Deer Velvet Antler Extracts Exert Anti-Inflammatory and Anti-Arthritic Effects on Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Distinct Mouse Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint deformity and disability. Deer velvet antler (DA), a traditional Chinese medicine, has been used to treat various types of arthritis for several thousands of years, but the underlying mechanisms are unknown. Herein, we investigated the anti-arthritic and anti-inflammatory effects of DA in vitro and in vivo. The ethyl acetate layer of DA ethanol extract (DA-EE-EA) was used to treat tumor necrosis factor (TNF)-[Formula: see text]-stimulated fibroblast-like synoviocyte MH7A cells, collagen-induced arthritis DBA/1 mice, and SKG mice with zymosan-induced arthritis. DA-EE-EA reduced nitric oxide production, prostaglandin E2 levels, and levels of pro-inflammatory cytokines including interleukin (IL)-1[Formula: see text], IL-6, and IL-8 in MH7A cells. DA-EE-EA also downregulated the phosphorylation of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and the translocation of nuclear factor kappa B p65. Intraperitoneal injection of DA-EE-EA for 3 weeks substantially reduced clinical arthritis scores in vivo models. Pathohistological images of the hind paws showed that DA-EE-EA reduced immune cell infiltration, synovial hyperplasia, and cartilage damage. The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, IL-1[Formula: see text], IL-6, IL-8, IL-17A, and interferon-gamma, decreased in the hind paw homogenates of DA-EE-EA-treated mice. We also identified several potential components, such as hexadecanamide, oleamide, erucamide, and lysophosphatidylcholines, that might contribute to the anti-inflammatory effects of DA-EE-EA. In conclusion, DA-EE-EA has the potential to treat RA by regulating inflammatory responses. However, the individual components of DA-EE-EA and the underlying anti-inflammatory mechanisms need further investigation in future studies.

Astragalus mongholicus Bunge Water Extract Exhibits Anti-inflammatory Effects in Human Neutrophils and Alleviates Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice.

Neutrophils are the primary immune cells in innate immunity, which are related to various inflammatory diseases. Astragalus mongholicus Bunge is a Chinese medicinal herb used to treat various oxidative stress-related inflammatory diseases. However, there are limited studies that elucidate the effects of Astragalus mongholicus Bunge in human neutrophils. In this study, we used isolated human neutrophils activated by various stimulants to investigate the anti-inflammatory effects of Astragalus mongholicus Bunge water extract (AWE). Cell-free assays were used to examine free radicals scavenging capabilities on superoxide anion, reactive oxygen species (ROS), and nitrogen-centered radicals. Imiquimod (IMQ) induced psoriasis-like skin inflammation mouse model was used for investigating anti-psoriatic effects. We found that AWE inhibited superoxide anion production, ROS generation, and elastase release in human neutrophils, which exhibiting a direct anti-neutrophil effect. Moreover, AWE exerted a ROS scavenging ability in the 2,2'-Azobis (2-amidinopropane) dihydrochloride assay, but not superoxide anion in the xanthine/xanthine oxidase assay, suggesting that AWE exhibited anti-oxidation and anti-inflammatory capabilities by both scavenging ROS and by directly inhibiting neutrophil activation. AWE also reduced CD11b expression and adhesion to endothelial cells in activated human neutrophils. Meanwhile, in mice with psoriasis-like skin inflammation, administration of topical AWE reduced both the affected area and the severity index score. It inhibited neutrophil infiltration, myeloperoxidase release, ROS-induced damage, and skin proliferation. In summary, AWE exhibited direct anti-inflammatory effects by inhibiting neutrophil activation and anti-psoriatic effects in mice with IMQ-induced psoriasis-like skin inflammation. Therefore, AWE could potentially be a pharmaceutical Chinese herbal medicine to inhibit neutrophilic inflammation for anti-psoriasis.

Paeoniae radix reduces PDGF-stimulated hepatic stellate cell migration.

Hepatic stellate cells (HSCs) play a key role in the pathogenesis of liver fibrosis. In chronic liver injury, HSCs undergo transdifferentiation to an activated myofibroblastic phenotype and migrate to injured areas in response to chemotactic factors, producing extracellular matrix proteins such as collagen type I to repair the damage as well as overexpression of α-smooth muscle actin (α-SMA). Paeoniae Radix, the root of Paeonia lactiflora Pall, was investigated for PDGF-BB-induced HSC chemotaxis. Rat HSCs and LX-2, a human HSC cell line, were used for the in vitro experiments. Cell migration was analyzed by wound-healing and transwell assays. An ELISA and a Sircol collagen assay kit were used to detect the expressions of α-SMA and of collagen, respectively. Phosphorylations of mitogen-activated protein kinases, including ERK 1/2, p38, and JNK, were evaluated with immunoblotting. Results indicated that PDGF-BB increased migration as well as α-SMA and collagen expression in HSCs. Paeoniae Radix extracts and its active components, paeonol and 1,2,3,4,6-penta- O-galloyl- ß-D-glucose (PGG), inhibited PDGF-BB-induced HSC migration and α-SMA and collagen expressions in a concentration-dependent manner. The inhibitory effects were associated with downregulation of PDGF receptor- α, ERK, p38, and JNK activation. Both paeonol and PGG participate in HSC migration, but via differential mechanisms.

Changes of hepatic proteome in bile duct ligated rats with hepatic fibrosis following treatment with Yin-Chen-Hao-Tang.

Yin-Chen-Hao-Tang (YCHT) is recognized as a hepatoprotective agent for various types of liver diseases. Proteomics approaches were used to study hepatic and serum protein expression changes in bile duct ligated (BDL) rats following YCHT treatment for 27 days. Two-dimensional gel electrophoresis was used to analyze proteome changes. Of the proteins that exhibited changes, 17 were identified by means of matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry. The major effect of YCHT was evident in cytoskeleton related protein, plectin-1. In addition, proteins involved in metabolism of lipids were also shown to be affected, including low-density lipoprotein receptor-related protein 2 precursor (glycoprotein 330) and apolipoprotein A-I precursor (ApoA-I). Significant up-regulation of keratin 8 and 19 was found in liver tissue of BDL rats. Supplementation with YCHT also triggered alterations in the above proteins. Interestingly, YCHT treatment caused a statistically significant down-regulation in the secretion of monocyte chemoattractant protein-1 (MCP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in BDL rats with fibrosis. Our results suggested that YCHT may be useful for treatment of liver fibrosis because of its possible antiapoptotic properties, and the therapeutic effects of YCHT on liver diseases might be associated with its lipid biosynthesis regulation.

Herb medicine Yin-Chen-Hao-Tang ameliorates hepatic fibrosis in bile duct ligation rats.

The accumulation of hydrophilic bile acids in the liver is considered to play a pivotal role in the induction of hepatic injury. Yin-Chen-Hao-Tang (YCHT) decoction is an aqueous extract from three different herbs: Artemisia capillaries Thunb (Compositae), Gardenia jasminoides Ellis (Rubiaceae), Rheum officinale Baill (Polygonaceae), which has been recognized as a hepatoprotective agent for various types of liver diseases. Therefore, we used an experimental of biliary atresia model to test that YCHT plays a regulatory role in the pathogenesis of hepatic fibrosis. Hepatic damage with fibrosis was produced by common bile duct ligation (BDL) for 27 days in experimental cholestasis animal model. After surgery, YCHT (250 and 500mg/kg BW) oral administration once a day continued for 27 days. BDL caused a prominent liver collagen deposition that was supported by the increased alpha-SMA protein and mRNA expression of procollagen I. YCHT significantly decreased hepatic alpha-SMA protein levels and decreased in hydroxyproline and thiobarbituric acid reactive substances (TBARS) levels of BDL rats. On the other hand, the normalizing effect of YCHT (250mg/kg) on the TGF-beta1mRNA expression was independent on the dose of YCHT, 500mg/kg was not effectively changed the quantitative composition of mRNA levels. The study shows that hepatic hydroxyproline accumulation caused by hydrophilic bile acids accompanied by elevated hepatic lipid peroxidation, and hepatic collagen levels can be decreased in the presence of YCHT. In conclusion, long-term administration of YCHT in rats ameliorated the hydropholic bile acids induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis.