PUBLICATION
Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology
- Authors
- Yu, H.C., Bai, Q.R., Guo, J.J., Chen, M.Y., Wang, L., Tong, F.C., Zhang, S.L., Wu, J.
- ID
- ZDB-PUB-240902-8
- Date
- 2024
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 134: 155956155956 (Journal)
- Registered Authors
- Keywords
- Alcoholic liver disease, Hydroxysafflor yellow A, Molecular docking, Network pharmacology, Zebrafish
- MeSH Terms
-
- Quinones*/chemistry
- Quinones*/pharmacology
- Chalcone*/analogs & derivatives
- Chalcone*/chemistry
- Chalcone*/pharmacology
- Disease Models, Animal
- Signal Transduction/drug effects
- Carthamus tinctorius/chemistry
- Molecular Docking Simulation*
- Hepatocytes/drug effects
- Larva/drug effects
- Liver/drug effects
- Liver/metabolism
- Humans
- Animals, Genetically Modified
- Ethanol
- Zebrafish*
- Liver Diseases, Alcoholic*/drug therapy
- Oxidative Stress/drug effects
- Network Pharmacology*
- Animals
- Hep G2 Cells
- PubMed
- 39216301 Full text @ Phytomedicine
Citation
Yu, H.C., Bai, Q.R., Guo, J.J., Chen, M.Y., Wang, L., Tong, F.C., Zhang, S.L., Wu, J. (2024) Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology. Phytomedicine : international journal of phytotherapy and phytopharmacology. 134:155956155956.
Abstract
Background Alcoholic liver disease (ALD) significantly contributes to global liver-related morbidity and mortality. Natural products play a crucial role in the prevention and treatment of ALD. Hydroxysafflor yellow A (HSYA), a unique and primary component of Safflower (Carthamus tinctorius l.), exhibits diverse pharmacological activities. However, the impact and mechanism of HSYA on ALD have not been fully elucidated.
Purpose The purpose of this study was to employ an integrative pharmacology approach to assess the multi-targeted mechanism of HSYA against ALD.
Methods Network pharmacology and molecular docking techniques were used to analyze the potential therapeutic signaling pathways and targets of HSYA against ALD. An ALD model in zebrafish larvae was established. Larvae were pretreated with HSYA and then exposed to ethanol. Liver injury was measured by fluorescence expression analysis in the liver-specific transgenic zebrafish line Tg (fabp10a:DsRed) and liver tissue H&E staining. Liver steatosis was determined by whole-mount oil red O staining and TG level. Additionally, an ethanol-induced hepatocyte injury model was established in vitro to observe hepatocyte damage (cell viability, ALT level), lipid accumulation (oil red O staining, TC and TG), and oxidative stress (ROS, MDA, GPx and SOD) in HepG2 cells treated with or without HSYA. Finally, qRT-PCR combined with network pharmacology and molecular docking was employed to validate the effects of HSYA on targets.
Results HSYA exhibited a significant, dose-dependent improvement in ethanol-induced liver injury in zebrafish larvae and HepG2 cells. Network pharmacology analysis revealed that HSYA may exert pharmacological effects against ALD through 341 potential targets. These targets are involved in various signaling pathways, including lipid metabolism and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and ALD itself. Molecular docking studies displayed that HSYA had a strong binding affinity toward the domains of IL1B, IL6, TNF, PPARA, PPARG, HMGCR and ADH5. qRT-PCR assays demonstrated that HSYA effectively reversed the ethanol-induced aberrant gene expression of SREBF1, FASN, ACACA, CPT1A, PPARA, IL1B, IL6, TNFα, ADH5, and ALDH2 in vivo and in vitro.
Conclusion This study offers a comprehensive investigation into the anti-ALD mechanisms of HSYA using an integrative pharmacology approach. The potential targets of HSYA may be implicated in enhancing ethanol catabolism, reducing lipid accumulation, mitigating oxidative stress, and inhibiting inflammatory response.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping