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Rheum palmatum L ; Astragalus membranaceus (Fisch.), is referred to as 'Dahuang, Huangqi' in China. As an important medicinal plant, the rhizome of rhubarb and astragalus is traditionally used in the treatment of kidney diseases associated with renal failure, inflammation and tumors. Aim of the study : This study aimed to investigate the effect of a drug-containing serum of rhubarb-astragalus capsules (composed of rhubarb and astragalus) and to elucidate its mechanism in the epithelial-mesenchymal transformation of renal tubular epithelial cells. Epithelial-mesenchymal transformation (EMT) of HK-2 cells was induced by TGF-β1, and rhubarb-astragalus and losartan drug-containing serum from rats, as well as SB203580 (a specific inhibitor of p38 MAPK), were used. High-performance liquid chromatography analysis was performed to determine the main components of the drug-containing serum of rhubarb-astragalus from rats. Western blotting and immunofluorescence analysis were used to determine the levels of protein expression, and real-time quantitative PCR analysis was used to detect the levels of gene expression. The drug-containing serum of rhubarb-astragalus contained emodin (0.36 μg/ml) and danthraquinone (0.96 μg/ml). Rhubarb-astragalus significantly decreased the protein expression levels of α-SMA, FN, vimentin and N-cadherin in HK-2 cells that were increased by TGF-β1, while it significantly increased the E-cadherin protein expression level that was decreased by TGF-β1. Rhubarb-astragalus also significantly decreased the protein expression levels of TGF-β1 and p38 MAPK and the mRNA expression levels of α-SMA, vimentin, TGF-β1, p38 MAPK, Smad2 and Smad3 in HK-2 cells that were increased by TGF-β1. It is worth noting that SB203580 (a p38 MAPK inhibitor) had similar effects as rhubarb-astragalus in this study. The drug-containing serum of rhubarb-astragalus can inhibit EMT in HK-2 cells by downregulating the TGF-β1/p38 MAPK/Smad2/3 pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxin-induced sepsis. SHP had dual regulatory functions in a canonical transcription factor NF-?B signaling pathway, acting as both a repressor of transactivation of the NF-?B subunit p65 and an inhibitor of polyubiquitination of the adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an AMP-activated protein kinase-dependent signaling pathway. Our data identify a previously unrecognized role for SHP in the regulation of TLR signaling. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The water-soluble total flavonoids (WSTF) were extracted from Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a common folk herbal medicine in China, which has been recorded by the “Chinese Pharmacopoeia” in 2015 and used for prevention and clinical treatment of common diseases of liver and gall for many years. Objective of the study The aim of this study is to evaluate the effects of WSTF on apoptosis in HepG2 cell and investigate the relevant mechanisms underlying. Materials and methods C ytotoxicity was evaluated in HepG2 cells (human hepatoma cell lines) using MTT assay. The influence of the WSTF on the intracellular reactive oxygen species (iROS) and the mitochondrial membrane potential were also determinated. We used flow cytometry analysis to detect the effects of WSTF on apoptosis, cell cycle. Then we applied RT-PCR for genetic expression of main effectors and western blot analysis for activation of main effectors involved in the potential apoptosis signaling pathways. Results WSTF inhibited cell growth in HepG2 cells. Moreover, WSTF stimulates to increase amount of iROS, mitochondrial membrane potential, and the apoptotic relevant factors (cytochrome c, caspase-3) in HepG2 cells. WSTF could significantly induce apoptosis through downregulating apoptosis-antagonizing protein (Bcl-2, Survivin, mcl-1) and upregulating apoptosis-promoting proteins (Bax) and cell cycle G0/G1 arrest in HepG2 cells. Conclusion The results indicate that WSTF induces cell apoptosis through mitochondrial pathway in the HepG2 cells. Therefore, these studies suggest that WSTF could be used as a chemotherapeutic agent to treat hepatoma. [ABSTRACT FROM AUTHOR]