Iridoids rich fraction from Valeriana jatamansi Jones promotes axonal regeneration and motor functional recovery after spinal cord injury through activation of the PI3K/Akt signaling pathway

Yunyun Wang; Jiachun Lu; Hua Xiao; Lijuan Ding; Yongzhi He; Cong Chang; Wenchun Wang

doi:10.3389/fnmol.2024.1400927

Iridoids rich fraction from Valeriana jatamansi Jones promotes axonal regeneration and motor functional recovery after spinal cord injury through activation of the PI3K/Akt signaling pathway

Front Mol Neurosci. 2024 May 2:17:1400927. doi: 10.3389/fnmol.2024.1400927. eCollection 2024.

Authors

Yunyun Wang^#¹, Jiachun Lu^#², Hua Xiao¹, Lijuan Ding¹, Yongzhi He³, Cong Chang², Wenchun Wang¹

Affiliations

¹ Department of Rehabilitation Medicine, The General Hospital of Western Theater Command, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
² Chengdu Eighth People's Hospital (Geriatric Hospital of Chengdu Medical College), Chengdu, Sichuan, China.
³ North Sichuan Medical College, Chengdu, Sichuan, China.

^# Contributed equally.

Abstract

Valeriana jatamansi Jones (VJJ), renowned for its extensive history in traditional Chinese medicine and ethnomedicine within China, is prevalently utilized to alleviate ailments such as epigastric distension and pain, gastrointestinal disturbances including food accumulation, diarrhea, and dysentery, as well as insomnia and other diseases. Moreover, the Iridoid-rich fraction derived from Valeriana jatamansi Jones (IRFV) has demonstrated efficacy in facilitating the recuperation of motor functions after spinal cord injury (SCI). This study is aimed to investigate the therapeutic effect of IRFV on SCI and its underlying mechanism. Initially, a rat model of SCI was developed to assess the impact of IRFV on axonal regeneration. Subsequently, employing the PC12 cell model of oxidative damage, the role and mechanism of IRFV in enhancing axonal regeneration were explored using the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway inhibitor LY294002. Ultimately, the same inhibitor was administered to SCI rats to confirm the molecular mechanism through which IRFV promotes axonal regeneration by activating the PI3K/Akt signaling pathway. The results showed that IRFV significantly enhanced motor function recovery, reduced pathological injury, and facilitated axonal regeneration in SCI rats. In vitro experiments revealed that IRFV improved PC12 cell viability, augmented axonal regeneration, and activated the PI3K/Akt signaling pathway. Notably, the inhibition of this pathway negated the therapeutic benefits of IRFV in SCI rats. In conclusion, IRFV promote promotes axonal regeneration and recovery of motor function after SCI through activation of the PI3K/Akt signaling pathway.

Keywords: Iridoid-rich fraction derived from Valeriana jatamansi Jones; PI3K/Akt signaling; axonal regeneration; spinal cord injury; traditional Chinese medicine.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Special Research Project of Traditional Chinese Medicine from Sichuan Provincial Administration of Traditional Chinese Medicine (No.2018JC033).