Near-infrared fluorescent probe-mediated high-throughput discovery of a natural β-galactosidase inhibitor for senescence-associated atherosclerosis therapy.
6 affiliations
- 1School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- 2Beijing Hton Co., Ltd., Beijing, 100010, China.
- 3Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- 4College of Veterinary Medicine, Yunnan Agricultural University, Yunan, 650500, China.
- 5Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- 6Shandong Key Laboratory of Digital Traditional Chinese Medicine, Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
Abstract
Atherosclerosis (AS), a disease associated with aging, significantly compromises the health and quality of life of patients. β-galactosidase (β-gal), a key cell senescence biomarker, shows significantly increased activity in senescent cells. Upregulated β-gal in senescent cells amplifies a proinflammatory senescence-associated secretory phenotype (SASP), driving cellular dysfunction, monocyte recruitment, foam cell formation, and extracellular matrix remodeling, thereby promoting atherogenesis. Inhibiting β-gal activity is a potential strategy for delaying AS and other aging-related diseases. Herein, we designed and synthesized a novel near-infrared fluorescent probe activated by β-gal (NFP-gal). This probe exhibited high sensitivity and selectivity with low cytotoxicity and biotoxicity under the tested conditions. We used this fluorescence-guided screening method to evaluate the β-gal inhibitory activity of 58 traditional Chinese medicines (TCMs) and identified Arnebia euchroma (AE) as a strong candidate. Through targeted separation and identification of complex components in AE using ultra-high-performance liquid chromatography with quadrupole orbitrap high-resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS), we identified β,β-dimethyl-acryl-alkannin (DMAA) as a novel β-gal inhibitor. The pharmacodynamic effects of this compound were validated through in vitro cellular imaging using senescent cell and foam cell models, real-time in vivo fluorescence tracking in zebrafish models of AS, and histopathological analysis using apolipoprotein E-deficient (ApoE -/-) mice with high-fat diet (HFD)-induced AS. The findings confirmed the therapeutic potential of DMAA in mitigating senescence-associated vascular dysfunction. This study comprehensively evaluated the use of β-gal-based probes and natural compounds to suppress aging-related processes, highlighting their therapeutic implications for AS and other aging-associated diseases.
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BibTeX
@article{qin2026nearinfrared,
title = {{Near-infrared fluorescent probe-mediated high-throughput discovery of a natural β-galactosidase inhibitor for senescence-associated atherosclerosis therapy.}},
author = {Yujuan Qin and Ning Li and Wenjie Yang and Yi Wu and Zhixin Tang and Junhong Xin and Haiqiang Jiang},
journal = {Journal of pharmaceutical analysis},
year = {2026},
month = may,
doi = {10.1016/j.jpha.2026.101659},
url = {https://europepmc.org/article/MED/42908895},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Near-infrared fluorescent probe-mediated high-throughput discovery of a natural β-galactosidase inhibitor for senescence-associated atherosclerosis therapy.
AU - Yujuan Qin
AU - Ning Li
AU - Wenjie Yang
AU - Yi Wu
AU - Zhixin Tang
AU - Junhong Xin
AU - Haiqiang Jiang
PY - 2026
DA - 2026/05/14
JO - Journal of pharmaceutical analysis
DO - 10.1016/j.jpha.2026.101659
UR - https://europepmc.org/article/MED/42908895
AB - Atherosclerosis (AS), a disease associated with aging, significantly compromises the health and quality of life of patients. β-galactosidase (β-gal), a key cell senescence biomarker, shows significantly increased activity in senescent cells. Upregulated β-gal in senescent cells amplifies a proinflammatory senescence-associated secretory phenotype (SASP), driving cellular dysfunction, monocyte recruitment, foam cell formation, and extracellular matrix remodeling, thereby promoting atherogenesis. Inhibiting β-gal activity is a potential strategy for delaying AS and other aging-related diseases. Herein, we designed and synthesized a novel near-infrared fluorescent probe activated by β-gal (NFP-gal). This probe exhibited high sensitivity and selectivity with low cytotoxicity and biotoxicity under the tested conditions. We used this fluorescence-guided screening method to evaluate the β-gal inhibitory activity of 58 traditional Chinese medicines (TCMs) and identified Arnebia euchroma (AE) as a strong candidate. Through targeted separation and identification of complex components in AE using ultra-high-performance liquid chromatography with quadrupole orbitrap high-resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS), we identified β,β-dimethyl-acryl-alkannin (DMAA) as a novel β-gal inhibitor. The pharmacodynamic effects of this compound were validated through in vitro cellular imaging using senescent cell and foam cell models, real-time in vivo fluorescence tracking in zebrafish models of AS, and histopathological analysis using apolipoprotein E-deficient (ApoE -/-) mice with high-fat diet (HFD)-induced AS. The findings confirmed the therapeutic potential of DMAA in mitigating senescence-associated vascular dysfunction. This study comprehensively evaluated the use of β-gal-based probes and natural compounds to suppress aging-related processes, highlighting their therapeutic implications for AS and other aging-associated diseases.
SN - 2095-1779
SN - 2214-0883
ER -