The present study is designed to investigate the role of certain natural cranberry and rosemary extracts to improve the histological changes in the cardiac muscle toxicity of adult male albino rats weighing 110±5g (aged 3-4 weeks) induced by doxorubicin (DOX). To assessment of cardiotoxicity, the cardiac enzyme creatine kinase (CK-MB) and troponin I protein were measured. The animals were divided into 7 equal groups (10 rats /each); Gp. I: normal control rats group injected with saline solution 0.9 % intraperitoneally (i.p.) for three times per a week for three weeks, Gp. II: cranberry rats group administrated orally with 150 mg/kg/bw for three times per a week for three weeks, Gp III rosemary rats group administrated orally with 2g/kg/bw for three times per a week for three weeks, Gp IV: DOX rats group injected i.p. with 2.5mg/kg three times / week for two weeks, Gps: V, VI & VII: DOX rat groups administrated orally with cranberry or rosemary or both together in the same previous doses and duration. In the present research, the measurement of CK - MB enzyme and troponin I protein are recorded high values in the blood sera in DOX -rats group (Gp IV) in comparison with other control groups (Gps. I, II& III) and treated groups (Gps; V, VI & VII) in which the levels of CK-MP and troponin I are recorded approximately normal values as in control group (Gp. I). Histological study of the cardiac muscle of normal control rats group (Gp.I) revealed normal branched cardiomyocytes with normal striations and normal oval centrally located nuclei. Similar observations are seen in the cranberry and rosemary rat groups (Gps. II& III). In DOX rats group (Gp IV), the histological observations of the cardiac muscle demonstrated many alternations such as disarrangement, degeneration and vacuolation of the cardiomyocytes. The appearance of infiltration of inflammatory cells and necrotic areas in most cardiomyocytes as well as dilation and congestion of blood vessels in the dilated endomysia were also observed. The administration of either cranberry alone or cranberry with rosemary together to DOX rats group revealed an obvious improvement and harmony restoration of the histological structure with normal appearance of the cardiomyocytes with normal oval nuclei, and complete disappearance of dilated and congested blood vessels, more than those given rosemary only. In brief, DOX rats group given either cranberry alone or cranberry with rosemary together recorded marked recovery of the normal values of CK-MB and troponin I as well as the restoration of the architecture of the cardiac muscle to approximately normal form than those given rosemary only.

Increased consumption of fruits may decrease the risk of chronic inflammatory diseases including inflammatory bowel disease (IBD). Gut microbiota dysbiosis plays an important etiological role in IBD. However, the mechanisms of action underlying the anti-inflammatory effects of dietary cranberry (Vaccinium macrocarpon) in the colon and its role on gut microbiota were unclear. In this study, we determined the anti-inflammatory efficacy of whole cranberry in a mouse model of dextran sodium sulfate (DSS)-induced colitis, as well as its effects on the structure of gut microbiota. The results showed that dietary cranberry significantly decreased the severity of colitis in DSS-treated mice, evidenced by increased colon length, and decreased disease activity and histologic score of colitis in DSS-treated mice compared to the positive control group (p<0.05). Moreover, the colonic levels of pro-inflammatory cytokine (IL-1 beta , IL-6 and TNF- alpha ) were significantly reduced by cranberry supplementation (p<0.05). Analysis of the relative abundance of fecal microbiota in phylum and genus levels revealed that DSS treatment significantly altered the microbial structure of fecal microbiota in mice. alpha diversity was significantly decreased in the DSS group, compared to the healthy control group. But, cranberry treatment significantly improved DSS-induced decline in alpha -diversity. Moreover, cranberry treatment partially reversed the change of gut microbiota in colitic mice by increasing the abundance of potential beneficial bacteria, for example, Lactobacillus and Bifidobacterium, and decreasing the abundance of potential harmful bacteria, such as Sutterella and Bilophila. Overall, our results for the first time demonstrated that modification of gut microbiota by dietary whole cranberry might contribute to its inhibitory effects against the development of colitis in DSS-treated mice.

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

Anthocyanins and the broader class of polyphenols are strong antioxidants in vitro. Polyphenols are one of the major antioxidants in plant foods, and the beverages derived from them. There is extensive evidence in the literature that polyphenols are beneficial to health. In order to be bioactive in vivo, they need to be bioavailable and be transported from the circulation to target organs. To date, there have been few studies testing the extent to which polyphenols and especially anthocyanins affect the antioxidant capacity of animal organs. In our first pilot study, we investigated how three pure polyphenols (the flavonoids quercetin, catechin and hesperetin) given to rats by intraperitoneal injection (49 to 63 mg/kg) affected their organ antioxidant capacity. This was followed by a subsequent study that injected one ml of 100% cranberry juice (high in anthocyanins) to hamsters. Antioxidant capacity of animal organs was determined by using the ferric reducing antioxidant power (FRAP) colorimetric assay on methanolic extracts of select rat organs (i.e., liver, kidney, heart, prostate and brain) and in the hamster organs (i.e., liver, kidney, heart, bladder and brain). Overall the results showed that antioxidant capacity was significantly increased (p<0.05) in experimental vs. control organs. Analysis of organs by high performance liquid chromatography (HPLC) from both animal studies provided evidence of polyphenol metabolites in the organ extracts. Taken together, this study provides data that the administration of anthocyanins and other polyphenols cause an increase in organ antioxidant capacity in two animal models. This result supports the growing evidence for the hypothesis that dietary polyphenols reduce the risk and extent of various chronic disease at the disease site.