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

Introduction: models. Methods: , 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.