Chuanzhitongluo inhibits neuronal apoptosis in mice with acute ischemic stroke by regulating the PI3K/AKT signaling pathway

Background and purpose: Apoptosis is involved in the occurrence and development of acute ischemic stroke (AIS). This study aimed to assess whether Chuanzhitongluo (CZTL), a multi-target and multi-pathway compound preparation, plays a neuroprotective role in AIS by modulating neuronal Apoptosis via the PI3K/Akt signaling pathway.

Methods: A mouse model of AIS was established by photochemical processes. Cerebral infarction volume was measured by 2% staining with 2, 3, and 5-triphenyl tetrazole chloride (TTC). Neuron Apoptosis was assessed by TUNEL staining. Apoptosis RNA arrays were used to detect changes in apoptosis-related gene expression profiles. Western blotting was used to detect proteins involved in the PI3K/Akt signaling pathway.

Results: The study demonstrated that CZTL could potentially mitigate neuronal Apoptosis in AIS mice. This appears to be achieved via the up-regulation of certain genes such as Bcl-2, Birc6, and Others, coupled with the down-regulation of genes like Bax, Bid, and Casp3. Further validation revealed that CZTL could enhance the expression of Bcl-2 and reduce the expression of Cleaved Caspase-3 and Bax at both the gene and protein levels. The study also found that CZTL can enhance the phosphorylation level of the PI3K/Akt signaling pathway. In contrast to these findings, the PI3K Inhibitor LY294002 notably amplified neuronal Apoptosis in AIS mice.

Conclusions: These findings imply that CZTL's ability to inhibit neuronal Apoptosis may be linked to the activation of AIS's PI3K/Akt signaling pathway.

Acute ischemic stroke; Apoptosis; BAX; BCL-2; Chuanzhitongluo; PI3K/AKT.