Cassia mimosoides L. decoction improves non-alcoholic fatty liver disease by modulating the pregnane X receptor

Abstract

Ethnopharmacological relevance

Cassia mimosoides L. (CML) is a traditional Chinese medicine (TCM), which is frequently used in the clinical practice of TCM in the Lingnan region of China for the treatment of obesity. However, it is not clear whether decoction of cassia seeds has beneficial effects on non-alcoholic fatty liver disease (NAFLD).

Objectives

This study investigates the effect of CML on NAFLD and its underlying mechanisms.

Materials and methods

The high-fat diet (HFD) was used to induce NAFLD mice, and 40 male C57BL/6J mice were divided into Control, HFD, and CML groups (CML-low 1.5 g/kg, CML-medium 2.25 g/kg, CML-high 4.5 g/kg). The mouse primary hepatocytes (MPHs) of wild type (WT) and PXR^−/− mice were induced using OAPA and divided into Control, OAPA, and CML groups (10 mg/L, 100 mg/L). Glycolipid metabolism, inflammation, and oxidative stress levels were detected in vivo and in vitro.

Results

Compared to the HFD group, the CML groups demonstrated reduced body weight, triglycerides, total cholesterol, blood glucose, and mRNA levels of the lipid metabolism genes Srebp-1c and ACC1 in mice (p < 0.05 or 0.01). The ELISA results indicated that CML inhibited the production of IL-1β, IL-6, and TNF-α (p < 0.05). Furthermore, CML increased the SOD level (p < 0.01) to improve oxidative stress. RNA-seq expression showed that CML suppressed the transcriptional level of pregnane X receptor (PXR)(p < 0.05). In vitro experiments, the protective effect of CML against OAPA-induced lipid accumulation and inflammation observed in WT MPHs disappeared in PXR^−/− MPHs (IC₅₀: 1.04 mg/mL).

Conclusion

CML decoction ameliorates NAFLD mainly by inhibiting the PXR signaling pathway, which provides a theoretical basis for the broad application of CML in clinical practice.