A promising novel local anesthetic for effective anesthesia in oral inflammatory conditions through reducing mitochondria-related apoptosis.
10.1016/j.apsb.2025.09.001
- Author:
Haofan WANG
1
;
Yihang HAO
1
;
Wenrui GAI
2
;
Shilong HU
2
;
Wencheng LIU
3
;
Bo MA
1
;
Rongjia SHI
1
;
Yongzhen TAN
1
;
Ting KANG
2
;
Ao HAI
2
;
Yi ZHAO
2
;
Yaling TANG
1
;
Ling YE
1
;
Jin LIU
2
;
Xinhua LIANG
1
;
Bowen KE
2
Author Information
1. State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
2. Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
3. College of Computer Science, Sichuan University, Chengdu 610065, China.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Articaine;
Inflammatory;
Mitochondria;
Mitochondrial reactive oxygen species;
NRF2;
Oral local anesthetics;
Sodium
- From:
Acta Pharmaceutica Sinica B
2025;15(11):5854-5866
- CountryChina
- Language:English
-
Abstract:
Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na+/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.
