Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lea...Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.展开更多
BACKGROUND: Salvianolic acid B (SA-B), one of water soluble compounds derived from Radix salviae miltiorrhizae, had good action against liver fibrosis of patients with chro- nic hepatitis. Hepatic stellate cells (HSCs...BACKGROUND: Salvianolic acid B (SA-B), one of water soluble compounds derived from Radix salviae miltiorrhizae, had good action against liver fibrosis of patients with chro- nic hepatitis. Hepatic stellate cells (HSCs) is the cellular re- source for liver fibrogenesis, while transforming growth factor-β1 (TGF-β1) is most potent fibrogenic factor. In this study we investigated the mechanism of SA-B action against liver fibrosis relating to the interference with TGF- β1 signaling at HSC. METHODS: Hepatic stellate cells (HSCs) were isolated, cultured, and incubated with SA-B. The TGF-β1 content in the supernatant of subcultured HSCs was assayed with ELISA. Type I collagen and Smad3 protein in TGF-β1-sti- mulated primarily cultured HSCs for 4 days were detected by Western blot. RESULTS: TGF-β1 secreted in activated HSCs was more than in primary HSCs, and SA-B significantly decreased TGF-β1 secretion in activated HSCs. TGF-β1 increased the expression of type I collagen and Smad3 protein in d4 pri- mary HSCs, while SA-B inhibited their expression. CONCLUSIONS: SA-B inhibits TGF-β1 secretion in activa- ted HSCs and counteracts the expression of TGF-β1 stimu- lated type I collagen and Smad3. These actions are associat- ed with the effect of SA-B on liver fibrosis.展开更多
基金Supported by National Council of Science and Technology(Conacyt)of Mexico,No.253037
文摘Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix(ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma(HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor(TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells(HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase(MAPK), toll-like receptor(TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease(NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor(VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.
基金The project was supported by grants from the Scientific Research Foundationfor Returned Overseas Chinese Scholars, Education Ministry ( No. 2002-247 )China and Key Program of Shanghai Education Council.
文摘BACKGROUND: Salvianolic acid B (SA-B), one of water soluble compounds derived from Radix salviae miltiorrhizae, had good action against liver fibrosis of patients with chro- nic hepatitis. Hepatic stellate cells (HSCs) is the cellular re- source for liver fibrogenesis, while transforming growth factor-β1 (TGF-β1) is most potent fibrogenic factor. In this study we investigated the mechanism of SA-B action against liver fibrosis relating to the interference with TGF- β1 signaling at HSC. METHODS: Hepatic stellate cells (HSCs) were isolated, cultured, and incubated with SA-B. The TGF-β1 content in the supernatant of subcultured HSCs was assayed with ELISA. Type I collagen and Smad3 protein in TGF-β1-sti- mulated primarily cultured HSCs for 4 days were detected by Western blot. RESULTS: TGF-β1 secreted in activated HSCs was more than in primary HSCs, and SA-B significantly decreased TGF-β1 secretion in activated HSCs. TGF-β1 increased the expression of type I collagen and Smad3 protein in d4 pri- mary HSCs, while SA-B inhibited their expression. CONCLUSIONS: SA-B inhibits TGF-β1 secretion in activa- ted HSCs and counteracts the expression of TGF-β1 stimu- lated type I collagen and Smad3. These actions are associat- ed with the effect of SA-B on liver fibrosis.
