Shenqisherong pill ameliorates neuronal apoptosis by inhibiting the JNK/caspase-3 signaling pathway in a rat model of cervical cord compression

Ke Zhu; Pei-Min Pu; Gan Li; Long-Yun Zhou; Zhuo-Yao Li; Qi Shi; Yong-Jun Wang; Xue-Jun Cui; Min Yao

doi:10.1016/j.jep.2023.116901

Shenqisherong pill ameliorates neuronal apoptosis by inhibiting the JNK/caspase-3 signaling pathway in a rat model of cervical cord compression

J Ethnopharmacol. 2024 Jan 10;318(Pt A):116901. doi: 10.1016/j.jep.2023.116901. Epub 2023 Jul 10.

Authors

Ke Zhu¹, Pei-Min Pu², Gan Li³, Long-Yun Zhou⁴, Zhuo-Yao Li⁵, Qi Shi⁶, Yong-Jun Wang⁷, Xue-Jun Cui⁸, Min Yao⁹

Affiliations

¹ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: zhuke0021@163.com.
² Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: 546455370@qq.com.
³ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: 493224468@qq.com.
⁴ Rehabilitation Medicine Center, Jiangsu Provincial People's Hospital, Jiangsu, 210029, China. Electronic address: 228970442@qq.com.
⁵ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: 1255350201@qq.com.
⁶ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: 18917763017@163.com.
⁷ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: yjwang8888@126.com.
⁸ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: 13917715524@139.com.
⁹ Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: yaomin19871223@126.com.

PMID: 37437792
DOI: 10.1016/j.jep.2023.116901

Abstract

Ethnopharmacological relevance: The Shenqisherong (SQSR) pill is an empirical prescription of traditional Chinese medicine (TCM), which originated from the National Chinese Medical Science Master, Shi Qi. It has been widely used in the treatment of cervical spondylotic myelopathy (CSM) and promote the recovery of spinal cord function, but underlying molecular mechanism remains unclear.

Aim of the study: The objective of this study was to confirm the neuroprotective effects of the SQSR pill.

Materials and methods: A rat model of chronic compression at double-level cervical cord was used in vivo. The protective role of SQSR pill on CSM rats was measured by Basso, Beattie, and Bresnahan (BBB) locomotor scale, inclined plane test, forelimb grip strength assessment, hindlimb pain threshold assessment, and gait analysis. The levels of reactive oxygen species (ROS) were examined by Dihydroethidium (DHE) staining and 2',7'-Dichlorofluorescein (DCF) assay, and apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL) assay. The expression of apoptosis proteins was evaluated by immunofluorescence staining and Western blot.

Results: SQSR pill could facilitate locomotor function recovery in rats with chronic cervical cord compression, reduce local ROS in the spinal cord and downregulate the c-Jun-N-terminal kinase (JNK)/caspase-3 signaling pathway. In addition, the SQSR pill could protect primary rat cortical neurons from glutamate-treated toxicity in vitro by reducing the ROS and downregulating the phosphorylation of JNK and its downstream factors related to neuronal apoptosis meditated by the caspase cascade. Then, the neuroprotective effect was counteracted by a JNK activator.

Conclusions: Together, SQSR pill could ameliorate neuronal apoptosis by restraining ROS accumulation and inhibiting the JNK/caspase-3 signaling pathway, indicating that SQSR pill could be a candidate drug for CSM.

Keywords: Cervical spondylotic myelopathy; Neuronal apoptosis; Reactive oxygen species; Shenqisherong pill; c-Jun-N-Terminal kinase.

MeSH terms

Animals
Apoptosis
Caspase 3 / metabolism
Cervical Cord* / metabolism
Neuroprotective Agents* / pharmacology
Neuroprotective Agents* / therapeutic use
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Signal Transduction
Spinal Cord Injuries*

Substances

Reactive Oxygen Species
Caspase 3
Neuroprotective Agents