Zhuru extracts ameliorate lipid accumulation of MASLD via suppressing the mTORC1/SREBPs pathway

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide, primarily caused by poor lifestyle choices and dietary habits. Caulis Bambusae In Taenias, commonly known as Zhuru in Chinese, is a traditional Chinese medicinal material from the Bambusoideae family, frequently used for liver detoxification, liver protection, and lowering lipids.

The study aimed to reveal the protective effects and underlying mechanisms of Zhuru extracts (EZR) in treating MASLD.

High performance liquid chromatography, liquid chromatography-tandem mass spectrometry, and fourier infrared spectroscopy were used to identify the components of EZR. We utilized oleic acid-treated HepG2/LO2 cells as in vitro models and zebrafish on high-fat diets (HFD) as animal models, and conducted network pharmacology, RNA sequencing, and biological assays, including confocal fluorescence, commercial kits, western blotting, and quantitative PCR, to investigate the lipid-lowering effect of EZR and its underlying mechanisms.

EZR alleviated lipid accumulation in both in vitro and in vivo models. Analyses through network pharmacology and RNA sequencing revealed that the lipid-lowering properties of EZR were associated with pathways related to lipid biosynthesis, antioxidant functions, and anti-inflammatory mechanisms. Subsequent experimental validation confirmed that EZR decreased the expression levels of FASN, ACC1, HMGCR, ACLY, and LDLR. Additional findings indicated that EZR inhibited mTORC1 activation, leading to the suppression of SREBP1 and SREBP2, thereby mitigating lipid accumulation. Furthermore, EZR was found to downregulate oxidative stress and the levels of inflammatory cytokines.

EZR demonstrated the ability to lower lipid levels and alleviate HFD-induced MASLD. This is achieved by inhibiting mTORC1/SREBPs-related lipid biosynthesis and reducing oxidative stress and inflammation.