Yousuf Sumaira, Shabir Shabnam, Singh Mahendra P
School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India.
J Am Nutr Assoc. 2023 Jul;42(5):495-515. doi: 10.1080/27697061.2022.2089403. Epub 2022 Jun 30.
Hepatotoxicity caused by the overdose of various medications is a leading cause of drug-induced liver injury. Overdose of drugs causes hepatocellular necrosis. Nutraceuticals are reported to prevent drug-induced liver failure. The present article aims to review the protection provided by various medicinal plants against hepatotoxic drugs. Ayurveda is considered a conventional restorative arrangement in India. It is consistently used for ages and is still used today to cure drug-induced hepatotoxicity by focusing on antioxidant stress response pathways such as the nuclear factor erythroid-2 (Nrf-2) antioxidant response element signaling pathway. Nrf-2 is a key transcription factor that entangles Kelch-like ECH-associating protein 1, a protein found in the cell cytoplasm. Some antioxidant enzymes, such as gamma glycine cysteine ligase (γ-GCL) and heme oxygenase-1 (HO-1), are expressed in Nrf-2 targeted genes. Their expression, in turn, decreases the stimulation of hepatic macrophages and induces the messenger RNA (mRNA) articulation of proinflammatory factors including tumor necrosis factor α. This review will cover various medicinal plants from a mechanistic view and how they stimulate and interact with Nrf-2, the master regulator of the antioxidant response to counterbalance oxidative stress. Interestingly, therapeutic plants have become popular in the medical sector due to safer yet effective supplementation for the prevention and treatment of new human diseases. The contemporary study is expected to collect information on a variety of therapeutic traditional herbs that have been studied in the context of drug-induced liver toxicity, as nutraceuticals are the most effective treatments for oxidative stress-induced hepatotoxicity. They are less genotoxic, have a lower cost, and are readily available. Together, nutraceuticals exert protective effects against drug-induced hepatotoxicity through the inhibition of oxidative stress, inflammation, and apoptosis. Its mechanism(s) are considered to be associated with the γ-GCL/HO-1 and Nrf-2 signaling pathways.KEY TEACHING POINTSThe liver is the most significant vital organ that carries out metabolic activities of the body such as the synthesis of glycogen, the formation of triglycerides and cholesterol, as well as the formation of bile.Acute liver failure is caused by the consumption of certain drugs; drug-induced liver injury is the major condition.The chemopreventive activity of nutraceuticals may be related to oxidative stress reduction and attenuation of biosynthetic processes involved in hepatic injury via amelioration of the nuclear factor erythroid-2 (Nrf-2) signaling pathway.Nrf-2 is a key transcription factor that is found in the cell cytoplasm resulting in the expression of various genes such as gamma glycine cysteine ligase and heme oxygenase-1.Nutraceutical-rich phytochemicals possess high antioxidant activity, which helps in the prevention of hepatic injury.
各种药物过量引起的肝毒性是药物性肝损伤的主要原因。药物过量会导致肝细胞坏死。据报道,营养保健品可预防药物性肝衰竭。本文旨在综述各种药用植物对肝毒性药物的保护作用。阿育吠陀在印度被认为是一种传统的恢复性疗法。它已经沿用了很长时间,至今仍被用于治疗药物性肝毒性,其作用机制主要是通过关注抗氧化应激反应途径,如核因子红细胞2(Nrf-2)抗氧化反应元件信号通路。Nrf-2是一种关键的转录因子,它与一种存在于细胞质中的名为kelch样ECH相关蛋白1的蛋白质相互作用。一些抗氧化酶,如γ-谷氨酰半胱氨酸连接酶(γ-GCL)和血红素加氧酶-1(HO-1),在Nrf-2靶向基因中表达。它们的表达反过来会减少肝巨噬细胞的刺激,并诱导包括肿瘤坏死因子α在内的促炎因子的信使核糖核酸(mRNA)表达。本综述将从机制角度介绍各种药用植物,以及它们如何刺激抗氧化反应的主要调节因子Nrf-2并与之相互作用,以平衡氧化应激。有趣的是,治疗性植物由于在预防和治疗新型人类疾病方面具有安全有效的补充作用,在医疗领域越来越受欢迎。目前的研究预计将收集各种治疗性传统草药的信息,这些草药已在药物性肝毒性的背景下进行了研究,因为营养保健品是氧化应激诱导的肝毒性最有效的治疗方法。它们的基因毒性较小,成本较低,且易于获得。营养保健品通过抑制氧化应激、炎症和细胞凋亡,对药物性肝毒性发挥保护作用。其作用机制被认为与γ-GCL/HO-1和Nrf-2信号通路有关。
关键知识点
肝脏是人体最重要的重要器官,它执行身体的代谢活动,如糖原的合成、甘油三酯和胆固醇的形成以及胆汁的形成。
急性肝衰竭是由某些药物的使用引起的;药物性肝损伤是主要病症。
营养保健品的化学预防活性可能与通过改善核因子红细胞2(Nrf-2)信号通路减少氧化应激以及减轻肝损伤中涉及的生物合成过程有关。
Nrf-2是一种关键的转录因子,存在于细胞质中,可导致各种基因的表达,如γ-谷氨酰半胱氨酸连接酶和血红素加氧酶-1。
富含营养保健品的植物化学物质具有高抗氧化活性,有助于预防肝损伤。