Milk Thistle and NRF2 in Combating NASH
Milk Thistle, (Silybum marianum L.), considered a weed in many places, has been getting attention due to its active component, silybin. Silybin, part of silymarin, a standardized extract of milk thistle, has shown promising results in improving nonalcoholic steatohepatitis (NASH), a liver disease, in animals.
In a recent study, male C57BL/6 mice were fed a methionine-choline deficient (MCD) diet for 8 weeks to induce NASH. The mice were then administered silybin orally. The results showed that silybin treatment alleviated hepatic steatosis, fibrosis, and inflammation in the NASH-induced mice. Silybin also inhibited HSC activation and hepatic apoptosis, preventing the formation of Mallory-Denk bodies (MDBs) in the NASH liver.
Looking closer, silybin was found to partly reverse the abnormal expression of lipid metabolism-related genes in NASH. This suggests that silybin’s effect was related to the alteration of lipid metabolism-related gene expression, with the NRF2 signaling pathway as the mechanism behind silybin’s action. The study showed that this pathway played a crucial role in the silybin-derived antioxidant effect, as evidenced by the upregulation of NRF2 target genes in the silybin treatment group. Additionally, the silybin significantly downregulated the expression of inflammation-related genes and suppressed the activity of NF-κB signaling.
Silybin, by activating the NRF2 pathway and inhibiting the NF-κB signaling pathway in the NASH liver, was effective in preventing the MCD-induced increases in hepatic steatosis, fibrosis, and inflammation.
This discovery opens up new possibilities not only for the treatment of NASH, but potentially other liver diseases as well.
Research shows silybin works in several key ways:
- Binds to toxins and promotes their elimination from the body before they reach the liver.
- Puts the brakes on inflammation to calm an overactive or damaged liver.
- Provides antioxidants that neutralize DNA-damaging free radicals.
- Assists the liver in regenerating new cells so it can heal itself.
This multidimensional protection makes milk thistle promising for various liver conditions like hepatitis, fatty liver, cirrhosis, and toxin-induced damage.
“We evaluated the binding properties of SM compounds because experimental findings have pointed to them as potential activators of Nrf2. Our study combined docking and molecular dynamics (MD) simulations with the Poisson-Boltzmann and generalized Born and surface area (MMPBSA and MMGBSA) methods and quantum mechanics-molecular mechanics (QMMM) calculations to investigate Keap1-ligand interactions. Our results predicted that silybinA and 2,3-dehydrosilybin bind to Keap1, forming interactions with the same pockets as those observed for the cocrystallized Keap1-Cpd16 complex but with more favorable binding free energies. These findings indicate that both natural compounds are potential activators of Nrf2.”
(Bello 2023)
While human trials to date show mixed results on milk thistle for liver health, it seems to provide modest improvements in liver function, but experts emphasize the need for more rigorous studies.
Supplemental milk thistle and silymarin appear relatively safe for adults, with few side effects beyond stomach upset or diarrhea. But consult your doctor before trying it, especially if you have medical conditions or take medications.
While many questions remain about how well milk thistle works, it offers an intriguing example of traditional plant medicine that science is working to validate. The natural remedies we need might just be growing in the garden!
You can read more here:
Ou, Q., Weng, Y., Wang, S., Zhao, Y., Zhang, F., Zhou, J., & Wu, X. (2018). Silybin alleviates hepatic steatosis and fibrosis in NASH mice by inhibiting oxidative stress and involvement with the NF-κB pathway. Digestive Diseases and Sciences, 63(12), 3398-3408.
https://pubmed.ncbi.nlm.nih.gov/30191499/
Please note that while the results are promising, more research is needed to fully understand the mechanisms of silybin and its potential therapeutic applications. Always consult with a healthcare professional before starting any new treatment.