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

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

doi:10.3389/fphar.2022.949502

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

Front Pharmacol. 2022 Oct 7:13:949502. doi: 10.3389/fphar.2022.949502. eCollection 2022.

Authors

Zhen Li^{1

2

3}, Zehui Li^{1

2

3}, Zhenyue Chen^{4

3}, He Sun^{1

2

3}, Zhagen Yuan², Xiaochao Wang^{1

2

3}, Jinqiang Wei^{1

2

3}, Xuewei Cao², Decai Zheng²

Affiliations

¹ The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
² Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
³ Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
⁴ The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Abstract

Background: 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 Andrographis paniculata, 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. Methods: 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 in vitro model of SCI was established by treating cortical neurons with H₂O₂. The effects of Andro on apoptosis, oxidative stress and inflammation were evaluated as indicated. Results: 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 H₂O₂-stimulated cortical neurons in vitro. Conclusion: 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.

Keywords: andrographolide; apoptosis; inflammation; oxidative stress; spinal cord injury.