AUTHOR=Li Zhen , Li Zehui , Chen Zhenyue , Sun He , Yuan Zhagen , Wang Xiaochao , Wei Jinqiang , Cao Xuewei , Zheng Decai 

TITLE=Andrographolide contributes to spinal cord injury repair via inhibition of apoptosis, oxidative stress and inflammation

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.949502

DOI=10.3389/fphar.2022.949502

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Spinal cord injury (SCI) is a common disorder of the central nervous system with considerable socio-economic burden. Andrographolide (Andro), the main active component of <italic>Andrographis paniculata</italic>, has exhibited neuroprotective effects in different models of neurological diseases. The aim of this study was to evaluate the neuroprotective effects of Andro against SCI and explore the related mechanisms.</p><p><bold>Methods:</bold> SCI was induced in rats by the Allen method, and the modeled animals were randomly divided into sham-operated, SCI, SCI + normal saline (NS) and SCI + Andro groups. The rats were injected intraperitoneally with Andro (1 mg/kg) or the same volume of NS starting day one after the establishment of the SCI model for 28 consecutive days. Post-SCI tissue repair and functional recovery were evaluated by measuring the spinal cord water content, footprint tests, Basso-Beattie-Bresnahan (BBB) scores, hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis, oxidative stress and inflammation, as well as axonal regeneration and remyelination were analyzed using suitable markers. The <italic>in vitro</italic> model of SCI was established by treating cortical neurons with H<sub>2</sub>O<sub>2</sub>. The effects of Andro on apoptosis, oxidative stress and inflammation were evaluated as indicated.</p><p><bold>Results:</bold> Andro treatment significantly improved tissue repair and functional recovery after SCI by reducing apoptosis, oxidative stress and inflammation through the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf-2/HO-1) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, Andro treatment promoted M2 polarization of the microglial cells and contributed to axonal regeneration and remyelination to improve functional recovery after SCI. In addition, Andro also attenuated apoptosis, oxidative stress and inflammation in H<sub>2</sub>O<sub>2</sub>-stimulated cortical neurons <italic>in vitro</italic>.</p><p><bold>Conclusion:</bold> Andro treatment alleviated SCI by reducing apoptosis, oxidative stress and inflammation in the injured tissues and cortical neurons, and promoted axonal regeneration and remyelination for functional recovery.</p>