Sun Tao, Wang Ping, Deng Ting, Tao Xingbao, Li Bin, Xu Ying
Department of Pharmacology, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2021 Feb 9;11:572304. doi: 10.3389/fphar.2020.572304. eCollection 2020.
With the increase of the aging population, the high mortality and disability rates caused by ischemic stroke are some of the major problems facing the world, and they dramatically burden the society. (Burk) F. H. Chen, a traditional Chinese medicine, is commonly used for promoting blood circulation and removing blood stasis, and its main bioactive components are saponins (PNS). Therefore, we performed a meta-analysis on focal cerebral ischemia-reperfusion animal models established with middle cerebral artery occlusion (MCAO) surgery to evaluate the therapeutic effect of PNS. We systematically searched the reports of PNS in MCAO animal experiments in seven databases. We assessed the study quality using two literature quality evaluation criteria; evaluated the efficacy of PNS treatment based on the outcomes of the neurological deficit score (NDS), cerebral infarct volume (CIV), and biochemical indicators via a random/fixed-effects model; and performed a subgroup analysis utilizing ischemia duration, drug dosage, intervention time, and administration duration. We also compared the efficacy of PNS with positive control drugs or combination treatment. As a result, we selected 14 eligible studies from the 3,581 searched publications based on the predefined exclusion-inclusion criteria. PNS were significantly associated with reduced NDS, reduced CIV, and inhibited release of the inflammatory factors IL-1β and TNF-α in the focal MCAO rat models. The PNS combination therapy outperformed the PNS alone. In addition, ischemia time, drug dosage, intervention time, and administration duration in the rat models all had significant effects on the efficacy of PNS. Although more high-quality studies are needed to further determine the clinical efficacy and guiding parameters of PNS, our results also confirmed that PNS significantly relieves the focal cerebral ischemia-reperfusion in rat models. In the animal trials, it was suggested that an early intervention had significant efficacy with PNS alone or PNS combination treatment at a dosage lower than 25 mg/kg or 100-150 mg/kg for 4 days or longer. These findings further guide the therapeutic strategy for clinical cerebral ischemic stroke.
随着人口老龄化的加剧，缺血性中风导致的高死亡率和高致残率是世界面临的一些主要问题，给社会带来了沉重负担。中药（Burk）F.H. 陈，常用于活血化瘀，其主要生物活性成分是皂苷（PNS）。因此，我们对采用大脑中动脉闭塞（MCAO）手术建立的局灶性脑缺血再灌注动物模型进行了荟萃分析，以评估PNS的治疗效果。我们系统检索了七个数据库中关于PNS在MCAO动物实验中的报告。我们使用两种文献质量评估标准评估研究质量；通过随机/固定效应模型根据神经功能缺损评分（NDS）、脑梗死体积（CIV）和生化指标的结果评估PNS治疗的疗效；并利用缺血持续时间、药物剂量、干预时间和给药持续时间进行亚组分析。我们还将PNS的疗效与阳性对照药物或联合治疗进行了比较。结果，根据预先定义的排除纳入标准，我们从3581篇检索到的出版物中筛选出14项符合条件的研究。在局灶性MCAO大鼠模型中，PNS与降低NDS、减小CIV以及抑制炎症因子IL-1β和TNF-α的释放显著相关。PNS联合治疗优于单独使用PNS。此外，大鼠模型中的缺血时间、药物剂量、干预时间和给药持续时间均对PNS的疗效有显著影响。尽管需要更多高质量的研究来进一步确定PNS的临床疗效和指导参数，但我们的结果也证实了PNS能显著减轻大鼠模型中的局灶性脑缺血再灌注。在动物试验中，提示早期干预单独使用PNS或PNS联合治疗，剂量低于25mg/kg或100 - 150mg/kg，持续4天或更长时间具有显著疗效。这些发现进一步指导了临床脑缺血性中风的治疗策略。
