Background and aim: Resveratrol shows remarkable anti-inflammatory activities in experimental models. This study aims to evaluate the effect of resveratrol, as an adjuvant with meloxicam (Mlx), on the pain and functional activity during a 90-day period and monitor the adverse effects on kidney and liver functions, lipid profile, and hematological markers. Patients and methods: This study was a double-blind, placebo-controlled, randomized multi-center study that involved 110 patients with knee osteoarthritis (OA) and was performed at Sulaimani City, Iraq, from December 2016 to September 2017. To assess the effects of Mlx with or without resveratrol, pain severity and functional disability were evaluated at baseline and after 90 days using the Western Ontario and McMaster Universities Osteoarthritis Index. Fasting blood was collected to evaluate the lipid profile markers, hematological picture, and liver and kidney functions, in addition to vitamin D level. Results: Resveratrol significantly improves pain, functions, and associated symptoms compared with placebo. The clinical and biochemical markers indicated that 500 mg/day of resveratrol, as an adjuvant with Mlx, is safe and well tolerated by the knee OA patients. Conclusion: Resveratrol, as an “add-on” medication with Mlx, was superior in terms of safety and efficacy to Mlx alone for the treatment of pain and improvement of physical function in patients with knee OA.

Background: Current therapies for polycystic ovary syndrome (PCOS) are accompanied by unwanted effects. Silibinin; a flavonolignan has pleiotropic activities and favorable safety profile. Purpose: To investigate the efficacy of silibinin on estrous cyclicity, inflammation, oxidative stress and ovarian morphology in letrozole-induced PCOS in rats. Methods: Forty-eight female Wistar albino rats were divided into 2 sets. Rats of the first set (n = 12), assigned as a negative control (NC) received only the vehicle, rats of the second set (n = 36), assigned as PCOS rats, were given letrozole 1mg/Kg orally for 21 days. On day 21, six rats from the first set and six rats from the second set were euthanized for confirmation of PCOS-induction. The remaining animals from the first set assigned as group 1, those in the second set (n = 30) were equally divided into 5 groups and treated daily for 19 days as follows: group 2 (positive control) received only the vehicle, group 3 treated with metformin 300mg/Kg orally, groups 4 and 5 treated respectively with 100 and 200 mg/Kg silibinin intraperitoneally (IP), and group 6 treated with a combination of metformin 300mg/Kg orally and silibinin 100mg/Kg IP. On day 40, blood samples were examined for luteinizing hormone (LH), testosterone (TS) and estradiol (EST) levels, the anti-inflammatory and antioxidant parameters, ovarian and uterine morphology. Results: Silibinin alone or in combination with metformin was found to be effective in restoring the regularity of estrous cycle by ameliorating the abnormal alterations of LH, TS, EST, tumor necrosis factor (TNF)-α, and oxidative status and by resuming the appearance of corpora lutea and decreasing or even total absence of cystic follicles in the ovaries. Conclusion: Silibinin was effective in restoring estrous regularities and alleviating hormonal and histomorphological abnormalities of the ovarian and uterine tissues, this could be due to its anti-androgenic, anti-inflammatory and antioxidant properties.

Clinical investigation, with 110 eligible patients with OA assigned randomly to receive 15 mg a day meloxicam with either resveratrol 500 mg a day or placebo for 90 days. The standard tools for assessment of pain severity and physical functions were utilized. The tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in the blood were evaluated. Spearman's correlation coefficient test was used to determine the significance of correlations. RESULTS: The regression analysis to determine the correlation between reductions of the inflammatory biomarkers with the amelioration of the clinical scores showed a nonsignificant weak correlation between these variables. Total clinical scores of each assessment tool that was used “Knee Injury and OA Outcome Score (KOOS) and WOMAC” displayed a weak and nonsignificant correlation with TNF-α, IL-1β blood level. The Spearman's correlation shows a relatively nonsignificant association between IL-6 levels and KOOS, WOMAC, and Visual Analog Scale scores after incorporating resveratrol as an adjuvant with meloxicam for 90 days. CONCLUSION: A weak and nonsignificant correlation between serum biomarkers and the clinical outcomes has been suggested in patients with painful knee OA treated with meloxicam and resveratrol....

Treatment of knee osteoarthritis (OA) remains a challenging concern. Preclinical studies provided accumulating evidence on resveratrol efficacy in ameliorating degenerative articular damage. The present study was conducted to evaluate the effects of resveratrol as monotherapy on the serum level of type II collagen (Coll 2‐1) and aggrecan in patients with knee osteoarthritis. The study was an open‐labeled noncontrolled clinical trial. Resveratrol 500 mg/day in a single oral dose was given to the patients with knee osteoarthritis for 90 days. The serum levels of Coll‐2‐1, aggrecan, and biomarkers of inflammation were measured pre‐ and posttreatment. Hematological profiles and both hepatic and renal function markers were investigated at the baseline and at the end of the treatment for evaluating the tolerability and safety of resveratrol. Visual Analog Scale (VAS) for pain and Knee injury and Osteoarthritis Outcome Score (KOOS) for disease activity were clinically assessed monthly. Administration of 500 mg resveratrol for three months led to a nonsignificant decrease in the serum level of Coll 2‐1 while a significant increase in aggrecan serum level. Resveratrol significantly improves pain score measured by VAS and KOOS after 30 days. Improvements in patients’ activity and functional status were also evident at day 30 and kept on for three months which was reflected by KOOS subscale scores and with a significant improvement in all KOOS areas. In conclusion, oral administration of resveratrol as a monotherapy provides a remarkable improvement in the clinical status of the patients but has no significant effect on serum levels of Coll 2‐1.

Objective: The study aimed to investigate whether zofenopril (ZOF), thymoquinone (TQ), or their co-administration effectively ameliorates urotoxicity and nephrotoxicity following cyclophosphamide (CPH) treatment. Methods: A total of 48 Wister Albino female rats were divided into six groups each of eight rats; negative control (NC), positive control (PC), mesna (MS), ZOF, TQ, and ZOF+TQ groups. Normal saline, mesna, ZOF-15mg/kg, TQ-80mg/kg, and their combination were given orally for 19 days to the groups NC, MS, ZOF, TQ, and ZOF+TQ respectively. On the 17^th day, a single dose of CPH 200 mg/kg was given intraperitoneally for all the groups except the NC group. Urine was collected over 24 hours before animal scarification for urinalysis. After scarification, blood, and kidney tissue were obtained for assessment of conventional kidney function parameters, novel kidney injury biomarkers, pro-inflammatory cytokines, oxidative status, complete blood count (CBC), and histopathological examination. Results: CPH disturbed the urinary excretion of urea, creatinine, and protein, and significantly elevated novel biomarkers for kidney injury including cystatin-C (Cys-C) (p=0.019) and markedly kidney injury molecule-1 (KIM-1) (p=0.27), the semiquantitative measurement of hematuria revealed significant elevation of hematuria score (p=0.0002), urine pus and protein (p=0.0005). Additionally, CBC-derived inflammatory biomarkers including neutrophil-lymphocyte ratio (NLR) (p=0.001), neutrophil-monocyte ratio (NMR) (p=0.0004), pro-inflammatory cytokine interleukin (IL)-6 (p=0.016) and tumor necrosis factor (TNF)-α (p<=0.007), total antioxidant capacity (TAC) (p< 0.0001) were significantly increased. Evidence of obvious histopathological structural alteration was noticed in kidney tissue and bladder urothelium in CPH-treated animals. ZOF, TQ, and their co-treatment significantly prevented these deleterious effects associated with CPH treatment. Conclusion: This study demonstrated that ZOF and TQ provided uroprotective and nephroprotective effects against CPH-induced nephrotoxicity by reducing kidney injury biomarkers, and CBC-derived inflammatory markers, restoring antioxidant capacity, and improving histopathological outcomes. The suggested mechanism involves the anti-inflammatory and antioxidant activity of TQ and the sulfhydryl-angiotensin converting enzyme inhibitor ZOF.

Free radical formation in heme proteins is recognized as a factor in mediating the toxicity of many drugs. Xenobiotics and drug therapy-related toxicity, due to oxidative modification of hemoglobin (Hb), has been attributed in part to the uncontrolled oxidative reactions. A variety of antioxidant strategies to ameliorate potential oxidative damage in vivo have been suggested. The present study was designed to evaluate the dose-response relationship of the free radical scavenging properties of silibinin dihemisuccinate (SDH) in nitrite-induced Hb oxidation in vitro and in vivo. Different concentrations of SDH were added, before and after different intervals of inducing Hb oxidation in erythrocytes lysate, and formation of methemoglobin (MetHb) was monitored spectrophotometrically; the same approach was utilized to evaluate the effect of the same doses of SDH on the integrity of erythrocytes after induction of hemolysis. Moreover, the most effective dose of SDH was administered in rats before challenge with toxic dose of sodium nitrite, and MetHb formation was monitored as mentioned before. The results showed that in both in vitro and in vivo models, SDH successfully attenuates Hb oxidation after challenge with sodium nitrite; this protective effect was not related to the stage of the catalytic stage of Hb oxidation, though the effect was more prominent when the compound was administered before nitrite. In conclusion, SDH can effectively, in concentration-dependent pattern, attenuate sodium nitrite-induced Hb oxidation and maintain integrity of red blood cells both in vitro and in vivo.