Protective effect of water extracts of Veronicastrum latifolium (Hemsl.) Yamazaki on carbon tetrachloride-induced liver fibrosis in mice and its effect on intestinal flora.

Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl4-elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl4-induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl4-elicited liver fibrosis.

Berberine Ameliorates Oxygen-glucose Deprivation/Reperfusion-induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Autophagy in PC12 Cells.

This study aimed to elucidate the molecular mechanisms by which berberine protects against cerebral ischemia/reperfusion (I/R) injury. The oxygen-glucose deprivation/reperfusion (OGD/R) PC12 model was established. Cell counting kit-8 (CCK-8) was used to detect the toxicity of berberine and the viability of PC12 cells. Hoechst 33258 staining and flow cytometry were used to observe the nuclear morphology, and changes of apoptosis and reactive oxygen species (ROS), respectively. Western blotting and immunofluorescence assay were employed to detect autophagy-related proteins [microtubule-associated protein 1A/1B-light chain 3 (LC3), P62/SQSTM-1, Beclin-1] and endoplasmic reticulum (ER) stress-related markers [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Bcl-2-associated X (Bax) and cleaved caspase-3]. The GFP-RFP-LC3 adenovirus was used to assay the change of autophagic flux. Our results showed that berberine could increase the viability of PC12 cells, decrease the concentrations of ROS after OGD/R treatment, and suppress OGD/R-induced ER stress and autophagy. Moreover, the results revealed the involvement of the mammalian target of rapamycin (mTOR) pathway in the induction of autophagy, and berberine could activate the phosphorylation of mTOR and thus mitigate autophagy. In conclusion, our study suggested that berberine may protect against OGD/R-induced apoptosis by regulating ER stress and autophagy, and it holds promises in the treatment of cerebral I/R injury.