Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro
AbstractContext 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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2023.2208617 |
| _version_ | 1797234834886623232 |
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| author | Yuan Luo Zhenyuan Tan Yun Ye Xiaocong Ma Guihua Yue |
| author_facet | Yuan Luo Zhenyuan Tan Yun Ye Xiaocong Ma Guihua Yue |
| author_sort | Yuan Luo |
| collection | DOAJ |
| description | AbstractContext 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. |
| first_indexed | 2024-03-09T00:09:13Z |
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| id | doaj.art-6b947839c7f84b48b589d0f2ea5e0498 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-24T16:38:22Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-6b947839c7f84b48b589d0f2ea5e04982024-03-29T11:10:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162023-12-0161181582410.1080/13880209.2023.2208617Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitroYuan Luo0Zhenyuan Tan1Yun Ye2Xiaocong Ma3Guihua Yue4The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, P.R. ChinaGuangxi Medical University, Nanning, P.R. ChinaNo. 923 Hospital of the PLA Joint Logistics Support Force, Nanning, P.R. ChinaGuangxi University of Chinese Medicine, Nanning, P.R. ChinaGuangxi Internation Zhuang Medicine Hospital to Guangxi University of Chinese Medicine, Nanning, P.R. ChinaAbstractContext 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.https://www.tandfonline.com/doi/10.1080/13880209.2023.2208617Hypertensionangiotensin IIautophagyspontaneously hypertensive ratshuman umbilical vein endothelial cells |
| spellingShingle | Yuan Luo Zhenyuan Tan Yun Ye Xiaocong Ma Guihua Yue Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro Pharmaceutical Biology Hypertension angiotensin II autophagy spontaneously hypertensive rats human umbilical vein endothelial cells |
| title | Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro |
| title_full | Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro |
| title_fullStr | Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro |
| title_full_unstemmed | Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro |
| title_short | Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro |
| title_sort | qiqilian ameliorates vascular endothelial dysfunction by inhibiting nlrp3 asc inflammasome activation in vivo and in vitro |
| topic | Hypertension angiotensin II autophagy spontaneously hypertensive rats human umbilical vein endothelial cells |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2023.2208617 |
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