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

Overview

Journal Cell Biochem Biophys

Date 2025 Jan 31

PMID 39890704

Authors

Yi Fang

Jun Qiu

Yu Xu

Qing Wu

Xing-Chen Huo

Song-Hua Liu

Affiliations

Soon will be listed here.

Abstract

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.

References

Memtsoudis S, Bombardieri A, Ma Y, Walz J, Chiu Y, Mazumdar M . Mortality of patients with respiratory insufficiency and adult respiratory distress syndrome after surgery: the obesity paradox. J Intensive Care Med. 2011; 27(5):306-11. DOI: 10.1177/0885066611411410. View

Ware L, Matthay M . The acute respiratory distress syndrome. N Engl J Med. 2000; 342(18):1334-49. DOI: 10.1056/NEJM200005043421806. View

Li N, Liu B, Xiong R, Li G, Wang B, Geng Q . HDAC3 deficiency protects against acute lung injury by maintaining epithelial barrier integrity through preserving mitochondrial quality control. Redox Biol. 2023; 63:102746. PMC: 10199751. DOI: 10.1016/j.redox.2023.102746. View

Matthay M, Ware L, Zimmerman G . The acute respiratory distress syndrome. J Clin Invest. 2012; 122(8):2731-40. PMC: 3408735. DOI: 10.1172/JCI60331. View

Mu S, Liu Y, Jiang J, Ding R, Li X, Li X . Unfractionated heparin ameliorates pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization in acute lung injury. Respir Res. 2018; 19(1):220. PMC: 6238311. DOI: 10.1186/s12931-018-0925-6. View

van der Poll T, van de Veerdonk F, Scicluna B, Netea M . The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017; 17(7):407-420. DOI: 10.1038/nri.2017.36. View

Yin J, Lv L, Zhai P, Long T, Zhou Q, Pan H . Connexin 40 regulates lung endothelial permeability in acute lung injury via the ROCK1-MYPT1- MLC20 pathway. Am J Physiol Lung Cell Mol Physiol. 2018; 316(1):L35-L44. DOI: 10.1152/ajplung.00012.2018. View

Chang J, Shen C, Huang Y, Chien M, Ou J, Shieh B . Five new homoisoflavonoids from the tuber of Ophiopogon japonicus. J Nat Prod. 2002; 65(11):1731-3. DOI: 10.1021/np020204o. View

Chen S, Li X, Liu L, Liu C, Han X . Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice. FASEB J. 2017; 32(3):1139-1153. DOI: 10.1096/fj.201700741RR. View

10.

Li W, Ji L, Tian J, Tang W, Shan X, Zhao P . Ophiopogonin D alleviates diabetic myocardial injuries by regulating mitochondrial dynamics. J Ethnopharmacol. 2021; 271:113853. DOI: 10.1016/j.jep.2021.113853. View

11.

Qiao Y, Jiao H, Wang F, Niu H . Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats. Braz J Med Biol Res. 2020; 53(7):e9628. PMC: 7279694. DOI: 10.1590/1414-431X20209628. View

12.

Lei S, Feng Y, Huang P, Chen B, Bao K, Wu Q . Ophiopogonin D'-induced mitophagy and mitochondrial damage are associated with dysregulation of the PINK1/Parkin signaling pathway in AC16 cells. Toxicology. 2022; 477:153275. DOI: 10.1016/j.tox.2022.153275. View

13.

You W, Zhou T, Ma Z, Liang Q, Xiao C, Tang X . Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress. Acta Pharmacol Sin. 2016; 37(3):368-81. PMC: 4775850. DOI: 10.1038/aps.2015.146. View

14.

Ko H, Jee W, Lee D, Jang H, Jung J . Ophiopogonin D increase apoptosis by activating p53 ribosomal protein L5 and L11 and inhibiting the expression of c-Myc CNOT2. Front Pharmacol. 2022; 13:974468. PMC: 9780504. DOI: 10.3389/fphar.2022.974468. View

15.

Zhu X, Wang K, Chen Y . Ophiopogonin D suppresses TGF-β1-mediated metastatic behavior of MDA-MB-231 breast carcinoma cells via regulating ITGB1/FAK/Src/AKT/β-catenin/MMP-9 signaling axis. Toxicol In Vitro. 2020; 69:104973. DOI: 10.1016/j.tiv.2020.104973. View

16.

Bao S, Chen T, Chen J, Zhang J, Zhang G, Hui Y . Multi-omics analysis reveals the mechanism of action of ophiopogonin D against pulmonary fibrosis. Phytomedicine. 2023; 121:155078. DOI: 10.1016/j.phymed.2023.155078. View

17.

Wang L, Yang H, Qiao L, Liu J, Liao X, Huang H . Ophiopogonin D Inhibiting Epithelial NF-κB Signaling Pathway Protects Against Experimental Colitis in Mice. Inflammation. 2022; 45(4):1720-1731. DOI: 10.1007/s10753-022-01655-8. View

18.

Wang Y, Li D, Song L, Ding H . Ophiopogonin D attenuates PM2.5-induced inflammation via suppressing the AMPK/NF-κB pathway in mouse pulmonary epithelial cells. Exp Ther Med. 2020; 20(6):139. PMC: 7571316. DOI: 10.3892/etm.2020.9268. View

19.

Qian J, Jiang F, Wang B, Yu Y, Zhang X, Yin Z . Ophiopogonin D prevents H2O2-induced injury in primary human umbilical vein endothelial cells. J Ethnopharmacol. 2010; 128(2):438-45. DOI: 10.1016/j.jep.2010.01.031. View

20.

Ma X, Wen X, Yang X, Zhou D, Wu Q, Feng Y . Ophiopogonin D improves osteointegration of titanium alloy implants under diabetic conditions by inhibition of ROS overproduction via Wnt/β-catenin signaling pathway. Biochimie. 2018; 152:31-42. DOI: 10.1016/j.biochi.2018.04.022. View