Zhilong Huoxue Tongyu Capsule Alleviated the Pyroptosis of Vascular Endothelial Cells Induced by ox-LDL through miR-30b-5p/NLRP3

Abstract

Background. Our previous studies have demonstrated a protective role of Zhilong Huoxue Tongyu capsule in atherosclerosis (AS); however, the molecular mechanisms are unclear. Methods. Human coronary artery endothelial cells (HCAECs) were induced with oxidized low-density lipoprotein (ox-LDL) to obtain cellular AS models. Then, the medicated serum of Zhilong Huoxue Tongyu capsule was obtained and used for treatment with ox-LDL-induced HCAECs. The cell viability was detected by CCK-8 assay. Besides, the binding between miR-30b-5p and NLRP3 was determined by the dual-luciferase reporter gene system assay. Furthermore, ox-LDL-induced HCAECs were transfected with miR-30b-5p mimic or miR-30b-5p inhibitor. The pyroptosis of HCAECs was assessed by flow cytometry, LDH content detection, and qRT-PCR assays. Results. 10% medicated serum of Zhilong Huoxue Tongyu capsule was the maximum nontoxic concentration and it was used in subsequent assays. The rate of pyroptosis, LDH content, and the mRNA expression level of pyroptosis-related genes including NLRP3, ASC, Caspase 1, IL-1β, and IL-18 were prominently enhanced after HCAECs were induced by ox-LDL, which were markedly rescued with medicated serum of Zhilong Huoxue Tongyu capsule. In addition, the medicated serum of Zhilong Huoxue Tongyu capsule significantly enhanced the ox-LDL-induced reduction of miR-30b-5p level. NLRP3 could bind to miR-30b-5p and was negatively corrected with miR-30b-5p. Moreover, all the rates of pyroptosis, LDH content, and the mRNA expression levels of pyroptosis-related genes including NLRP3, ASC, Caspase 1, IL-1β, and IL-18 were further observably decreased after ox-LDL-induced HCAECs treated with medicated serum were transfected with miR-30b-5p mimic, while these were significantly rescued with transfection of miR-30b-5p inhibitor. Conclusion. Zhilong Huoxue Tongyu capsule alleviated the pyroptosis of vascular endothelial cells induced by ox-LDL through miR-30b-5p/NLRP3.

TXNIP‐NLRP3‐GSDMD axis‐mediated inflammation and pyroptosis of islet β‐cells is involved in cigarette smoke‐induced hyperglycemia, which is alleviated by andrographolide

“…Due to the inflammatory response and high expression of serum inflammatory factors, especially the elevation of IL‐1β, which is related to cell pyroptosis, 40 we further analyzed the level of cell pyroptosis in the mouse pancreas. The initiation of pyroptosis involves formation of the NLRP3 inflammasome, which triggers caspase‐1 activation.…”

Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion

“…Zhilong Huoxue Tongyu Capsule (ZLH) (Sichuan Medicine Z20070528) is an available traditional Chinese medicine (TCM) that could be utilized for the treatment of cerebral stroke ( Liang et al, 2021 ; Liu et al, 2022 ). As a complex preparation, ZLH, consisting of Astragalus , Cassia twig, leech, Panax notoginseng , and chuanxiong, is effective in dispelling wind and dampness and relieving pain for vascular headache and migraine.…”