Chinese herbs and their molecules: Clinical and pathophysiological implications for the liver

Abstract

Nature in China is rich in plants that are partially used as medicinal herbs for the treatment of several ailments and facilitated the development of herbal traditional Chinese medicine (TCM) in Chinese communities. Herbal TCM preparations often consist of several different herbs with numerous molecules of organic chemical structure as ingredients. On a molecular basis, some Chinese herbs are known for their hepatotoxic potency with its rare risk of a severe clinical course that requires liver transplantation if acute liver failure develops. The clinical diagnosis of hepatotoxicity by Chinese herbs is challenging due to the lack of diagnostic biomarkers except for the hepatic sinusoidal obstructive syndrome (HSOS), a specific liver disease caused by herbs containing unsaturated pyrrolizidine alkaloids. HSOS is the intrinsic form of liver injury, thereby predictable, reproducible in experimental animals, and dose dependent. Most other cases of liver injury by Chinese herbs are of idiosyncratic nature and experimentally not reproducible, emerge unpredictable, and occur independently of the dose. Injuries seem to be triggered mostly in the smooth endoplasmic reticulum of the liver cell by generation of reactive radicals, which initiate apoptosis and cell destruction. In cases of idiosyncratic liver injury, the individual molecular culprit commonly remains unclear due to herb multiplicity and lacking experimental reproducibility. In addition, the multiplicity of molecules also may cause clinically relevant metabolic interactions at the molecular and hepatocellular level. Thus, although Chinese herbs commonly are well tolerated, consumers should be aware of potential hepatotoxicity and metabolic interactions, preferring herbs with a low risk and an established efficacy.