Melognine, a novel monoterpenoid indole alkaloid from Melodinus fusiformis that induce apoptosis in BT549 cells.

A novel monoterpenoid indole alkaloid, melognine (1) possessing an unprecedented skeleton with a 6/6/5/5/6/6 hexatomic rearranged ring system was isolated from the stems of Melodinus fusiformis. The structure with absolute configuration of 1 was established by extensive spectroscopic analyses and quantum ECD calculations. Melognine showed significant cytotoxicity on human breast cancer BT549 cells with an IC50 value of 1.49 µM by MTT assay. Further mechanism of action study indicated that melognine demonstrated the ability to induce apoptosis by activation of caspase-3 and p53, and downregulation of Bcl-2 in BT549 cells.

Preparative Separation of Monoterpenoid Indole Alkaloid Epimers from Ervatamia yunnanensis Tsiang by pH-Zone-Refining Counter-Current Chromatography Combined with Preparative High-Performance Liquid Chromatography.

An effective method was developed for the preparative separation and purification of monoterpenoid indole alkaloid epimers from Ervatamia yunnanensis Tsiang using a combination of pH-zone-refining counter-current chromatography and preparative high-performance liquid chromatography. With this method, two pairs of MIA epimers including ervatamine (72 mg, 1), 20-epi-ervatamine (27 mg, 4), dregamine (95 mg, 2), tabernaemontanine (129 mg, 3), along with two MIAs, apparicine (112 mg, 5) and isovoacangine (15 mg, 6), were successfully purified from 2.1 g crude extract of E. yunnanensis, each with a purity of over 95% as determined by HPLC. The structures of the MIAs were identified by ESI-MS, 1D, and 2D NMR.

A novel monoterpenoid indole alkaloid with anticancer activity from Melodinus khasianus.

A novel monoterpenoid indole alkaloid with unprecedented 6/5/6/4/6 fused rings, khasuanine A (1), was isolated from the roots of Melodinus khasianus. The structure was determined by extensive analysis of its HR-MS, 1D-, and 2D-NMR spectra. Khasuanine A markedly inhibited the proliferation of PC3 cell with IC50 value of 0.45µM. Further study showed that khasuanine A was able to induce the apoptosis of PC3 cells by activation of caspase 3 and p53, and by inhibition of Bcl-2.

Preparation and antitumor activity of a tamibarotene-furoxan derivative.

Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.

[Effects of Radix Ginseng and Radix Ophiopogonis extract (SMF) on protein S-nitrosylation in ischemic myocardial tissue].

OBJECTIVE: To observe the effect of Radix Ginseng and Radix Ophiopogonis extract (SMF) on protein S-nitrosylation in rats myocardial with ischemia/reperfusion injury (MI/RI). METHOD: Myocardial ischemia/reperfusion in rats were produced by occlusion of the left anterior descending coronary artery. To study the cardioprotective effects of SMF on the acute MI/RI rats, the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), and nitric oxide (NO) were determined. The change of the expression of endothelial nitric oxide synthase (eNOS) was detected by Western blot. The content of related S-nitrosylation proteins in myocardial tissue was measured by Biotin-Switch method. RESULT: SMF significantly decreased the serum levels of CK and LDH as well as increased the serum levels of NO and the expression of eNOS in myocardial tissue. The contents of S-nitrosylation proteins were significantly increased from (4.42 +/- 0.60) micromol x g(-1) to (8.78 +/- 1.37) micromol x g(-1). The molecular weight of the majority S-nitrosylation proteins were in the range of 90 x 10(3)-117 x 10(3). CONCLUSION: Increased expression of eNOS and NO induced by SMF may activate S-nitrosylation of many proteins in rat hearts. The change of the activities or functions of those proteins by S-nitrosylation may be an important mechanism for myocardial protective effects of SMF.

[The association between gingival cervicular fluid Interleukin-6 level, serum estradiol status and periodontitis in Uyghur postmenopausal women].

PURPOSE: The purpose of this investigation was to analyze by cross-sectional design the association between GCF IL-6 level, serum E2 level and common clinical measurements of periodontitis in Uyghur postmenopausal women. METHODS: 79 subjects within 5 years after menopause were enrolled in the study. 30 GCF samples were harvested from healthy sites, 49 GCF samples from chronic periodontitis sites. Clinical measurements of each tooth were recorded after obtaining GCF samples. GCF IL-6 and serum E2 levels were measured by radioimmunoassay (RIA). RESULTS: The mean concentration of GCF IL-6 from healthy sites was (1088.10+/-102.33)pg/ml.The mean concentration of IL-6 from chronic periodontitis sites was significantly higher than that of healthy sites (P<0.005). Positive correlation was found between GCF IL-6 level and clinical measurements (GI, PPD and CAL) (r=0.564, P<0.005; r=0.335, P<0.05; r=0.324, P<0.05). Clinical measurements and GCF IL-6 levels of chronic periodontitis subjects were not different between E2-deficient and E2-sufficient subjects. CONCLUSIONS: These findings suggest that there is lower IL-6 level in GCF from healthy sites; the increasing production of IL-6 may be associated with the initiation and progress of periodontitis. IL-6 may be a valuable indicator of the severity of periodontitis; E2 level is not associated with clinical measurements and GCF IL-6 level of chronic periodontitis of Uyghuy woman in early menopause.

[The association between interleukin-1 receptor antagonist genotype and chronic periodontitis of Uighur patients].

OBJECTIVE: To investigate interleukin-1 receptor antagonist (IL-1ra) genotype and its association with the susceptibility of chronic periodontitis in Uighur patients of Xinjiang. METHODS: Genomic DNA was obtained from buccal swabs of 41 subjects with severe chronic periodontitis (CP), 43 subjects with moderate CP, 49 subjects with mild CP and 92 ethnically matched healthy control individuals. Genotypes of IL-1RN intron 2 VNTR was analyzed by SSP-PCR method. Then compared the differences in distribution of each genotype. RESULTS: A significant over-representation of IL-1RN intron 2 VNTR allele 2 was found in severe chronic periodontitis group. CONCLUSION: IL-1RN intron 2 VNTR allele 2 may be a risk indicator for the susceptibility of severe chronic periodontitis in Uighur patients of Xinjiang.