Tropaeolum majus L. and low dose gamma radiation suppress liver carcinoma development via EGFR-HER2 signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers around the world and remain asymptomatic in early stage. An alcoholic extract prepared from leaves of Tropaeolum majus L. (Tropaeolaceae) was assessed for its potential activity against diethylnitrosamine-induced liver carcinoma in vivo. Oral administration of the extract significantly decreased the inflammatory marker translation NF-kB and supressed HCC progression in combination with 0.5 Gy gamma radiation via EGF-HER-2 pathway. Histopathological and immunohistopathological features also showed the recovery of a hepatic architecture. Immunohistochemical study showed the T. majus and LDR enhancement effect on proapoptotic markers (caspase-3 and Bax) and inhibition of anti-apoptotic factor (BCl2). HPLC-DAD-MSn analysis of the extract revealed the annotation of twelve compounds. T. majus could mediate a defensive influence against diethylnitrosamine-induced hepatocarcinogenesis and serve as a respectable option in amelioration of the hepatocellular carcinoma development in combination with low dose of gamma radiation.

Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines: Effects of O-Methylation on Taxifolin and Quercetin as Preliminary Natural Leads.

Six flavonoids present in Pulicaria jaubertii, i.e., 7,3'-di-O-methyltaxifolin (1), 3'-O-methyltaxifolin (2), 7-O-methyltaxifolin (3), taxifolin (4), 3-O-methylquercetin (5), and quercetin (6), were tested for their anticancer activities. The methylated flavonoids, compounds 1-3 and 5, were evaluated for their anticancer activities in comparison to the non-methylated parent flavonoids taxifolin (4) and quercetin (6). The structures of the known compounds were reconfirmed by spectral analyses using 1H and 13C NMR data comparisons and HRMS spectrometry. The anticancer activity of these compounds was evaluated in colon cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT antiproliferative assays. The caspase-3 and caspase-9 expressions and DAPI (4', 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 µg/mL for compounds 1 to 6, respectively. All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6. The viability of the HEK-293 normal cells was found to be significantly higher than the viability of the cancerous cells at all of the tested concentrations, thus suggesting that all the compounds have better inhibitory activity on the cancer cell line. Apoptotic features such as chromatin condensation and nuclear shrinkage were also induced by the compounds. The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2.

Proposed Mechanism for Emodin as Agent for Methicillin Resistant Staphylococcus Aureus: In Vitro Testing and In Silico Study.

In the search for a new anti-MRSA lead compound, emodin was identified as a good lead against methicillin-resistant Staphylococcus aureus (MRSA). Emodin serves as a new scaffold to design novel and effective anti-MRSA agents. Because rational drug discovery is limited by the knowledge of the drug target, α-hemolysin of Staphylococcus aureus was used in this study because it has an essential role in Staphylococcus infections and because emodin shares structural features with compounds that target this enzyme. In order to explore emodin's interactions with α-hemolysin, all possible ligand binding pockets were identified and investigated. Two ligand pockets were detected based on bound ligands and other reports. The third pocket was identified as a cryptic site after molecular dynamics (MD) simulations. MD simulations were conducted for emodin in each pocket to identify the most plausible ligand site and to aid in the design of potent anti-MRSA agents. Binding of emodin to site 1 was most stable (RMSD changes within 1 Å), while in site 2, the binding pose of emodin fluctuated, and it left after 20 ns. In site 3, it was stable during the first 50 ns, and then it started to move out of the binding site. Site 1 is a possible ligand binding pocket, and this study sheds more light on interaction types, binding mode, and key amino acids involved in ligand binding essential for better lead design. Emodin showed an IC50 value of 6.3 µg/mL, while 1, 6, and 8 triacetyl emodin showed no activity against MRSA. A molecular modeling study was pursued to better understand effective binding requirements for a lead.

Phytochemical Characterization, In Vitro Anti-Inflammatory, Anti-Diabetic, and Cytotoxic Activities of the Edible Aromatic Plant; Pulicaria jaubertii.

Pulicaria jaubertii is a medicinal herb that alleviates inflammations and fever. Chromatographic separation, phytochemical characterization, and in vitro biological activities of the plant n-hexane extract were conducted for the first time in this study. Six compounds were isolated for the first time from the n-hexane fraction of Pulicaria jaubertii aerial parts and were identified on the bases of NMR and MS analyses as pseudo-taraxaterol (1), pseudo-taraxasterol acetate (2), 3ß-acetoxytaraxaster-20-en-30-aldehyde (3), calenduladiol-3-O-palmitate (4), stigmasterol (5), and α-tocospiro B (6). Compound (6) was a rare tocopherol-related compound and was isolated for the first time from family Asteraceae, while compound (3) was isolated for the first time from genus Pulicaria. The total alcoholic extract and n-hexane fraction were tested for their anti-inflammatory, antidiabetic, and cytotoxic activities. The n-hexane fraction has dose dependent red blood cells (RBCs) membrane stabilization and inhibition of histamine release activities with IC50: 60.8 and 72.9 µg/mL, respectively. As antidiabetic activity, the alcoholic extract exerted the most inhibition on the activity of yeast α-glucosidase, with an IC50: 76.8 µg/mL. The n-hexane fraction showed cytotoxic activity against hepatocarcinoma (HepG-2), breast carcinoma (MCF-7), and prostate carcinoma (PC-3) cell lines with IC50: 51.8, 90.8 and 62.2 µg/mL, respectively. In conclusion, the anti-inflammatory effect of Pulicaria jaubertii might be attributed to the triterpenoid constituents of the n-hexane extract of the plant.