Picroside I, a hepatoprotectant isolated from Picrorhiza kurroa Royle ex Benth and P. scrophulariiflora Pennell, can reduce liver injury in humans and animals. However, its anti-
fibrosis effect remains elusive. This work aimed to explore the mechanism underlying the hepatoprotective effect of
picroside I against hepatic
fibrosis. Male mice (12 mice per group) were randomly divided into six groups: the control group; the model group, which received
thioacetamide (TAA); the positive group, which received TAA + S-(5'-adenosyl)-l-methionine (SAMe, 10 mg/kg); the low-dose group, which received TAA +
picroside I (25 mg/kg); the middle-dose group, which received TAA +
picroside I (50 mg/kg); and the high-dose group, which received TAA +
picroside I (75 mg/kg). Serum biochemical indicators were detected, and histological evaluation was performed. Metabolomics and proteomic analyses were conducted via liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS). Data showed that
picroside I could decrease the serum levels of
alanine transaminase (ALT),
aspartate transaminase (AST),
collagen type IV (CIV), N-terminal
peptide of
type III procollagen (
PIIINP),
laminin (LN), and
hyaluronic acid (HA) and reduced
fibrosis area.
Picroside I altered metabolomic profiles, including energy,
lipid, and
glutathione (GSH) metabolism, in
ice with
fibrosis. Additionally, 25 differentially expressed
proteins in the
picroside I high-dose-treated group were reversed relative to in the model group. These
proteins were involved in the
sphingolipid signaling pathway, primary
bile acid biosynthesis, and
peroxisome proliferator-activated receptor (
PPAR) signaling pathway. Moreover, this study revealed how
picroside I could protect against TAA-induced
liver fibrosis in mice. Results indicated that
picroside I can serve as a candidate drug for hepatic
fibrosis.