Portulaca oleracea L. extract relieve mice liver fibrosis by inhibiting TLR-4/NF-κB, Bcl-2/Bax and TGF-ß1/Smad2 signalling transduction.

Portulaca oleracea L. are annual herb, which has various pharmacological effects including hepatoprotective property. However, the effect of Portulaca oleracea L. (POL-1) in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and its mechanism of action have not been clarified. POL-1 ameliorated the CCl4-induced liver fibrosis in mice, as shown by decreased collagen deposition and the decreased expression of liver fibrosis marker collagen I and α-smooth muscle actin (α-SMA) mRNA. In addition, treatment with POL-1 suppressed the proliferation of activated human hepatic stellate cell line (LX-2). POL-1 inhibited the oxidative stress and inflammation in fibrotic livers of mice. Mechanistically, POL-1 inhibited the CCl4-induced expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κBp65) p65, Bcl2-associated X (Bax), transforming growth factor-ß1 (TGF-ß1) and drosophila mothers against decapentaplegic 2 (Smad2) proteins, upregulated B-cell lymphoma -2 (Bcl-2) proteins in livers of mice. These findings suggested that POL-1 attenuated liver fibrosis.

Chemical characterisation of essential oil from Sambucus williamsii Hance leaves and its hepatoprotective effects.

This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.

A polysaccharide from Codonopsis pilosula roots attenuates carbon tetrachloride-induced liver fibrosis via modulation of TLR4/NF-κB and TGF-ß1/Smad3 signaling pathway.

The present work reported the extraction, purification, characterization of a polysaccharide from roots of Codonopsis pilosula (CPP-A-1) and its effect on liver fibrosis. The findings exhibited that the molecular weight of CPP-A-1 was 9424 Da, and monosaccharide composition were glucose and fructose and minor contents of arabinose. Structural characterization of CPP-A-1 has a backbone consisting of→(2-ß-D-Fruf-1)n→ (n ≈ 46-47). Treatment with CPP-A-1 inhibited the proliferation of transforming growth factor-beta 1 (TGF-ß)-activated human hepatic stellate cell line (LX-2), and induced cell apoptosis. We used carbon tetrachloride (CCl4) to construct mice model of liver fibrosis and subsequently administered CPP-A-1 treatment. The results showed that CPP-A-1 alleviated CCl4-induced liver fibrosis as demonstrated by reversing liver histological changes, decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) contents, collagen deposition, and downregulated fibrosis-related collagen I and α-smooth muscle actin (α-SMA), and inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and its inhibitor (TIMPs). Moreover, CPP-A-1 improved anti-oxidation effects detected by promoting liver superoxide dismutase (SOD), glutathione (GSH) and Mn-SOD levels, and inhibition of liver malondialdehyde (MDA) and iNOS levels. CPP-A-1 also ameliorated the inflammatory factor (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6), and expression of inflammatory factor genes (TNF-α, IL-11 mRNA). In addition, our results showed that CPP-A-1 inhibited Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and transforming growth factor-ß1 (TGF-ß1)/drosophila mothers against decapentaplegic 3 (Smad3) signaling pathways. Furthermore, In vitro tests of LX-2 cells demonstrated that CPP-A-1 not only inhibited α-SMA expression with lipopolysaccharide (LPS) or TGF-ß1 stimulation, but also inhibited TLR4/NF-κB and TGF-ß1/Smad3 signaling, similar to corresponding small-molecule inhibitors. Therefore, CPP-A-1 might exert suppressive effects against liver fibrosis by regulating TLR4/NF-κB and TGF-ß1/Smad3 signaling, our findings support a possible application of CPP-A-1 for the treatment of liver fibrosis.

Hepatoprotective effect of a polysaccharide from Radix Cyathulae officinalis Kuan against CCl4-induced acute liver injury in rat.

Radix Cyathulae officinalis Kuan, one of the most well-known Chinese medicine, is widely used for invigorating livers and kidneys. The aim of this study is to investigate the hepatoprotective effects of polysaccharide from Radix Cyathulae officinalis Kuan (RCPS) against CCl4-induced liver damage in rat. In vivo experiment showed that oral administrated of RCPS significantly decreased the production of ALT, AST, ALP, LDH, TNF-α, IL-6, IL-1ß, MDA in serum, and reduced the expression of TLR4, P-iκBα, iκBα, NF-κBp65 in hepatic tissue. RCPS pretreatment also increased antioxidant enzyme activities Superoxide dismutase (SOD), Glutathione peroxidase (GSH-PX) and non-enzyme antioxidants glutathione (GSH), total antioxidant capacity (T-AOC) compared with CCl4-induced. Furthermore, hepatic histopathological changes induced by CCl4 were significantly normalized by RCPS pretreatment. These results indicated that RCPS had hepatoprotective effect against CCl4-induced acute liver injure.

Polysaccharide from Ephedra sinica Stapf inhibits inflammation expression by regulating Factor-ß1/Smad2 signaling.

Mahuang, a famous traditional Chinese medicine, is widely used for the treatment of common cold and inflammatory diseases in China. We investigated the protective effects of polysaccharide from Ephedra sinica Stapf (ESP-B4) against airway and pulmonary inflammation. Animal model was made in SD rats via intratracheal instillation of Lipopolysaccharides (LPS) on day1 and 14 and inhalation of Cigarette Smoke (CS) for 4 weeks. ESP-B4 was administered by oral gavage for 2 weeks. We studied the number of inflammatory cells in serum, production of TNF-α, IL-6, IL-8 and MMP-9 in lung homogenization buffer, and the expression of TGF-ß1, P-Smad2 and P-Smad3 in lung tissue. In vitro, model was made in A549 cells with LPS and cigarette smoke extract. We investigated the levels of TNF-α, IL-6 and IL-8, and the expression of TGF-ß1, P-Smad2, P-Smad3 and Smad7. Our results revealed that ESP-B4 lowered the recruitment of inflammatory cells; and decreased the production of TNF-α, IL-6, IL-8 and MMP-9, significantly reduced the expression of TGF-ß1, P-Smad2 and P-Smad3, increased the expression of Smad7. These results indicated that ESP-B4 reduced airway and pulmonary inflammation by regulating inflammatory cytokines and the TGF-ß1/Smad2 pathway, thus providing a potential treatment for chronic obstructive pulmonary diseases (COPD).