A sulfated polyphenols-rich extract from Sabal yapa exhibits antitumor activities in Ehrlich ascites carcinoma.

Cancer is the second leading cause of mortality accounting for one in every six deaths globally. Plant secondary metabolites, among them polyphenols, represent an effective and much safer alternative approach to the currently available medications. In this work, utilizing LC-MS/MS, we characterized the constituents of S. yapa leaves extract and evaluated its antioxidant and anticancer properties. In total, 34 secondary metabolites, mainly flavonoids (Tricin, luteolin, and apigenin and their glucosides as well as sulfated derivatives) were identified. The extract manifested substantial antioxidant activity in DPPH assay, and high total phenolic content determined by Folin Ciocalteu method. The extract was safe up to 4800 mg/kg b.wt. when administered orally in mice and neither affected the hematological parameters nor the liver enzyme levels at the studied dose (LD50, 480 mg, kg b.wt.). In the treated animals, the extract surpassed the reference drug (5-flouro uracil) and significantly reduced the tumor volume and weight by 71.50 and 85.46%, respectively, increased the median survival time to 53.2 days and the lifespan by 116%. The extract improved all the hematological parameters, where it increased the hemoglobin (Hb) concentration, red blood cell (RBC) count, packed cell volume (PVC) and platelets by 58.21, 8.98, 9.89 and 120%, respectively, compared to the untreated EAC bearing animals. Additionally, the extract significantly declined the elevated levels of ALT and AST enzymes by 29.18% and 59.88%, respectively. In molecular docking, the annotated flavonoids displayed appreciable binding affinities to the active sites of VEGFR1 and VEGFR2. In conclusion, Saba yapa is a promising plant that can be introduced to further advanced clinical studies for the development of novel anticancer drugs with lower side effects.

Epigallocatechin gallate-capped gold nanoparticles enhanced the tumor suppressors let-7a and miR-34a in hepatocellular carcinoma cells.

Epigallocatechin gallate (EGCG), major constituent of green tea, possesses antioxidant, antiviral, and anticancer activities. Gold nanoparticles (AuNPs) play an important role in drug delivery due to their stability, ease of surface functionalization, and unique optical properties. This study aimed to investigate the influence of EGCG-capped AuNPs on tumor suppressor miRNAs (miR-34a and let-7a) and their targeted cell death mediators in HepG2 cells, compared with celastrol. EGCG-AuNPs were prepared and characterized. antioxidant activity was estimated by DPPH scavenging assay; cytotoxicity was assessed by MTT assay; let-7a and miR-34a expression was analyzed by qPCR; and miRNAs targets (c-Myc and caspase-3) were assessed by ELISA and immunocytofluorescence, respectively. The average size of EGCG-AuNPs was 35 nm, with a λmax of ~535 nm. EGCG-AuNPs exerted cytotoxicity on HepG2 cells stronger than that of EGCG alone. EGCG-AuNPs and EGCG presented half-maximal radical scavenging concentrations (SC50) of 539 µg/ml and 45 µg/ml, respectively. The expression levels of let-7a and miR-34a were significantly elevated in HepG2 cells after EGCG-AuNP treatment for 72 h. c-Myc protein expression was reduced, whereas caspase-3 expression was increased following treatment with EGCG-AuNPs. In conclusion, Au-NPs are effective carrier for EGCG, and EGCG-AuNPs are promising anti-cancer agent.

Anticancer Effect of Amygdalin (Vitamin B-17) on Hepatocellular Carcinoma Cell Line (HepG2) in the Presence and Absence of Zinc.

BACKGROUND: Amygdalin (Vitamin B-17) is a naturally occurring vitamin found in the seeds of the fruits of Prunus Rosacea family including apricot, bitter almond, cherry, and peach. OBJECTIVE: The purpose of this study was to examine the effect of amygdalin with and without zinc on hepatocellular carcinoma (HepG2) cell line. METHODS: MTT assay was used to evaluate the cytotoxicity of amygdalin without zinc, amygdalin + 20µmol zinc, and amygdalin + 800µmol zinc on HepG2 cell lines. The cell cycle distribution assay was determined by flow cytometry. Apoptosis was confirmed by Annexin V-FITC/PI staining assay. Moreover, the pathway of apoptosis was determined by the percentage of change in the mean levels of P53, Bcl2, Bax, cytochrome c, and caspase-3. RESULTS: Amygdalin without zinc showed strong anti-HepG2 activity. Furthermore, HepG2 cell lines treatment with amygdalin + 20µmol zinc and amygdalin + 800µmol zinc showed a highly significant apoptotic effect than the effect of amygdalin without zinc. Amygdalin treatment induced cell cycle arrest at G2/M and increased the levels of P53, Bax, cytochrome c, and caspase-3 significantly, while it decreased the level of anti-apoptotic Bcl2. CONCLUSION: Amygdalin is a natural anti-cancer agent, which can be used for the treatment of hepatocellular carcinoma. It promotes apoptosis via the intrinsic cell death pathway (the mitochondria-initiated pathway) and cell cycle arrest at G/M. The potency of amygdalin in HepG2 treatment increased significantly by the addition of zinc.

Chemical composition and protective role of Pulicaria undulata (L.) C.A. Mey. subsp. undulata against gastric ulcer induced by ethanol in rats.

Pulicaria undulata subsp. undulata (Family; Asteraceae) is a medicinal plant used to treat inflammation. The objective of this study is to explore the protective effect of the ethanol extract of P. undulata subsp. undulata aerial parts against ethanol induced gastric ulcer in rats. The chemical composition of plant extract, the unsaponifiable matter and the fatty acid methyl esters were analyzed. The biological evaluation was carried out through measuring ulcer indices, oxidative stress markers, certain marker enzymes, inflammatory index and the histopathological assessment of the stomach in rats. The total unsaponifiable matter (94.29%) and the fatty acid methyl ester (82.96%) content were identified. Gastric ulcer recorded significant increase in gastric volume and lesion counts (p < 0.0001). Drastic changes in all biochemical parameters under investigation were observed. Protection with plant extract reversed the action of ethanol by variable degrees of improvement in comparison with the reference drug. The presence of carbohydrates and proteins that acted as a mucilage lining the stomach inner wall give its protective action. In conclusion, P. undulata subsp. undulata succeeded to have anti-ulcerative protective effect. The measured biomarkers served as a good mirror to predict gastric ulcer and the presence of carbohydrates, protein and fibers present in the plant extract acted as a mucilage lining the inner intestinal wall and protect against ethanol induced gastric ulcer. Future study will be carried out to identify the biologically active compounds responsible for plant protection against the gastric ulcer.

Pulicaria crispa mitigates gastric ulcer induced by ethanol in rats: role of treatment and auto healing.

Context: Stomach ulcers are the common gastrointestinal disorders worldwide. Objective: This study aimed to investigate the therapeutic impact of Pulicaria crispa aerial parts ethanol extract against gastric ulcer in rats. Materials and methods: Ulcer was induced by one oral dose of ethanol (0.5 ml/100g body weight) on 24 hours empty stomach, then the plant extract (500 mg/kg b.wt.) was orally administered daily for one week. Ranitidine (100 mg/kg b.wt.); as a reference drug was evaluated. Stomach acidity and volume, as well as lesion counts were measured. Levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were estimated. Assay of different marker enzymes; succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP) and 5'-nucleotidase (5'NT) were determined. Interlukin-10 (IL-10), intracellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-α) were also determined. Stomach histopathological assessment was detected. Results: Gastric ulcer showed drastic changes in oxidative stress, cell organelles and inflammatory markers. These biomarkers served as good tools to identify the presence of gastric ulcer. Treatment with P. crispa recorded amelioration in most parameters exceeding the auto healing effect. Conclusion: Healing potency of P. crispa is possibly related to its content of glycosides, coumarins, flavonoids, tannins, sterols and triterpenes.

Effects of N-glycan processing inhibitors on signaling events and induction of apoptosis in galectin-1-stimulated Jurkat T lymphocytes.

To elucidate the role of N-linked glycans in triggering T-cell functions, the effects of the N-glycan processing inhibitors 1-deoxymannojirimycin (1-DMM) and swainsonine (SW) were investigated on signaling events and induction of apoptosis in galectin-1 (gal-1)-stimulated Jurkat T lymphocytes. The treatment of Jurkat E6.1 cells with 1-DMM and SW strongly reduced the cell binding of gal-1-biotin, conjugate binding to cell lysate glycoproteins, and to cluster of differentiation (CD) 3 immunoprecipitates on blots as well as the binding of CD2 and CD3 to immobilized gal-1. The mannosidase inhibitors efficiently decreased gal-1-induced calcium mobilization. Both phases originated from a transient Ca(2+) release of internal stores, and the sustained influx across the plasma membrane was found to be involved. Both inhibitors suppressed in transiently transfected Jurkat T lymphocytes the gal-1-induced expression of the luciferase (luc) reporter gene constructs pNFAT-TA-Luc and pAP1(phorbol-12-myristate-13-acetate [PMA])-TA-Luc. The data provide evidence that gal-1 triggers through binding to N-linked glycans a Ca(2+)-sensitive apoptotic pathway.