J Ethnopharmacol. 2025 Jul 24:120325. doi: 10.1016/j.jep.2025.120325. Online ahead of print.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola tangutica (Maxim.) S. H. Fu (TS) (RT), as a traditional Tibetan medicine, has been used for treating acute and chronic mountain sickness in Qinghai Province of China for a long time. High altitude retinopathy (HAR), exposed to acute hypobaric hypoxia, is a retinal vascular endothelial dysfunction disease. Retinal vascular endothelial cells (ECs) play a significant role in inner blood-retinal barrier (iBRB) disruption. However, the effect and molecular mechanism of RT on iBRB dysfunction of HAR remains elusive.
AIM OF THE STUDY: Studies focusing on the pharmacological mechanism and effect of RT on acute hypobaric hypoxia-induced iBRB dysfunction.
MATERIALS AND METHODS: In vivo, the rat models of acute hypobaric hypoxia-injured retina were established by simulating 5,000 m altitude for 3 days. The animal models were administrated RT for 10 days. Retinal morphological changes, central retinal artery (CRA) hemodynamics, iBRB ultrastructure, retinal vascular leakage, nitric oxide (NO) generation, arginase activity assay, and the protein expression of HIF-1α/eNOS pathway were measured. In vitro, 1% O2-injured rat retinal microvascular endothelial cells (rRMECs) were used to detect RT effect on NO production and cell proliferation. The eNOS associated proteins were determined to explore underlying mechanism of RT by eNOS inhibitor L-NAME. Chemical profile of ethanol extract of RT was analyzed by ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS).
RESULTS: RT increased CRA hemodynamic indices in the rat models of acute hypobaric hypoxia-injured retina. RT improved TJ length and lowered the percentage of swollen mitochondria in vascular endothelial ultrastructure of hypobaric hypoxia-injured retina. RT also ameliorated hypobaric hypoxia-induced retinal leakage by up-regulating VE-cadherin and ZO-1 protein levels, and down-regulating HIF-1α/eNOS/NO pathway. In addition, RT increased 1% O2 -injured rRMECs viability by inhibiting eNOS/NO signaling. Salidroside is the main ingredient of RT.
CONCLUSION: RT exerted protective effect on acute hypobaric hypoxia-induced iBRB dysfunction through suppressing HIF-1α/eNOS/NO pathway.
PMID:40714061 | DOI:10.1016/j.jep.2025.120325