What question did this study set out to answer?

This research aims to examine the role of baicalin-geniposide in reducing pulmonary inflammation and vascular injury after stroke.

April 19, 2026Open Access

Baicalin-geniposide attenuates pulmonary inflammation and vascular injury via HMGB1 blockade: insights from a cerebral ischemia-reperfusion model and implications for pulmonary hypertension

Puntos clave

This research aims to examine the role of baicalin-geniposide in reducing pulmonary inflammation and vascular injury after stroke.
Investigated BG's effects using both in vitro and in vivo models.
Co-cultured LPS-stimulated BV2 microglia and RAW264.7 macrophages for in vitro studies.
Utilized a rat model of middle cerebral artery occlusion/reperfusion for in vivo insights.
Administered BG at doses of 25-50 mg/kg in rat models.
Analyzed the impact on inflammatory markers and HMGB1 translocation.
BG decreased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and nitric oxide levels.
Significant reduction in cerebral infarct volume and neurological deficits observed.
BG effectively inhibited HMGB1 nucleocytoplasmic translocation via the JAK2/STAT3 pathway.
BG reduced lung edema and serum HMGB1 levels in treated rats.

Resumen

Introduction Pulmonary complications following stroke are a leading cause of death, with no targeted therapies available. Inflammation drives both post‐stroke neurological damage and secondary acute lung injury (CIS-ALI). High mobility group box 1 (HMGB1), a key mediator in cerebral ischemia stroke (CIS), translocates from the nucleus to cytoplasm and is released extracellularly, triggering inflammatory cascades. The combination of two bioactive metabolites, baicalin and geniposide (BG), exhibits anti‐inflammatory and neuroprotective properties, but its efficacy against CIS-ALI remains unexplored. This study investigated BG’s mechanisms using in vitro and in vivo models. Methods This study investigated the mechanisms of BG using in vitro and in vivo models. In vitro , LPS‐stimulated BV2 microglia and RAW264.7 macrophages were co‐cultured. In vivo , a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. BG was administered at doses of 25—50 mg/kg in rats. Results BG dose-dependently suppressed pro-inflammatory cytokines (TNF‐α, IL‐1β, IL‐6) and nitric oxide (NO), while attenuating HMGB1 nucleocytoplasmic translocation via JAK2/STAT3 inhibition. BG (25—50 mg/kg) reduced cerebral infarct volume, neurological deficits, and lung edema. Mechanistically, BG blocked HMGB1 nuclear export in ischemic brains, thereby decreasing HMGB1 levels in serum and lungs, and disrupting inflammatory cross-talk. Discussion These findings highlight BG’s unique capacity to concurrently mitigate cerebral injury and secondary ALI by targeting the JAK2/STAT3 axis, offering a safe, multi‐targeted strategy against CIS‐related complications. Given the shared pathological features between ALI and PH–including inflammation, vascular hyperpermeability, and JAK2/STAT3‐driven injury cascades–these findings provide a mechanistic rationale for exploring BG as a potential therapeutic candidate for pulmonary hypertension and related pulmonary vascular diseases.

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