OBJECTIVETo observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats.

METHODSSixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10): normal group, CIA model group(model group), NCTD low-dose group [1.35 mg/(kg•d)], NCTD middle-dose group [2.7 mg/(kg•d)], NCTD high-dose group [5.4 mg/(kg•d)] and methotrexate (MTX) group [1.8 mg/(kg/w)]. Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration. The arthritis scores were evaluated twice a week. The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining. The serum levels of interleukin (IL) 1β, IL-6, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression of retinoid-related orphan nuclear receptorγt (RORγt) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction.

RESULTSMTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats' ankle joints compared with the model group (P<0.05 or P<0.01). All doses of NCTD significantly inhibited the serum levels of IL-6, IL-17 and TNF-α in CIA rats (P<0.05). Only middle- and high-dose of NCTD prominently decreased serum IL-1β and TGF-β levels of CIA rats (P<0.05). However, NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats. The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P<0.05). The mRNA expression of RORγt in NCTD high-dose group was decreased apparently in comparison with the model group (P<0.05).

CONCLUSIONSNCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.

Animals ; Arthritis, Experimental ; blood ; drug therapy ; pathology ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; therapeutic use ; Cytokines ; blood ; Forkhead Transcription Factors ; metabolism ; Joints ; drug effects ; pathology ; Male ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats, Sprague-Dawley

Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.
Acetophenones ; pharmacology ; therapeutic use ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Benzopyrans ; pharmacology ; therapeutic use ; Benzylisoquinolines ; pharmacology ; therapeutic use ; Catechols ; pharmacology ; therapeutic use ; Heterocyclic Compounds, 4 or More Rings ; pharmacology ; therapeutic use ; Humans ; Isothiocyanates ; pharmacology ; therapeutic use ; Naphthoquinones ; pharmacology ; therapeutic use ; Neoplasms ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Signal Transduction ; drug effects

Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.
Animals ; Anti-Asthmatic Agents ; pharmacology ; therapeutic use ; Asthma ; drug therapy ; Heterocyclic Compounds ; pharmacology ; Humans ; Phenylurea Compounds ; therapeutic use ; Piperidines ; pharmacology ; therapeutic use ; Pyridazines ; pharmacology ; Receptors, CCR1 ; antagonists & inhibitors ; Receptors, CCR3 ; antagonists & inhibitors ; Receptors, CCR4 ; antagonists & inhibitors ; Receptors, CXCR4 ; antagonists & inhibitors ; Receptors, Chemokine ; antagonists & inhibitors

In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.
Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Fungi ; drug effects ; Heterocyclic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Lipopeptides ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Mycoses ; drug therapy ; Nitriles ; chemistry ; pharmacology ; therapeutic use ; Plant Extracts ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Pyridines ; chemistry ; pharmacology ; therapeutic use ; Quinazolines ; chemistry ; pharmacology ; therapeutic use ; Quinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Thiazoles ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use

Heat shock protein 90 is a new target of antitumor drug, the inhibitor of Hsp90 fight against tumor by destroy and degrade the structure of protein. In recent years, looking for Hsp90 inhibitor is not only via structure modifying of natural products, but also via high throughput screening and computer aided drug design to find and synthesize new kinds of Hsp90 inhibitor. Anyway, Hsp90 inhibitor has considered as an important biology target and to pay more and more attention. This review describes recent developments of small molecule Hsp90 inhibitors.
Adenine ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Anisoles ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; therapeutic use ; Benzoquinones ; chemistry ; therapeutic use ; Catechin ; analogs & derivatives ; chemistry ; pharmacology ; Cell Line, Tumor ; Crystallization ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; chemistry ; Heterocyclic Compounds, 2-Ring ; chemistry ; pharmacology ; Humans ; Lactams, Macrocyclic ; chemistry ; therapeutic use ; Macrolides ; chemistry ; pharmacology ; Molecular Structure ; Neoplasms ; drug therapy ; pathology ; Pyrazoles ; chemistry ; pharmacology ; Structure-Activity Relationship

CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro. In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.
Animals ; *Bleomycin ; Bronchoalveolar Lavage Fluid/chemistry ; Cell Movement/drug effects ; Cells, Cultured ; Chemokine CXCL12/chemistry/metabolism ; Cytoprotection/drug effects ; Down-Regulation/drug effects ; Drug Evaluation, Preclinical ; Female ; Heterocyclic Compounds/pharmacology/*therapeutic use ; Lung/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis/*chemically induced/*prevention & control ; Receptors, CXCR4/*antagonists & inhibitors/metabolism