{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:48:35Z","timestamp":1785829715246,"version":"3.56.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Background and aim<\/jats:title>\n Currently, the preparation and evaluation of botanical placebos for decoctions lack standardization. This study conducted a multidimensional evaluation of an inert excipient decoction placebo for Chaihu-Shugan-San (CSS) and three low-dose CSS formulations, to determine the optimal CSS formulation for use in the control group of clinical randomized controlled trials. The Four Pillars of Best Practice in Ethnopharmacology guided the analysis.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n CSS was diluted 40-fold, 20-fold, and 10-fold, according to traditional simulated decoction production methods, to obtain 2.5% CSS, 5% CSS, and 10% CSS formulations. These were evaluated together with a pure excipient placebo (pure excipient PBO), consisting solely of excipients and additives. Four CSS decoction formulations were compared for color, odor, and taste using a human scoring method (Likert scale, n = 30). Along with intelligent sensory tools such as a colorimeter, electronic nose, and electronic tongue. Concurrently, the potential pharmacological effects of 4\u00a0CSS decoction formulations were examined in animal experiments, including gastric emptying and small intestinal propulsion (n = 80), hot plate analgesia, and the xylene ear swelling test (n = 49).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Manual scoring method indicated that the 10% CSS, 5% CSS and 2.5% CSS (difference, 1.57, 1.26 and 0.96 points, respectively,\n P<\/jats:italic>\n &lt; 0.01, power = 0.95) scored higher than the pure excipient PBO, with no significant difference in similarity between 5% CSS and 10% CSS (\n P<\/jats:italic>\n &gt; 0.05, power = 0.95). The intelligent sensory instrument results revealed that pure excipient PBO displayed the closest color match to the CSS decoction (\n \u0394E<\/jats:italic>\n = 2.05), while 10% CSS most closely approximated the CSS decoction in odor. Taste differences between the 4\u00a0CSS formulations and CSS were significant. Pharmacological studies found no statistically significant differences between the 4\u00a0CSS formulation groups and the control group in gastric emptying rate or small intestine propulsive motility (\n P<\/jats:italic>\n &gt; 0.05, power = 0.95) nor in ear swelling intensity (\n H<\/jats:italic>\n = 8.935,\n P<\/jats:italic>\n = 0.177) or pain threshold (\n P<\/jats:italic>\n &gt; 0.05, power = 0.004).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n 10% CSS and 5% CSS, while most similar in appearance to the CSS decoction, did not show superior in improving gastrointestinal motility, anti-inflammatory properties, or analgesic efficacy. However, their safety profile still requires future validation through animal models and quantitative mass spectrometry analysis.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1806757","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:23:44Z","timestamp":1785828224000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional evaluation of four chaihu-shugan-san simulated decoction for use as placebo controls: a comparative study"],"prefix":"10.3389","volume":"17","author":[{"given":"Kaiyue","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]},{"name":"Graduate School, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese, Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","volume-title":"Standards for the Conduct of Clinical Trials of Pharmaceutical Products","author":"Agency","year":"2018"},{"key":"B2","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cct.2007.06.005","article-title":"Who controls the placebo? 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