Atractylodes macrocephala in Ulcerative Colitis: Bioactive Constituents, Microbiota, and Translational Gaps

Atractylodes macrocephala Koidz. rhizome (Atractylodis Macrocephalae Rhizoma, AMR; Bai-Zhu) is a widely used medicinal plant, and its specialized metabolites are now being mapped onto defined molecular targets. Existing reviews of this material are genus-wide, formula-level, or restricted to a single constituent class, and none grades the ulcerative-colitis (UC) evidence constituent by constituent while separating what has been demonstrated in colitis models from what is extrapolated from other disease contexts; that gap is the rationale for the present review. Here we review, constituent by constituent, how AMR acts in UC. The sesquiterpenoid lactones account for much of the activity: atractylenolide I protects the epithelial barrier (RhoA/ROCK/MLC; S100A9/AMPK/mTOR), reshapes intestinal metabolism and the microbiota (SPHK1/B4GALT2) and limits carbonic anhydrase IX-mediated ferroptosis, whereas atractylenolide II drives Nrf2-dependent antioxidant responses (in non-colitis models), and interleukin-17 receptor A is nominated as a candidate direct target of atractylenolide III—awaiting independent replication—through which it may curb macrophage M1 polarization. The polysaccharides rebalance Th17/Treg immunity and remodel the gut microbiota and its tryptophan metabolites with pregnane X receptor-associated signaling, while the volatile oil and vesicle-like particles are likewise protective. We grade each mechanism by the strength of the underlying colitis-model evidence and stay explicit about what remains extrapolation. Controlled human trials are still lacking, with only very preliminary clinical observation to date. Finally, we single out endothelial-leukocyte adhesion—already exploited by anti-adhesion biologics—as a promising but still untested hypothesis for translating these constituents toward the clinic.