Introduction Owing to their great quantity of hydrolyzable anthocyanins and tannins, the peel and seeds of pomegranate are edible and possess potent anti-oxidant and anti-inflammatory characteristics. This work aims to trace the pomegranate seed and peel ethanolic extracts’ anticancer activity against liver cancer cell line, namely HepG2 and related histopathological, immunohistochemical, genetic and oxidative stress profile. Methods In vitro study for both seed and peel extract showed the prevalence of phenols, polyphenols and acids, those have anti-proliferative potential against liver cancer cell line (HepG2) with 50% inhibitory concentration (IC50) of seed significantly reduced that of peel. Toxicity of test extracts was concentration dependent and accompanied with cell cycle arrest and cell death at theG0/G1 and S phases but not at the G2/M phase. Cell arrest was supplemented with raised ROS, MDA and decreased SOD, GSH and Catalase. Results and discussion Apoptosis-related genes showed significant up-expression of pro-apoptotic gene ( P53 ), Cy-C , Bax , and casp-3 and down expression of anti-apoptotic gene ( Bcl-2 ). Also, Casp-3 and P53 proteins were substantially expressed under the effect of test extracts. Histopathological study demonstrated that the untreated cells (control group) were regular cells with nuclear pleomorphism and hyperchromatic nuclei, while seed and peel extracts-treated cells showed necrosis, mixed euchromatin and heterochromatin, intra-nuclear eosinophilic structures, burst cell membranes, and the shrunken apoptotic cells with nuclear membranes and irregular cells. Finally, PCNA gene detected by immunohistochemistry was down regulated significantly under the effect of seed extract treatment than in case of cell medication with peel extract.

Gentamicin is considered one of the most typical causes of testicular damage. Oxidative stress is a significant contributor to testicular tissue damage. Zamzam water (alkaline in nature) has an antioxidant effect. The purpose of this study was to assess the potential palliative effect of Zamzam water against gentamicin-induced testicular damage. Thirty Rats were separated into three groups, each with ten rats, as follows: The Control received only normal saline. The gentamicin group received 100 mg/kg/day of gentamicin intraperitoneally for six days from day 15 to the end of the experiment. The gentamicin +Zamzam Water group received a dose of gentamicin 100 mg/kg/day intraperitoneally with Zamzam water as their sole source of drinking from day one to day 21. Hormonal assay in serum, histological, immunohistochemical, and ultrastructural examination of testicular tissue with a molecular study were obtained. Pretreatment with Zamzam water significantly p < 0.001 increased serum levels of testosterone, FSH, and LH, as well as the percentage of sperm motility and progressive motility. It also upregulated SOD, CAT, GPx enzymatic activity, gene expression of Nrf2/HO-1, and immunoexpression of PCNA. While the percentage of dead sperm and abnormal sperm, immunoexpression of NFκB, Caspase 3, inflammatory cytokines TNFα, IL-1β, IL-6, and MDA levels significantly( p < 0.001) declined with histological improvement. It was concluded that Zamzam water as alkaline water possesses antioxidant, anti-inflammatory, and antiapoptotic effects against gentamicin-induced testicular toxicity in vivo.

Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway.

Our research work examined the potential protection of Stevia rebaudiana extract against monosodium urate crystals (MSU)-induced acute gouty arthritis in a rat model and its possible underlying mechanism. Forty rats were allocated into four groups (n = 10); a control group; an MSU group, whose rats received 0.1 of MSU single intra-articular injection in the ankle joint on the fifth day of the experiment; an MSU + Stevia group, which received 250 mg/kg/day of Stevia extract orally for seven days and MSU crystals on the fifth day; and an MSU + colchicine group, which was administered colchicine at 0.28 mg/kg daily for seven days and MSU crystals on the fifth day. Pretreatment with Stevia extract mitigated MSU-induced inflammation as evidenced by a decrease of the ankle edema and inflammatory cell infiltration and a significant downregulation of the protein level of NFκB, TNFα, IL-1β, IL6, and IL18 as well as NLRP3 gene expression. Additionally, there was a markedly increased PPARγ gene expression (p < 0.001) compared with the MSU group (p < 0.001) and alleviated oxidative stress via significant upregulating of Nrf2/HO-1. Moreover, the pretreatment attenuated apoptosis by significantly decreasing cytochrome c, Bax, Caspase-3, and by increasing Bcl-2 protein. In conclusion, Stevia extract exhibited strong anti-inflammatory, antioxidant, and antiapoptotic effects against MSU-induced gouty arthritis similar to the standard anti-inflammatory colchicine drugs.