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L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway
Yunfeng Pan1, Xiao Sun1, Yu Tian1
1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing, China.
Introduction:
L-NRB is a compound formed as a ring cleavage product of butylphthalide and borneol in a molar ratio 1:2. This study aimed to explore the therapeutic effect of L-NRB on amyotrophic lateral sclerosis (ALS) and its possible mechanism.
Methods:
SOD1-G93A mice were used as an ALS model. Behavioral tests, histopathological staining, Nissl staining, immunohistochemistry, enzyme-linked immunosorbent assays, and Western blotting were used to analyze the therapeutic effect. The underlying mechanism of L-NRB in treating ALS was investigated using transcriptomic analyses.
Results:
It was found that L-NRB alleviated motor dysfunction, pathological changes in the gastrocnemius muscle, and motor neuron injuries. The results indicated that L-NRB had a neuroprotective function associated with the inhibition of neuroinflammation. The anti-apoptotic effect of L-NRB was found to be related to the regulation of the P11-Htr4 signaling pathway.
Conclusion:
In summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS.
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