The effects of topical triptolide in an animal model of contact dermatitis

published_or_final_versio

Pharmacological Effects of Active Compounds on Neurodegenerative Disease with Gastrodia and Uncaria Decoction, a Commonly Used Poststroke Decoction

published_or_final_versio

B cells from SLE patients display accelerated apoptosis and reduced anti-apoptotic response to sIgM and CD40 ligation

published_or_final_versio

Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages

Cimicifuga species have been used as traditional medicinal herbs to treat inflammation and symptoms associated with menopause in Asia, Europe, and North America. However, the underlying mechanism of their anti-inflammatory effects remains to be investigated. With bioactivity guided purification involving the use of partitioning extraction and high performance liquid chromatography, we isolated one of the key bioactive constituents from the rhizome extracts of Cimicifuga racemosa. By NMR spectroscopy, the molecule was identified to be cimiracemate A (1). This compound (140 μM) suppressed the lipopolysaccharide-induced TNF-R production in the blood macrophages by 47 (19% and 58 (30% at LPS concentrations of 1 ng/mL and 10 ng/mL, respectively. The antiinflammatory activity of compound 1 may be due to its modulation of a signaling mitogen activated protein kinase and transcription factor nuclear factor-kappaB activities. Compound 1 was found in other Cimicifuga species. Our data indicate that compound 1 or its chemical analogues may have the potential to be further developed as a new class of therapeutic agent. © 2009 American Chemical Society.link_to_subscribed_fulltex

Anti-inflammatory mechanisms of black cohosh on human primary blood macrophages via its downregulation of signal transduction and transcription factor activation

The submitted titles' web site is located at http://www.nottingham.ac.uk/cgcm2009/abstracts.htm

Bioactivity-guided identification and cell signaling analysis to investigate the immunomodulatory effects of ginseng on U937 cells

Poster Presentation 2Panax ginseng (Ginseng) is one of the most commonly used medicinal herbs worldwide. It is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng’s effects remain to be investigated. We hypothesize that some biological effects of ginseng are due to its anti-inflammatory activities. To investigate the effects of ginseng on inflammation, human monocytic cells (U937) were treated sequentially with 70% ethanol–water extracts of Panax ginseng (PGSE) and tumor necrosis factor-alpha (TNF-α). Gene expression profiles of the cells were examined by genechip analysis (Human Genome U133 Plus 2.0 arrays, Affymetrix) and validated by Taqman quantitative RT-PCR, and protein expressions were assayed by ELISA. The composition of ginsenosides in 70% ethanol–water extracts of ginseng was analyzed by HPLC. Activation of signaling kinases was examined by Western blot analysis and the respective anti-phospho-protein kinase antibodies. PGSE significantly inhibited the transcription and secretion of CXCL-10 following TNF-α stimulation. Nine ginsenosides including Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3 and Rh1 were identified in the PGSE by HPLC. Seven out of nine ginsenosides could significantly inhibit TNF-α-induced CXCL-10 expression in U937 cells but the CXCL-10 suppressive effects of individual ginsenosides was less than that of the crude extract or the mixture of reconstituted ginsenosides. The suppressive effect of the reconstituted mixture of nine ginsenosides at the corresponding doses was comparable to the PGSE treatment in a dose-dependent manner. Furthermore, the CXCL-10 suppression can be correlated with the inactivation of ERK1/2 pathways by the PGSE. In summary, our results provide evidence that ginseng can suppress TNF-α-inducible cytokines and signaling proteins in promonocytic cells

Anti-inflammatory compounds from medicinal herbs capable of modulating cytokines expression in human primary blood macrophages

Poster Presentation IIInflammation plays a pivotal role in the pathogenesis of many diseases including rheumatoid arthritis, autoimmune diseases, atherosclerosis, stroke, and cancer. Current therapeutic agents such as steroid, methotrexate, cyclophosphamide and monoclonal anti-TNF-α are effective in treat ing these diseases. However, many of these agents are associated with severe adverse effects including gastrointestinal irritation and bleeding. An alternative approach of using medicinal herbs has gained popularity, especially in Asia, to treat inflammation related diseases. Black cohosh (BC), a well known plant that is native to North America and Canada, has been used historically to treat inflammatory diseases. Two other medicinal herbs, specifically Ligusticum chuanxiong (LCX) and Radix Paeoniae rubra (RPR), have also been used as anti-inflammatory agents in Asian countries. In this project, we selected these three historically important herbs (BC, LCX and RPR) to investigate whether they have immunomodulatory effects on human primary blood macrophages (PBMac). We hypothesize that the constituents from these herbs are capable of exhibiting suppressive effects on the over-production of cytokines. Using a bioassay guided fractionation and identification scheme, we isolated compounds from these herbs and then investigated their immunomodulatory effects i n a PBMac model using lipopolysaccharide (LPS) or Bacillus Calmette-Guérin (BCG) as cytokine inducers. Our results demonstrated that compounds isolated from these herbs could significantly down-regulate the production of cytokines such as TNF-α or IL-10 in LPS- or mycobacteria-treated PBMac, while other cytokines, e.g., IL-6, are not affected. Furthermore, we showed that the LPS-induced phosphorylation of extracellularsignal-regulated protein kinase −1 and −2 (ERK1/2) can be abrogated by these compounds. In addition, the nuclear translocation of p65 subunit of NF-kB induced by LPS could be suppressed. Taken together, compounds isolated from these medicinal herbs can modulate pathogen-induced inflammatory responses via the regulation of specific signaling pathways, which lead to reduced cytokine expression in immune cells