Triptolide mediates Wnt/β-catenin signalling pathway to reduce cerebral ischemia-reperfusion injury in rats

Abstract

Introduction: Triptolide, extracted from Chinese medicinal materials Tripterygium wilfordii Hook F (TwHF), has immunosuppressive, anti-inflammatory and anti-tumour effects. The purpose of this study was to examine whether triptolide has the neuroprotective effect on cerebral ischemia-reperfusion (I/R) injury and to explore its possible mechanism. Material and methods: The rat model of focal cerebral I/R was established by the suture-occluded method. The SD rats were randomly divided into five groups: sham operation group (Sham group), ischemia-reperfusion model group (I/R group), low concentration of triptolide group (12.5 mg/kg, TL-L group), medium concentration of triptolide group (25 mg/kg, TL-M group) and high concentration of triptolide group (50 mg/kg, TL-H group). The neurological function of the rats was scored, the degree of brain oedema was detected by the dry-wet method, and the cerebral infarction area was determined by TTC staining. Nissl staining was used to detect neuronal damage. The contents of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were also detected. Meanwhile, the expression level of proteins related to Wnt/β-catenin signalling pathway was measured by Western blot. Results: Compared with the I/R group, cerebral oedema, infarct volume, neurological impairment, the contents of MDA and ROS were reduced, while the SOD level was increased in the TL-L, TL-M, and TL-H groups. The results of Nissl staining showed that triptolide could reduce the nerve cell injury caused by cerebral I/R. In addition, the results of Western blot confirmed that the expression of Wnt1, β-catenin, c-Myc, and Cyclin-D1 were down-regulated after triptolide intervention, that is, inhibited the activation of Wnt/β-catenin signalling pathway. Conclusions: Triptolide mediates Wnt/β-catenin signalling pathway to alleviate cerebral I/R injury in rats. This study provides ideas and experimental basis for the treatment of ischemic stroke patients.

The therapeutic potential of triptolide and celastrol in neurological diseases

“…Pan et al also reported the therapeutic effects of triptolide on MCAO. In their experimental results, triptolide could improve neurobehavioral scores, reduce brain damage, exert anti-inflammatory and antioxidant effects (reduce levels of malondialdehyde (MDA) and ROS, increase superoxide dismutase (SOD) level), and these effects were associated with inhibition of Wnt/β-catenin signaling pathway ( Pan and Xu, 2020 ). In addition, right unilateral common carotid artery occlusion (rUCCAO), which simulates chronic cerebral hypoperfusion, can also be used for cerebral ischemia related research ( Yoshizaki et al, 2008 ).…”

Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury

“…Wnt/β-catenin pathway is abnormally activated in I/RI and exacerbates I/RI [ 20 – 22 ]. Therefore, this study speculates that circARAP1 may activate the Wnt/β-catenin pathway by affecting the miR-379-5p/KLF9 axis.…”

“…Wnt/β-catenin pathway plays a key role in cell growth, differentiation, migration, polarity and death [ 37 ]. Recently, the wnt/β-catenin pathway has been shown to be abnormally activated in I/RI [ 20 – 22 ]. The present study exhibited that circARAP1 activates the Wnt/β-catenin pathway by regulating the miR-379-5p/KLF9 axis to affect cardiomyocyte H/R injury and MI/RI in mice.…”

Scalp Electroacupuncture Promotes Angiogenesis after Stroke in Rats by Activation of Wnt/β-Catenin Signal Pathway

“…Our results showed that the protein and mRNA expression of Wnt3a and β -catenin increased in the brain tissues from the model group at all three time points, which might be a built-in antidamage mechanism (Figures 4 and 5 ). Notably, no significant increases of TCF4 and cyclin D1 were observed, suggesting that the activation of the Wnt/ β -catenin pathway caused by cerebral IR injury was insufficient to protect brain tissues from cerebral IR injury [ 28 , 29 ]. After scalp electroacupuncture treatment, the mRNA and protein expression levels of Wnt3a and β -catenin rose in the infarct area of brain tissue and further resulted in cascade upregulation of TCF4 and cyclin D1 (Figures 4 and 5 ).…”