Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward
liver cirrhosis, and even
hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of
liver fibrosis.
Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with
therapeutic effects on
liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of
geniposide on metabolic regulations in
liver fibrosis. We used
carbon tetrachloride (CCl4) to construct a mouse model of
liver fibrosis and subsequently administered
geniposide treatment.
Therapeutic effects of
geniposide on
liver fibrosis were accessed through measuring the levels of hepatic
enzymes in serum and the pathological changes in liver. We also investigated the effects of
geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind
geniposide on
liver fibrosis. Our results demonstrated that
geniposide could reduce the levels of hepatic
enzymes in serum and ameliorate the pathological changes in
liver fibrosis mice.
Geniposide enhanced the activities of
superoxide dismutase (SOD) and
glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic
aldehyde (MDA) levels in liver.
Geniposide treatment also decreased the levels of
interleukin (IL)-6, IL-1β, and
tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate.
Terminal deoxynucleotidyl transferase-mediated dUTP-
biotin nick end labeling assay (TUNEL) staining demonstrated that
geniposide could reduce the apoptosis of hepatocytes.
Geniposide increased the
protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the
protein expression of Bcl-2 Associated X (Bax), cleaved-
Caspase 3, and cleaved-
Caspase 9. Serum untargeted metabolomics analysis demonstrated that
geniposide treatment improved the metabolic disorders including
glycerophospholipid metabolism,
arginine and
proline metabolism, and
arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of
geniposide on
liver fibrosis. We found that
geniposide could treat
liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating
glycerophospholipid, and
arginine,
proline, and AA metabolism processes.