Liver fibrosis results from the hepatic accumulation of the extracellular matrix accompanied by a failure of the mechanisms responsible for matrix dissolution. Pathogenesis of liver fibrosis is associated with many proteins from different cell types. In the present study, in silico molecular docking analysis revealed that curcumin may inhibit the fibrosis-mediating proteins PDGF, PDGFRB, TIMP-1, and TLR-9 by direct binding. Nano-formulation can overcome curcumin problems, increasing the efficacy of curcumin as a drug by maximizing its solubility and bioavailability, enhancing its membrane permeability, and improving its pharmacokinetics, pharmacodynamics and biodistribution. Therefore, green silver nanoparticles (AgNPs) were synthesized in the presence of sunlight by means of the metabolite of Streptomyces malachiticus, and coated with curcumin-chitosan mixture to serve as a drug delivery tool for curcumin to target CCl4-induced liver fibrosis mouse model. Fibrosis induction significantly increased hepatic gene expression of COL1A1, α-SMA, PDGFRB, and TIMP1, elevated hepatic enzymes, increased histopathological findings, and increased collagen deposition as determined by Mason’s trichrome staining. Treatment with naked AgNPs tended to increase these inflammatory effects, while their coating with chitosan, similar to treatment with curcumin only, did not prevent the fibrogenic effect of CCl4. The induction of liver fibrosis was reversed by concurrent treatment with curcumin/chitosan-coated AgNPs. In this nano form, curcumin was found to be efficient as anti-liver fibrosis drug, maintaining the hepatic architecture and function during fibrosis development. This efficacy can be attributed to its inhibitory role through a direct binding to fibrosis-mediating proteins such as PDGFRB, TIMP-1, TLR-9 and TGF-β.

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Background: Methotrexate (MTX) is an anticancer drug that induces testicular abnormalities but, thyme is antioxidant compound, which scavenges oxidative damage. Objective: this study aimed to investigate the protective role of thyme leave extract on the histological and immunohistochemical testicular changes induced by MTX. Material and Methods: forty adult male rats were used and categorized into 4 equal groups (10 rats/each); Group I: control rats group without treatment. Group ΙΙ: control rats administrated thyme only for a month, Group ΙΙΙ: rats injected (i.p) with MTX for four weeks, Group ΙV: rats injected with MTX and administrated thyme extract. Results: the control rat testes stained with H&E showed normal histological structure of testes; rats administrated thyme demonstrated normal structure similar to the normal control. Rats injected with MTX showed damaged testicular tissue but, rats co-treated with MTX and thyme demonstrated improvement in the testicular structure. The caspase-3 immunostain was expressed in the control and the thyme group as weak reaction in the spermatogonic cells. However, MTX group showed dense reaction for caspase-3 and group of MTX and thyme detected obviously reduction of caspase -3. Normal intense immunoreactive of PCNA was realized in the control and thyme groups. But, MTX group showed an obvious decrement of immunoreactivity and MTX and thyme group expressed more reduction in the immunoreactivity. Conclusion: thyme extract had the ability to ameliorate the abnormalities occurred in the testes of rats after MTX treatment.

In this study, we evaluated the inflammatory responses induced by aluminum silicate (AS) cytotoxicity in rat lungs. The prophylactic effect of propolis extract was evaluated in 60 adult male albino rats. The rats were divided into six groups: (1) a normal, healthy control group; (2) a normal group fed with 200 mL of propolis extract/Kg; (3) a low-dose positive control group injected with 5 mg/kg of AS; (4) a treated group given propolis and a low dose of AS; (5) a high-dose positive control group injected with 20 mg/kg of AS; and (6) a treated group given propolis with a high-dose of AS. At the end of the two-month experiment, the rats’ lungs were removed. For each pair of lungs, one portion was subjected to biochemical analysis and the other underwent hematoxylin and eosin (H&E) staining in order to study its histology. The rats that received AS doses displayed significant disorders in their antioxidant contents as well as in their enzymatic activities and their histopathological structures revealed severe damage to their lung tissues. Upon the rats being treated with propolis, the enzymatic and antioxidant contents improved and partial improvements in the lung structures appeared, including minimized congestion, a reduced hemorrhage of blood vessels and preserved bronchioles, alveolar ducts, and alveoli. The prophylactic effectiveness of propolis extract on the cytotoxicity of AS, owing to the antioxidant properties of propolis, were studied.

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