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Ziziphus spina-christi leaf extract ameliorates schistosomiasis liver granuloma, fibrosis, and oxidative stress through downregulation of fibrinogenic signaling in mice.

ABSTRACT: Schistosomiasis is a widespread parasitic infection that affects humans, as well as wild and domestic animals. It ranks second after malaria, with a significant health and socio-economic impact in the developing countries. The objective of this study was to assess the anti-schistosomal impact of Ziziphus spina-christi leaf extract (ZLE) on Schistosoma mansoni-induced liver fibrosis in CD-1 Swiss male albino mice. S. mansoni infection was achieved by dipping of mouse tails in schistosomal cercariae. ZLE treatment was initiated at 46 days post-infection by administering a dose of the extract on a daily basis for 10 consecutive days. S. mansoni infection resulted in liver granuloma and fibrosis, with a drastic elevation in liver function factors, nitric oxide, and lipid peroxidation, which were associated with a reduction in glutathione content and substantial inhibition of antioxidant enzyme activities compared to those of the control. Induction of hepatic granuloma, oxidative stress, and fibrosis in the liver was controlled by ZLE administration, which also produced inhibition of matrix metalloproteinase-9, alpha-smooth muscle actin, transforming growth factor-β, and tissue inhibitors of metalloproteinases expressions. In addition, the S. mansoni-infected group exhibited an increase in Bax and caspase-3 levels and a decrease in Bcl-2 level. However, treatment with ZLE mainly mitigated apoptosis in the liver. Thus, the findings of this study revealed that Ziziphus spina-christi had anti-apoptotic, anti-fibrotic, antioxidant, and protective effects on S. mansoni-induced liver wounds. The benefits of Ziziphus spina-christi extract on S. mansoni were partly partially mediated by enhancing anti-fibrinogenic and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways.

SUBMITTER: Almeer RS

PROVIDER: S-EPMC6166951 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The objective of the study was to assess the effect of diets supplemented with Ziziphus spina-christi leaf on digestive fermentation, antioxidant status, and haemato-biochemical indices of growing rabbits. Ziziphus leaves (ZLs) of Ziziphus spina-christi were collected from Sidr trees scattered throughout the city of Medina, Saudi Arabia. Three formulated diets containing 0, 10, and 20?g Ziziphus spina-christi/Kg diet as supplementation were offered ad libitum. The organic matter content of ZL was higher. Chemical compositions were comparable in all of the contents of the tested diet. Quantities of gas released from the control diet were higher, and then the gases released decreased significantly (P < 0.05) with the addition of ZL. The values of NH3-N were taken as the same trend. The addition of a high level of ZL to rabbit diets led to a decrease (P < 0.05) in the total count of bacteria as well as the number of E. coli and Clostridium spp. However, the number of Enterococcus bacteria was not affected by supplementation. Haemoglobin parameters of the control group and groups 2 and 3 were compared: white blood cell count and red blood cell count. These observations of total protein and albumin within the range of reference values were reported in healthy rabbits, while glucose significantly decreased with the addition of ZL and AST in the blood increased significantly. The values of TP, albumin, and ALT measurements showed no significant differences among groups fed on test diets. Significant differnces in serum immunoglobulins were observed between the groups, while the high levels of ZL supplement led to a significant (P < 0.05) increase in the serum IgA, IgG, and IgM levels. Antioxidants expressed as T-AOC, GSH-Px, T-SOD, and CAT in the blood of animals fed on diets containing high levels of ZL were significantly higher. Higher serum T-AOC, T-SOD, and CAT activities were observed in rabbits supplemented with a high level of ZL compared with the control group (P < 0.05). The supplementation of ZL tended to increase serum GSH-Px activity. The addition of ZL to rabbit diets led to an increase in dry matter intake. On the other hand, there was no significant change in the apparent digestion coefficient of DM, OM, CP, and fat. Conclusion. Dried ZL supplementation up to 20?g/Kg diet might improve the bacterial community, antioxidants, biochemical parameters and blood constituents of rabbits, and digestibility.

Project description:In this research, a simple, green approach was employed to synthesize silver nanoparticles with the aid of Ziziphus spina-christi (L.) methanol root extract, which can act as a reducing, capping agent to treat obesity and inflammation. Globally, Ziziphus spina-christi (Jujube) root is used in traditional therapy as a lipolysis promoter. GC-MS results confirmed the availability of kaempferol (flavonol), cannabinol and indole-3-carboxylic acid in Ziziphus spina-christi root methanol extract (ZSE). ZSE silver nanoparticles (ZS-Ag-NPs) were synthesized and their effect on mitochondrial fatty acid oxidation capacity and adipokine levels in maturing adipocytes were analyzed. Maturing adipocytes treated with 0.4 µg/dL of ZSE and ZS-Ag-NPs significantly reduced the lipid content in adipocytes by 64% and 82%, respectively. In addition, lipolysis-related genes such as LPL (1.9 fold), HSL (2.3 fold), PGC-1α (3 fold), UCP-1 (4.1 fold), PRDM16 (2 fold) and PPARα (2.7 fold) increased significantly in ZS-Ag-NPs treated maturing adipocytes. The ZS-Ag-NPs treatment significantly decreased insulin resistance and metabolic inflammation-related LTB4-R, TNF-α, IL-4 and STAT-6 mRNA levels. Mitochondrial thermogenesis stimulating capacity of ZS-Ag-NPs was further confirmed by the significantly enhanced CREB-1 and AMPK protein levels in adipocytes. Furthermore, ZS-Ag-NPs treated adipokines (condition media, CM) were treated with human umbilical vein endothelial cells (HUVECs) to determine cytotoxicity and pro-inflammatory stimulus capacity. We found that ZS-Ag-NPs treated adipocyte CM effectively increased mRNA expression levels of the vascular endothelial cell growth factor (VEGF), and down-regulated oxidative stress (LPO, eNOS, and HO) and vascular cell inflammation (ICAM, VCAM, TNF-α, IL-1β, and NF-κB). In conclusion, ZS-Ag-NPs displayed an action at the molecular level in mitochondrial fatty acid oxidation, decreased adipokine secretion in adipocytes, and enhanced vascular endothelial cell growth. This molecular mechanical action of ZS-Ag-NPs reduced effectively obesity progressions and metabolic inflammatory pathogenesis associated with aging.

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Ziziphus spina-christi leaf extract ameliorates schistosomiasis liver granuloma, fibrosis, and oxidative stress through downregulation of fibrinogenic signaling in mice.

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