Crotalaria assamica Benth alleviated acetaminophen-induced liver injury through the upregulation of Nrf2 pathway.

Ethnopharmacological relevance: Crotalaria assamica Benth, one of the folk medicinal plants in the "Dai" of China, is commonly used to treat liver and bile related diseases. However, its bioactive compounds and the mechanism related to traditional use remain unclear.

Aim of the study: To investigate the protective compounds and mechanism of C. assamica on drug-induced liver injury.

Materials and methods: The acetaminophen (APAP)-induced mice and cell model were carried out to reveal the liver protection of the extract of C. assamica (ECA) and bioactive compounds in vitro and in vivo. The protective pathway was explored using transcriptome analysis, and binding targets were predicted by structure-based binding prediction and dynamic simulation, which were further supported by qPCR and Western Blot experiments on the livers of treated mice.

Results: ECA reduced the contents of serum lactate dehydrogenase, aspartate transaminase, and alanine transaminase significantly, adjusted the oxidative indices of serum and liver tissues, and ameliorated inflammation and necrosis of liver tissues, as well as up-regulated expressions of NQO1, HO-1, Nrf2, p-AKT, BCL-2, AKT, and IL-6 in vivo. Moreover, its bioactive compound sarosiensin V increased the viability of APAP-induced HepG2 cells, and restored liver function activity, accompanied by enhanced antioxidation and mitochondrial membrane potential significantly.

Conclusion: C. assamica and its bioactive compound sarosiensin V inhibited oxidative stress, inflammation, apoptosis and necrosis of liver tissues, which was associated with the upregulation of the Nrf2 pathway, and then supporting its traditional use for liver protection.