Ophiopogonin D Alleviates Sepsis-Induced Acute Lung Injury Through Improving Microvascular Endothelial Barrier Dysfunction via Inhibition of HIF-1α-VEGF Pathway.

Pulmonary endothelial barrier dysfunction is a hallmark of sepsis-induced acute lung injury (ALI). Ophiopogonin D (OP-D), isolated from the roots of Ophiopogon japonicus, is involved in regulating inflammation, apoptosis and intestinal permeability. However, the role of OP-D in ALI has not been reported and the related mechanisms remain unclear. In this study, cecal ligation and puncture (CLP) was used to establish a septic ALI model in mice. We found that OP-D effectively alleviated lung pathological damage. Moreover, OP-D decreased pulmonary microvascular permeability, restrained the inflammatory response and apoptosis in murine lung tissues and LPS-exposed PMVECs. Specifically, OP-D exerted the beneficial effects via mediating the inactivation of HIF-1α-VEGF pathway, which was partly abrogated by the overexpression of HIF-1α. Collectively, our findings showed that OP-D protected against sepsis-induced ALI through improving pulmonary microvascular endothelial barrier dysfunction via suppressing HIF-1α-VEGF pathway.
Competing Interests: Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests. Ethical Approval: All animal procedures were conducted in accordance with the Guide for the Institutional Animal Care and Use and approved by the Institutional Animal Care and Use Committee of Affiliated Changsha Central Hospital to Nanhua University.
(© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)