Biochemical and toxicity evaluation of Retama sphaerocarpa extracts and in-silico investigation of phenolic compounds as potential inhibitors against HPV16 E6 oncoprotein.

Cervical cancer is a type of cancer which affects the cervix cells. The conventional treatments for cervical cancer including surgery, chemotherapy, and radiotherapy are only effective in premature stages and less effective in late stages of this tumor. Therefore, the therapeutic strategies based on biologically active substances from plants are needed to develop for the treatment of cervical cancer. The aim of the present study was to assess in vivo toxicity, hematological and biochemical blood parameters in Wistar rats fed Retama sphaerocarpa aqueous leaf extract (RS-AE), as well as to perform in silico molecular docking studies and dynamic simulation of phenolic compounds against HPV16 oncoprotein E6 in order to identify potential inhibitors. RS-AE was found not to induce acute or sub-acute oral toxicity or significant alterations in hematological and biochemical blood parameters in Wistar rats. A total of 11 phenolic compounds were identified in RS-AE, including dihydrodaidzein glucuronide, chrysoperiol pentoside, genistin and vitexin, which turned out to have the highest binding affinity to HPV16 oncoprotein E6. Based on these results, these RS-AE phenolic compounds could be used as natural drugs against the HPV16 E6 oncoprotein.

Genetic diversity of Moroccan date palm revealed by microsatellite markers.

The genetic diversity between 23 Moroccan date palm cultivars collected from the National Palm Collection at the INRA (National Agricultural Research Institute) experimental field in Zagora was assessed using SSR markers that are specifically designed for date palm. Among the 16 tested SSR, 13 were successfully amplified, and were selected to carry out this study. 208 bands were amplified, ranging from 10 to 25 bands per cultivar with an average of 16 alleles per cultivar. The value of heterozygosity of the studied markers ranged from 0.11 to 0.30. The pairwise genetic distances between those cultivars ranged from 0.06 to 0.46. The hierarchical cluster analysis distributed the 23 genotypes into four different groups of one to ten cultivars.

Thymus atlanticus polyphenol-rich extract regulates cholesterol metabolism by inhibiting its biosynthesis without affecting its excretion in hamsters fed a high-fat diet.

CONTEXT: Thymus atlanticus has been reported to have significant hypolipidaemic effect in animal models. However, the mechanism of this hypolipidaemic action still unknown. OBJECTIVE: To determinate the possible mechanism(s) of hypolipidaemic action of a Thymus atlanticus polyphenol-rich extract (PRE). MATERIALS AND METHODS: Plasma, faecal, and liver cholesterol, bile acid content in the faeces, and gene expression level of HMG-CoA reductase, CYP7A1, ABCG5 and ABCG8 were analysed after 9 weeks in hamsters feeding normal diet, high-fat diet (HFD) or HFD supplemented with 400 mg/kg body weight/day of PRE. RESULTS: PRE significantly decreased total cholesterol content (p < .05) and HMG-CoA reductase expression (p < .05), but did not affect the faecal cholesterol, bile acid contents and CYP7A1 and ABCG5/G8 expression (p > .05). CONCLUSION: We can conclude that the T. atlanticus extract is efficient in the alleviation of chronic hyperlipidaemia by acting as cholesterol biosynthesis inhibitor.

Effect of supplementation with polyphenol extract of Thymus atlanticus on paraoxonase-1 activity, insulin resistance, and lipid profile in high-fat diet-fed hamsters.

Thymus atlanticus has been used by Moroccan people to treat a variety of health problems, particularly metabolic disorders. In this study, hamsters fed a high-fat diet daily received distilled water (a positive control) or a single dose of Thymus atlanticus polyphenols (Pp) for 63 days. The negative control was fed a normal diet and received distilled water. Results showed that the supplementation of HFD with Pp significantly (p < .001) reduced the levels of MDA and LDL cholesterol, restored insulin level, and increased the activities of serum paraoxonase-1 and HDL cholesterol levels, but did not affect (p > .05) the activity of superoxide dismutase and glutathione peroxidase when compared with the group feeding HFD alone. Thymus atlanticus could be an effective agent against dyslipidemia, oxidative stress, and insulin resistance. PRACTICAL APPLICATIONS: HFD consumption is a risk factor for oxidative stress and the development of metabolic disorders, such as hyperlipidemia and insulin resistance, which may result in atherosclerosis and related cardiovascular diseases, the leading causes of death globally. The management of these alterations is an important strategy to prevent and treat heart complications. Our results showed thatT. atlanticus effectively alleviated HFD-induced hyperlipidemia and insulin resistance and improved PON1 activity. T. atlanticus is a source of biomolecules that may be an effective supplement for controlling HFD-related metabolic disorders. Therefore, the findings of this study may be helpful in the preparation of effective supplements from T. atlanticus to control metabolic disorders and related complications.

Camphor, Artemisinin and Sumac Phytochemicals as inhibitors against COVID-19: Computational approach.

Covid-19 is an emerging infectious disease caused by coronavirus SARS-CoV-2. Due to the rapid rise in deaths resulted from this infection all around the world, the identification of drugs against this new coronavirus is an important requirement. Among the drugs that can fight this type of infection; natural products are substances that serve as sources of beneficial chemical molecules for the development of effective therapies. In this study, Camphor, Artemisinin and 14 Sumac phytochemicals were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). We have also performed molecular dynamic simulation at 100 ns with MM-GBSA/PBSA analysis for the structures with the best affinity in the binding site of the studied enzyme (Hinokiflavone and Myricetin) after docking calculations to consider parameters like RMSD, covariance, PCA, radius of gyration, potential energy, temperature and pressure. The result indicates that Hinokiflavone and Myricetin are the structures with best affinity and stability in the binding site of the studied enzyme and they respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties; so, these compounds have important pharmacokinetic properties and bioavailability, and they could have more potent antiviral treatment of COVID-19 than the other studied compounds.

New dehydroabietic acid (DHA) derivatives with anticancer activity against HepG2 cancer cell lines as a potential drug targeting EGFR kinase domain. CoMFA study and virtual ligand-based screening.

Liver cancer has become the third type of cancer that causes death; this is why the design of new chemotherapeutic drugs against this disease is a major need. With this idea, a series of Dehydroabietic Acid-Based Acylhydrazones have been used to generate a CoMFA model to design new anticancer agents. In this study, we employed a Comparative Molecular Field Analysis studies, we performed those methods on Dehydroabietic Acid-Based Acylhydrazones against HepG2 human cancer cell line. The statistical results are encouraging with Q2 equal to 0.527 and R2 equal to 0.962. The predictive ability of this model was determined using a test set of Dehydroabietic Acid-Based Acylhydrazones that gave an acceptable predictive correlation (R2test) value of 0.614. The developed model guides to design five new molecules with enhanced activity as potential drugs. On the other hand to determine a potential target to these ligands we have established a virtual screening using reverse docking with the most active molecule and 42 antiproliferative targets. Based on the affinity of complex ligand-Target, the intracellular domain of EGFR shows high stability. This suggests that our designed molecules can inhibit the target EGFR which is an important target on targeted therapy of many types of cancer.Communicated by Ramaswamy H. Sarma.

Phytocompounds from Anvillea radiata as promising anti-Covid-19 drugs: in silico studies and in vivo safety assessment.

As an alternative strategy in combating the COVID-19 pandemic, phytoconstituents from medicinal plants are getting attention worldwide. The current investigation focused on the efficacy of the essential phytocompounds identified in Anvillea radiata to target the main protease (Mpro) of SARS-COV-2 through molecular docking and dynamic analyses; in addition to the safety assessment of this herb in vivo. In silico, the 6LU7 structure of Mpro was prepared as a target by Discovery Studio 2020. The virtual screening of phytocompounds from Anvillea radiata was performed through iGEMDOCK program, followed by an evaluation of the potential inhibitors based on the docking scores calculated using AutoDock Vina and MGL Tools programs, as well as complexes stability assessment through MD simulation. In vivo toxicity studies of Anvillea radiata aqueous extract were also conducted in Wistar rats. Among the phytocompounds evaluated in this study, 3,5-Dicaffeoylquinic acid, Spinacetin, 9α-Epoxyparthenolide, Hispidulin, Quercetin, jaceosidin, Nepetin, and isorhamnetin were predicted to have the highest binding affinity for the Main protease (Mpro) target of SARS-CoV-2. The aqueous extract of Anvillea radiata did not induce any signs of toxicity. 3,5-Dicaffeoylquinic acid, Spinacetin, 9α-Epoxyparthenolide, jaceosidin, and isorhamnetin from Anvillea radiata were selected as potential inhibitors of SARS-Cov-2 to develop new drugs anti-COVID-19.

Effect of Aqueous Extract and Polyphenol Fraction Derived from Thymus atlanticus Leaves on Acute Hyperlipidemia in the Syrian Golden Hamsters.

Thymus atlanticus, an endemic plant of Morocco, is traditionally used as a liniment or a drink to treat various diseases. However, there are few available scientific data regarding its biological effects. In this connection, the present study aimed to investigate the hypolipidemic and antioxidant effects of aqueous extract and polyphenol fraction of Thymus atlanticus in Syrian golden hamsters treated with Triton WR-1339 (triton, 20 mg/100 g body weight). The hamsters orally received the extracts (400 mg/kg), and blood samples were collected after 24 h of treatment to determine plasma lipid, insulin, and fasting blood glucose levels. Plasma malondialdehyde level and plasma total antioxidant (TAS) were also evaluated. The T. atlanticus extracts significantly decreased triglycerides, total cholesterol, VLDL-C, and LDL-C and increased HDL-C when compared with the hyperlipidemic group. Both extracts suppressed the effect of the triton injection on TAS and reduced the level of plasma malondialdehyde. The extracts produced no significant change in the blood glucose level but effectively prevented the mild hyperinsulinemia induced by triton. These findings suggest that T. atlanticus may be a useful alternative treatment for the control of hyperlipidemia and its related diseases.

Study of novel triazolo-benzodiazepine analogues as antidepressants targeting by molecular docking and ADMET properties prediction.

In this study, we have selected a series of a new family of molecules bearing Triazolo-benzodiazepines, an eleven membered heterocyclic ring has been studied for antidepression activity. Docking studies suggested that all the eleven ligands interacted well within active site of Drosophila melanogaster dopamine transporter (dDAT) (PDB ID: 4M48). Most ligands formed H-bond with amino acid Phe43, Asp46, Asp475, Tyr123, Ser421 and/or Gln316 and also exhibited Pi and Pi-Pi interactions with amino acid residues Tyr124, Phe319, Phe43, Phe325, Ala479 and Val120. In silico ADME evaluations of compounds showed more than 96% intestinal absorption for all compounds. During in vitro Toxicity properties prediction, the Triazolo-benzodiazepines derivatives: M1, M2, M3 and M11 showed less toxicity than the other studied molecules against algae, for daphnia the molecules M1, M2, M3, M8, M10 and M11 showed less toxicity than the reference molecule (Nortriptyline).