Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice
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Xiaolu Zhang1, Yingxin Sun2, Qun Yu1
1Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Background:
Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimer's disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI.
Methods:
MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissl's/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells.
Results:
It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus.
Conclusion:
JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice.
Insights
Jia-Wei-Kai-Xin-San (JWKXS) improves learning and memory in mild cognitive impairment (MCI) models by reducing neuroinflammation and neuronal apoptosis. This study elucidates JWKXS
Area of Science:
- Neuroscience
- Pharmacology
- Traditional Chinese Medicine
Background:
- Mild cognitive impairment (MCI) is a precursor to Alzheimer's disease (AD), necessitating effective interventions.
- Jia-Wei-Kai-Xin-San (JWKXS) is a traditional Chinese medicine used for AD with MCI, but its mechanism remains unclear.
- This study investigates the therapeutic effects and underlying mechanisms of JWKXS in a mouse model of MCI.
Purpose of the Study:
- To evaluate the efficacy of JWKXS in improving cognitive function in a mouse model of MCI.
- To elucidate the molecular mechanisms by which JWKXS exerts its neuroprotective effects.
- To identify key signaling pathways modulated by JWKXS in the context of MCI.
Main Methods:
- Establishment of MCI models in SAMP8 mice at different ages (4, 6, and 8 months).
- Administration of JWKXS for 8 weeks, followed by behavioral tests (Morris water maze) and histological analyses (HE/Nissl, immunohistochemistry).
- Integration of UPLC-Q-TOF/MS and system pharmacology for mechanism prediction, with in vitro and in vivo validation using cell cultures and mouse models.
Main Results:
- SAMP8 mice at 4 months exhibited MCI; JWKXS treatment for 2 months improved learning and memory and reduced hippocampal damage.
- Network pharmacology identified four key pathways: TLR4/NF-κB, NLRP3 inflammasome, and intrinsic/extrinsic apoptosis.
- JWKXS attenuated neuroinflammation by inhibiting microglial activation and suppressed both TLR4/NF-κB and NLRP3 inflammasome pathways, thereby blocking neuronal apoptosis.
Conclusions:
- JWKXS demonstrates neuroprotective effects against MCI by promoting anti-inflammatory and anti-apoptotic responses.
- The study provides mechanistic insights into JWKXS's efficacy, highlighting its potential for treating MCI.
- Further research with larger sample sizes and longer durations is warranted to fully explore its clinical applicability for Alzheimer's disease.
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