The American journal of Chinese medicine
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Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF. ⋯ Additionally, EASM inhibited TGF- β 1/Smad3 signaling by downregulating protein kinase C delta (PKC- δ ) and Smad3 phosphorylation (p-Smad3), which led to suppression of the TGF- β 1-induced fibrogenic response. These results indicate that EASM exhibits potent antifibrotic activity in vitro and in vivo, which might be associated with activation of Nrf2 pathway and inhibition of TGF- β 1/Smad3 pathway. Our findings support that EASM may act as an effective antifibrotic remedy for PF.
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Sageretia thea (S. thea) commonly known as Chinese sweet plum or Chinese bird plum has been used for treating hepatitis and fevers in Korea and China. S. thea has been reported to exert anti-oxidant, anticancer and anti-human immunodeficiency virus activity. However, there is little study on the anti-inflammatory activity of S. thea. ⋯ ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing NF- κ B and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.
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Acute liver injury (ALI) induced by acetaminophen (APAP) is the main cause of drug-induced liver injury. Previous reports indicated liver failure could be alleviated by saponins (ginsenosides) from Panax ginseng against APAP-induced inflammatory responses in vivo. However, validation towards ginsenoside Rb1 as a major and marker saponin may protect liver from APAP-induced ALI and its mechanisms are poorly elucidated. ⋯ Histological examination further proved Rb1's protective effects. Importantly, Rb1 mitigated the changes in the phosphorylation of MAPK and PI3K/Akt, as well as its downstream factor NF- κ B. In conclusion, experimental data clearly demonstrated that Rb1 exhibited a remarkable liver protective effect against APAP-induced ALI, partly through regulating MAPK and PI3K/Akt signaling pathways-mediated inflammatory responses.
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Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF-β1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague-Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor-β1 (TGF-β1) in LX2 cells and liver tissues were determined. ⋯ After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF-β1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of α-SMA and COL1A1 in liver tissues and TGF-β1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF-β1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis.
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Activation of brown adipose tissue (BAT) has been proposed as a promising target against obesity due to its increased capacity for thermogenesis. In this study, we explored the effect of β -Lapachone ( β L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of β L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr -∕- mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). ⋯ Taken together, β L exerts anti-obese effects by inducing thermogenesis mediated by AMPK signaling pathway, suggesting that β L may have a potential therapeutic implication of obesity. Taken together, β L exerts anti-obese effects by not only inducing thermogenesis on brown adipocytes but also inducing the browning of white adipocytes. The anti-obese effect of β L is mediated by AMPK signaling pathway, suggesting that β L may have potential therapeutic implication of obesity.