Background and purpose: Paracetamol is the most implicated xenobiotic in inducing hepatotoxicity. Our study aimed to determine the impact of some kaempferol glycosides isolated from the leaves of Cedrela odorata L. on paracetamol hepatotoxicity. Experimental approach: The methanolic extract of dried leaves of C. odorata L . was subjected to the combination of spectroscopic methods ( 1 H and 13 CNMR). Six kaempferol glycosides were isolated: kaempferol-3- O -β-D-glycopyranoside (astragalin), kaempferol-3- O -β-L-rhamnopyranoside, kaempferol-3- O -β-D-rutinoside, kaempferide-3- O -β-D-rutinoside, kaempferide-3- O -β-Drutinosyl-7- O -β-D-rhamnopyranoside, and kaempferol-3- O -β-D- rutinosyl-7- O -a-D-arabinopyranoside. Fifty-four female Swiss Albino mice were divided randomly into 9 groups including (1) control negative (1 mL/kg saline; IP), (2) control positive (paracetamol 300 mg/kg; IP), (3) silymarin 50 mg/kg (IP). Animals of groups 4-9 were injected with 6 different samples of isolated compounds at 100 mg/kg (IP). One h later, groups 3-9 were injected with paracetamol (300 mg/kg IP). Two h later, tissue samples were taken from all animals to assess nitrotyrosine, c-Jun N-terminal protein kinase (c-JNK), Raf -1kinase, and oxidative stress biomarkers viz . reduced glutathione (GSH) and malondialdehyde (MDA). Findings/Results: Isolated glycosides had a prominent anti-apoptotic effect via inhibition of c-JNK and Raf-1 kinase. They also exerted a powerful antioxidant effect by modulating the oxidative stress induced by paracetamol via increasing GSH, reducing MDA and nitrotyrosine concentrations compared to positive control. The glycoside (1) showed a better effect than silymarin (standard) in ameliorating the formation of nitrotyrosine, Raf-1 kinase, c-JNK, and GSH. Conclusion and implication: Kaempferol glycosides isolated for the first time from C. odorata L. leaves exerted antioxidant and antiapoptotic effects via amelioration of oxidative stress and inhibition of Raf/MAPK pathway.

Aim:We report the diagnostic evaluation of a confirmatory reverse transcription-PCR (RT-PCR) kit targeting the Middle East respiratory syndrome coronavirus (MERS-CoV) N gene. Material & methods: 33 patient samples from two collections sites in Riyadh, Saudi Arabia, which were pre-characterized via real-time RT-PCR targeting MERS-CoV orf1a and upE, and were tested using the MERS-CoV N gene, as a confirmatory assay. This diagnostic procedure follows a two-step diagnostics scheme, recommended by the WHO. Results: 18/33 samples tested positive, 11/33 tested negative for MERS-CoV RNA and 2/33 showed uncertain results. Conclusion: The results suggest, that the RealStar R MERS-CoV (N gene) RT-PCR kit 1.0 can be considered a suitable and reliable confirmatory assay in combination with the RealStar MERS-CoV RT-PCR kit 1.0 according to the diagnostic scheme recommended by WHO.

A comprehensive analysis of the polyphenols constituents found in Thunbergia alata leaves using (UPLC-Triple TOF-MS/MS) and natural polyphenols' antiviral properties have motivated us to perform in silico binding affinity study of flavonoids and coumarins identified in T. alata leaves extract against different proteins of SARS-COV-2; (Mpro) main protease (PDB ID: 6LU7) and 2′-Omethyltransferase (PDB ID: 6wkq) using a cocrystalized ligands N3 and Sinefungin respectively. 30 compounds were tentatively identified in T. alata leaves extract by UPLC-Triple TOF-MS/MS and characterized as 8-phenolic acids; 12-flavonoids; 3-coumarins and remain compounds unidentified. In silico virtual screening of both flavonoids and coumarins as the most common classes of polyphenols; flavonoids have the best potential to act as COVID-19 Mpro & MTase inhibitors; especially Kaempferol-3-O-(6ˈˈˈ-p-coumaroyl)-glucoside; Comp. (17) which gave very best docking score{ -9.2 kcal/mol} (docking energy score of N3 -7.6 kcal/mol). It bind by nine hydrogen bonds (with TRY54, CYS145, GLN192, PHE140, LEU141, THR26, ARG188 and ASN142), and Pi-Sulfur interaction (with MET165), hydrophobic interactions via five Pi-Alkyl bond (with MET49, CYS145 and PRO168) and also scored energy binding -10.2 (docking energy score of Sinefungin -7.8 kcal/mol); formed H-bond with ASN6841, ASN6899, CYS6913, LYS6968, GLY6869, GLY6871, ASP6928, ASN6996 and TRY6930. Moreover, 17 binds with LYS6844, LYS6935, LEU6898 and CYS6913 via hydrophobic interactions. While coumarins in comparison with the current flavonoids had less energy binding score. However, further research is important to investigate their potential medicine value.

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In the current study, antiproliferative effects of 3 ß-hydroxyl-Olean -12 -en -28 -oic acid (Oleanolic acid ; OA) & 3-ß-hydroxyolean -12-en-27, 28 dioic acid (Cincholic acid; CA); triterpene sapogenins isolated from the ethyl-acetate fraction of Lotus glaber-mill herb were evaluated against three human cancer cell lines, the liver cancer cell line( HepG-2), the colon cancer cell line (HCT-116), & the breast cancer cell line (MCF-7). The structures of isolated phytoconstituents were identified by careful analysis of 1D NMR spectra and negative ESI-MS data. Oleanolic acid & Cincholic acid displayed cytotoxic activities against the tested cell lines. Oleanolic acid has lower IC50 than Cincholic acid for both MCF-7 & HCT-116 at 27.99 & 18.66µg/ml respectively.While Cincholic acid has a lower IC50 in HEPG-2 than Oleanolic acid at 22.81µg/ml. Further investigations have shown that Oleanolic acid & Cincholic acid-induce apoptosis and cause cell cycle arrest at the G2/M phase.