ObjectiveTo investigate the molecular mechanism of kaempferol-induced apoptosis in hepatic stellate cells （HSC） via the mitochondrial pathway. MethodsHSC were divided into five groups： blank control， transforming growth factor-β1（TGF-β1） （10 ng/mL） group， and groups treated with different concentrations of kaempferol （8， 16， 32 µmol/L）. Cell counting kit-8（CCK-8） assay was used to evaluate chrysin's effect on HSC proliferation. Transwell assay was used to assess chrysin's impact on HSC migration. Flow cytometry was used to detect apoptosis， reactive oxygen species （ROS） expression， and mitochondrial permeability transition pore （mPTP） opening across groups. 5，5′，6，6′-Tetrachloro-1，1′，3，3′-tetraethylimidacarbocyanine iodide （JC-1） assay was used to test mitochondrial membrane potential. Western blot analysis was performed to determine the expression levels of mitochondrial apoptosis-associated proteins， namely B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Cleaved-Caspase3， Cleaved-Caspase9， and sirtuin 3 （SIRT3）. Transmission electron microscopy was used to examine mitochondrial structural alterations. Molecular docking and kinetic simulations were used to analyze the targeted interaction between kaempferol and NAD-dependent deacetylase sirtuin-3 （SIRT3）. ResultsCompared with the blank control group： in the TGF-β1 group， HSC proliferation and migration rates increased （P<0.01）， ROS levels and mPTP opening both increased （P<0.05）， the JC-1 red/green fluorescence ratio increased （P<0.01）， and the expression of Cleaved-Caspase-3， Cleaved-Caspase-9 and Bcl-2 increased （P<0.05）， whilst SIRT3 expression decreased （P<0.01）； the number of mitochondria increased （P<0.05）， and mitochondrial length decreased （P<0.01）. Compared with the TGF-β1 group： treatment with all groups of kaempferol reduced HSC proliferation and migration rates （P<0.01）， whilst simultaneously increasing the HSC apoptosis rate （P<0.01）； HSC ROS levels and mPTP opening both increased （P<0.05）； the JC-1 red/green fluorescence ratio decreased （P<0.01）， and the expression levels of Bax， Cleaved-Caspase-3 and Cleaved-Caspase-9 were upregulated （P<0.01）， whilst the expression levels of Bcl-2 and SIRT3 were downregulated （P<0.01）， and the number of mitochondria increased （P<0.05）； mitochondrial length was reduced （P<0.01）. Molecular docking and dynamics simulations revealed that the docking energy for kaempferol with SIRT3 was 108.89 kcal/mol； the RMSD curve stabilized after 20 ns； and RMSF analysis indicated that most residues exhibited minimal fluctuations. ConclusionKaempferol induces HSC apoptosis through the mitochondrial pathway， potentially via targeting SIRT3 and disrupting mitochondrial function.

In recent years, studies have shown that transplanted neural stem cells (NSCs) help neural tissues regenerate and return to normal through paracrine action rather than just replacing cells. Exosomes are essential paracrine mediators that can participate in cell communication through substance transmission. This review focuses on NSCs regulated by exosomes and their application in treatment of nervous system diseases, in order to provide important references for further research and clinical application of NSCs exosomes..