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Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rheumatoid arthritis (RA) is a systemic autoimmune disorder in which persistent synovitis drives progressive joint damage, often leading to functional limitation and a reduced quality of life.\n                      <jats:italic>Caulophyllum robustum<\/jats:italic>\n                      Maxim. (\n                      <jats:italic>C. robustum<\/jats:italic>\n                      ) has long been used in traditional medicine to manage RA. Although increasing experimental evidence has demonstrated its therapeutic potential, relevant studies remain fragmented across various fields.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      This review aims to systematically integrate current knowledge on the ethnopharmacology, phytochemistry, pharmacokinetics, anti-RA pharmacological mechanisms, and applications of emerging technologies related to\n                      <jats:italic>C. robustum<\/jats:italic>\n                      . By synthesizing evidence across multiple disciplines, we seek to clarify its material basis, mechanistic rationale, and therapeutic relevance in RA, thereby providing guidance for future research and drug development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To compile evidence on\n                      <jats:italic>C. robustum<\/jats:italic>\n                      , we searched multiple databases (Web of Science, PubMed, Google Scholar, Baidu Scholar, and CNKI) and additionally consulted classical Chinese medical texts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      To date, more than 100 compounds have been isolated and identified from\n                      <jats:italic>C. robustum<\/jats:italic>\n                      , among which triterpenoid saponins and alkaloids represent the principal bioactive constituents associated with anti-RA activity. Notably, saponin components exhibit interconversion and biotransformation behaviors\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Pharmacokinetic studies indicate rapid absorption but relatively slow elimination of key active constituents. Mechanistically,\n                      <jats:italic>C. robustum<\/jats:italic>\n                      extracts and representative components exert anti-RA effects by suppressing inflammatory responses, attenuating synovial hyperplasia, inhibiting pannus formation, protecting bone integrity, and restoring immune homeostasis. These actions appear to involve coordinated regulation of several pathways, notably NF-\u03baB, MAPK, JAK\/STAT, and PI3K\/Akt signaling. In addition, molecular docking, biomolecular interaction analyses, and multi-omics approaches provide further preclinical evidence that saponins and alkaloids from\n                      <jats:italic>C. robustum<\/jats:italic>\n                      interact with key targets, including HDACs and CD\n                      <jats:sub>81<\/jats:sub>\n                      . Through complementary, multi-target, and network-level regulation, these components collectively contribute to its anti-RA pharmacological activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This review provides a comprehensive and integrated overview of\n                      <jats:italic>C. robustum<\/jats:italic>\n                      , systematically consolidating research progress across diverse disciplines. By identifying current knowledge gaps and unresolved issues, it highlights critical directions for future investigation. Notably, all current pharmacological evidence for\n                      <jats:italic>C. robustum<\/jats:italic>\n                      is drawn exclusively from preclinical studies, with human pharmacokinetic or clinical validation still urgently needed.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1863086","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T09:45:47Z","timestamp":1783331147000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Caulophyllum robustum Maxim in the management of rheumatoid arthritis: a comprehensive review of ethnopharmacology, phytochemistry, pharmacokinetics, and pharmacological mechanisms"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyue","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of the Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Harbin University of Commerce","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyan","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixue","family":"Kuang","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowa","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10579","DOI":"10.1007\/s11033-023-08839-x","article-title":"Conjugated linoleic acid and glucosamine supplements may prevent bone loss in aging by regulating the RANKL\/RANK\/OPG pathway","volume":"50","author":"Abdulrahman","year":"2023","journal-title":"Mol. 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