Cryptotanshinone Reduces Liver Scarring by Blocking Fat Breakdown in Liver Cells

Jenn Hoskins
28th June, 2024

Cryptotanshinone Reduces Liver Scarring by Blocking Fat Breakdown in Liver Cells

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at Henan University of Chinese Medicine found that cryptotanshinone (CTS) inhibits the activation of liver cells that cause fibrosis
  • CTS works by reducing fatty acid oxidation, which is crucial for the energy supply of these liver cells
  • The study showed that CTS targets the STAT3 pathway, reducing cell proliferation and survival, and effectively alleviates liver fibrosis in mice
Liver fibrosis is a serious condition characterized by the excessive accumulation of extracellular matrix proteins, leading to scarring and impaired liver function. Hepatic stellate cells (HSCs) are central to this process, as they become activated and proliferate, contributing to fibrogenesis. A recent study by researchers at Henan University of Chinese Medicine has provided new insights into the mechanisms by which cryptotanshinone (CTS), a compound derived from Salvia miltiorrhiza Bunge, inhibits HSC activation and alleviates liver fibrosis[1]. Previous studies have highlighted the role of HSCs in liver fibrosis and other liver diseases. For instance, HSCs are the principal collagen-producing cells in the liver and their activation is a key step in the development of liver fibrosis[2]. Additionally, HSCs play a role in non-fibrotic liver diseases such as cholestasis, portal hypertension, and hepatocellular carcinoma (HCC)[3]. Moreover, abnormalities in liver iron homeostasis have been linked to conditions like non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), where iron overload in HSCs promotes their fibrogenic activation[4]. The current study focuses on the anti-fibrotic mechanisms of CTS. The researchers found that CTS exhibited strong inhibitory effects on the proliferation and activation of HSCs, specifically the HSC-LX2 cell line. They observed that CTS could induce a lipocyte phenotype in both mouse primary HSCs and HSC-LX2 cells. This suggests that CTS has the potential to revert activated HSCs to a more quiescent state. To understand how CTS exerts its effects, the researchers performed transcriptomic sequencing and quantitative PCR (qPCR). They discovered that CTS regulates fatty acid metabolism and inhibits the expression of CPT1A and CPT1B, which are critical enzymes involved in fatty acid oxidation (FAO). FAO is a metabolic process that provides energy for the rapid proliferation of activated HSCs. By inhibiting FAO, CTS effectively reduces the energy supply required for HSC activation. Further investigation revealed that CTS targets the STAT3 pathway, a key signaling pathway involved in cell proliferation and survival. The researchers found that CTS inhibits the phosphorylation and nuclear translocation of STAT3, thereby reducing its activity. This inhibition of the STAT3 pathway leads to decreased levels of ATP and acetyl-CoA, indicating a reduction in FAO. The study also demonstrated that overexpression of CPT1A could reverse the inhibitory effects of CTS on HSCs, confirming the importance of CPT1A in the anti-fibrotic action of CTS. In vivo experiments showed that CTS treatment attenuated liver fibrosis induced by carbon tetrachloride (CCl4) in mice. The treatment reduced collagen production and HSC activation, as evidenced by lower levels of α-SMA and p-STAT3, two markers of HSC activation. These findings are significant as they provide a detailed understanding of the molecular mechanisms by which CTS inhibits HSC activation and alleviates liver fibrosis. By targeting the p-STAT3/CPT1A-dependent FAO pathway, CTS effectively disrupts the metabolic processes that sustain HSC activation and proliferation. This makes CTS a promising candidate for the development of new therapeutic strategies to treat liver fibrosis. In summary, the study from Henan University of Chinese Medicine demonstrates that cryptotanshinone (CTS) can inhibit hepatic stellate cell activation by targeting the STAT3 pathway and reducing fatty acid oxidation. This research builds on previous findings that have identified the central role of HSCs in liver fibrosis and other liver diseases[2][3][4]. The results suggest that CTS could be a valuable addition to the arsenal of treatments aimed at combating liver fibrosis, offering hope for improved outcomes in patients suffering from this debilitating condition.

MedicineHealthBiochem

References

Main Study

1) Cryptotanshinone alleviates liver fibrosis via inhibiting STAT3/CPT1A-dependent fatty acid oxidation in hepatic stellate cells.

Published 25th June, 2024

https://doi.org/10.1016/j.cbi.2024.111119

Related Studies

2) Molecular and cellular mechanisms of liver fibrosis and its regression.

https://doi.org/10.1038/s41575-020-00372-7

3) Hepatic stellate cells in the injured liver: Perspectives beyond hepatic fibrosis.

https://doi.org/10.1002/jcp.30582

4) Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis.

https://doi.org/10.1016/j.cmet.2022.07.006


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