In vivo antiulcer activity, phytochemical exploration, and molecular modelling of the polyphenolic-rich fraction of Crepis sancta extract.

Bioactivity-guided investigation of the methanol extract of Crepis sancta aerial parts, collected off Al-Tafilah, South Jordan, was applied, and in this study, the extract was explored for its phytochemical components and in vivo antiulcer activity. In addition, a docking study involving the purified compounds with the newly crystalized gastric proton pump (PDB # 5YLU) was performed. In-depth phytochemical investigation using the state-of-the-art chromatographic and analytical techniques was implemented resulting in the identification of two eudesmane-type sesquiterpenoids, 3-oxo-γ-costic acid (1) and its methyl ester (2) together with seven different methoxylated flavonols (3-9) as the extract's major components. The in vivo antiulcer study at three different doses (50, 100, and 200 mg/kg) against ethanol-induced gastric ulcer in male albino rats, compared to omeprazole (20 mg/kg) as a standard proton pump inhibitor antiulcer drug, revealed that the tested extract, at the middle and the highest doses, featured comparable or even superior activities relative to omeprazole as deduced from histopathological examination, in particular with regard to reducing inflammatory cell infiltration and ceasing mucosal haemorrhage. The tested extract revealed also a dose-dependent reduction in the volume and titrable acidity of the gastric juice together with a dose-dependent increase in the protective gastric mucin content which may explain the noticeable gastroprotective effect. Molecular modelling study of the isolated compounds showed a binding mode similar to the co-crystallized substrate vonoprazan in 5YLU which strengthens the importance of the tested extract as a potential natural remedy for treating gastric ulcer.

Anti-inflammatory, antiallergic and COVID-19 protease inhibitory activities of phytochemicals from the Jordanian hawksbeard: identification, structure-activity relationships, molecular modeling and impact on its folk medicinal uses.

On Wednesday 11th March, 2020, the world health organization (WHO) announced novel coronavirus (COVID-19, also called SARS-CoV-2) as a pandemic. Due to time shortage and lack of either a vaccine and/or an effective treatment, many trials focused on testing natural products to find out potential lead candidates. In this field, an edible and folk medicinal Jordanian plant Crepis sancta (Asteraceae) was selected for this study. Phytochemical investigation of its enriched polyphenolic extract afforded four eudesmane sesquiterpenes (1-4) together with (6S,9R)-roseoside (5) and five different methylated flavonols (6-10). Structure elucidation of isolated compounds was unambiguously determined based on HRESIMS, X-ray crystallography, and exhaustive 1D and 2D NMR experiments. All isolated compounds were assessed for their in vitro anti-inflammatory, antiallergic and in silico COVID-19 main protease (Mpro) inhibitory activities. Among the tested compounds, compounds 5-10 revealed potent anti-inflammatory, antiallergic and COVID-19 protease inhibitory activities. Chrysosplenetin (10) is considered as a promising anti-inflammatory and antiallergic lead structure adding to the phytotherapeutic pipeline. Moreover, its inhibitory activity against SARS-CoV-2 Mpro, supported by docking and molecular dynamic studies, strengthens its potential as a lead structure paving the way toward finding out a natural remedy to treat and/or to control the current COVID-19 pandemic.