Shengma Biejia Decoction Suppresses Acute Myeloid Leukemia by Regulating Mitochondrial Dynamics through the PI3K/AKT Signaling Pathway
Siyuan Cui, Wenjian Wei, Yuping Si, Lulu Li, Yaru Wang, Jingbo Shi, Changnian Li, Yan Wang, Ruirong Xu, Chenchen MaIntroduction:
This study aimed to identify the principal bioactive compounds of Shengma Biejia Decoction (SMBJD), evaluate its anti-acute myeloid leukemia (AML) activity in vivo, and clarify the underlying molecular mechanisms.
Methods:
Thirty NSG female mice were randomly assigned to the normal control (NC), AML model, and SMBJD treatment groups (low, medium, and high dose). After AML model establishment, SMBJD was administered by gavage, and anti-AML efficacy was evaluated by histopathology, bone marrow cytology, immunohistochemistry, flow cytometry, immunofluorescence, Western blotting, and transmission electron microscopy. UHPLC-MS/MS was used to characterize the chemical constituents of SMBJD. Network pharmacology was used to predict potential targets and pathways, and molecular docking was performed to assess the interactions between representative active compounds and key targets.
Results:
SMBJD showed significant anti-AML activity in vivo, and 51 major active constituents were identified. Network pharmacology analysis yielded 662 overlapping targets and 153 enriched pathways, among which the PI3K/AKT signaling pathway was prioritized. In vivo validation showed that SMBJD inhibited PI3K/AKT signaling, decreased mitochondrial fusion, increased mitochondrial fission, and promoted apoptosis in AML-bearing mice.
Discussion:
These findings suggest that SMBJD exerts anti-AML effects by suppressing PI3K/AKT signaling and shifting mitochondrial dynamics toward fission, thereby promoting apoptosis.
Conclusion:
In conclusion, SMBJD inhibited AML progression in vivo, at least in part, by regulating mitochondrial dynamics through suppression of the PI3K/AKT signaling pathway.