ABSTRACT
Celastrus orbiculatus Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of C. orbiculatus extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds 1-17, including undescribed podocarpane-type trinorditerpenoid (3), were purified from C. orbiculatus and their chemical structure were determined by high-resolution electrospray ionization mass (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data. To investigate the anti-inflammatory activity of compounds 1-17, nitric oxide (NO) secretion was evaluated in LPS-treated murine macrophages, RAW264.7 cells. Among compounds 1-17, deoxynimbidiol (1) and new trinorditerpenoid (3) showed the most potent inhibitory effects (IC50: 4.9 and 12.6 µM, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor- (TNF-) α. Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) κB and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-κB (IκB), extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. Therefore, these results demonstrated that diterpenoids 1 and 3 obtained from C. orbiculatus may be considered a potential candidate for the treatment of inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Celastrus/chemistry , Diterpenes/pharmacology , Macrophage Activation/drug effects , Macrophages/drug effects , Phytochemicals/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cell Survival/drug effects , Cytokines/metabolism , Diterpenes/chemistry , Diterpenes/isolation & purification , Inflammation Mediators/metabolism , Lipopolysaccharides/immunology , Macrophage Activation/immunology , Macrophages/immunology , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Nitric Oxide/metabolism , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Extracts/chemistry , Plant Extracts/pharmacology , RAW 264.7 CellsABSTRACT
PURPOSE: Transcutaneous partial oxygen tension (TcpO2) is considered the gold standard for assessment of tissue oxygenation, which is an essential factor for wound healing. The purpose of this study was to evaluate the association between macrocirculation and TcpO2 in persons with diabetes mellitus. SUBJECTS AND SETTING: Ninety-eight patients with diabetic foot ulcers participated in the study (61 men and 37 women). The subjects had a mean age of 66.6 years (range, 30-83 years) and were treated at the Diabetic Wound Center of Korea University Guro Hospital, Seoul, Republic of Korea. METHODS: Macrocirculation was evaluated using 2 techniques: computed tomographic angiography and Doppler ultrasound. Macrocirculation scores were based on the patency of the two tibial arteries in 98 patients. Computed tomographic angiography and Doppler ultrasound scores (0-4 points) were given according to intraluminal filling defects and arterial pulse waveform of each vessel, respectively. Tissue oxygenation was measured by TcpO2. Macrocirculation scores were statistically analyzed as a function of the TcpO2. RESULTS: Statistical analysis revealed no significant linear trend between the macrocirculation status and TcpO2. Biavariate analysis using the Fisher exact test, Mantel-Haenszel tests, and McNemar-Bowker tests also found no significant relationship between macrocirculation and TcpO2. CONCLUSIONS: Computed tomographic angiography and Doppler ultrasound are not sufficiently reliable substitutes for TcpO2 measurements in regard to determining the optimal treatment for diabetic patients.
