Hepatic steatosis, a pathological condition defined by the abnormal buildup of lipids within liver tissue, can be mitigated through the upregulation of autophagy. Polygoni Cuspidati Rhizoma et Radix (PCRR), a botanical remedy conventionally prescribed for the management of atherosclerosis, hepatitis, and cholelithiasis, has recently been shown to exert anti-steatotic properties in hepatic environments. Nevertheless, the precise bioactive components and the molecular pathways driving these effects have not yet been fully elucidated. The present study explored whether an aqueous extract of PCRR attenuates steatosis by regulating hepatic autophagic flux. Our results demonstrate that the PCRR aqueous extract stimulated autophagic flux, accelerated lysosomal biogenesis, and reduced intracellular lipid deposition in both hepatic cell lines and the liver tissue of steatotic rat models. From a mechanistic standpoint, the PCRR aqueous extract suppressed the activity of mechanistic target of rapamycin complex 1 (mTORC1), which induced the dephosphorylation and subsequent nuclear translocation of transcription factor EB (TFEB)—a pivotal master regulator of lipophagy. Conversely, the silencing of TFEB via knockdown experiments diminished the PCRR-induced enhancement of lipophagy in hepatic cell lines. Additionally, interrupting the autophagic pathway using chloroquine (CQ) neutralized the protective efficacy of PCRR against liver steatosis in rats maintained on a high-fat diet (HFD). Collectively, these data indicate that the aqueous extract of PCRR functions as an innovative autophagy promoter and represents a promising therapeutic agent for the treatment of hepatic steatosis.
