Preclinical Evidence and Mechanism of Xingnaojing Injection for Cerebral Ischemia: A Systematic Review and Meta-Analysis of Animal Studies

OBJECTIVES: Cerebral ischemia can cause severe harm to people's health with the characteristics of high incidence, high disability, and high mortality. Xingnaojing injection (XNJI) is widely used in the treatment of cerebral ischemia. The aim of this review is to evaluate the efficacy and mechanism of XNJI in animal models of cerebral ischemia. METHODS: Total seven electronic databases in English or Chinese (CNKI, Wanfang, VMIS, PubMed, MEDLINE, Embase, and the Cochrane Library) about most experiments and studies which came out before June 2018 of XNJI for cerebral ischemia have been searched. Data extraction, quality assessment, and meta-analysis are conducted according to the Cochrane standards and RevMan 5.3 software. RESULTS: We have identified 23 eligible studies and made a meta-analysis based on these studies. Meta-analysis shows that XNJI contributes significantly to reduction in neurological deficit score (P = 0.0002, MD = −1.25, 95% CI: −1.92, −0.58) compared with the control group of cerebral ischemia. Subgroup analytic results demonstrate that XNJI has been more effective in animal model of cerebral ischemia-reperfusion injury (P = 0.009, MD = −1.35, 95%CI: −2.36, −0.34) than that of permanent cerebral ischemia (P = 0.0002, MD = −1.08, 95%CI: −1.66, −0.51). Compared with control group, XNJI could remarkably reduce cerebral infarction area (P < 0.00001, MD = −14.98, 95%CI: −21.36, −8.59), brain edema (P < 0.00001, MD = −4.64, 95%CI: −5.38, −3.90), and neuronal cell apoptosis (P < 0.0001, MD = −12.21, 95%CI: 18.05, −6.37). Meanwhile, the meta-analysis shows that XNJI has a significant anti-inflammatory effect, and the levels of TNF-α, IL-6, and IL-1β are significantly reduced by XNJI (P = 0.001, MD = −4.13, 95%CI:−6.68, −1.58; P < 0.00001, MD = −119.23, 95%CI: −138.04, −100.43; P = 0.21, MD = −228.69, 95% CI: −586.20, 128.83). Additionally, XNJI could raise the body's antioxidant function and the level of SOD and GSH-Px (P = 0.002, MD = 53.02, 95% CI: −20.52, 85.78; P = 0.01, MD = 8.65, 95% CI: 1.77, 15.48) and decrease the level of MDA (P < 0.00001, MD = −4.16, 95% CI: −5.50, −2.82). CONCLUSION: XNJI might be effective in cerebral ischemia by regulating oxidative stress and inflammatory reaction.