Phenolic glycosides and indole alkaloids isolated from the roots and rhizomes of Clematis chinensis and their anti-inflammatory activity.

Six undescribed compounds, including three phenolic glycosides (1-3) and three indole alkaloids (4-6), together with ten known alkaloids (7-16) and three known phenolic glycosides (17-19), were isolated from 70% EtOH aqueous extracts of the roots and rhizomes of Clematis chinensis Osbeck. The structures were elucidated by NMR, HRESIMS and X-ray diffraction spectroscopies. The anti-inflammatory activity of these compounds was evaluated, and twelve compounds showed significant inhibitory activity against TNF-α with an inhibition ratio from 47.87% to 94.70% at a dose of 10 µM. Compound 7 exhibited significant inhibitory activity against TNF-α and IL-6 with IC50 values of 3.99 µM and 2.24 µM, respectively. Compound 8 displayed potent anti-inflammatory activity against mouse ear edema induced by croton oil. A mechanistic study suggested that compounds 7 and 8 decreased the activation of the NF-κB signaling pathway to reduce the secretion of inflammatory factors in LPS-induced RAW 264.7 cells.

New indole alkaloids from the seeds of Datura metel L.

Four new indole alkaloids, daturametelindoles A-D (1-4) were isolated from the EtOAc soluble partition of the ethanol extract of the Datura metel seeds. The structures of the new compounds were determined based on spectroscopic evidence, including their 1D- and 2D-NMR spectra and mass spectrometry. In particular, compounds 1-4 were all racemes, confirmed by the optical rotations and CD spectra. Unfortunately, the chiral monomers were not obtained due to the amount, but the developments of their chiral separation and chiral resolution were completed. All isolated compounds were evaluated for cytotoxic effects against human gastric adenocarcinoma cells (SGC-7901), human hepatoma (Hepg2), and human breast cancer (MCF-7).

Steroids from the seeds of Datura metel.

Two new steroids meteloside F (1) and meteloside G (2), together with six known ones (3-8), were isolated and identified from the seeds of Datura metel L. The chemical constituents were isolated by silica gel, ODS chromatogram columns. and preparative HPLC. The structures of these compounds were established by one- and two-dimensional NMR spectra and HR-ESI-MS. The compounds exhibited inhibition on the nitric oxide release of lipopolysaccharide-induced RAW 264.7 cells with IC50 values from 30.2 to 44.8 µM. [Formula: see text].

New Glycosides from the Fruits of Nicandra physaloides.

Three new glycosides (1-3) and 15 known ones (4-18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4-18) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values from 26.9 to 47.5 µM.

Phenylpropanoids from the fruits of Nicandra physaloides and their anti-inflammatory activities.

Twenty-one phenylpropanoids, including 1 new (1) and 20 known phenylpropanoids (2-21), were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra referring to the literatures, together with mass spectrometry. It was found that the isolated compounds, except for 7, 18 and 19, showed the different levels of inhibitions on NO production by LPS-induced RAW 264.7 cells at IC50 values from 27.0 to 97.3 µM.

Development and preclinical evaluation of a biodegradable ventricular septal defect occluder.

OBJECTIVES: This study evaluated the feasibility, effectiveness, and safety of a biodegradable (BD) occluder for closure of ventricular septal defect (VSD) in an acute canine model. BACKGROUND: All current available VSD occluders are permanent implants which consist of a metal framework and synthetic fabrics. However, the septal occluder in vivo plays the role of a temporary bridge that facilitates the ingrowth of fibrous connective tissue and endothelialization. The ideal occluder may be a temporary scaffold which can be gradually absorbed in vivo and replaced by "native" tissue. METHODS: The BD VSD occluder consists of a polydioxanone (PDO) framework and two pieces of poly-L-lactic acid (PLLA) fabrics. Percutaneous transcatheter closure of interventionally created VSDs was performed in 16 dogs using the BD occluders. Follow-up consisted of electrocardiography, transthoracic echocardiography, and fluoroscopy from 1 week to 24 weeks post-implantation. Gross pathology and histopathology were obtained at 6, 12, and 24 weeks follow-up. RESULTS: Implantation of the BD occluders was successful in 15 animals. The devices became well integrated into the ventricular septum with complete endothelialization at 12 weeks after implantation. After 24 weeks in vivo, the PDO framework of devices was largely absorbed and replaced by the ingrowth of collagenous fibers, and the PLLA fabric within disks was partly degraded. Neither occluder dislocation nor VSD recanalization occurred during follow-up. CONCLUSIONS: The BD occluder proved safe and effective for VSD closure. This device is characterized by compatible mechanical properties, a fully BD property, and a good match between the degradation of occluder and the healing response of organism.

Animal experimental study of the fully biodegradable atrial septal defect (ASD) occluder.

This study was conducted to evaluate the feasibility, safety, biocompatibility, and degradation features of a fully biodegradable occluder for closure of atrial septal defect (ASD) in an acute canine model. The ASD was created in 20 healthy mongrel dogs by the brockenbrough needle, and the fully biodegradable occluders were implanted by self-made delivery system. The success rate and complications were observed. Acute ASD models were successfully created in 18 dogs, and 16 occluders were successfully implanted in the ASD models. Animals were sacrificed at different times after procedure. The cardiac gross anatomy showed that all occluders were stable in the interatrial septum, no vegetation or thrombus formation was observed on the surface of all occluders. They were embedded into endogenous host tissue gradually at 12-week follow-up. Different periods of pathological observations suggested that the occluders degraded gradually over about 24 weeks and essentially became an integral part of the septum. Transcatheter closure of ASD in acute canine model using the fully biodegradable ASD occluder has the potential of a high successful rate of technique, excellent biocompatibility, and fewer complications with adequate, immediate, and short-term results.

Percutaneous valved stent implantation above the coronary ostia.

BACKGROUND: In recent years, some experimental and clinical studies on transcatheter aortic valve implantation (TAVI) have been conducted. TAVI is indicated in patients with calcified pure or predominant aortic stenosis. The risk of this technique is still high. Aortic valved stent implantation above the coronary ostia might avoid blocking the coronary ostia. METHODS AND RESULTS: Twenty healthy dogs were selected to establish a canine model of acute aortic valve rupture. The dogs were randomly divided into 2 groups: the rupture model group without any treatment and the valved stent group with percutaneous valved stent implantation above the coronary ostia. The 2 groups of animals were followed up for 3 months. Echocardiography and other tests were performed to assess aortic regurgitation and ventricular function. Acute aortic valve rupture models were successfully established in 16 of 20 dogs. In the rupture model group, the mean aortic regurgitation was 6.8 ± 1.9 ml/s; only 3 of 8 animals survived for 3 months. In the valved stent group, the mean aortic regurgitation was 7.0 ± 2.1 ml/s; valved stents were successfully implanted in 8 animals. Instant post-implantation anatomy showed that the stents were located appropriately. Seven dogs survived for 3 months. CONCLUSIONS: Percutaneous valved stent implantation above the coronary ostia is feasible and effective as a transitional treatment for acute aortic valve rupture.

Percutaneous valve stent insertion to correct the pulmonary regurgitation: an animal feasibility study.

BACKGROUND: Pulmonary regurgitation leads to progressive right ventricular dysfunction, susceptibility to arrhythmias, and sudden cardiac death. Percutaneous valve replacement has been developed in recent years, providing patients with an alternative option. Percutaneous pulmonary valve replacement has been recently introduced into clinical practice. The goal of this study was to evaluate the feasibility of percutaneous valve stent insertion to correct the pulmonary regurgitation in sheep using a cup-shaped valve stent. METHODS: Pulmonary regurgitation was created by percutaneous cylindrical stent insertion in native pulmonary annulus of 8 sheep. One month after the initial procedure, the sheep with previous cylindrical stent implanted underwent the same implantation procedure of pulmonary valve stent. The valve stent consisted of a cup-shaped stent and pericardial valves. Hemodynamic assessments of the bioprosthetic pulmonary valve were obtained by echocardiography at immediately post-implant and at 2 months follow up. RESULTS: Successful transcatheter cylindrical stent insertion was performed in 7 sheep but failed in 1 sheep because the cylindrical stent was released to right ventricle outflow tract. After one month the 7 sheep with pulmonary regurgitation underwent valve stent implantation successfully. Echocardiography confirmed the stents were in desired position during the follow-up. No evidence of pulmonary valve insufficiency occurred in any animals. Echocardiography showed all heart function markers were normal. CONCLUSIONS: Percutaneous cylindrical stent insertion to induce significant pulmonary regurgitation in sheep was feasible, simple and reproducible. Percutaneous pulmonary valve stent implantation can reduce pulmonary regurgitation in a sheep model. Further development of animal model and clinical trials are warranted.

Percutaneous establishment of tricuspid regurgitation: an experimental model for transcatheter tricuspid valve replacement.

BACKGROUND: Valve replacement or repair is recommended in patients with tricuspid regurgitation when deterioration of their clinical status occurs as a consequence of right ventricular dysfunction. Percutaneous valve replacement was developed in recent years. To investigate the feasibility, effectiveness and long-term results of percutaneous tricuspid valve replacement, an experimental model with tricuspid regurgitation is needed. We developed a simple and reproducible percutaneous approach for the creation of tricuspid regurgitation in sheep. METHODS: A specially designed grasping forceps were used to grasp chordae tendineae or the tricuspid valve leaflets through a catheter. Transcatheter creation of tricuspid regurgitation was performed on 7 healthy sheep. These sheep were followed up shortly after the procedure and at 6th month post-procedure with echocardiography. Additionally, all the sheep were sacrificed for anatomic evaluation at 6th month after the procedure. RESULTS: Creation of tricuspid regurgitation was successfully accomplished in all sheep. Necropsy confirmed that damage was done to the tricuspid valve apparatus in all animals (tearing of the anterior leaflet of the tricuspid valve in five animals and posterior leaflet of the tricuspid valve in two animals). At the six-month follow-up, there was no significant increase in the right ventricle dimension and ejection fraction measured by echocardiography. Autopsy examinations demonstrated the tearing of tricuspid valve leaflets. CONCLUSIONS: The creation of an animal model of tricuspid regurgitation via a percutaneous approach using forceps to sever one or more tricuspid leaflets is feasible and will allow investigation of devices designed replace the tricuspid valve via a percutaneous approach. Despite significant tricuspid regurgitation, the hemodynamics did not change during the follow-up period in this model.

An integrated pericardial valved stent special for percutaneous tricuspid implantation: an animal feasibility study.

BACKGROUND: Various percutaneous valve replacement approaches have been reported in animals to replace the aortic and pulmonary valve. To broaden the indications of percutaneous approach to atrioventricular valves replacement, we developed a novel valved stent and evaluated the feasibility and safety of percutaneous implantation of the device in the tricuspid position. MATERIALS AND METHODS: A unidirectional semilunar valve of porcine pericardium was sutured to a valvular ring. Then the ring with pericardial valve was mounted on a double-edge nitinol stent to construct the tricuspid valved stent. Transcatheter tricuspid valved stent implantation was performed on 10 healthy sheep. These sheep were followed up shortly after procedure with echocardiography evaluation and 64-slice CT imaging examination during the periodical follow-up at 1 mo and at 6 mo post-implantation. Additionally, two sheep were sacrificed after the procedure for anatomic and histological evaluation one at 1 h and the other at 1 mo, respectively. RESULTS: Percutaneous valve implantation was successful in eight of 10 sheep. Two sheep died during the procedure due to migration of stent and fatal arrhythmia. The pressure of right heart did not significantly change after the procedure. Further echocardiography and imaging confirmed the stents were in desired position during the follow-up. The remaining six sheep with normal valvular and cardiac functionality survived for 6 mo after implantation. CONCLUSIONS: The tricuspid stent with a valvular ring and pericardial valve can be implanted in tricuspid annulus percutaneous. The double-edge stent could substitute the native tricuspid valve chronically.

Percutaneous reimplantation of a pulmonary valved stent in sheep: a potential treatment for bioprosthetic valve degeneration.

OBJECTIVE: Percutaneous pulmonary valve replacement has been recently introduced into clinical practice. Patients with transcatheter pulmonary valve replacement will definitely face the problems of valve degeneration. In addition to surgical re-replacement of the degenerated bioprosthetic valves, we studied the replacement of degenerated bioprosthetic valves with transcatheter reimplantation of stent-mounted pulmonary valves. METHODS: Percutaneous pulmonary valve replacement was first performed in 6 sheep used a homemade valved stent. Two months after the initial procedure, the 6 sheep previously implanted with a valved stent underwent the same implantation procedure of a pulmonary valved stent. Hemodynamic assessment of the bioprosthetic pulmonary valve was obtained by echocardiography immediately post-implant and at 2 months follow-up. RESULTS: All 6 sheep had successful transcatheter stent-mounted pulmonary valve replacement in the first experiment. After 2 months, reimplantation was successful in 5 sheep but failed in 1 sheep because the first valved stent was pushed to the bifurcation of the pulmonary artery by the delivery sheath. Echocardiography confirmed the stents were in the desired position during the follow-up. The remaining 5 sheep with normal valvular and cardiac functionality survived for 3 months after implantation. CONCLUSION: Transcatheter stent-mounted bioprosthetic pulmonary valve reimplantation is feasible in an animal model and more convenient than open chest reimplantation.