Hepatic
fibrosis is a dynamic process which ultimately leads to
cirrhosis in almost patients with chronic hepatic injury. However, progressive
fibrosis is a reversible
scarring response. Activation of hepatic stellate cells (HSCs) is the prevailing process during hepatic
fibrosis.
Osthole is an active component majorly contained in the fruit of Cnidium monnieri (L.) Cusson. This present study investigated the
therapeutic effects of
osthole on rat
liver fibrosis and HSC activation.
RESULTS: We established the
thioacetamide (TAA)-model of Sprague-Dawley (SD) rats to induce hepatic
fibrosis. Rats were divided into three groups: control, TAA, and TAA + osthole (10 mg/kg). In vivo,
osthole significantly reduced liver injury by diminishing levels of plasma AST and ALT, improving histological architecture, decreasing
collagen and α-SMA accumulation, and improving hepatic
fibrosis scores. Additionally,
osthole reduced the expression of
fibrosis-related genes significantly.
Osthole also suppressed the production of
fibrosis-related
cytokines and
chemokines. Moreover, nuclear translocation of p65 was significantly suppressed in
osthole-treated liver.
Osthole also ameliorated TAA-induced injury through reducing cellular oxidation.
Osthole showed inhibitory effects in
inflammation-related genes and
chemokines production as well. In vitro, we assessed
osthole effects in activated HSCs (HSC-T6 and LX-2).
Osthole attenuated TGF-β1-induced migration and invasion in HSCs. Furthermore,
osthole decreased TNF-α-triggered NF-κB activities significantly. Besides,
osthole alleviated TGF-β1- or ET-1-induced HSCs contractility.
CONCLUSIONS: Our study demonstrated that
osthole improved TAA-caused liver injury, fibrogenesis and
inflammation in rats. In addition,
osthole suppressed HSCs activation in vitro significantly.