ABSTRACT
Toll-like receptor 4(TLR4)is a member of the TLRs superfamily,mainly capable of identifying bacterial endotoxin,lipopolysaccharides and lipooligosaccharides of Gram-negative bacte?ria cell walls to prevent microbial invasion. Activation of TLR4 can induce production of proinflammato?ry cytokines and inflammatory chemokines and regulate natural immunity. However,dysregulation of TLR4 can lead to autoimmune diseases. This review summarized the biological structure of TLR4 and recognition mechanisms between TLR4 and its ligands,surveyed TLR4 ligands including lipid A ana?logues,natural products and synthetic small molecules,discussed the structure-activity relationship of TLR4 modulators and the ligand-receptor and protein-protein interactions in the complex,and outlined the prospect of future research and development of TLR4 ligands.
ABSTRACT
Aim To investigate the effects of Y-IP5 on morphine-induced behavioral sensitization and CPP in mice.Methods Locomotor activity was detected after Y-IP5 administration or co-administration of Y-IP5 with morphine in mice.Mice were treated with morphine to induce behavioral sensitization. Then the effects of Y-IP5 on the development, transfer and expression of morphine-induced behavioral sensitization were investigated. Mice were treated with morphine to induce CPP. Then the effect of Y-IP5 on the acquisition of morphine-induced CPP was studied.Results Y-IP5 itself didn′t influence locomotor activity of mice.Co-administration of Y-IP5 with morphine inhibited morphine-induced hyperactivity (P<0.05) and the development of morphine-induced behavioral sensitization in mice (P<0.05), however, did not influence the transfer and expression of morphine-induced behavioral sensitization.Co-administration of Y-IP5 with morphine also inhibited the acquisition of morphine-induced CPP (P<0.05).Conclusion Y-IP5 may inhibit the psychological dependence induced by morphine.
ABSTRACT
AIM Our investigation is to screen bioactive novel compounds using the isolated rat aortic rings and depending on the similar and distinct characteristics between the endothelial target for acetylcholine(ETA) and muscarinic receptors and to investigate the mechanisms of vasodilatory effects of candidate compounds. METHODSIn isolated rat aorta precontracted with NE, the vasodilatory effects of novel structure compounds were investigated. We Compared the maximal relaxation of endothelium denuded aorta with that of the endothelium intact aorta elicited by the 8 candidate compounds respectively. The aortas were precubated with L NAME, indomethacine and atropine before using NE, and measured the changes of the maximum vasodilatory rate of candidate compound. RESULTS AND CONCLUSION Among 81 compounds, we found 8 novel compounds which induced relaxation. Their maximal relaxation rates ranged of from 50 percent to 85 percent. The endothelium dependent relaxation induced by DMHPPP and PPVP was blocked by indomethacin and L NAME, but not by atropine. DMHPPP and PPVP also enhanced the maximal endothelium dependent relaxation induced by acetylcholine. These suggest that novel compounds may regulate functions of endothelial cell target for acetylcholine(ETA) to induce relaxation of isolated rat aortic rings, which may involve the prostacycline and nitric oxide pathways.
ABSTRACT
Recent evidence suggests that, in spite of the redundancy of angiogenic factors involved in pathological angiogenesis , strategies aimed at inhibiting specific endothelial cell angiogenic factors at their release or receptor level may form the basis for effective and safe treatment of angiogenic mediated disease processes. Physiologic angiogenesis is fundamental to reproduction, development and repair. Pathological angiogenesis sustains the progression of many neoplastic and proinflammatory diseases. And endothelial cell is an important target especially for the angiogenesis. The target represents a novel strategy for the treatment of the human disorders where pathological angiogenesis is involved.