Potent immunosuppressive and anti-inflammatory bisindole alkaloids from Melodinus fusiformis.

Phytochemical investigation of Melodinus fusiformis led to a new aspidosperma-aspidosperma bisindole alkaloid (BIA), bis-19ß-hydroxyvenalstonidine (1), together with three known BIAs (2-4). The structures were established by extensive analysis of their HRESIMS, NMR data, and comparing with the reported data. BIA 1 is an almost symmetrical structure, linked by C3-C14' bond, while BIAs 2-4 are reported for the first time from the plant. The cytotoxic, immunosuppressive and anti-inflammatory activities of BIAs 1-4 were evaluated in vitro. BIAs 1, 3 and 4 showed good toxicity against MOLT-4 cell lines with IC50 values in the range of 1.5-17.5 -M. BIA 2 exhibited the strongest inhibitory effect against MCF-7 cell lines with an IC50 value of 7.1 µM. BIA 1 significantly inhibited Con A-stimulated mice splenocytes proliferation equal to that of the positive control (DXM) in a concentration-dependent manner. BIAs 1 and 2 were able to decrease the NO production in LPS-induced RAW 264.7 cells at 30 µM concentration. BIA 2 showed similar inhibition of nitric oxide release, compared to that of DXM. Furthermore, BIA 2 remarkably inhibited the levels of IL-6 and TNF-α compared to the LPS induced group. Interestingly, BIA 2 displayed an inhibitory effect on TNF-α production similar to that of dexamethasone at a concentration of 20 µM.

Two new sesquiterpene aryl esters from Armillaria gallica 012m.

Two new sesquiterpene aryl esters, armimelleolides A and B (1 and 2), and four known ones, were isolated from the EtOAc extract of Armillaria gallica 012 m by column chromatography on silica gel, reversed-phase C18 silica gel and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods, including extensive 1 D NMR, 2 D NMR and MS. All these compounds showed potential antitumor activities against at least one of the human cancer cell lines (A549, HCT-116, M231 and W256), with IC50 ranging from 2.57 to 19.94 µM.

Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR.

Effects of spironolactone towards rabbit atrial remodeling with rapid pacing.

This study aimed to observe the effects of spironolactone towards the rabbit atrial remodeling with rapid atrial pacing (RAP). 30 rabbits were randomly divided into control group, RAP group and spironolactone group, with 10 rabbits in each group. RAP was performed at the speed of 800 beats/min for 8 h, atrial effective refractory period (AERP) was determined before and at the 1(st), 2(nd), 4(th), 6(th) and 8(th) of the pacing, the expressions of atrial muscular calcium channel α1C subunit and ß1 subunit mRNA were performed the RT-PCR detection, and ultrastructural changes of atrial myocytes were observed. AERP of RAP group shortened, with poor frequency adaptability; the expressions of calcium channel α1C subunit and ß1 subunit mRNA decreased 22% and 26%, respectively, when compared with the control group; ultrastructure of atrial myocytes changed significantly. AERP of spironotlactone group shortened less that RAP group, and the frequency adaptability was maintained, the decreased expressions of calcium channel α1C subunit and ß1 subunit mRNA significantly reduced. RAP could cause atrial remodeling, while spironolactone could inhibit RAP-induced atrial remodeling.

Clinical Evaluation of Coronary In-Stent Restenosis Using Dual-Source Computed Tomography.

OBJECTIVE: To explore the feasibility of dual-source computed tomography (DSCT) in the evaluation of coronary in-stent restenosis (ISR) by comparing the results of DSCT and selective coronary angiography (CAG). METHODS: In-stent restenosis examination results from DSCT were compared with those obtained using CAG. RESULTS: Among 173 stents studied, 156 yielded good quality images when evaluated with DSCT. CAG identified 38 ISR cases, while DSCT found 40. Among the 112 stents in the study with an inner diameter ≥3.0 mm, CAG identified 29 as having ISR, while DSCT reported the same finding in 30; among the 44 stents with inner diameter <3.0 mm, CAG identified ISR in 9, while DSCT found ISR in 10. CONCLUSIONS: Stent inner diameter is a key factor influencing the imaging of the stent lumen. DSCT demonstrated a higher negative predictive value in ISR assessment, suggesting that it could replace CAG for assessing the patency of stents with a larger inner diameter (≥3 mm).

Two new phenylpropanoids from Micromelum integerrimum.

AIM: To investigate the chemical and bioactive constituents from the stems and leaves of Micromelum integerrimum. METHOD: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20, and HPLC. Their structures were mainly elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. Their cytotoxicity and antimicrobial activities were tested by the SRB and turbidimetric methods, respectively. RESULTS: Two new phenylpropanoids and two known coumarins were obtained, and their structures were identified as microintegerrin A (1), microintegerrin B (2), scopoletin (3), and scopolin (4). All of the compounds were tested for their cytotoxicity against three cancer cell lines (HeLa, A549, and BGC-823) and for antimicrobial activity against the fungus Candida albicans and the bacterium Staphylococcus aureus. CONCLUSION: Two new phenylpropanoids 1 and 2 were isolated and identified from the stems and leaves of M. intgerrimum. None of the compounds showed cytotoxic or antimicrobial activity at the tested concentration of 20 µg·mL(-1).

Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 µM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 µM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 µM.

Astataricusones A-D and astataricusol A, five new anti-HBV shionane-type triterpenes from Aster tataricus L. f.

Five new shionane-type triterpenes, astataricusones A-D (compounds 1-4) and astataricusol A (5), together with one known shionane-type triterpene 6 were obtained from the roots and rhizomes of Aster tataricus L. f. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configurations of 1 and 4 was determined by single crystal X-ray diffraction and CD analysis. Compound 2 showed inhibitory activity on HBsAg secretion with an IC50 value of 23.5 µM, while 2 and 6 showed inhibitory activities on HBeAg secretion with IC50 values of 18.6 and 40.5 µM, and cytotoxicity on HepG 2.2.15 cells with CC50 values of 172.4 and 137.7 µM, respectively. Compounds 2 and 6 also exhibited inhibitory activities on HBV DNA replication with IC50 values of 2.7 and 30.7 µM, respectively.

[Effect of Fe-Mn-Si on the biomass structure of Eichhornia crassipes].

Eichhornia crassipes (water hyacinth) was cultivated under different iron (Fe), manganese (Mn) and silicon (Si) nutrient treatments for its biomass characteristics research which was determined by various items including nutrient element content (Fe, Mn and Si), adsorption sites and active function groups. The results show that Mn and Si can enhance acidic sites of the plant, in which Mn plays a great role, but Fe reduces the acidic sites. The sequence of acidic sites' amount among three parts of the plant is root > stem > leaf, in the treatment of Fe, Mn and their combination, and leaf > stem > root in Si treatment. The amount of alkaline sites is less than that of acidic sites, and the difference in their distributions among three parts of the plant is not great. Mn and Si treated Eichhornia crassipes stalks have more amorphous material, such as lignin, pectin and xylan (hemicellulose), which have more functional groups of -OH, -COOH and acidic sites.

[Effects of Salviae miltiorrhizae and Platycodon grandiflorum in Tianwang Buxin decoction for microcirculation of brain meninx vascullosa in rats].

OBJECTIVE: To investigat the effects of Salviae miltiorrhizae and Platycodon grandiflorum in Tianwang Buxin decoction for microcirculation of brain meninx vascullosa in rats. METHOD: The rats were equally and randomly divided into six groups. Control, Tianwang Buxin decoction, P. grandiflorum-absenced Tianwang Buxin decoction, Radix S. miltiorrhizae, Radix S. miltiorrhizae and P. grandiflorum, P. grandiflorum. The effect on brain meninx vascullosa in rats were observed through an inverted microscope, doppler perfusion imager and blood reheology measurement meter. RESULT: The effect of Tianwang Buxin decoction was best among the six groups in dilatation of the diameter of arterial and venule, and velocity of blood flow. The effect of Radix Salviae miltiorrhizae was postponed and decreased when P. grandflorum was removed of from this prescription. However, it was minimal advance of blood apparent-viscosity for Tianwang Buxin decoction. CONCLUSION: It is indeed that P. grandiflorum leads S. miltiorrhizae to main and collaterall channel, goes up like the boat and oar and aims to reinforce affection for the other drugs of Tianwang Buxin decoction to mprove the microcirculation of brain meninx vascullosa of rats.