HES1 and Hepatic fibrosis: For example, costunolide (COS), which is isolated from Saussurea lappa, is involved in the WW domain-containing protein 2 (WWP2)-mediated notch homologue protein 3 (Notch3) degradation through ubiquitin-dependent lysosome pathways and subsequent restriction of the Notch3-hairy/enhancer of split-1 (HES1) pathway, thereby alleviating liver fibrosis [111].