Dataset Information

Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro.

ABSTRACT:

Context

Previous studies have highlighted significant therapeutic effects of Qiqilian (QQL) capsule on hypertension in spontaneously hypertensive rats (SHRs); however, its underlying molecular mechanism remains unclear.

Obejective

We investigated the potential mechanism by which QQL improves hypertension-induced vascular endothelial dysfunction (VED).

Materials and methods

In vivo, SHRs were divided into four groups (20 per group) and were administered gradient doses of QQL (0, 0.3, 0.6, and 1.2 g/kg) for 8 weeks, while Wistar Kyoto rats were used as normal control. The vascular injury extent, IL-1β and IL-18 levels, NLRP3, ASC and caspase-1 contents were examined. In vitro, the effects of QQL-medicated serum on angiotensin II (AngII)-induced inflammatory and autophagy in human umbilical vein endothelial cells (HUVECs) were assessed.

Result

Compared with the SHR group, QQL significantly decreased thickness (125.50 to 105.45 μm) and collagen density (8.61 to 3.20%) of arterial vessels, and reduced serum IL-1β (96.25 to 46.13 pg/mL) and IL-18 (345.01 to 162.63 pg/mL) levels. The NLRP3 and ACS expression in arterial vessels were downregulated (0.21- and 0.16-fold, respectively) in the QQL-HD group compared with the SHR group. In vitro, QQL treatment restored NLRP3 and ASC expression, which was downregulated approximately 2-fold compared with that of AngII-induced HUVECs. Furthermore, QQL decreased LC3II and increased p62 contents (p < 0.05), indicating a reduction in autophagosome accumulation. These effects were inhibited by the autophagy agonist rapamycin and enhanced by the autophagy inhibitor chloroquine.

Conclusion

QQL effectively attenuated endothelial injury and inflammation by inhibiting AngII-induced excessive autophagy, which serves as a potential therapeutic strategy for hypertension.

SUBMITTER: Luo Y

PROVIDER: S-EPMC10599261 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation <i>in vivo</i> and <i>in vitro</i>.

Luo Yuan Y Tan Zhenyuan Z Ye Yun Y Ma Xiaocong X Yue Guihua G

Pharmaceutical biology 20231201 1

<h4>Context</h4>Previous studies have highlighted significant therapeutic effects of Qiqilian (QQL) capsule on hypertension in spontaneously hypertensive rats (SHRs); however, its underlying molecular mechanism remains unclear.<h4>Obejective</h4>We investigated the potential mechanism by which QQL improves hypertension-induced vascular endothelial dysfunction (VED).<h4>Materials and methods</h4><i>In vivo,</i> SHRs were divided into four groups (20 per group) and were administered gradient doses ...[more]

PMID: 37194678

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