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Protective Effects of Red Ginseng Against Tacrine-Induced Hepatotoxicity: An Integrated Approach with Network Pharmacology and Experimental Validation.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2024 Feb 23; Vol. 18, pp. 549-566. Date of Electronic Publication: 2024 Feb 23 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress.<br />Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins.<br />Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000μg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection.<br />Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.<br />Competing Interests: The authors report no conflicts of interest in this work.<br /> (© 2024 Kim et al.)
- Subjects :
- Mice
Animals
Tacrine pharmacology
Tacrine therapeutic use
Acetylcholinesterase metabolism
Network Pharmacology
AMP-Activated Protein Kinases
Cholinesterase Inhibitors pharmacology
Alzheimer Disease drug therapy
Chemical and Drug Induced Liver Injury drug therapy
Chemical and Drug Induced Liver Injury prevention & control
Panax
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 18
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 38419811
- Full Text :
- https://doi.org/10.2147/DDDT.S450305