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已发表论文
龙骨纳米颗粒通过激活钙依赖性 5-羟色胺释放和迷走神经 - 延髓头端腹外侧核通路改善失眠症状
Authors Liu Z, Wang Q, Fan X, Ye X, Wang Q, Huang Y, Wu C
Received 30 July 2025
Accepted for publication 22 November 2025
Published 2 December 2025 Volume 2025:20 Pages 14329—14341
DOI https://doi.org/10.2147/IJN.S553405
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Lijie Grace Zhang
Zibo Liu,1 Qian Wang,1 Xinyun Fan,1 Xun Ye,1 Qinyu Wang,1 Yongliang Huang,2 Chunjie Wu3,4
1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2Pharmacy Department, the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People’s Republic of China; 3Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 4Sichuan Engineering Research Center for Endangered Medicinal Animals, Chengdu, 611137, People’s Republic of China
Correspondence: Chunjie Wu, Email wuchunjie@cdutcm.edu.cn Yongliang Huang, Email hyl@cdutcm.edu.cn
Background: Os draconis (OD), a traditional Chinese medicine from fossil mammalian bones, effectively treats insomnia and anxiety. Its usage conflicts with the laws, causing a shortage. This research clarifies OD’s pharmacodynamic mechanisms, aiming to establish a scientific basis for developing novel artificial substitutes.
Methods: This research used a mouse chronic insomnia paradigm to assess an os draconis decoction (DOD). DOD was digested in vitro, and the resultant nanoparticles (OD-NPs) were analyzed by scanning electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. The in vivo effects were evaluated using behavioral tests, Nissl staining, neuronal activity in the nucleus tractus solitarii (NTS), and plasma 5-HT levels. In vitro mechanistic investigations used FITC-labeled OD-NPs to detect cellular uptake. The research used calcium channel blockers to examine changes in intracellular Ca2⁺ concentration and critical protein expression in 5-HT-related pathways.
Results: After DOD treatment, significantly improved movement in the Open field, brain malondialdehyde (MDA) and plasma tumor necrosis factor-α (TNF-α) were reduced, increased hippocampal Nissl bodies, and alleviated neuronal damage. Digested DOD formed numerous sub-1000 nm spindle particles. Its composition remained carbonate hydroxyapatite (F-rich), but crystallinity decreased. DOD elevated plasma 5-HT and c-fos expression in the NTS. In vitro, OD-NPs were uptaken by cells, increasing supernatant 5-HT and cytosolic calcium. This upregulated TPH1 and DdC expression, a trend unaffected by Ca2⁺ channel blockade, unlike the filtrate group.
Conclusion: This is the first research to suggest that oral DOD is digested into OD-NPs, which are then internalized by enterochromaffin cells. This absorption initiates calcium signaling, boosts 5-HT release, and then activates the vagus nerve-NTS pathway, thereby regulating central nervous system activity. This research provides scientific proof for the clinical application of OD, lays the groundwork for the development of artificial alternatives, and generates ideas for future traditional Chinese medicine research.
Keywords: os draconis, apatite, nanoparticles, intestinal chromaffin cells, vagus, insomnia
1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2Pharmacy Department, the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People’s Republic of China; 3Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 4Sichuan Engineering Research Center for Endangered Medicinal Animals, Chengdu, 611137, People’s Republic of China
Correspondence: Chunjie Wu, Email wuchunjie@cdutcm.edu.cn Yongliang Huang, Email hyl@cdutcm.edu.cn
Background: Os draconis (OD), a traditional Chinese medicine from fossil mammalian bones, effectively treats insomnia and anxiety. Its usage conflicts with the laws, causing a shortage. This research clarifies OD’s pharmacodynamic mechanisms, aiming to establish a scientific basis for developing novel artificial substitutes.
Methods: This research used a mouse chronic insomnia paradigm to assess an os draconis decoction (DOD). DOD was digested in vitro, and the resultant nanoparticles (OD-NPs) were analyzed by scanning electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. The in vivo effects were evaluated using behavioral tests, Nissl staining, neuronal activity in the nucleus tractus solitarii (NTS), and plasma 5-HT levels. In vitro mechanistic investigations used FITC-labeled OD-NPs to detect cellular uptake. The research used calcium channel blockers to examine changes in intracellular Ca2⁺ concentration and critical protein expression in 5-HT-related pathways.
Results: After DOD treatment, significantly improved movement in the Open field, brain malondialdehyde (MDA) and plasma tumor necrosis factor-α (TNF-α) were reduced, increased hippocampal Nissl bodies, and alleviated neuronal damage. Digested DOD formed numerous sub-1000 nm spindle particles. Its composition remained carbonate hydroxyapatite (F-rich), but crystallinity decreased. DOD elevated plasma 5-HT and c-fos expression in the NTS. In vitro, OD-NPs were uptaken by cells, increasing supernatant 5-HT and cytosolic calcium. This upregulated TPH1 and DdC expression, a trend unaffected by Ca2⁺ channel blockade, unlike the filtrate group.
Conclusion: This is the first research to suggest that oral DOD is digested into OD-NPs, which are then internalized by enterochromaffin cells. This absorption initiates calcium signaling, boosts 5-HT release, and then activates the vagus nerve-NTS pathway, thereby regulating central nervous system activity. This research provides scientific proof for the clinical application of OD, lays the groundwork for the development of artificial alternatives, and generates ideas for future traditional Chinese medicine research.
Keywords: os draconis, apatite, nanoparticles, intestinal chromaffin cells, vagus, insomnia