Tongqiao Huoxue decoction alleviates neurological impairment following ischemic stroke via the PTGS2/NF-kappa B axis.

Traditional Chinese medicine has emerged as promising targets for ischemic stroke (IS) therapy, yet the mechanism remains elusive. The current study was performed with an aim to investigate the action and mechanism of Tongqiao Huoxue decoction (TQHXD) affecting the neurological impairment secondary to IS based on network pharmacology. Based on network pharmacology and bioinformatics analysis, target genes and pathways involved in the treatment of TQHXD against IS were predicted. Serum containing TQHXD was prepared through blood collection from C57BL/6 mice after intragastric administration of TQHXD. The main results exhibited that Prostaglandin-endoperoxide synthase 2 (PTGS2) exhibited an abundance in IS and enrichment in the NF-kappa B signaling pathway, holding the potential as targets related to TQHXD treatment for IS. TQHXD was found to rescue cell viability, inhibit apoptosis, and alleviate inflammation under oxygen and glucose deprivation and reoxygenation (OGD/R) exposure. Furthermore, our in vivo experiment validated the protective function of TQHXD in ischemic brain damage stimulated by middle cerebral artery occlusion (MCAO). This protective action of TQHXD could be attenuated by overexpressing nuclear factor (NF)-kappa B, which was dependent on PTGS2. Collectively, TQHXD was demonstrated to ameliorate IS-induced neurological impairment by blocking the NF-kappa B signaling pathway and down-regulating PTGS2.

The neuroprotective effect of YaoYi-moxibustion on ischemic stroke by attenuating NK-κB expression in rats.

Background: Traditional Chinese medicine (TCM) has become a crucial direction for ischemic stroke treatment. This study sought to explore the underlying roles of YaoYi-moxibustion (YY-moxi) in ischemic stroke. Methods: A total of 75 Sprague-Dawley rats were randomly divided into the following 5 groups: (I) the sham-operated group; (II) the middle cerebral artery occlusion model (MCAO) group; (III) the YY-moxi group; (IV) the antioxidant (N-acetylcysteine, NAC) group; and (V) the NAC + YY-moxi group. After the model had been established, the NAC group received intracerebroventricular injections of NAC, the YY-moxi group received YY-moxi, and the NAC + YY-moxi group received a combination of these 2 interventions. The neurological deficit score was confirmed, and the cerebral infarction was examined by triphenyl tetrazolium chloride (TTC) staining. In the ischemia site of stroke, terminal deoxynucleotidyl transferase-mediated Dutp nick end labeling staining was applied to examine the apoptotic cells. Additionally, the apoptosis-associated genes and protein expressions in the ischemic brains were investigated by the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry, and western blot analysis. Results: YY-moxi alone and YY-moxi combined with NAC significantly reduced the neurological scores and cerebral infarction area of the MCAO rats. Additionally, YY-moxi alone and the combined application of YY-moxi and NAC improved the pathological status of ischemic brain tissues. Further, we found that YY-moxi alone and YY-moxi in combination with NAC could enhanced the antioxidation ability and reduced the inflammatory response of the MCAO model rats. We also proved that YY-moxi alone and YY-moxi combined with NAC significantly suppressed apoptosis-related proteins in the MCAO model rats. Conclusions: These findings indicate that YY-moxi exerts a protective effect on cerebral ischemic injury by reducing apoptosis. The study suggests that the mechanism may be related to its downregulating the expression of nuclear factor kappa B (NK-κB).

MiR-23a transcriptional activated by Runx2 increases metastatic potential of mouse hepatoma cell via directly targeting Mgat3.

MicroRNAs (miRNAs) and aberrant glycosylation both play important roles in tumor metastasis. In this study, the role of miR-23a in N-glycosylation and the metastasis of mouse hepatocellular carcinoma (HCC) cells was investigated. The miRNA expression array profiles that were confirmed by qPCR and Western blot analyses revealed higher miR-23a expression levels in Hca-P cells (with lymphatic metastasis potential) than in Hepa1-6 cells (with no lymphatic metastasis potential), while the expression of mannoside acetylglucosaminyltransferase 3 (Mgat3) was negatively associated with metastasis potential. Mgat3 is a key glycosyltransferase in the synthesis of the bisecting (ß1,4GlcNAc branching) N-glycan structure. Bioinformatics analysis indicated that Mgat3 may be a target of miR-23a, and this hypothesis was verified by dual-luciferase reporter gene assays. Furthermore, we found that the transcription factor Runx2 can directly bind to the miR-23a gene promoter and promote its expression, as shown in dual-luciferase reporter gene assays and ChIP assays. Collectively, these results indicate that miR-23a might increase the metastatic potential of mouse HCC by affecting the branch formation of N-glycan chains presented on the cell surface through the targeting of the glycosyltransferase Mgat3. These findings may provide insight into the relationship between abnormal miRNA expression and aberrant glycosylation during tumor lymphatic metastasis.