Related Experiment Video
Updated: Feb 4, 2026
A Tripeptide-Stabilized Nanoemulsion of Oleic Acid
Published on: February 27, 2019
Effect of silibinin on CFLAR-JNK pathway in oleic acid-treated HepG2 cells
Yayun Liu1, Qingqing Yu1, Yong Chen1
1Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan, Hubei, 430062, PR China.
Aims:
Silibinin is a flavonolignan from milk thistle with many pharmacological activities including lipid-lowering and antioxidant. Caspase 8 and Fas-associated protein with death domain-like apoptosis regulator (CFLAR) is an important target gene in regulating non-alcoholic steatohepatitis (NASH). At present, the effect of silibinin on CFLAR-JNK pathway related to NASH was unknown. Here the effect of silibinin on CFLAR-JNK pathway and its downstream target genes involved in lipid metabolism, glucose uptake, oxidative stress and inflammatory response were studied in oleic acid (OA)-treated HepG2 cells.
Main Methods:
OA-treated HepG2 cells were employed as a in vitro model of steatosis, insulin resistance and oxidative stress. The model cells were then treated by silibinin (5, 20, 50, and 100 μM) for 24 h and detected for the related indicators as follows: (1) cellular triglycerides (TG), nitric oxide (NO) and glucose uptake; (2) the mRNA levels of the sterol regulatory element binding protein-1C (SREBP-1C), patatin-like phospholipase domain containing 3 (PNPLA3) and peroxisome proliferator activated receptor-α (PPARα); (3) the protein levels of PPARα, SREBP-1C, PNPLA3, CFLAR, phosphorylated c-Jun N-terminal kinase (pJNK), phosphatidylinositol 3-kinase (PI3K), phosphorylated serine-threonine protein kinase (pAKT), nuclear factor E2-related factor 2 (NRF2), cytochrome P450 2E1 (CYP2E1) and 4A (CYP4A).
Key Findings:
Compared to the control, OA-treatment led to a result as follows: (1) increased the intracellular levels of TG and NO; (2) up-regulated the protein expression of SREBP-1C, PNPLA3, pJNK, CYP 2E1 and CYP 4A; (3) decreased the uptake of 2-NBDG; (4) down-regulated the protein expression of CFLAR, PPARα, PI3K, pAKT and NRF2. Compared to OA-treated HepG2 cells, silibinin treatment could improve the indicators as follows: (1) decreased the intracellular levels of TG and NO; (2) down-regulated the protein expression of SREBP-1C, PNPLA3, pJNK, CYP 2E1 and CYP 4A; (3) increased the uptake of 2-NBDG; (4) up-regulated the protein expression of CFLAR, PPARα, PI3K, pAKT and NRF2.
Significance:
Silibinin can ameliorate some metabolic alterations and induce some molecular changes by activating the CFLAR-JNK pathway and thereby regulating its downstream target genes involved in lipid metabolism (PPARα, SREBP-1C and PNPLA3), glucose uptake (PI3K-AKT), oxidative stress (NRF2, CYP2E1, CYP4A) and inflammatory response(NO) in OA-treated HepG2 cells demonstrating its possible use in ameliorating various symptoms of NASH.
Insights
Silibinin improves non-alcoholic steatohepatitis (NASH) by regulating lipid metabolism, glucose uptake, and oxidative stress. It activates the CFLAR-JNK pathway, offering potential therapeutic benefits for NASH symptoms.
Area of Science:
- Hepatology and Gastroenterology
- Molecular Biology
- Pharmacology
Background:
- Non-alcoholic steatohepatitis (NASH) involves complex metabolic dysregulation.
- Caspase 8 and Fas-associated protein with death domain-like apoptosis regulator (CFLAR) is a key regulator in NASH pathogenesis.
- The effect of silibinin on the CFLAR-JNK pathway in NASH remains largely unexplored.
Purpose of the Study:
- To investigate the impact of silibinin on the CFLAR-JNK pathway in an in vitro model of NASH.
- To evaluate silibinin's effects on downstream target genes related to lipid metabolism, glucose uptake, oxidative stress, and inflammation.
Main Methods:
- Oleic acid (OA)-treated HepG2 cells were utilized as an in vitro model for NASH.
- Cells were treated with varying concentrations of silibinin (5–100 μM) for 24 hours.
- Key indicators including cellular triglycerides, nitric oxide, glucose uptake, and protein/mRNA levels of specific genes (e.g., CFLAR, JNK, SREBP-1C, PPARα, NRF2) were measured.
Main Results:
- OA treatment increased triglycerides, nitric oxide, and specific protein expressions (SREBP-1C, PNPLA3, pJNK, CYP2E1, CYP4A), while decreasing glucose uptake and other protein expressions (CFLAR, PPARα, PI3K, pAKT, NRF2).
- Silibinin treatment reversed these effects, decreasing triglycerides and nitric oxide, down-regulating specific proteins, increasing glucose uptake, and up-regulating key protective proteins.
Conclusions:
- Silibinin ameliorates metabolic alterations in OA-treated HepG2 cells.
- Activation of the CFLAR-JNK pathway by silibinin regulates downstream genes involved in lipid metabolism, glucose uptake, oxidative stress, and inflammation.
- Silibinin demonstrates potential therapeutic value for NASH management.
Related Concept Videos
01:29Amino Acid Biosynthetic Pathways
01:27C4 Pathway and CAM
C4 Pathway
The C4 pathway is used by plants such as...
02:36The Citric Acid Cycle
01:24Other Glycolytic Pathways
01:15Auditory Pathway
When viewed cross-sectionally, the cochlea reveals the scala vestibuli and scala tympani flanking...
01:45ER Retrieval Pathway
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...