Picrosides I and II Ameliorate Steatosis by Modulating Lipogenesis, Mitochondrial Biogenesis, and Autophagy in Hepatic Cells.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is marked by excessive fat accumulation in the hepatocytes. In the present study, the protective efficacy of picroside I and II against steatosis was studied using combination of in silico and in vitro approaches. The in silico studies revealed moderate to high binding affinity of the picroside I and II with the various proteins involved in mitochondrial biogenesis and autophagy. Further, picrosides I and II treatment significantly reduced the lipid accumulation and triglyceride levels in the palmitate-oleate (PO)-treated Huh7 cells. Picrosides significantly downregulated various lipogenic markers (SREBP1c, ChREBP, SCD1, and FAS) and upregulated AMPKα. The PO treatment elevated ROS production and lipid peroxidation (MDA) in the hepatic cells, which was significantly lowered by picrosides. PO treatment also led to mitochondrial dysfunction; however, picrosides significantly restored mitochondrial function by improving mitochondrial membrane potential (MMP), mitochondrial DNA levels and upregulating the mitochondrial biogenesis (PGC1α, TFAM, NRF1 and NRF2). Further, picrosides lowered the levels of inflammatory cytokines (TNF-α, IL6 and IL1β) and expressions of NFκB in the PO-treated Huh7 cells. PO treatment impaired the autophagy by altering the expressions of autophagy markers (SQSTM1, BECN1, MAPLC3A, ATG5, and ATG7) in the PO-treated Huh7 cells. Picroside treatment improved the autophagic flux by modulating the expressions of various autophagy biomarkers. In conclusion, the picroside I and II effectively prevented the steatohepatitis by lowering the lipogenesis, oxidative stress and inflammation, which improved the mitochondrial biogenesis and autophagic reflux in the hepatic cells.

Key Findings

• Picrosides I and II reduce lipid accumulation and triglyceride levels in palmitate-oleate-treated hepatic cells.
• Picrosides downregulate lipogenic markers and upregulate AMPKα, improving mitochondrial function and biogenesis including NRF2 expression.
• Picrosides decrease ROS production, lipid peroxidation, inflammatory cytokines, and improve autophagic flux in steatotic hepatic cells.

Clinical Significance

Citation

Katoch Swati, Jatin, Acharya Vishalet al.. Picrosides I and II Ameliorate Steatosis by Modulating Lipogenesis, Mitochondrial Biogenesis, and Autophagy in Hepatic Cells. Cell biology international. 2026-Jun.