Cordycepin Helps Reverse Liver Scarring by Aging Scar Cells

Jenn Hoskins
4th April, 2024

Cordycepin Helps Reverse Liver Scarring by Aging Scar Cells

Image Source: Natural Science News, 2024

Key Findings

  • Study at Jiangnan University finds Cordycepin (CRD) reduces liver scarring in mice
  • CRD inhibits liver cells responsible for fibrosis, lessening disease severity
  • CRD's effects linked to blocking a pathway involved in both liver fibrosis and some cancers
Liver fibrosis is a condition characterized by the excessive buildup of scar tissue in the liver, which can lead to serious complications like cirrhosis and liver failure. The condition is often the result of chronic liver diseases and can sometimes necessitate a liver transplant. While researchers have identified the cells responsible for this scarring and some of the signals that trigger their activity, finding effective treatments has been a challenge. A breakthrough study from Jiangnan University[1] has now shed light on a potential new treatment using a compound called Cordycepin (CRD), derived from a type of fungus known as Cordyceps militaris. Cordycepin has been previously recognized for its various biological activities, including potential benefits in treating liver disease. The new study aimed to determine whether CRD could also improve liver fibrosis by targeting the activation of hepatic stellate cells (HSCs), which are central to the development of the condition. These cells, when activated by certain signals in the liver, start producing the collagen-rich scar tissue that defines fibrosis. In the study, researchers used a mouse model induced with liver fibrosis by a chemical known as Diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC). They observed that treatment with CRD significantly reduced liver injury and inhibited the activation of HSCs, thereby lessening the extent of fibrosis. These findings were further supported by experiments conducted in vitro, where CRD was shown to suppress the proliferation, migration, and pro-fibrotic functions of HSCs that had been activated by a fibrogenic cytokine called TGF-β1. To understand how CRD was exerting its effects, the researchers conducted RNA sequencing (RNA-seq) analysis, which revealed that CRD influences pathways related to cellular senescence and the cell cycle. Specifically, CRD increased the number of senescent cells, indicated by an uptick in senescence-associated beta-galactosidase positive cells and the senescence marker p21. It also caused S phase arrest, where cells stop dividing, in activated HSCs. Interestingly, CRD was also found to inhibit a signaling pathway involving the yes-associated protein (YAP). This pathway is known to be active in other types of cells, such as mesothelioma cancer cells, where glutamine addiction and YAP signaling are associated with tumor growth and survival[2]. In the context of liver fibrosis, CRD's inhibition of YAP signaling in HSCs led to a significant reduction in glutaminolysis, the process by which cells metabolize glutamine. This is particularly noteworthy because targeting glutamine metabolism has been suggested as a therapeutic strategy for glutamine-addicted cancers like mesothelioma[2]. The study's findings are promising for several reasons. Firstly, they highlight a novel therapeutic avenue for treating liver fibrosis through the modulation of HSC activation and metabolism. Secondly, they provide a potential link between the mechanisms at play in liver fibrosis and certain types of cancer, suggesting that treatments targeting similar pathways might have broad applicability. As with any preclinical study, the next steps involve confirming these results in human subjects. The safety and efficacy of CRD for treating liver fibrosis in humans remain unknown. However, the study builds on the emerging understanding of antifibrotic strategies[3] and the importance of drug repurposing in the fight against diseases like SARS-CoV-2, where compounds like cordycepin have shown potential against viral enzymes[4]. The findings from Jiangnan University thus contribute to a growing body of research that underscores the versatility of natural compounds in treating complex diseases and the importance of understanding the underlying biological mechanisms.



Main Study

1) Cordycepin alleviates hepatic fibrosis in association with the inhibition of glutaminolysis to promote hepatic stellate cell senescence.

Published 1st April, 2024

Related Studies

2) Mesothelioma cancer cells are glutamine addicted and glutamine restriction reduces YAP1 signaling to attenuate tumor formation.

3) Liver fibrosis.

Journal: The Journal of clinical investigation, Issue: Vol 115, Issue 2, Feb 2005

4) Cordycepin as a Promising Inhibitor of SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp).

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