Herb-induced liver injury (HILI) has become a great concern worldwide due to the widespread usage of herbal products. Among these products is Dictamni Cortex (DC), a well-known
Traditional Chinese Medicine (TCM), widely used to treat chronic
dermatosis. Dictamni Cortex has drawn increasing attention because of its hepatotoxicity caused by the hepatotoxic component,
dictamnine. However, the potential hepatotoxicity mechanism of
dictamnine remains unclear. Therefore, this study aimed to use the multi-omics approach (transcriptomic, metabolomic, and proteomic analyses) to identify genes, metabolites, and
proteins expressions associated with
dictamnine-induced hepatotoxicity. A study on mice revealed that a high dose of
dictamnine significantly increases serum
aspartate aminotransferase (AST) activity, total
bilirubin (TBIL), and direct
bilirubin (DBIL) levels, the relative liver weight and liver/brain weight ratio in female mice (P < 0.05 and P < 0.01), compared to the normal control group. Liver histologic analysis further revealed a high dose of
dictamnine on female mice caused hepatocyte vesicular steatosis characterized by hepatocyte microvesicles around the liver lobules. The expressed genes,
proteins, and metabolites exhibited strong associations with
lipid metabolism disorder and oxidative stress.
Dictamnine caused increased oxidative stress and early hepatic apoptosis via up-regulation of
glutathione S transferase a1 (GSTA1) and Bax/Bcl-2 ratio and down-regulation of the antioxidative
enzymes superoxide dismutase (SOD),
catalase, and
glutathione peroxidase 1 (GPx-1). Besides, the up-regulation of
Acyl-CoA synthetase long-chain family member 4 (ACSL4) and down-regulation of
acetyl-coa acetyltransferase 1 (ACAT1) and
fatty acid binding protein 1 (FABP-1)
proteins were linked to
lipid metabolism disorder. In summary,
dictamnine induces dose-dependent hepatotoxicity in mice, which impairs lipid metabolism and aggravates oxidative stress.