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Jingshu Keli and Its Components Notoginsenoside R1 and Ginsenoside Rb1 Alleviate the Symptoms of Cervical Myelopathy through Kir3.1 Mediated Mechanisms

[ Vol. 18 , Issue. 8 ]

Author(s):

Renjie Yan, Rui Chen, Jiahui Wang, Jian Shi, Wagner Ferreira dos Santos, Zhiru Xu and Li Liu*   Pages 631 - 642 ( 12 )

Abstract:


Background & Objective: Cervical Spondylotic Myelopathy (CSM) is one of the most serious spinal cord disorders in adults. Pharmacological modulation of ion channels is a common strategy to interfere with CSM and prevent neuronal damage.

Methods: Here, we investigated the effects of Jingshu Keli (JSKL), a traditional Chinese herbal formula, on CSM-related gait abnormality, mechanical allodynia and thermal hyperalgesia, and assessed the neuronal mechanisms of JSKL on cultured brainstem cells. Behavioral tests and patch clamp recordings were performed to make this assessment.

Results: In our study, we found that JSKL significantly recovered the gait performance (P<0.001) and decreased the levels of mechanical pain in 18.9% (P<0.01) and thermal pain in 18.1% (P<0.05). Further investigation suggested that JSKL and its containing ginsenoside Rb1 (GRb1), notoginsenoside R1 (NGR1) reduced the action potential frequency in 38.5%, 27.2%, 25.9%, and hyperpolarized resting membrane potential in 15.0%, 13.8%, 12.1%, respectively. Kir channels, not KV channels and KCa channels, were the major intermediate factors achieving treatment effects. Finally, immunostaining results showed that the phosphorylation of Kir3.1 was promoted, whereas the total expression level did not change.

Conclusion: Our study reveals a novel strategy of treating CSM by using Traditional Chinese Medicines (TCMs) containing active components.

Keywords:

Jingshu granule, cervical spondylotic myelopathy, ginsenoside Rb1, notoginsenoside R1, Kir3.1, cultured brainstem neurons.

Affiliation:

State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Jingan District, Shanghai, China; State Institute of Pharmaceutical Industry, Shanghai 200437, State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Jingan District, Shanghai, China; State Institute of Pharmaceutical Industry, Shanghai 200437, State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Jingan District, Shanghai, China; State Institute of Pharmaceutical Industry, Shanghai 200437, Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, Laboratory of Neurobiology and Venoms, Department of Biology, FFCLRP, University of Sao Paulo, Sao Paulo, State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Jingan District, Shanghai, China; State Institute of Pharmaceutical Industry, Shanghai 200437, State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Jingan District, Shanghai, China; State Institute of Pharmaceutical Industry, Shanghai 200437



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