Dinebra retroflexa Herbal Phytotherapy: A Simulation Study Based on Bleomycin-Induced Pulmonary Fibrosis Retraction Potential in Swiss Albino Rats.

Background and Objectives: Fibrotic lung disease is one of the main complications of many medical conditions. Therefore, the use of anti-fibrotic agents may provide a chance to prevent, or at least modify, such complication. The aim of this study was to evaluate the protective pulmonary anti-fibrotic and anti-inflammatory effects of Dinebra retroflexa. Materials and methods: Dinebra retroflexa methanolic extract and its synthesized silver nanoparticles were tested on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/5 mL/kg-Saline) as a supposed model for induced lung fibrosis. The weed evaluation was performed by intratracheal instillation of Dinebra retroflexa methanolic extract and its silver nanoparticles (35 mg/100 mL/kg-DMSO, single dose). Results: The results showed that both Dinebra retroflexa methanolic extract and its silver nanoparticles had a significant pulmonary fibrosis retraction potential, with Ashcroft scores of three and one, respectively, and degrees of collagen deposition reduction of 33.8 and 46.1%, respectively. High-resolution UHPLC/Q-TOF-MS/MS metabolic profiling and colorimetrically polyphenolic quantification were performed for further confirmation and explanation of the represented effects. Such activity was believed to be due to the tentative identification of twenty-seven flavonoids and one phenolic acid along with a phenolic content of 57.8 mg/gm (gallic acid equivalent) and flavonoid content of 22.5 mg/gm (quercetin equivalent). Conclusion: Dinebra retroflexa may be considered as a promising anti-fibrotic agent for people at high risk of complicated lung fibrosis. The results proved that further clinical trials would be recommended to confirm the proposed findings.

Inhibition of cell-intrinsic NF-κB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from Asphodelus microcarpus.

Anthraquinones are a major class of compounds naturally occurring in Asphodelus microcarpus. The pharmacological actions of anthraquinones in cancer cells are known to induce apoptosis or autophagy, and revert multidrug resistance. In this study, five anthraquinone-type analogs were isolated from the methanol extract of A. microcarpus leaves and identified as, emodin, rhein, physcion, aloe-emodin, and emodic acid. Among them, aloe-emodin and emodic-acid strongly inhibited the proliferation, cells-intrinsic NF-κB activity and metastatic ability of breast cancer. Although aloe-emodin inhibited p38 and ERK phosphorylation, emodic-acid more markedly inhibited JNK, in addition to p38 and ERK phosphorylation. Both aloe-emodin and emodic-acid inhibited the secretion of the pro-tumorigenic cytokines IL-1ß and IL-6, and VEGF and MMP expression, and subsequently inhibited the invasive and migratory potential of 4T1 cells. Thus, our study demonstrated the effects of aloe-emodin and emodin-acid in controlling the migratory and invasive ability of 4T1 breast cancer cells, in addition to inhibiting NF-κB activity and the expression of its downstream target molecules.

Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach.

Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.

A new flavan-3-ol dimer from Ficus spragueana leaves and its cytotoxic activity.

BACKGROUND: Isolation and structure elucidation of flavan-3-ol constituents from the leaves of Ficus spragueana and their cytotoxic activity. MATERIALS AND METHODS: Different open silica gel column chromatographic techniques with different solvent systems were used for the separation of the constituents of the ethyl acetate-soluble fraction of the alcoholic extract of Ficus spragueana leaves. The structures of these compounds were assigned on the basis of spectroscopic analyses and comparison with literature data. MTT colorimetric assay method (Viability assay) was used for the evaluation of cytotoxic activity of compound 1 against human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines. RESULTS: The isolation of one flavan-3-ol dimer and was identified as (-)-afzelechin-(4α→8)-epicatechin 1, and two flavan-3-ol monomers and were identified as (-)-epiafzelechin 2 and (-)-epicatechin 3. Compound 1 was relatively inactive against human breast cancer (MCF-7) cell line at the tested concentrations as compared with the standard. However, at a concentration (50 ΅g) it was found to give inhibition upon the proliferation of examined human liver (HepG2) tumor cell line. CONCLUSIONS: Compound 1 is a new flavan-3-ol dimer and it showed a potent cytotoxic activity against human liver (HepG2) tumor cell line.