Effects of Enzymatically Depolymerized Low Molecular Weight Heparins on CCl₄-Induced Liver Fibrosis

With regard to identifying the effective components of LMWH drugs curing hepatic fibrosis disease, we carried out a comparative study on the efficacy of enzymatically depolymerized LMWHs on CCl₄ induced mouse liver fibrosis. The results showed that the controlled enzymatic depolymerization conditions resulted in LMWHs with significantly different activities. The LMWH product depolymerized by Heparinase I (I-11) with a Mw of 7160, exhibited a significant advantage in reducing the liver inflammation by suppressing TNF-α and IL-1β secretion, and minimizing hepatic fibrogenesis. The products prepared by only Heparinase II (II-11), and combined Heparinase III and II (III-II-5) showed limited positive effect on hepatic inflammation and fibrosis. On the contrary, the products by combined Heparinase III and I (III-I-9, III-I-5) showed no effect or stimulation effect on the hepatic fibrogenesis. Our results provided the basis for structure-activity relationship insight for inhibition of liver fibrosis activities of LMWHs, which might have significant implications for generic anti-fibrosis disease drug development.