Mesalazine, an osteopontin inhibitor: The potential prophylactic and remedial roles in induced liver fibrosis in rats.

Liver fibrosis is a major health issue leading to high morbidity and mortality. The potential anti-fibrotic activity and the effect of mesalazine on osteopontin (OPN), an extra cellular matrix (ECM) component were evaluated in TAA-induced liver fibrosis in rats. For this purpose, forty-two adult male Wistar rats were divided into six groups. All animals, except the normal control, were intraperitoneally injected with TAA (200 mg/kg) twice per week for 6 weeks. In the hepato-protective study, animals were administered mesalazine (50 and 100 mg/kg, orally) for 4 weeks before induction of liver fibrosis then concomitantly with TAA injection. In the hepato-therapeutic study, animals were administered mesalazine for 6 weeks after TAA discontinuation with the same doses. In both studies, mesalazine administration improved liver biomarkers through decreasing serum levels of AST, ALT and total bilirubin when compared to fibrotic group with significant increase in total protein and albumin levels. Mesalazine significantly decreased hepatic MDA level and counteracted the depletion of hepatic GSH content and SOD activity. Additionally, it limits the elevation of OPN and TGF-ß1 concentrations and suppressed TNF-α as well as α-SMA levels in hepatic tissue homogenate. Histopathologically, mesalazine as a treatment showed a good restoration of the hepatic parenchymal cells with an obvious decreased intensity and retraction of fibrous proliferation, while as a prophylaxis it didn't achieve enough protection against the harmful effect of TAA, although it decreased the intensity of portal to portal fibrosis and pseudolobulation. Furthermore, mesalazine could suppress the expression of both α-SMA and caspase-3 in immunohistochemical sections. In conclusion, mesalazine could have a potential new indication as anti-fibrotic agent through limiting the oxidative damage and altering TNF-ɑ pathway as an anti-inflammatory drug with down-regulating TGF-ß1, OPN, α-SMA and caspase-3 signaling pathways.

Effect of a topical copper indomethacin gel on inflammatory parameters in a rat model of osteoarthritis.

OBJECTIVE: We aimed to investigate the effect of topical application of a Copper indomethacin (Cu-Indo) gel preparation on monosodium iodoacetate (MIA) induced arthritis of the knee joint of rats and to test our hypothesis that copper complex of indomethacin could be a more potent anti-inflammatory agent than its parent compound. METHODS: After induction of osteoarthritis by the intracapsular injection of 50 µL with 40 mg/mL MIA, we compared the anti-inflammatory efficacy and safety of a topical application of 1% indomethacin gel in a dose of 1 g/kg of the gel (equivalent to 10 mg/kg of the active substance) daily for 3 weeks versus three decremental dose levels of Cu-Indo gel: an equivalent dose, half the dose, and 25% of the dose of indomethacin. Anti-inflammatory efficacy was assessed in all treated groups by measurement of serum inflammatory cytokines: interleukin 6, interleukin 8, and tumor necrosis factor alpha; and by the weekly assessment of knee joint swelling. Joint mobility and motor coordination were also assessed once weekly by the accelerating rotarod apparatus; histopathological examination of affected joints was also performed. Safety of topical application of Cu-Indo (0.25, 0.5, and 1 g/kg) for up to 3 months to rats' skin was determined by the estimation of a complete blood count, liver and kidney functions, and histopathologic examination for target tissues. RESULTS: Cu-Indo gel at lower doses was superior to or at least as effective as its parent substance, indomethacin, in most of the studied parameters of inflammation. The lowest tested dose of Cu-Indo, corresponding to 25% of the parent substance indomethacin, exhibited the highest efficacy in reducing the elevated serum-tested interleukins and in increasing the time of duration on the rotarod test, whereas its effect on reduction of edema and tumor necrosis factor alpha was comparable to that of the others. After 3 months of daily application, there were no notable changes in studied safety parameters with the lowest Cu-Indo dose, but the group treated with the higher dose showed a small but statistically significant increase in serum-unconjugated bilirubin and a slight decrease in hemoglobin levels, red blood cells, and platelet count, with normal indices denoting a slight hemolytic effect at the highest dose. CONCLUSION: Cu-Indo gel has potent anti-inflammatory activity against joint inflammation in the MIA-treated rat model of osteoarthritis at doses of 0.25, 0.5, and 1 g/kg. The lowest studied dose was better on both safety and efficacy parameters.

Comparative DNA profiling, phytochemical investigation, and biological evaluation of two Ficus species growing in Egypt.

AIM AND BACKGROUND: A comparison between two Ficus species, cultivated in Egypt, was carried out in this study. Their DNA analysis revealed that they are not closely related. MATERIALS AND METHODS: The pharmacopoeial constants of the leaves showed higher total ash and acid insoluble ash in F. lyrata than in F. platypoda. The other parameters were close in both species. Preliminary phytochemical screening revealed the presence of carbohydrate and/or glycosides, tannins, flavonoids, sterols, and triterpenes in their leaves and was detected in traces in their stems. RESULTS: Saponification of n-hexane extract of the leaves yielded 46% and 74.8% for the unsaponifiable matters and 20% and 15% for the fatty acids for F. platypoda and F. lyrata, respectively. n-Docosane (21.69%) and n-heptacosane (33.77%) were the major hydrocarbons in F. platypoda and F. lyrata, respectively. b-Sitosterol was the main sterol, palmitic (22.07%) and carboceric (35.72%) acids were the major identified saturated fatty acids in both species, while linoleic acid was the main unsaturated fatty acid (18.66% and 16.7%) in both species, respectively. The acute toxicity study revealed that the two species were safe up to 2 g/kg. The antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and pyrogallol as the standard was more significant for F. platypoda (232.6 µg/ml) than for F. lyrata, (790.9 µg/ml). The oral antihyperglycemic activity in diabetic rats using alloxan revealed that the 80% ethanolic extract of the leaves of F. platypoda was more active than that of the leaves of F. lyrata in decreasing the blood glucose level at 200 mg/kg/day (107.9 ± 5.817, 127.2 ± 4.359) and 400 mg/kg/day (64.11 ± 4.358, 127.7 ± 6.889), respectively, when compared with the diabetic control gliclazide (172.3 ± 2.089). CONCLUSION: The results of this study provide evidence that the two Ficus species have antioxidant and antihyperglycemic activity, in the order F. platypoda and then F. lyrata.