Astragaloside IV Improves Cyclophosphamide-Induced Liver Injury in Mice by Mediating Immunosuppression and Oxidative Stress Through the PI3K/Akt Signaling Pathway: A Randomized Trial
| Author | Yue e Sun | en |
| Author | Jiahui Cao | en |
| Author | Mengtao Li | en |
| Author | Jingwen Ma | en |
| Author | Weidong Wang | en |
| Issued Date | 2025-12-31 | en |
| Abstract | Background: Cyclophosphamide (CTX) can lead to hepatotoxicity and low immunity. Astragaloside IV (AS-IV) can enhance the body's immune function. Objectives: This study aimed to investigate whether AS-IV can improve CTX-induced liver injury in mice through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways and to explore whether its mechanism is related to immunosuppression and oxidative stress. Methods: Forty-eight BALB/C mice aged 6 - 8 weeks were randomly divided into control groups, CTX group, AS-IV group, CTX+AS-IV low, medium, and high dose treatment groups, CTX+LY294002 group, and CTX+AS-IV-H+LY294002 group (n = 6 mice in each group). Mice in the control group and CTX group were given 1% starch paste by gavage daily. Mice in the AS-IV group and CTX+AS-IV groups were intragastrically administered AS-IV every day. Mice in the LY294002 group were intraperitoneally injected with LY294002 every 2 days. After 14 days, CTX was intraperitoneally injected for 2 consecutive days to induce a mouse liver injury model. The immune function of the mice was evaluated using HE staining and an Enzyme-Linked Immunosorbent Assay (ELISA) kit. The degree of oxidative stress and liver injury was detected by DHE fluorescent probe and ELISA kit. The PI3K/Akt axis protein expressions were detected using Western blot. Results: Compared with the CTX group, AS-IV significantly increased the cytokines and immunoglobulin levels (P < 0.05) and reduced the levels of reactive oxygen species (ROS). Malondialdehyde (MDA) levels reduced from 0.788 nmol/mg to 0.475 nmol/mg, and liver injury indices increased. Superoxide dismutase (SOD) levels increased from 5.393 U/mg to 9.867 U/mg, and catalase (CAT) levels increased from 4.617 U/mg to 8.248 U/mg, restoring the integrity and clarity of liver cell structure (P < 0.05). The AS-IV also significantly increased protein levels; p-PI3K increased from 0.526 to 0.880, and p-Akt increased from 0.263 to 0.720. After LY294002 was applied on the basis of AS-IV intervention, CTX-caused liver damage was aggravated again. The cytokines, immunoglobulin, SOD, and CAT levels were significantly decreased, and the levels of liver injury indicators were significantly increased (P < 0.05). Conclusions: The AS-IV improved CTX-induced immunosuppression and oxidative damage in mice by activating the PI3K/Akt axis and played a hepatoprotective role. | en |
| DOI | https://doi.org/10.5812/hepatmon-164840 | en |
| Keyword | Astragaloside IV | en |
| Keyword | Liver Injury | en |
| Keyword | PI3K/Akt Pathway | en |
| Keyword | Immunosuppression | en |
| Keyword | Oxidative Stress | en |
| Keyword | Cyclophosphamide | en |
| Publisher | Brieflands | en |
| Title | Astragaloside IV Improves Cyclophosphamide-Induced Liver Injury in Mice by Mediating Immunosuppression and Oxidative Stress Through the PI3K/Akt Signaling Pathway: A Randomized Trial | en |
| Type | Research Article | en |