Department of Bioinformatics and Biotechnology, 72594Government College University, Faisalabad, Pakistan.
NICM Health Research Institute, 6489Western Sydney University, Westmead, Australia.
J Evid Based Integr Med. 2022 Jan-Dec;27:2515690X221113327. doi: 10.1177/2515690X221113327.
Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs.This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors.Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included.Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB.Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.
内皮功能障碍是心血管疾病 (CVDs) 的早期标志。由于复杂的多因素途径，单药治疗受到限制。天然产物的多成分和多靶点方法有可能治疗 CVDs。本综述旨在全面深入了解天然产物组合在保护内皮免受各种心血管危险因素方面的协同机制。检索了数据库（PubMed、MEDLINE 和 EMBASE）和 Google Scholar，并整理了 2000 年 1 月至 2022 年 2 月期间以英文发表的研究。包括与药物联合使用或不联合使用的天然产物组合的临床前和临床研究，与单药治疗相比，或提出保护内皮功能的潜在机制。四项临床研究表明，天然产物组合或天然产物-药物组合改善了内皮功能。这与多靶点效应或改善体内活性物质的吸收有关。十七项临床前研究表明，天然产物组合在保护内皮免受高血脂、高血压、糖尿病、血小板激活、氧化应激和高同型半胱氨酸血症方面产生协同（通过组合指数或 Bliss 独立性模型证明）或增强作用。分子靶点包括活性氧、Nrf2-HO-1、p38MAPK、PI3K/Akt 和 NF-κB。因此，目前针对内皮功能障碍的天然产物组合的证据主要来自临床前研究。这些研究已经证明了协同/增强的药理活性，并提出了相关的机制。然而，来自更大、设计良好的临床试验的证据仍然薄弱。需要在临床前和临床数据之间建立更多的一致性，以支持天然产物组合预防或减缓 CVDs 的进展。
