Catecholic Isoquinolines from Portulaca oleracea and Their Anti-inflammatory and ß2-Adrenergic Receptor Agonist Activity.

Isoquinoline alkaloids possess a wide range of structural features and pharmaceutical activities and are promising drug candidates. Ten water-soluble catecholic isoquinolines were isolated from the medicinal plant Portulaca oleracea, including three new (1-3) and seven known compounds (4-10), along with the known catecholamines 11 and 12 and four other known compounds (13-16). A method of polyamide column chromatography using EtOAc-MeOH as the mobile phase was developed for the isolation of catecholic isoquinolines. Alkaloids 1-12 exhibited anti-inflammatory activities (EC50 = 18.0-497.7 µM) through inhibition of NO production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among these compounds, 11, 2, 5, 4, and 8 were more potent than was the positive control, 3,4-dihydroxybenzohydroxamic acid (EC50 = 82.4 µM), with EC50 values of 18.0, 18.1, 35.4, 36.3, and 58.7 µM, respectively. Additionally, at 100 µM, compounds 1-12 showed different degrees of ß2-adrenergic receptor (ß2-AR) agonist activity in the CHO-K1/GA15 cell line which stably expressed ß2-AR as detected by a calcium assay. The EC50 values of 2 and 10 were 5.1 µM and 87.9 nM, respectively.

11C-CHO PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas.

OBJECTIVE: We explored the clinical values of (11)C-choline ((11)C-CHO) PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas. METHODS: Sixteen patients with the pathological confirmation of the diagnosis of gliomas prior to receiving radiotherapy (postoperative) were included, and on whom both MRI and CHO PET scans were performed at the same position for comparison of residual tumors with the two techniques. (11)C-CHO was used as the tracer in the PET scan. A plain T1-weighted, T2-weighted and contrast-enhanced T1-weighted imaging scans were performed in the MRI scan sequence. The gliomas' residual tumor volume was defined as the area with CHO-PET high-affinity uptake and metabolism (V(CHO)) and one with MRI T1-weighted imaging high signal intensity (V(Gd)), and was determined by a group of experienced professionals and clinicians. RESULTS: (1) In CHO-PET images, the tumor target volume, i.e., the highly metabolic area with a high concentration of isotopes (SUV 1.016-4.21) and the corresponding contralateral normal brain tissues (SUV0.1-0.62), was well contrasted, and the boundary between lesions and surrounding normal brain tissues was better defined compared with MRI and (18)F-FDG PET images. (2) For patients with brain gliomas of WHO Grade II, the SUV was 1.016-2.5; for those with WHO Grades III and IV, SUVs were >26-4.2. (3) Both CHO PET and MRI were positive for 10 patients and negative for 2 patients. The residual tumor consistency between these two studies was 75%. Four of the 10 CHO-PET-positive patients were negative on MRI scans. The maximum distance between V(Gd) and V(CHO) margins was 1.8 cm. (4) The gross tumor volumes (GTVs) and the ensuing treatment regimens were changed for 31.3% (5/16) of patients based on the CHO-PET high-affinity uptake and metabolism, in which the change rate was 80% (4/5), 14.3 % (1/7) and 0% (0/4) for patients with WHO Grade II III, and IV gliomas, respectively. CONCLUSION: Our data demonstrate that difference exists between CHO PET and MRI by which to judge and identify residual tumor for patients with brain gliomas. CHO PET is considered to be a supplementary diagnostic approach for MRI. Biological tumor target volume (BTV) displayed in the CHO PET images is useful in determining or delineating the radiotherapy target volume and making decisions in selecting treatment regimens. Tumor target volume may be defined more accurately and rationally when the CHO PET is combined with MRI.