Schisandra chinensis in sepsis intervention through multi-target mechanisms and organ protection

Sepsis is a life-threatening syndrome characterized by overwhelming inflammation, oxidative stress, immune imbalance, endothelial dysfunction, and progressive multiple organ injury. Schisandra chinensis (S. chinensis) and its bioactive constituents possess anti-inflammatory, antioxidant, immunomodulatory, and organ-protective properties, but their sepsis-related evidence has not been comprehensively summarized. This narrative review critically summarizes the current evidence on S. chinensis and its bioactive constituents in sepsis, with emphasis on inflammatory regulation, immune homeostasis, oxidative stress, endothelial dysfunction, regulated cell death, and sepsis-associated organ injury. PubMed/MEDLINE, Web of Science, Scopus, Google Scholar, China National Knowledge Infrastructure, and Wanfang Data were searched without restriction on publication year, and the reference lists of relevant publications were also screened. Eligible studies were narratively synthesized according to intervention type, experimental model, biological effects, signaling pathways, and organ outcomes, with evidence from isolated or chemically characterized constituents distinguished from that derived from multicomponent preparations. Current evidence, derived predominantly from in vitro and LPS- or CLP-induced animal studies, indicates that S. chinensis constituents may attenuate inflammatory responses, oxidative stress, ferroptosis, endothelial barrier disruption, and sepsis-associated lung and myocardial injury through the TLR4/MyD88/NF-κB, JAK2/STAT3, NLRP3, Nrf2/GPX4, RhoA/ROCK1/MLC and MAPK pathways. However, clinical evidence remains limited and is mainly based on multicomponent traditional Chinese medicine preparations, preventing determination of the independent contribution of S. chinensis. Overall, S. chinensis is a promising but investigational adjunctive candidate for sepsis. Future studies should prioritize chemically standardized preparations, pharmacokinetic and safety characterization, causal validation of reproducible mechanisms, and biomarker-based identification of responsive sepsis phenotypes before early-phase and randomized clinical trials.