Total saponins of Trillium tschonoskii Maxim alleviate neuronal damage in vascular dementia rats by regulating Shh signaling pathway
10.3969/j.issn.1000-4718.2025.02.017
- VernacularTitle:延龄草总皂苷通过调控Shh信号通路减轻血管性痴呆大鼠神经元损伤
- Author:
Jianhong GAO
1
;
Yawen CHEN
;
Chaoxi TIAN
;
Hong ZHU
;
Fangyu ZHAO
;
Yiduo HE
;
Xin LIU
;
Xianbing CHEN
Author Information
1. 湖北民族大学风湿性疾病发生与干预湖北省重点实验室,湖北 恩施 445000;湖北民族大学医学部,湖北 恩施 445000
- Publication Type:Journal Article
- Keywords:
Trillium tschonoskii Maxim;
vascular dementia;
neurons;
astrocytes;
Shh/Ptch1/Gli1 signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(2):354-361
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To observe the neuroprotective effects of total saponins of Trillium tschonoskii Maxim(TST)on rats with vascular dementia(VD)and explore the drug's impact on astrocytes and the Sonic Hedgehog(Shh)pathway as well as its mechanisms of action.METHODS:A rat model of vascular dementia was established by bilateral common carotid artery occlusion.Subsequently,the rats were randomly divided into four groups:donepezil hydrochloride group,TST group,model group,and sham group,with 18 rats in each group.After 5 weeks of gavage,samples were collected.Cognitive function was evaluated by the water maze test.Histopathological changes in brain tissue were examined with HE and Nissl staining.The ultrastructure of astrocytes was analyzed by transmission electron microscopy.The localization and expression of the neuronal nuclear antigen(NeuN),glial fibrillary acidic protein(GFAP),Shh,and glioma-associated oncogene homolog 1(Gli1)were identified using immunohistochemistry.Immunofluorescence was also employed to exam-ine the expression of NeuN and GFAP.Finally,Western blot analysis was used to measure the protein levels of NeuN,GFAP,Shh,Patched 1(Ptch1),Gli1,Bax,Bcl-2,tumor necrosis factor-α(TNF-α),and interleukin-10(IL-10)in the hippocampus.RESULTS:Compared to the sham group,the model rats demonstrated prolonged escape latency,disorga-nized and loosened neuronal arrangement in the hippocampus and cortex,reduced Nissl bodies,and significant neuronal damage.Astrocytes displayed chromatin aggregation,swollen mitochondria with disrupted cristae structures,and swollen endoplasmic reticulum regions.The expression of NeuN,Shh,and Gli1 positive cells significantly decreased,while GFAP positive cells significantly increased.Additionally,the protein levels of NeuN,Shh,Ptch1,Gli1,IL-10,and Bcl-2 in the hippocampus were reduced(P＜0.05),whereas those of GFAP,Bax,and TNF-α were elevated(P＜0.01).Com-pared to the model group,the donepezil hydrochloride and TST groups effectively improved the aforementioned indicators.CONCLUSION:Total saponins of trillium tschonoskii maxim can effectively alleviate pathological damage to neurons in VD rats,thereby improving learning and memory abilities.The underlying mechanisms may involve inhibiting the overacti-vation of astrocytes,activate the Shh/Ptch1/Gli1 signaling pathway,suppress neuroinflammation,and reduce neuronal apoptosis.
