Ligustrazine exerts neuroprotective effects via circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury

Li, Litao; Zhang, DingWen; Yao, Wentao; Wu, Zongkai; Cheng, Ju Chien; Ji, Yingxiao; Dong, Lipeng; Zhao, Chenchen; Wang, Hebo

doi:10.1016/j.brainresbull.2022.10.011

Cited by 8 publications

(8 citation statements)

References 56 publications

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“…Two studies ( Chang et al, 2007 ; Li et al, 2022 ) reported caspase-3 levels, and the heterogeneity test showed no significant variation ( p = 0.67, I 2 = 0%). Therefore, a fixed effects model was used.…”

Section: Resultsmentioning

confidence: 93%

“…A total of 3,398 relevant documents were retrieved. After applying the inclusion and exclusion criteria, 32 studies ( Liao et al, 2004 ; Kao et al, 2006 ; Chang et al, 2007 ; Li et al, 2008 ; Qi et al, 2008 ; Ren et al, 2008 ; Zhang et al, 2008 ; Jia et al, 2009 ; Zhu et al, 2009 ; Hu et al, 2010a ; Hu et al, 2010b ; Chen et al, 2010 ; Fang et al, 2010 ; Ma and Chen, 2010 ; Xiao et al, 2010 ; Yang and Ren, 2011 ; Zhang et al, 2011 ; Kao et al, 2013 ; Li et al, 2013 ; Han et al, 2014 ; Tian et al, 2014 ; Tan et al, 2015 ; Liu, 2016 ; Li et al, 2017 ; Gong et al, 2019 ; Zhu et al, 2020 ; Ge et al, 2021 ; Li et al, 2022 ; Liang et al, 2022 ; Chang et al, 2023 ; Feng et al, 2023 ; Gao et al, 2023 ) were included. The detailed literature search and screening process is illustrated in Figure 3 .…”

Section: Resultsmentioning

confidence: 99%

“…A total of 32 studies were included in this study. Among these, three studies used Wistar rats ( Chang et al, 2007 ; Li et al, 2008 ; Zhang et al, 2011 ) weighing 250–320 g, two studies used Kunming mice ( Hu et al, 2010a ; Hu et al, 2010b ) weighing 30–40 g, and one study used C57BL/6 mice ( Li et al, 2022 ), but the weight of the mice was not reported. The remaining 26 studies utilized SD rats weighing 220–350 g. Five studies employed the MCAO model, while 27 studies used the MCAO/reperfusion model.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 18 studies ( Li et al, 2008 ; Qi et al, 2008 ; Ren et al, 2008 ; Jia et al, 2009 ; Zhu et al, 2009 ; Fang et al, 2010 ; Yang and Ren, 2011 ; Zhang et al, 2011 ; Kao et al, 2013 ; Han et al, 2014 ; Tian et al, 2014 ; Tan et al, 2015 ; Liu, 2016 ; Li et al, 2017 ; Gong et al, 2019 ; Li et al, 2022 ; Liang et al, 2022 ; Gao et al, 2023 ) reported NDS. The heterogeneity test showed a significance of p = 0.02, with an I 2 value of 44%.…”

Section: Resultsmentioning

confidence: 99%

“…A total of nine studies ( Kao et al, 2006 ; Fang et al, 2010 ; Kao et al, 2013 ; Tan et al, 2015 ; Liu, 2016 ; Li et al, 2017 ; Gong et al, 2019 ; Li et al, 2022 ; Chang et al, 2023 ) reported the percentage of infarct volume. The heterogeneity test showed p = 0.09 and I 2 = 41%.…”

Section: Resultsmentioning

confidence: 99%

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The protective effects of ligustrazine on ischemic stroke: a systematic review and meta-analysis of preclinical evidence and possible mechanisms

Wang,

Wu,

Miao

et al. 2024

Front. Pharmacol.

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Introduction: The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action.Materials and Methods: The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5).Results: A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = −1.84, 95% CI −2.14 to −1.55, P < 0.00001). It also reduced the percentage of cerebral infarction (SMD = −2.97, 95% CI −3.58 to −2.36, P < 0.00001) and brain water content (SMD = −2.37, 95% CI −3.63 to −1.12, P = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = −7.53, 95% CI −11.34 to −3.72, P = 0.0001), IL-1β (SMD = −2.65, 95% CI −3.87 to −1.44, P < 0.0001), and IL-6 (SMD = −5.55, 95% CI −9.32 to −1.78, P = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, P = 0.0003), NOS (SMD = −1.52, 95% CI −2.98 to −0.06, P = 0.04), MDA (SMD = −5.31, 95% CI −8.48 to −2.14, P = 0.001), and NO (SMD = −5.33, 95% CI −8.82 to −1.84, P = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = −5.21, 95% CI −7.47 to −2.94, P < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, P < 0.0001).Conclusion: Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.

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Section: Resultsmentioning

confidence: 93%