Hepatoprotection and hepatotoxicity of Chinese herb Rhubarb (Dahuang): How to properly control the “General (Jiang Jun)” in Chinese medical herb

The relationship between hepatoprotection and hepatotoxicity caused by Rhubarb administration. When Rhubarb are prepared and administered into human body, its active compounds will play the role of liver protection, while unreasonable dosage control, transformation of metabolites, and even individual differences can finally trigger the occurrence of hepatotoxicity. [Display omitted] •The Chinese herb Rhubarb has both protective and toxic effects on human liver.•Multiple signal pathways contribute to Rhubarb’ hepatoprotective effects.•Compounds in Rhubarb and some external factors, can trigger the hepatotoxicity.•Some clinical guiding proposals are put forward for better application of Rhubarb. Chinese herb Rhubarb (Dahuang), one of the most widely used traditional Chinese medicine in clinical application for over a thousand years and known as the “General (Jiang Jun)” in Chinese medical herb, currently used clinically for long-term treatment of gastrointestinal diseases and chronic liver diseases. Through previous researches, it has been identified that Rhubarb possessed a good hepatoprotective effect, which primarily protected liver from oxidation, fibrosis and cirrhosis, liver failure, hepatocellular carcinoma and various types of hepatitis. Meanwhile, it has been recently reported that long-term administration of Rhubarb preparation may undertake the risk of liver damage, which has aroused worldwide doubts about the safety of Rhubarb. Therefore, how to correctly understand the "two-way" effect of Rhubarb on liver protection and liver toxicity provides a basis for scientific evaluation of Rhubarb's efficacy on liver and side effects, as well as guiding clinical rational drug use. In this review, the mechanisms of Rhubarb how to play a role in hepatoprotection and why it causes hepatotoxic potential will be elaborated in detail and critically. In addition, some positive clinical guidances are also advised on how to reduce its hepatotoxicity in medical treatment.