Dihydrotanshinone I Attenuates Atherosclerosis via Inhibiting NLRP3 Inflammasome Activation and Modulating Gut Microbiota
Abstract
Atherosclerosis (AS), a primary contributor to cardiovascular disease, is driven by hyperlipidemia, chronic inflammation, and gut dysbiosis. Although Salvia miltiorrhiza Bunge (Danshen) has long been used to treat atherosclerotic disorders, its most potent anti-inflammatory constituent remains unclear. Screening 12 constituents from Danshen revealed that dihydrotanshinone I (DHT) was the most potent inhibitor of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in vitro. In an atherosclerotic mouse model, DHT treatment effectively attenuated dyslipidemia and reduced atherosclerotic plaque burden in the aorta and aortic sinus. Mechanistically, DHT significantly downregulated the aortic mRNA expression of key inflammasome components (NLRP3, ASC, Caspase-1, and IL-1β) and significantly suppressed the aortic protein levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, gut microbiota analysis indicated that DHT alleviated high-fat diet-induced gut dysbiosis by restoring gut microbial diversity. This was characterized by a decrease in pathobionts (Rikenellaceae_RC9_gut_group, Muribaculum, and [Eubacterium]_ventriosum_group) and an increase in beneficial genera (Akkermansia and Allobaculum). Fecal microbiota transplantation (FMT) confirmed that these atheroprotective effects were transferable via the gut microbiota, highlighting the key role of microbial modulation. Collectively, DHT exerts its anti-atherosclerotic effects by simultaneously improving lipid metabolism, inhibiting NLRP3 inflammasome activation, and restoring gut microbial homeostasis.
Related
- Ginsenoside Rd alleviates atherosclerosis by inhibiting adipocyte ferroptosis in perivascular adipose tissues
- Molecular mechanisms of NLR proteins in inflammasome activation
- Bergapten Alleviates Periodontitis by Suppressing NLRP3 Inflammasome Activation via Mitophagy-Induced Disruption of NEK7-NLRP3 Interaction.
- Possible Links Between PM2.5-Induced NLRP3 Inflammasome Activation and Its Role in Lung Cancer Progression and Drug Resistance
- O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ
BibTeX
@article{li2026dihydrotanshinone,
title = {{Dihydrotanshinone I Attenuates Atherosclerosis via Inhibiting NLRP3 Inflammasome Activation and Modulating Gut Microbiota}},
author = {Haozhen Li and Chengyi Ban and Jiasen An and Jianhang Yang and Jinzhao Ren and Yuhang Wu and Zenan Shen and Jiandong Zhang and Xiaolong Gu and Hongbin Liu},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = jul,
doi = {10.1248/bpb.b26-00124},
url = {https://www.jstage.jst.go.jp/article/bpb/49/7/49_b26-00124/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Dihydrotanshinone I Attenuates Atherosclerosis via Inhibiting NLRP3 Inflammasome Activation and Modulating Gut Microbiota
AU - Haozhen Li
AU - Chengyi Ban
AU - Jiasen An
AU - Jianhang Yang
AU - Jinzhao Ren
AU - Yuhang Wu
AU - Zenan Shen
AU - Jiandong Zhang
AU - Xiaolong Gu
AU - Hongbin Liu
PY - 2026
DA - 2026/07/23
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00124
UR - https://www.jstage.jst.go.jp/article/bpb/49/7/49_b26-00124/_article
AB - Atherosclerosis (AS), a primary contributor to cardiovascular disease, is driven by hyperlipidemia, chronic inflammation, and gut dysbiosis. Although Salvia miltiorrhiza Bunge (Danshen) has long been used to treat atherosclerotic disorders, its most potent anti-inflammatory constituent remains unclear. Screening 12 constituents from Danshen revealed that dihydrotanshinone I (DHT) was the most potent inhibitor of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in vitro. In an atherosclerotic mouse model, DHT treatment effectively attenuated dyslipidemia and reduced atherosclerotic plaque burden in the aorta and aortic sinus. Mechanistically, DHT significantly downregulated the aortic mRNA expression of key inflammasome components (NLRP3, ASC, Caspase-1, and IL-1β) and significantly suppressed the aortic protein levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, gut microbiota analysis indicated that DHT alleviated high-fat diet-induced gut dysbiosis by restoring gut microbial diversity. This was characterized by a decrease in pathobionts (Rikenellaceae_RC9_gut_group, Muribaculum, and [Eubacterium]_ventriosum_group) and an increase in beneficial genera (Akkermansia and Allobaculum). Fecal microbiota transplantation (FMT) confirmed that these atheroprotective effects were transferable via the gut microbiota, highlighting the key role of microbial modulation. Collectively, DHT exerts its anti-atherosclerotic effects by simultaneously improving lipid metabolism, inhibiting NLRP3 inflammasome activation, and restoring gut microbial homeostasis.
SN - 1347-5215
SN - 0918-6158
ER -