Network Pharmacology Reveals the Mechanism of Activity of Tongqiao Huoxue Decoction Extract Against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia-Reperfusion Injury

Abstract

Several clinical therapies such as tissue repair by replacing injured tissues with functional ones have been reported; however, there is great potential for exploring traditional herbal-induced regeneration with good safety. Tongqiao Huoxue Decoction (TQHXD), a well-known classical traditional Chinese medicinal formula, has been widely used for clinical treatment of stroke. However, biological activity and mechanisms of action of its constituents toward conferring protection against cerebral ischemia-reperfusion (I/R) injury remain unclear. In this present study, we evaluated TQHXD quality using HPLC; then, it was screened for its potential active ingredients using a series of indices, such as their drug-likeness and oral bioavailability. Subsequently, we analyzed the potential mechanisms of TQHXD anti-I/R using gene ontology functional enrichment analyses. The network pharmacological approach enabled us to screen 265 common targets associated with I/R, indicating that TQHXD had remarkable protective effects on infarction volume, neurological function scores, and blood-brain barrier (BBB) injury. In addition, TQHXD significantly promoted the recovery of regional cerebral blood flow (rCBF) 7 days after reperfusion compared to rats in the vehicle group. Immunofluorescence results revealed a significantly higher CD34 expression in TQHXD-treated rats 7 days after reperfusion. TQHXD is not merely effective but eventually develops a secretory profile composed of VEGF and cerebral blood flow, a typical signature termed the angiogenesis-associated phenotype. Mechanistically, our data revealed that TQHXD (6 g/kg) treatment resulted in a marked increase in expression of p-focal adhesion kinase (FAK) and p-Paxillin proteins. However, Ki8751-mediated inhibition of VEGFR2 activity repealed its angiogenesis and protective effects and decreased both p-FAK and p-Paxillin protein levels. Taken together, these findings affirmed the potential of TQHXD as a drug for the management of stroke, which might be exerted by increasing the angiogenesis via the VEGF pathway. Therefore, these results provide proof-of-concept evidence that angiogenesis is a major contributor to TQHXD-treated I/R and that TQHXD is a promising traditional ethnic medicine for the management of this condition.

Puerarin inhibited oxidative stress and alleviated cerebral ischemia-reperfusion injury through PI3K/Akt/Nrf2 signaling pathway

“…These rats could get food and water at will and were fed adaptively for 3 days before the experiment. After anesthesia, the in vivo (MCAO/R) model of experimental rats was established according to the previous studies ( Wu et al, 2020 ). Tweezers were used to separate the left carotid artery and internal carotid artery, then a waxed thread was inserted to block the middle cerebral artery (MCA), and 2 h later it was pulled out to the site of MCAO/R injury for reperfusion.…”

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

“…The expression of MMP-9, VEGF, and VEGFR2 plays an important role in neuroinflammation and angiogenesis [ 14 , 15 ]. As shown in Figure 5(a) , compared with that in the sham group (0.580 ± 0.135), the protein expression level of MMP-9 in the model group (1.057 ± 0.025) was increased significantly.…”

“…However, there was no statistically significant difference compared with the model group, and no significant difference was observed between the HQCFT and HQCFT-SR groups (p > 0.05). [14,15]. As shown in Figure 5(a), compared with that in the sham group (0.580 ± 0.135), the protein expression level of MMP-9 in the model group (1.057 ± 0.025) was increased significantly.…”

Circular RNA PUM1 performs as a competing endogenous RNA of microRNA-340-5p to mediate DEAD-box helicase 5 to mitigate cerebral ischemia-reperfusion injury

“…After washing the slides with 0.01 mol/L phosphate-buffered saline, Triton X-100 solution was added and 0.3% H 2 O 2 was supplemented to block the endogenous peroxidase. The sections were incubated with anti-GFAP (G3893, MilliporeSigma), and Iba-1 (MABN92, Sigma-Aldrich) overnight, and with the secondary antibody (#4409; CST) for 2 h. DAPI staining was applied to identify nuclei and a fluorescence microscope (Olympus BX51-DP70) to observe images [ 24 , 25 ].…”