Berberine alleviates pre‐eclampsia by modulating M1/M2 macrophage polarization and T helper (Th1/Th2) cells cytokine balance

Background and Purpose Pre‐eclampsia (PE) is a pregnancy‐associated disorder characterized by immune imbalance, inflammation and gut dysbiosis. It remains a major cause of maternal and foetal complications. This study aimed to explore the therapeutic effects of berberine, a key active compound from Coptidis Rhizoma , on immune regulation and gut microbiota in an LPS‐induced pre‐eclampsia mouse model. Experimental Approach In vivo , pregnant mice were administered lipopolysaccharide (LPS) to induce pre‐eclampsia‐like symptoms, followed by berberine treatment. Physiological parameters, placental histology, cytokine profiles and gut microbiota compositions were assessed. In vitro assays evaluated berberine impact on macrophage polarization and inflammatory responses. Key Results In vivo , berberine significantly reduced systolic and diastolic blood pressure, urinary protein levels and placental structural damage, while improving foetal and placental weights. It restored Th1/Th2 balance by reducing M1 macrophage markers (iNOS, IL‐1β, TNF‐α) and increasing M2 markers (ARG1, IL‐10, TGFβ1). Gut microbiota analysis revealed higher alpha diversity and distinct microbial composition in berberine‐treated mice, with genus‐level changes, including increased Muribaculaceae and reduced Mucispirillum . Functional predictions suggested pathways related to amino acid metabolism were modulated. In vitro assays confirmed that berberine promoted M2 polarization and suppressed M1‐related inflammatory responses in RAW264.7 macrophages. Mechanistically, berberine may interact with the HSP90/NF‐κB pathway to modulate M1/2 polarization. Conclusions and Implications Berberine exhibits potential as a multi‐target therapeutic agent for pre‐eclampsia by modulating immune responses and gut microbiota composition. These findings demonstrate berberine potential as a multi‐target therapeutic agent for pre‐eclampsia by modulating immune responses and gut microbiota.