ABSTRACT
Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF-β1/Smad signaling pathway.
ABSTRACT
5R-5-hydroxytriptolide (LLDT-8) is a new drug candidate which is in clinical trial treating rheumatoid arthritis. Polymorph screening of the compound was carried out in this study. Polymorph of LLDT-8 was prepared by evaporative crystallization and antisolvent crystallization methods and was characterized by powder X-ray diffraction (p-XRD), infrared spectrometry (IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). It was found that p-XRD patterns, DSC curves, TG curves and IR spectra of the LLDT-8 samples prepared by the above recrystallization methods were all consistent. The 20 of main peaks in the p-XRD patterns appeared at 7.58 degrees, 8.14 degrees, 8.66 degrees, 15.46 degrees, 16.46 degrees, 29.54 degrees, 31.16 degrees and 38.26 degrees, while the infrared absorption peaks appeared at 3 471.3, 2 962.2, 2 887.0, 1 762.6, 1 677.8, 1 432.9, 1 365.4, 1 247.7, 1 080.0, 1 031.7 and 877.5 cm(-1). LLDT-8 was decomposed at 271.2 degrees C based on the determination from DSC and TG. It was showed in single crystal X-ray diffraction study that LLDT-8 crystal was monoclinic with the space group being P2 (1). The cell parameters were found to be: a = 11.460 1 (11), b = 6.320 5 (6), c = 13.028 1 (12), alpha = 90.00, beta = 115.557 (2) and gamma = 90.00. The crystal was a hydrogen-bonded dimmer. The slurry experiments, which were further conducted in solvents with different polarities, confirmed the stability of solid state of LLDT-8 based on the p-XRD determination. The polymorph of LLDT-8 made assurance of its efficacy consistence during its clinical trials.