The Compatibility of Astragali Radix and Angelicae Sinensis Radix Attenuates Atherosclerosis by Suppressing Vascular Endothelial PANoptosis via the p38 MAPK/p53 Pathway: A Multi-Omics and Experimental Study
- 1Key Laboratory of Hunan Provincial for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Hunan 410208, China
Abstract
Previous studies have reported that the combination of Astragali Radix and Angelicae Sinensis Radix (AR-ASR) can ameliorate atherosclerosis (AS) through anti-inflammatory effects; however, the exact mechanistic underpinnings still await further clarification. The present study investigates the anti-atherosclerotic action of AR-ASR from the perspective of PANoptosis (encompassing apoptosis, pyroptosis, and necroptosis). To ascertain the chief active ingredients of the AR plus ASR mixture, UPLC-MS/MS detection was utilized. To predict potential therapeutic targets, a multi-faceted bioinformatics strategy was applied, integrating transcriptomics, single-cell sequencing, network pharmacology, molecular docking, and molecular dynamics simulations. In vivo, male ApoE-deficient mice were allocated at random into the model cohort, AR-ASR low-, medium-, and high-dose groups (AR-ASR L, AR-ASR M, and AR-ASR H, respectively), atorvastatin group (ATV), and control group (age-matched wild-type C57BL/6J mice). Atherosclerosis was induced by 12 weeks of high-fat diet feeding, followed by 4 weeks of oral gavage treatment. Assessment parameters included aortic intimal hyperplasia thickness, serum lipid levels, vascular inflammatory factor expression, endothelial function, and the gene and protein expression levels of PANoptosis- and p38MAPK/p53 signaling pathway-related molecules. For in vitro experiments, POVPC-stimulated AVECs were used as an oxidative damage model and then treated with AR-ASR-containing serum. Cell proliferation activity, cell injury rate, and the expression levels of PANoptosis markers and p38MAPK/p53 signaling pathway-related molecules were measured. Furthermore, in the presence of a p38MAPK agonist, the protective effect of AR-ASR on AVECs and its underlying mechanism were investigated. Bioinformatics analysis suggested that AR-ASR modulates PANoptosis and interferes with AS via the p38MAPK/p53 signaling axis. In vivo, AR-ASR treatment reduced serum lipid levels, attenuated aortic intimal hyperplasia, decreased plasma inflammatory cytokine levels and vascular inflammatory factor expression, improved endothelial function, and suppressed both vascular PANoptosis and p38MAPK/p53 pathway activation. In vitro, POVPC induced oxidative damage and PANoptosis in AVECs. AR-ASR-containing serum promoted AVEC viability, reduced LDH release, inhibited the expression of PANoptosis-related markers, and downregulated p38MAPK/p53 signaling pathway protein expression. Furthermore, in the presence of a p38MAPK agonist, the inhibitory effects of AR-ASR on cellular PANoptosis and p38MAPK/p53 pathway activation were significantly attenuated. The AR-ASR compatibility suppresses p38MAPK/p53 pathway activation, thereby inhibiting vascular endothelial PANoptosis-driven inflammatory responses and ameliorating atherosclerotic vascular pathology.
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BibTeX
@article{li2026compatibility,
title = {{The Compatibility of Astragali Radix and Angelicae Sinensis Radix Attenuates Atherosclerosis by Suppressing Vascular Endothelial PANoptosis via the p38 MAPK/p53 Pathway: A Multi-Omics and Experimental Study}},
author = {Wanyu Li and Qingyin Long and Xinying Fu and Yanling Li and Lu Ma and Wei Tan and Zhongji Hu and Yanyan Zhang and Yan She and Wei Zhang and Changqing Deng},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27188330},
url = {https://www.mdpi.com/1422-0067/27/18/8330},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Compatibility of Astragali Radix and Angelicae Sinensis Radix Attenuates Atherosclerosis by Suppressing Vascular Endothelial PANoptosis via the p38 MAPK/p53 Pathway: A Multi-Omics and Experimental Study
AU - Wanyu Li
AU - Qingyin Long
AU - Xinying Fu
AU - Yanling Li
AU - Lu Ma
AU - Wei Tan
AU - Zhongji Hu
AU - Yanyan Zhang
AU - Yan She
AU - Wei Zhang
AU - Changqing Deng
PY - 2026
DA - 2026/09/19
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27188330
UR - https://www.mdpi.com/1422-0067/27/18/8330
AB - Previous studies have reported that the combination of Astragali Radix and Angelicae Sinensis Radix (AR-ASR) can ameliorate atherosclerosis (AS) through anti-inflammatory effects; however, the exact mechanistic underpinnings still await further clarification. The present study investigates the anti-atherosclerotic action of AR-ASR from the perspective of PANoptosis (encompassing apoptosis, pyroptosis, and necroptosis). To ascertain the chief active ingredients of the AR plus ASR mixture, UPLC-MS/MS detection was utilized. To predict potential therapeutic targets, a multi-faceted bioinformatics strategy was applied, integrating transcriptomics, single-cell sequencing, network pharmacology, molecular docking, and molecular dynamics simulations. In vivo, male ApoE-deficient mice were allocated at random into the model cohort, AR-ASR low-, medium-, and high-dose groups (AR-ASR L, AR-ASR M, and AR-ASR H, respectively), atorvastatin group (ATV), and control group (age-matched wild-type C57BL/6J mice). Atherosclerosis was induced by 12 weeks of high-fat diet feeding, followed by 4 weeks of oral gavage treatment. Assessment parameters included aortic intimal hyperplasia thickness, serum lipid levels, vascular inflammatory factor expression, endothelial function, and the gene and protein expression levels of PANoptosis- and p38MAPK/p53 signaling pathway-related molecules. For in vitro experiments, POVPC-stimulated AVECs were used as an oxidative damage model and then treated with AR-ASR-containing serum. Cell proliferation activity, cell injury rate, and the expression levels of PANoptosis markers and p38MAPK/p53 signaling pathway-related molecules were measured. Furthermore, in the presence of a p38MAPK agonist, the protective effect of AR-ASR on AVECs and its underlying mechanism were investigated. Bioinformatics analysis suggested that AR-ASR modulates PANoptosis and interferes with AS via the p38MAPK/p53 signaling axis. In vivo, AR-ASR treatment reduced serum lipid levels, attenuated aortic intimal hyperplasia, decreased plasma inflammatory cytokine levels and vascular inflammatory factor expression, improved endothelial function, and suppressed both vascular PANoptosis and p38MAPK/p53 pathway activation. In vitro, POVPC induced oxidative damage and PANoptosis in AVECs. AR-ASR-containing serum promoted AVEC viability, reduced LDH release, inhibited the expression of PANoptosis-related markers, and downregulated p38MAPK/p53 signaling pathway protein expression. Furthermore, in the presence of a p38MAPK agonist, the inhibitory effects of AR-ASR on cellular PANoptosis and p38MAPK/p53 pathway activation were significantly attenuated. The AR-ASR compatibility suppresses p38MAPK/p53 pathway activation, thereby inhibiting vascular endothelial PANoptosis-driven inflammatory responses and ameliorating atherosclerotic vascular pathology.
SN - 1422-0067
ER -