■糖尿病肾病(DKD)是终末期肾病(ESRD)的主要原因,这是一个具有重大经济负担的公共卫生问题。严重的不良反应,比如低血压,高钾血症,和泌尿生殖系统感染,以及增加不良心血管事件,限制了可用药物的临床应用。大量随机对照试验(RCT),荟萃分析(MA)和系统评价(SRs)已经证明,许多疗法已经在医疗实践中使用了很长时间,包括中成药(CPM),中药处方,提取物有效缓解DKD,但是它们的工作机制仍然未知。目前,靶向炎症是DKD药物开发的核心策略。此外,许多实验研究已经确定了许多中药处方,具有缓解DKD潜力的草药和提取物。他们工作的部分机制已经被发现。
目的:这篇综述旨在总结已被RCT证明有效的疗法,MA和SR,包括CPM,中药处方,和提取物。本文还重点介绍了中药处方的效率和潜在目标,在改善DKD免疫炎症的实验研究中发现的草药和提取物。
方法:我们在以下数据库中搜索了相关的科学文章:PubMed,谷歌学者,和WebofScience。我们总结了有效的CPM,中药处方,和RCT的提取物,MA和SR。阐述了中药方剂的信号通路和分子机制,根据不同的实验研究,中药和提取物可以减轻DKD中的炎症。
结果:在概述了大量证据等级较低的RCT以及异质性较强的MA和SR之后,我们仍然发现CPM,中药处方,提取物对DKD具有良好的保护作用。然而,没有足够的证据证明中药的安全性。至于实验研究,体外和体内实验联合证明了中药的疗效(中药方剂,DKD治疗中的草药和提取物)。中药能够调节信号通路以改善DKD的炎症,比如toll样受体,NLRP3炎性体,Nrf2信号通路,AMPK信号通路,MAPK信号通路,JAK-STAT,年龄/愤怒
结论:中药(中药处方,草药和提取物)可以改善DKD的炎症。对于在随机对照试验中有效的药物,应鉴定和分离潜在的生物活性成分或提取物。应注意其安全性和药代动力学。急性,亚急性,亚慢性毒性研究应旨在确定人类或动物副作用的程度和耐受性。对于在实验研究中被证明有效的药物,RCTs的设计应该为临床翻译提供可靠的证据。一句话,针对DKD免疫炎症的中药是一个有前途的方向。
UNASSIGNED: Diabetic kidney disease (
DKD) is the main cause of end-stage renal disease (ESRD), which is a public health problem with a significant economic burden. Serious adverse effects, such as hypotension, hyperkalemia, and genitourinary infections, as well as increasing adverse cardiovascular events, limit the clinical application of available drugs. Plenty of randomized controlled trials(RCTs), meta-analysis(MAs) and systematic reviews(SRs) have demonstrated that many therapies that have been used for a long time in medical practice including Chinese patent medicines(CPMs), Chinese medicine prescriptions, and extracts are effective in alleviating DKD, but the mechanisms by which they work are still unknown. Currently, targeting inflammation is a central strategy in
DKD drug development. In addition, many experimental studies have identified many Chinese medicine prescriptions, medicinal herbs and extracts that have the potential to alleviate
DKD. And part of the mechanisms by which they work have been uncovered.
OBJECTIVE: This review aims to summarize therapies that have been proven effective by RCTs, MAs and SRs, including CPMs, Chinese medicine prescriptions, and extracts. This review also focuses on the efficiency and potential targets of Chinese medicine prescriptions, medicinal herbs and extracts discovered in experimental studies in improving immune inflammation in
DKD.
METHODS: We searched for relevant scientific articles in the following databases: PubMed, Google Scholar, and Web of Science. We summarized effective CPMs, Chinese medicine prescriptions, and extracts from RCTs, MAs and SRs. We elaborated the signaling pathways and molecular mechanisms by which Chinese medicine prescriptions, medicinal herbs and extracts alleviate inflammation in DKD according to different experimental studies.
RESULTS: After overviewing plenty of RCTs with the low hierarchy of evidence and MAs and SRs with strong heterogeneity, we still found that CPMs, Chinese medicine prescriptions, and extracts exerted promising protective effects against DKD. However, there is insufficient evidence to prove the safety of Chinese medicines. As for experimental studies, Experiments in vitro and in vivo jointly demonstrated the efficacy of Chinese medicines(Chinese medicine prescriptions, medicinal herbs and extracts) in DKD treatment. Chinese medicines were able to regulate signaling pathways to improve inflammation in DKD, such as toll-like receptors, NLRP3 inflammasome, Nrf2 signaling pathway, AMPK signaling pathway, MAPK signaling pathway, JAK-STAT, and AGE/RAGE.
CONCLUSIONS: Chinese medicines (Chinese medicine prescriptions, medicinal herbs and extracts) can improve inflammation in DKD. For drugs that are effective in RCTs, the underlying bioactive components or extracts should be identified and isolated. Attention should be given to their safety and pharmacokinetics. Acute, subacute, and subchronic toxicity studies should be designed to determine the magnitude and tolerability of side effects in humans or animals. For drugs that have been proven effective in experimental studies, RCTs should be designed to provide reliable evidence for clinical translation. In a word, Chinese medicines targeting immune inflammation in
DKD are a promising direction.