ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Naoxintong Capsule decreases circulating exosomes of miR-382-5p to protect LPS-induced vascular endothelial cell injury by targeting STC1 in vitro
Provisionally accepted
- Sun Yat-Sen University, Guangzhou, China
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Background: Cardiovascular and cerebrovascular diseases, major health threats in aging populations, involve vascular endothelial injury as a key pathological factor. Circulating exosomes, a type of extracellular vesicles involved in substance transport and signal transduction, serve as regulatory mediators in vascular diseases. Naoxintong Capsule (NXT), a traditional Chinese medicine with three decades of clinical application, protects vascular diseases via multifaceted mechanisms, yet its circulating exosome-mediated endothelial protection remains unclear. Methods: Circulating exosomes were isolated from NXT-treated (NXT-Exo) and saline-treated (Ctl-Exo) SD rats. The effect of NXT-Exo and Ctl-Exo on lipopolysaccharide (LPS) induced human microvascular endothelial cells (HMEC-1) injury was studied using molecular biology experiments. RNA-seq and miRNA-omics analysis were performed to elucidate the mechanisms of NXT-Exo. Western blot and enzyme linked immunosorbent assay (ELISA) were used to validate the therapeutic target of NXT-Exo. Results: NXT-Exo attenuated LPS-induced HMEC-1 injury by suppressing apoptosis, inflammation, oxidative stress, and endothelial dysfunction, while Ctl-Exo showed no effect. RNA-seq revealed the TLR4/TRIF/NF-κB signaling pathway might play a crucial role in NXT-Exo's effect. miRNA-omics suggested miR-382-5p as a pivotal mediator, and ELISA confirmed that its downregulation contributes to the protective effect of NXT-Exo. Integrated analysis indicated Stanniocalcin-1 (STC1) may be a miR-382-5p target. Western blot results showed that STC1 silencing aggravated the pro-injury effects of miR-382-5p. Conclusions: Our findings elucidated that NXT protected HMEC-1 from injury and dysfunction by downregulating miR-382-5p in circulating exosomes, potentially via targeting STC1 and inhibiting the TLR4/TRIF/NF-κB pathway.
Keywords: circulating exosomes, MiR-382-5p, Naoxintong capsule (NXT), protective effect, stanniocalcin-1 (STC1), TLR4/TRIF/NF-κB pathway, vascular endothelial injury
Received: 28 Jun 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Xu, Wu, Fan, Meng, Hu, Zou, Chen, Su and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Peibo Li
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