Baicalein Attenuates Pyroptosis and Endoplasmic Reticulum Stress Following Spinal Cord Ischemia-Reperfusion Injury via Autophagy Enhancement

Abstract

Background: Spinal cord ischemia-reperfusion injury (SCIRI) is the main complication after the repair of a complex thoracoabdominal aortic aneurysm. Many clinical treatments are not ideal due to the complex pathophysiological process of this injury. Baicalein (BA), a component derived from the roots of the herb Scutellaria baicalensis, may contribute to the successful treatment of ischemia/reperfusion injury. Purpose: In the present study, the effects of BA on spinal cord ischemia-reperfusion injury and the underlying mechanisms were assessed. Materials and Methods: Spinal cord ischemia was induced in C57BL/6 mice by blocking the aortic arch. Fifty-five mice were then randomly divided into four groups: Sham, SCIR+Vehicle, SCIR+BA, and SCIR+BA +3MA groups. At 0 and 24 h pre-SCIRI and at 24 h and 7 days post-SCIRI, evaluations with the Basso mouse scale (BMS) were performed. On postoperative 24 h, the spinal cord was harvested to assess pyroptosis, endoplasmic reticulum stress mediated apoptosis and autophagy. Results: BA enhanced the functional recovery of spinal cord ischemia-reperfusion injury. In addition, BA attenuated pyroptosis, alleviated endoplasmic reticulum stress-mediated apoptosis, and activated autophagy. However, the effects of BA on the functional recovery of SCIRI, pyroptosis and endoplasmic reticulum stress-mediated apoptosis were reversed by the inhibition of autophagy. Conclusions: In general, our findings revealed that BA enhances the functional recovery of spinal cord ischemia-reperfusion injury by dampening pyroptosis and alleviating endoplasmic reticulum stress-mediated apoptosis, which are mediated by the activation of autophagy.

The P2X7 Receptor in Osteoarthritis

“…Fourth, resveratrol reduces mitochondrial damage and increases autophagy, thereby inhibiting NLRP3 activation and reducing inflammation ( Chang et al, 2015 ). Fifth, baicalein, a Chinese herbal ingredient, promotes autophagy degradation, and reduces unfolded protein accumulation and mitochondrial dysfunction caused by spinal cord ischemia-reperfusion injury, thereby alleviating pyroptosis ( Wu et al, 2020 ). Sixth, metformin activates AMPK, inhibits mTOR, relieves pyroptosis, and treats diabetic heart disease in obese mice ( Yang et al, 2019 ).…”

Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway

“…Autophagy, key cellular process for removing cytosolic waste and damaged organelles 21 , 22 , plays a key role in the pathophysiology of neurological diseases 23 . Overall, activation of autophagy is considered protective in SCI, which can attenuate pyroptosis 24 and improve functional recovery 25 . More specifically, increased autophagy stimulates mitophagy (autophagic degradation of damaged mitochondria), restricts the production of ROS, dampen the activation of NLRP3 inflammasomes, and suppress the secretion of IL-1β and IL-18, ultimately inhibiting pyroptosis 22 , 26 , 27 .…”

Using Network Pharmacology to Systematically Decipher the Potential Mechanisms of Jisuikang in the Treatment of Spinal Cord Injury

“…Tanshinone IIA improves functional recovery after SCI-induced lower urinary tract dysfunction [42]. Baicalein contributes to the functional recovery of SCI by dampening pyroptosis and alleviating endoplasmic reticulum stress-mediated apoptosis [43].…”