Modulation of the VEGF/AKT/eNOS signaling pathway to regulate liver angiogenesis to explore the anti-hepatic fibrosis mechanism of curcumol

Ethnopharmacological relevance: Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease. Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol.

Aim: To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis.

Materials and methods: We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, Akt, eNOS, CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group.

Results: The results of the MTT test found that the proliferation rate of each group was higher. The results of the Molecular Biology tests found that curcumol inhibited the activity of the VEGF/Akt/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group.

Conclusions: Curcumol inhibits the activity of the VEGF/Akt/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.