DONG Jing-yi,DU Wen-ran,WANG Dan-ping,et al.Mechanistic study on the effects of salidroside on neuroinflammation and behavioral disorders in rat pups with autism spectrum disorder[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(08):683-687.
DONG Jing-yi,DU Wen-ran,WANG Dan-ping,et al.Mechanistic study on the effects of salidroside on neuroinflammation and behavioral disorders in rat pups with autism spectrum disorder[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(08):683-687.DOI: 10.11659/jjssx.12E025083.
Mechanistic study on the effects of salidroside on neuroinflammation and behavioral disorders in rat pups with autism spectrum disorder
To explore the effects of salidroside on neuroinflammation and behavioral disorders in rat pups with autism spectrum disorder by regulating the high-mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE) pathway.
Methods
2
Rat pups with autism spectrum disorder models were established by sodium valproate, and the rat pups were divided into the autism model group, the salidroside group, and the salidroside+activator group, with 12 pups in each group. An additional 12 healthy rat pups were taken as the control group. Open field testing, three-chamber social preference test, elevated plus maze testing, and novel object recognition testing were used to assess behavioral disorders of rat pups. HE staining was performed to detect the histological changes in rat pups hippocampal tissue. ELISA was performed to detect the serum levels of inflammatory factors, including interleukin(IL)-10, tumor necrosis factor-alpha (TNF-α), and IL-6 in rat pups. In addition, Western blot was performed to detect the HMGB1 and RAGE protein expression levels in hippocampal tissue.
Results
2
Compared with the control group, the autism model group showed reduced central area dwell time (
P
<
0.05), decreased social ability index (SI), social preference index (SPI), anxiety index (AI), discrimination index, and IL-10 level (
P
<
0.05),increased IL-6 and TNF-α levels,as well as HMGB1 and RAGE protein expression levels(
P
<
0.05),loose arrangement and necrosis of neurons. Compared with the autism model group, the salidroside group showed increased central area dwell time (
0.05), and increased IL-6 and TNF-α levels, as well as HMGB1 and RAGE protein expression levels (
P
<
0.05), aggravated neuronal necrosis.
Conclusion
2
Salidroside alleviates neuroinflammation and behavioral disorders in rat pups with autism spectrum disorder by inhibiting the HMGB1/RAGE pathway.
关键词
Keywords
references
Bührer C , Endesfelder S , Scheuer T , et al . Paracetamol (acetaminophen) and the developing brain [J]. Int J Mol Sci , 2021 , 22 ( 20 ): 11156 . doi: 10.3390/ijms222011156 http://dx.doi.org/10.3390/ijms222011156 .
You M , Li S , Yan S , et al . Exposure to nonylphenol in early life causes behavioural deficits related with autism spectrum disorders in rats [J]. Environ Int , 2023 , 180 ( 1 ): 108228 . doi: 10.1016/j.envint.2023. 108228 http://dx.doi.org/10.1016/j.envint.2023.108228 .
Nakhal MM , Aburuz S , Sadek B , et al . Repurposing SGLT2 inhibitors for neurological disorders:a focus on the autism spectrum disorder [J]. Molecules , 2022 , 27 ( 21 ): 7174 . doi: 10.3390/molecules27217174 http://dx.doi.org/10.3390/molecules27217174 .
Liang K , Ma S , Luo K , et al . Salidroside:an overview of its promising potential and diverse applications [J]. Pharmaceuticals (Basel) , 2024 , 17 ( 12 ): 1703 . doi: 10.1016/j.ejmech.2025.118451 http://dx.doi.org/10.1016/j.ejmech.2025.118451 .
Yang S , Xie Z , Pei T , et al . Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer's disease mice and glutamate-injured HT22 cells [J]. Chin Med , 2022 , 17 ( 1 ): 82 . doi: 10.1186/s13020-022-00634-3 http://dx.doi.org/10.1186/s13020-022-00634-3 .
Wu Q , Shan X , Li X , et al . Salidroside ameliorates neuroinflammation in autistic rats by inhibiting NLRP3/Caspase-1/GSDMD signal pathway [J]. Brain Res Bull , 2025 , 220 ( 1 ): 111132 . doi: 10.1016/j.brainresbull.2024.111132 http://dx.doi.org/10.1016/j.brainresbull.2024.111132 .
Singh H , Agrawal DK . Therapeutic potential of targeting the HMGB1/RAGE axis in inflammatory diseases [J]. Molecules , 2022 , 27 ( 21 ): 7311 . doi: 10.3390/molecules27217311 http://dx.doi.org/10.3390/molecules27217311 .
Jung H , Youn DH , Park JJ , et al . Bone-marrow-derived mesenchymal stem cells attenuate behavioral and cognitive dysfunction after subarachnoid hemorrhage via HMGB1-RAGE axis mediation [J]. Life (Basel) , 2023 , 13 ( 4 ): 881 . doi: 10.3390/life13040881 http://dx.doi.org/10.3390/life13040881 .
Tian Y , Xiao X , Liu W , et al . TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway [J]. Mol Brain , 2024 , 17 ( 1 ): 12 . doi: 10.1186/s13041-024-01081-x http://dx.doi.org/10.1186/s13041-024-01081-x .
Wang L , Wang B , Wu C , et al . Autism spectrum disorder:neurodevelopmental risk factors,biological mechanism,and precision therapy [J]. Int J Mol Sci , 2023 , 24 ( 3 ): 1819 . doi: 10.3390/ijms24031819 http://dx.doi.org/10.3390/ijms24031819 .
Zhang X , Xie L , Long J , et al . Salidroside:a review of its recent advances in synthetic pathways and pharmacological properties [J]. Chem Biol Interact , 2021 , 339 ( 1 ): 109268 . doi: 10.1016/j.cbi. 2020.109268 http://dx.doi.org/10.1016/j.cbi.2020.109268 .
Li L , Yao W . The therapeutic potential of salidroside for Parkinson's disease [J]. Planta Med , 2023 , 89 ( 4 ): 353 - 363 . doi: 10.1055/a-1948-3179 http://dx.doi.org/10.1055/a-1948-3179 .
Zhang N , Nao J , Dong X . Neuroprotective mechanisms of salidroside in Alzheimer's disease:a systematic review and meta-analysis of preclinical studies [J]. J Agric Food Chem , 2023 , 71 ( 46 ): 17597 - 17614 . doi: 10.1021/acs.jafc.3c06672 http://dx.doi.org/10.1021/acs.jafc.3c06672 .
Jin M , Wang C , Xu Y , et al . Pharmacological effects of salidroside on central nervous system diseases [J]. Biomed Pharmacother , 2022 , 156 ( 1 ): 113746 . doi: 10.1016/j.biopha.2022.113746 http://dx.doi.org/10.1016/j.biopha.2022.113746 .
Mo Y , Chen K . Review:the role of HMGB1 in spinal cord injury [J]. Front Immunol , 2023 , 13 ( 1 ): 1094925 . doi: 10.3389/fimmu.2022. 1094925 http://dx.doi.org/10.3389/fimmu.2022.1094925 .
Dong H , Zhang Y , Huang Y , et al . Pathophysiology of RAGE in inflammatory diseases [J]. Front Immunol , 2022 , 13 ( 1 ): 931473 . doi: 10.3389/fimmu.2022.931473 http://dx.doi.org/10.3389/fimmu.2022.931473 .
Fan H , Tang HB , Chen Z , et al . Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury [J]. J Neuroinflammation , 2020 , 17 ( 1 ): 295 . doi: 10.1186/s12974-020-01973-4 http://dx.doi.org/10.1186/s12974-020-01973-4 .
Zhang Z , Jiang J , He Y , et al . Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiation-induced brain injury [J]. J Neuroinflammation , 2022 , 19 ( 1 ): 231 . doi: 10.1186/s12974-022-02596-7 http://dx.doi.org/10.1186/s12974-022-02596-7 .
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