SILIBININ EXERTS AN ANTI-FIBROTIC EFFECT THROUGH GAS6/AXL PATHWAY
15. INTERNATIONAL GEVHER NESİBE MEDICAL SCIENCES CONFERENCE, Ankara, Turkey, 28 - 30 September 2025, pp.362-363, (Summary Text)
- Publication Type: Conference Paper / Summary Text
- City: Ankara
- Country: Turkey
- Page Numbers: pp.362-363
- Open Archive Collection: AVESIS Open Access Collection
- Erciyes University Affiliated: Yes
Abstract
stimuli that damage the liver. GAS6/AXL pathway may be a new therapeutic target in various
liver diseases with liver fibrosis by participating in hepatic stellate cell (HSC) activation. In the
liver, GAS6 and its receptor AXL are reported to be expressed in macrophages, progenitor cells,
and myofibroblasts, and GAS6 deficiency causes delayed liver repair in response to acute injury
by reducing inflammation and myofibroblast activation.
Phosphatidylserine (PS), a cell membrane phospholipid, is externalized during apoptosis, which
is essential for the resolution of liver fibrosis, especially cirrhosis..
Silibinin is the main component of flavonolignan extract isolated from the seeds of milk thistle
plants. In addition, due to its antioxidant, anti-inflammatory and antifibrotic power, it is
frequently used in different liver diseases, especially chronic liver diseases, cirrhosis and
hepatocellular carcinoma.
In this study; we investigated the relationship of silibinin with the GAS6/AXL pathway, PS and
interleukin 6 (IL-6) in the human LX2 cell line.
Cell cycle assay analysis assayed with using by muse cell analyzer. The wound widths pixel
were measured using the Image J. GAS6, sAXL, IL-6, and PS levels were quantified using
enzyme- linked immunosorbent assay method. In our study, we applied 50 μM silibinin to LX2
cells for 96 hours and found that silibinin significantly
inhibited migration (p<0.001) compared to the control group. In the cell cycle, we found that
silibinin significantly arrested hepatic stellate cells in G0/G1 phase (p<0.001). However, we
observed that silibinin significantly increased GAS6 and PS levels (p<0.05, p<0.05), and
decreased AXL and IL-6 levels (p<0.01, p<0.05). It was determined that silibinin administration
increased GAS6 levels, decreased AXL and IL-6 levels, and elevated PS levels during the
hepatic fibrosis process. Moreover, silibinin significantly reduced colony formation and led to a
marked increase in the G0/G1 phase of the cell cycle. These findings indicate that silibinin not
only suppresses the proliferation of hepatic stellate cells but also attenuates inflammatory
signaling through the downregulation of IL-6, thereby slowing down and potentially reversing
the fibrosis process. Taken together, silibinin emerges as a potent anti-fibrotic agent in hepatic
fibrosis, exerting its effects through the modulation of the GAS6/AXL signaling pathwaysuppression of IL-6–mediated inflammation, and regulation of the cell cycle. However, further
molecular investigations are required to fully elucidate these mechanisms.
Key Words: Hepatic fibrosis; LX2, GAS6/ AXL; PS; Silybum Marianum