Taiwanese Green Propolis and Propolin G Protect the Liver from the Pathogenesis of Fibrosis via Eliminating TGF-β-Induced Smad2/3 Phosphorylation

Abstract

Pathogenesis of fibrosis is a common process leading to chronic liver diseases and liver cirrhosis. New compounds for disease treatment and adjuvant therapy have been important issues in recent years. In this study, we isolated propolin G from Taiwanese green propolis (TGP) and investigated its antifibrotic effects by utilizing active hepatic stellate cells (HSCs) fibrosis model. Our results showed that TGP and propolin G inhibited α-SMA, collagen expression, and proliferation of HSC-T6 cells after TGF-β treatment. They also reduced the accumulation of extracellular matrix (ECM) components such as collagen Iα1 (Col Iα1) through down-regulating JNK signaling. Subsequently, mRNA and protein expression of Smad2/3 but no other Smad members was specifically down-regulated in the presence of propolin G. This effect also significantly induced apoptosis-associated expression of cleaved caspase-3 and caspase-7 proteins for fibrotic cell clearance. In in vivo experiments, we found that propolin G and TGP can reduce plasma alanine aminotransferase (ALT) activation and perhaps lead to the prevention of alcohol-induced liver cirrhosis. Furthermore, TGP can significantly decrease the malondialdehyde (MDA) level but has no influence on plasma or hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, suggesting TGP protects the liver from alcohol-induced injury through antioxidant-independent pathways. In conclusion, this study provides a new perspective of propolin G and TGP on liver protection, and its application has potential for health management by daily supplement or adjuvant therapy in related diseases.

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats

“…TGF-β1 is considered a key activator of HSCs and the most potent fibrogenic factor. α-SMA is a typical index for the activated HSCs during fibrotic process [36]. The expressions of α-SMA and type I collagen increases in TGF-β1-induced HSC-T6 cells [37].…”

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“…It protected the renal tissue against toxicity, free radicals and other adverse effects induced by diatrizoate (Baykara et al ., ). Taiwanese green propolis protected the liver from the pathogenesis of fibrosis (Su et al ., ). Propolis extract protected the testis from doxorubicin‐induced toxicity without reducing its anticancer potential (Rizk et al ., ).…”

Wogonoside Shows Antifibrotic Effects in an Experimental Regression Model of Hepatic Fibrosis

“…a-SMA is a typical index for the activated HSCs during fibrotic process [22]. The expressions of a-SMA and type I collagen increased in TGF-b-induced HSC-T6 cells [23].…”