Anti-inflammatory properties of Ajuga bracteosa in vivo and in vitro study and their effects on mouse model of liver fibrosis

Ethnopharmacological relevanceThe entire plant of Ajuga bracteosa Wall has been used to treat various inflammatory disorders, including hepatitis, in Taiwan.AimThis study evaluated the hepatoprotective ability of Ajuga bracteosa extract (ABE).Materials and methodsWe investigated the inhibitory action of a chloroform fraction of ABE (ABCE) on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and Kupffer cells. Hepatic fibrosis was induced in mice through the administration of CCl4 twice a week for 8 weeks. Mice in three CCl4 groups were treated daily with water and ABE throughout the duration of the experiment.ResultsIn LPS-stimulated RAW264.7 cells and Kupffer cells, ABCE inhibited the production of NO and/or TNF-α and also blocked the LPS-induced expression of NO synthase. ABCE inhibited the activation of NF-κB induced by LPS, associated with the abrogation of IκBα degradation, with a subsequent decrease in nuclear p65 and p50 protein levels. The phosphorylation of MAPKs in LPS-stimulated RAW264.7 cells was also suppressed using ABCE. In the in vivo study, ABE protected the liver from injury by reducing the activity of plasma aminotransferase, and by improving the histological architecture of the liver. RT-PCR analysis showed that ABE inhibited the hepatic mRNA expression of LPS binding protein, CD14, TNF-α, collagen(α1)(I), and α-smooth actin.ConclusionThese results indicate that ABE alleviated CCl4-induced liver fibrosis, and that this protection is probably due to the suppression of macrophage activation.

Graphical abstractThe hepatoprotective mechanisms for ABE. ABE inhibits the activation of Kupffer cells.Figure optionsDownload full-size imageDownload as PowerPoint slide