Huoxiang Zhengqi dropping pills alleviate exertional heat stroke–induced multiple organ injury through sustaining intestinal homeostasis via regulating MAPK/NF-κB pathway and gut microbiota in rats

Exertional heat stroke (EHS) is a life-threatening condition characterized by hyperthermia and multi-organ dysfunction, often associated with intestinal barrier disruption. This study evaluated the protective effects of Huoxiang Zhengqi Dropping Pills (HXZQD) against EHS in a rat model. HXZQD was administered via oral gavage at low, medium, and high doses, followed by EHS induction through exercise under high-temperature and high-humidity conditions. The findings revealed that high-dose HXZQD significantly delayed the onset of EHS, reduced core body temperature elevations, and mitigated multi-organ injury, as evidenced by biochemical markers and histopathological examination. This study showed that HXZQD alleviated EHS-induced intestinal damage by preserving barrier proteins (ZO-1, Occludin, and Ecadherin) and maintaining intestinal barrier integrity. Transmission electron microscopy confirmed the preservation of tight junction structures. Further analysis indicated that HXZQD modulated the MAPK/NF-κB signaling pathways, inhibiting heat stress-induced activation and reducing inflammation. Additionally, HXZQD positively regulated gut microbiota, increasing the proportion of beneficial Lactococcus and decreasing harmful Streptococcus . These findings suggest that HXZQD maintains intestinal homeostasis during EHS by preserving barrier function and modulating gut microbiota, offering a promising preventive approach for EHS management.