Citation: Chunlei Hui, Xiuqing Li, Ying Liang, Qingqiu Huang, Li Fan, Li Su, Yuanqing Gao. Nasal gel-delivered adenosine A1 receptor agonist induces torpor-like hypothermia and improves survival in a hemorrhagic shock model[J]. Chinese Chemical Letters, ;2026, 37(2): 111017. doi: 10.1016/j.cclet.2025.111017 shu

Nasal gel-delivered adenosine A1 receptor agonist induces torpor-like hypothermia and improves survival in a hemorrhagic shock model

Chunlei Hui ^{a, 1} ,
Xiuqing Li ^{b, 1} ,
Ying Liang ^b ,
Qingqiu Huang ^b ,
Li Fan ^{c, *,} ,
Li Su ^{a, *,} ,
Yuanqing Gao ^{b, *,}

a.
Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
b.
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
c.
Department of Pharmaceutical Science, School of Pharmacy, Naval Medical University, Shanghai 200433, China

smmuyjfl@163.com

suli1020@shu.edu.cn

yuanqinggao@njmu.edu.cn

Received Date: 2 December 2024
Revised Date: 24 February 2025
Accepted Date: 27 February 2025
Available Online: 27 February 2025

Figures(3)

Hemorrhagic shock (HS) is a leading cause of death worldwide, particularly within the first 24 h post-injury. Current treatments are limited, especially in low-resource settings. Therapeutic hypothermia (TH) offers potential benefits by reducing metabolic demands and protecting organs, but its application in HS is challenged by cooling difficulties and side effects. This study introduces a novel nasal gel formulation of N6-cyclohexyladenosine (CHA), an adenosine A1 receptor agonist, designed to enhance brain delivery while minimizing peripheral side effects. In a mouse model of HS, administration of CHA nasal gel significantly improved survival rates, reduced metabolic rates, and protected major organs without worsening coagulopathy. Metabolomics analysis revealed a shift towards fatty acid oxidation and increased antioxidant capacity. These findings demonstrate that CHA nasal gel effectively induces TH, offering a safe and innovative treatment strategy for HS, particularly in resource-limited environments.
- Nasal delivery,
- Hypothermia,
- A1 adenosine receptor,
- Hemorrhagic shock,
- N6-cyclohexyladenosine
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