Hydroxysafflor yellow A protects against chronic carbon tetrachloride-induced liver fibrosis.

Hydroxysafflor yellow A (HSYA) was isolated from the dried flower of Carthamus tinctorius L. which was extensively used in traditional Chinese medicine to treat cirrhosis. However, the potential protective effect of HSYA in liver fibrosis is still unknown. In the present study, we investigated the effects of HSYA in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Sprague-Dawley (SD) rats were subjected to biweekly CCl4 injections over 12 weeks, while controls were given isovolumetric injections of olive oil. HSYA was given in a daily dose of 5 mg/kg by means of intraperitoneal concurrent with CCl4. Hepatic fibrosis was quantified by digital analysis of Masson's trichrome stained slides and hydroxyproline content. mRNA expression was quantified by real-time polymerase chain reaction (PCR), and protein was quantified by western blot or enzyme-linked immunosorbent assay (ELISA). CCl4 treatment induced micronodular liver fibrosis with a pronounced deposition of collagen fibers. HSYA significantly reduced liver fibrosis. HSYA down regulates α-smooth muscle actin (SMA), collagen α type I, matrix metalloproteinases (MMP)-9, and tissue inhibitors of metalloproteinases (TIMP)-1 gene expression. This was accompanied by a decreased expression of transforming growth factor (TGF)-β1 and phosphorylation of Smad4. These results indicate that HSYA might be a promising antifibrotic agent in chronic liver disease.

Zhang Y ，Guo J ，Dong H ，Zhao X ，Zhou L ，Li X ，Liu J ，Niu Y ... -  《-》

Therapeutic efficacy of Traditional Chinese Medicine 319 recipe on hepatic fibrosis induced by carbon tetrachloride in rats.

Cheung KF ，Ye DW ，Yang ZF ，Lu L ，Liu CH ，Wang XL ，Poon RT ，Tong Y ，Liu P ，Chen YC ，Lau GK ... -  《-》

Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling.

Liu Q ，Wang CY ，Liu Z ，Ma XS ，He YH ，Chen SS ，Bai XY ... -  《-》

Hydroxysafflor yellow A attenuates carbon tetrachloride-induced hepatic fibrosis in rats by inhibiting ERK5 signaling.

Zhang YB ，Dong HY ，Zhao XM ，Fan L ，Zou Y ，Zhang C ，Li G ，Liu JC ，Niu YC ... -  《-》

Activation of PPARγ is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress.

Oxidative stress caused hepatic fibrosis by activating hepatic stellate cells (HSCs), which were implemented by depressing PPARγ activation. Hydroxysafflor yellow A (HSYA) as a nature active ingredient with antioxidant capacity was able to effectively attenuate oxidative stress mediated injury. So it will be very interesting to study effect of HSYA on HSCs activation and liver fibrosis, and reveal the role of PPARγ·CCl4 and H2O2 were used to mimic oxidative stress mediated hepatic injury in vitro and in vivo respectively. The anti-fibrosis effects of HSYA were evaluated and its mechanisms were disclosed by applying western blot, histopathological analysis, flow cytometry, RT-PCR and ELISA. Our results showed that HSCs activation and proliferation could be induced by oxidative stress, and the expressive levels of TGF-β1 and TIMP-1, the serum levels of ALT, AST, HA, LN, III-C and IV-C were also enhanced by oxidative stress, which is correlated with liver fibrosis (p<0.05 or p<0.01). HSYA was able to effectively inhibit oxidative stress mediated hepatic injury by increasing the activities of antioxidant enzymes, up regulating the expression of PPARγ and MMP-2, and down regulating the expression of TGF-β1 and TIMP-1, and reducing α-SMA level. The protective effect of HSYA can be significantly attenuated by GW9662 via blocking PPARγ (p<0.05 or p<0.01). Taken together, these results demonstrate that HSYA is able to significantly protect the liver from oxidative stress, which requires for HSYA to stimulate PPARγ activity, reduce cell proliferation and suppress ECM synthesis.

Wang CY ，Liu Q ，Huang QX ，Liu JT ，He YH ，Lu JJ ，Bai XY ... -  《-》