Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury / 中国天然药物

The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.

Advances in the study of nitric oxide-donating drugs / 药学学报

Nitric oxide (NO) as a messenger and/or effector plays important roles in vivo. The decreased availability of NO or dysfunction in NO signaling has often been implicated in the development and progression of diseases, and design and research of NO-donating drugs has become one of the important strategies in drug discovery. In connection with authors' scientific practice, this article reviews the recent advances in the research of NO-donating drugs.

Proliferation of retinal pigment epithelial cells induced by (R,R)-XY-10 and (S,S)-XY-10 and their action mechanisms / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells(ARPE-19).METHODS: Human retinal pigmented epithelial cells(ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth,and their mechanisms of proliferative action by using ERK、 AKT、PI3K、Protein kinase C (PKC)and Nitric oxide synthase (NOS) inhibitors.RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation,but not on HUVECs. When treated with proliferative inhibitors,H7(5μmol/L)、hypericin(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5 (10μmol/L) and L-NAME (100μmol/L),the proliferative effect was reduced by H7、hypericin、PD98059 and LY294002,but not by SH-5 and L-NAME.CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway. KEYWORDS: age-related macular degeneration; (R,R)-XY-10; (S,S)-XY-10; ARPE-19 cells; human umbilical vein endothelial cells; proliferation

Effects of enantiomers(R,R)-XY and(S,S)-XY on ocular blood flow in rabbits / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the effects of two series of enantiomers [(R, R)-XY-1 through (R, R)-XY-12 and (S,S)-XY-1 through (S, S)-XY-12] on ocular blood flow in rabbits.·METHODS; Colored microsphere technique was used for in vivo experiments to determine the ocular blood flow in various tissues of ocular hypertensive (40mmHg) rabbit eyes.·RESULTS; Of the twelve compounds of ( R, R)-XY series examined, four increased choroidal blood flow at 10g/L, 50uL instilled into eyes. All compounds of (S, S)-XY series were not effective on ocular blood flow.·CONCLUSION; Some compounds of (R, R)-XY series increased the ocular blood flow, which might be useful for the prevention and treatment of ocular blood flow related eye diseases. Among all twenty-four compounds, (R, R)-XY-1and (R, R)-XY-9 seem to be the most potent ones.KEYWORDS; ocular blood flow; ischemia; enantiomer

A novel class of anti-inflammatory and analgesic drugs--NO-donating NSAIDs / 药学学报

Traditional non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors are among the most widely used drugs. However, their significant side effects in gastrointestinal and cardiovascular systems limited the use of these drugs. Recently, research and development of NO-donating NSAIDs (NO-NSAIDs) have become one of the most important strategies to reduce these side effects. NO-NSAIDs may exert a broad range of positive effects in terms of NO-mediated gastrointestinal and cardiovascular safety as well as comparable or increased anti-inflammatory, analgesic properties relative to NSAIDs. This review briefly deals with chemistry of NO-NSAIDs, more details are focused on biological significance, mechanism of action, and therapeutic potential of this novel class of drugs.

Effects of ZX-5 and its optical isomers on ocular blood flow in rabbits and retinal function recovery in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: The effects of ZX-5, as nitric oxide (NO) donor, on ocular blood flow has been investigated using colored microsphere technique in previous study. The relationship between the production of NO by ZX-5 and ocular blood flow has been evaluated. ZX-5 has been shown to have strong positive effect on increasing choroidal blood flow. However,the effect of ZX-5 on retinal function recovery, the effects of its optical isomers, (R, R)-ZX-5 and (S, S)-ZX-5, on choroidal blood flow and retinal function recovery have not been studied and merit investigation.METHODS: Colored microsphere technique was used for in vivo experiments to determine choroidal blood flow of ocular hypertension (40mmHg) in rabbit eyes. Electroretinography was used to measure the b-wave recovery as an indication of retinal function recovery.RESULTS: (R, R)-ZX-5 increased choroidal blood flow at 10g/L, 50μL instillation into eyes at all time points (P＜0.05).(S, S)-ZX-5 was not effective in increasing choroidal blood flow. ZX-5 and (R, R)-ZX-5 showed significant effects in retinal function recovery after ischemia of the retina at all time points (P＜0.05); whereas (S, S)-ZX-5 did not show significant effect on recovery of b-wave after ischemia at most time points except at 120 and 240 minutes.CONCLUSION: ZX-5 and (R, R)-ZX-5 have high potency in increasing the choroidal blood flow and improving the retinal function recovery. It is hoped that they could be used for the prevention/treatment of ocular blood flow related eye diseases.

Synthesis and antithrombotic activity of acetylsalicyl ferulic acid-coupling furoxans and nitrates / 药学学报

<p><b>AIM</b>To synthesize and study the antithrombotic activity of NO-donating aspirin derivatives.</p><p><b>METHODS</b>Furoxans and nitrates were incorporated to aspirin via antioxidant ferulic acid as a linker, and the target compounds were screened for in vitro and in vivo inhibitory activities of platelet aggregation, and for inhibitory effect on A-V hypass thromhosis in rats.</p><p><b>RESULTS</b>Fourteen novel compounds I(1-14), were synthesized and their structures were confirmed Iy MS, IR, 1H NMR and elemental analysis. Biological screening results demonstrated that some tested compounds exhibited potential antithrombotic activ it.</p><p><b>CONCLUSION</b>Acetylsalicyl ferulic acid-coupling furoxans and nitrates might he used as a lead for further study.</p>

Structural characterization of chlorobenzylidine / 药学学报

<p><b>AIM</b>To study the structure and crystal forms of chlorobenzylidine.</p><p><b>METHODS</b>Karl Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction were used for the studies of the structure of chlorobenzylidine and for the identification of two forms of chlorobenzylidine.</p><p><b>RESULTS</b>Chlorobenzylidine and its diastereoisomer have been studied in this article. They can be distinguished by their different melting points. Two crystal forms of chlorobenzylidine (form A and form B) have also been detected and studied. Form A was studied by single-crystal X-ray diffraction, it crystallized in the triclinic system, space group P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry, FTIR, thermal analysis and powder X-ray diffraction were used for identification of the two forms.</p><p><b>CONCLUSION</b>The studies of structure and crystal forms of chlorobenzylidine are very useful for the clinical research and the selection of recrystallization process.</p>

Studies on the chemical constituents of Cirsium japonicum DC / 药学学报

<p><b>AIM</b>In order to look for new bioactive compounds, investigation on the chemical constituents, especially on the typical polyacetylenes from the rhizomes of Cirsium japonicum DC. was carried out.</p><p><b>METHODS</b>Chromatographic techniques including silica column chromatography and preparative silica thin-layer chromatography were used to separate and purify the constituents. Their structures were elucidated by physicochemical properties and spectral analyses including UV, IR, 1HNMR, 13CNMR, HMQC, HMBC and HREIMS.</p><p><b>RESULTS</b>Twelve compounds were isolated from the rhizomes of Cirsium japonicum DC., and their structures were identified as cis-8, 9-epoxy-heptadeca-1-ene-11, 13-diyne-10-ol (1), ciryneol A (2), 8,9,10-triacetoxyheptadeca-1-ene-11,13-diyne (3), ciryneone F (4), cireneol G (5), ciryneol H (6), ciryneol C (7), p-coumaric acid (8), syringin (9), linarin (10), beta-sitosterol (11) and daucosterol (12).</p><p><b>CONCLUSION</b>Compounds 4, 5 and 6 are new compounds, compound 3 is a new natural product and compound 8 was isolated from this plant for the first time.</p>

Synthesis and anti-inflammatory analgesic activities of phenylfuroxan-coupled diclofenac / 药学学报

<p><b>AIM</b>To search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.</p><p><b>METHODS</b>Coupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.</p><p><b>RESULTS</b>Fifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.</p><p><b>CONCLUSION</b>Compound II2 is worthy to be intensively studied.</p>