Caulophyllum robustum extracts show anti-inflammatory and bone protective activity in preclinical models of rheumatoid arthritisCaulophyllum robustum Shows Potential Activity Against Rheumatoid Arthritis

BackgroundRheumatoid 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. Caulophyllum robustum Maxim. (C. robustum) 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.PurposeThis review aims to systematically integrate current knowledge on the ethnopharmacology, phytochemistry, pharmacokinetics, anti-RA pharmacological mechanisms, and applications of emerging technologies related to C. robustum. 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.MethodsTo compile evidence on C. robustum, we searched multiple databases (Web of Science, PubMed, Google Scholar, Baidu Scholar, and CNKI) and additionally consulted classical Chinese medical texts.ResultsTo date, more than 100 compounds have been isolated and identified from C. robustum, among which triterpenoid saponins and alkaloids represent the principal bioactive constituents associated with anti-RA activity. Notably, saponin components exhibit interconversion and biotransformation behaviors in vivo. Pharmacokinetic studies indicate rapid absorption but relatively slow elimination of key active constituents. Mechanistically, C. robustum 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-κB, 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 C. robustum interact with key targets, including HDACs and CD81. Through complementary, multi-target, and network-level regulation, these components collectively contribute to its anti-RA pharmacological activity.ConclusionThis review provides a comprehensive and integrated overview of C. robustum, 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 C. robustum is drawn exclusively from preclinical studies, with human pharmacokinetic or clinical validation still urgently needed.