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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\u2010oleate (PO)\u2010treated Huh7 cells. Picrosides significantly downregulated various lipogenic markers (\n                    <jats:italic>SREBP1c<\/jats:italic>\n                    ,\n                    <jats:italic>ChREBP, SCD1<\/jats:italic>\n                    , and\n                    <jats:italic>FAS<\/jats:italic>\n                    ) and upregulated\n                    <jats:italic>AMPK\u03b1<\/jats:italic>\n                    . 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 (\n                    <jats:italic>PGC1\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>TFAM<\/jats:italic>\n                    ,\n                    <jats:italic>NRF1<\/jats:italic>\n                    and\n                    <jats:italic>NRF2<\/jats:italic>\n                    ). Further, picrosides lowered the levels of inflammatory cytokines (TNF\u2010\u03b1, IL6 and IL1\u03b2) and expressions of\n                    <jats:italic>NF\u03baB<\/jats:italic>\n                    in the PO\u2010treated Huh7 cells. PO treatment impaired the autophagy by altering the expressions of autophagy markers (\n                    <jats:italic>SQSTM1<\/jats:italic>\n                    ,\n                    <jats:italic>BECN1<\/jats:italic>\n                    ,\n                    <jats:italic>MAPLC3A<\/jats:italic>\n                    ,\n                    <jats:italic>ATG5<\/jats:italic>\n                    , and\n                    <jats:italic>ATG7<\/jats:italic>\n                    ) in the PO\u2010treated 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.\n                  <\/jats:p>","DOI":"10.1002\/cbin.70170","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:02:15Z","timestamp":1779886935000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Picrosides I and II Ameliorate Steatosis by Modulating Lipogenesis, Mitochondrial Biogenesis, and Autophagy in Hepatic Cells"],"prefix":"10.1002","volume":"50","author":[{"given":"Swati","family":"Katoch","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Laboratory, Dietetics &amp; Nutrition Technology Division CSIR\u2010Institute of Himalayan Bioresource Technology  Palampur H.P. 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