Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis

Cornus officinalis, a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis, both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl4, while in vitro HSCs were exposed to transforming growth factor-β (TGF-β). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl4-induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and Sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. siRNA experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.