ABSTRACT
OBJECTIVE@#Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses.@*METHODS@#THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration (CC) and 50% effective concentration (EC). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2 (COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation.@*RESULTS@#The CC and EC of C. carbonica were found to be 43.26 and 11.99 µg/mL, respectively. The cell survival assay showed a 1.192-fold (P = 0.0129), 1.443-fold (P = 0.0009) and 1.605-fold (P = 0.0004) increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds (P = 0.0001), 2.181 folds (P = 0.0001) and 2.071 folds (P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNF-α levels by 1.395 folds (P = 0.0013), 1.541 folds (P = 0.0005) and 1.550 folds (P = 0.0005) at 24, 48 and 72 h, respectively. In addition, a 1.193-fold reduction (P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.@*CONCLUSION@#C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-α level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.
ABSTRACT
OBJECTIVE@#Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses.@*METHODS@#THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration (CC) and 50% effective concentration (EC). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2 (COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation.@*RESULTS@#The CC and EC of C. carbonica were found to be 43.26 and 11.99 µg/mL, respectively. The cell survival assay showed a 1.192-fold (P = 0.0129), 1.443-fold (P = 0.0009) and 1.605-fold (P = 0.0004) increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds (P = 0.0001), 2.181 folds (P = 0.0001) and 2.071 folds (P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNF-α levels by 1.395 folds (P = 0.0013), 1.541 folds (P = 0.0005) and 1.550 folds (P = 0.0005) at 24, 48 and 72 h, respectively. In addition, a 1.193-fold reduction (P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.@*CONCLUSION@#C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-α level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.
ABSTRACT
BACKGROUND: Oxidative stress is a major mediator in the pathophysiology of several kidney diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of reactive oxygen species (ROS) in the stationary state (oxidative stress). Therefore, interventions favoring the scavenging and/or depuration of ROS should attenuate or prevent the oxidative stress, thereby safeguarding the kidneys against damage. In this sense, this study attempts to evaluate the extent of oxidative stress in experimental urolithiasis by measuring some parameters of oxidant stress and antioxidant defenses in rat kidneys, before and after Berberis vulgaris homeopathic preparation supplementation, and to assess the role, if any, of homeopathic treatment in mitigating free radical toxicity in kidney stone disease. METHODS: Rat model of urolithiasis was established by administering 0.75% ethylene glycol (EG) in drinking water, and the effects of a homeopathic preparation of B. vulgaris root bark (HPBV) on the renal antioxidative defense system as well as on potent markers of free radical activities were investigated. RESULTS: HPBV brought about an augmentation in the activities of enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase and improved the nonenzymatic antioxidants, e.g., tocopherol, ascorbic acid, and glutathione. HPBV ameliorated the malondialdehyde and protein carbonyl levels and restored renal thiols almost completely. CONCLUSION: Thus, it is shown that HPBV acts as a renoprotective remedy in alleviating the renal calculi-associated oxidative damage by upregulating the antioxidant status.
