functions of Kampo medicine can also be explained by modern pharmacological activities.<\/jats:p>","DOI":"10.3390\/molecules30020416","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T10:32:15Z","timestamp":1737369135000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Crude Drugs for Clearing Heat Contain Compounds Exhibiting Anti-Inflammatory Effects in Interleukin-1\u03b2-Treated Rat Hepatocytes"],"prefix":"10.3390","volume":"30","author":[{"given":"Airi","family":"Fujii","sequence":"first","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Onishi","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nodoka","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Kajimura","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3828-4796","authenticated-orcid":false,"given":"Keita","family":"Minamisaka","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-5085","authenticated-orcid":false,"given":"Yuto","family":"Nishidono","sequence":"additional","affiliation":[{"name":"Research Organization of Science and Technology, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Shirako","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2383-4801","authenticated-orcid":false,"given":"Yukinobu","family":"Ikeya","sequence":"additional","affiliation":[{"name":"Research Organization of Science and Technology, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"},{"name":"Faculty of Pharmacy, Daiichi University of Pharmacy, Fukuoka 815-8511, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1117-2807","authenticated-orcid":false,"given":"Mikio","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, Faculty of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Shiga, Japan"},{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang 65113, East Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,19]]},"reference":[{"key":"ref_1","first-page":"77","article-title":"Anti-inflammatory effect of foods and crude drugs in relation to bitter and spicy tastes","volume":"2","author":"Ikeya","year":"2019","journal-title":"Bioact. 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