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.

Phenolic Compound, Antioxidant, Antibacterial, and In Silico Studies of Extracts from the Aerial Parts of Lactuca saligna L.

Medicinal plants are considered a major source for discovering novel effective drugs. To our knowledge, no studies have reported the chemical composition and biological activities of Moroccan Lactuca saligna extracts. In this context, this study aims to characterize the polyphenolic compounds distributed in hydro-methanolic extracts of L. saligna and evaluate their antioxidant and antibacterial activities; in addition, in silico analysis based on molecular docking and ADMET was performed to predict the antibacterial activity of the identified phenolic compounds. Our results showed the identification of 29 among 30 detected phenolic compounds with an abundance of dicaffeoyltartaric acid, luteolin 7-glucoronide, 3,5-di-O-caffeoylquinic acid, and 5-caffeoylquinic acid with 472.77, 224.30, 196.79, and 171.74 mg/kg of dried extract, respectively. Additionally, antioxidant activity assessed by DPPH scavenging activity, ferric reducing antioxidant power (FRAP) assay, and ferrous ion-chelating (FIC) assay showed interesting antioxidant activity. Moreover, the results showed remarkable antibacterial activity against Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and Listeria monocytogenes with minimum inhibitory concentrations between 1.30 ± 0.31 and 10.41 ± 0.23 mg/mL. Furthermore, in silico analysis identified three compounds, including Apigenin 7-O-glucuronide, Quercetin-3-O-glucuronide, and 3-p-Coumaroylquinic acid as potent candidates for developing new antibacterial agents with acceptable pharmacokinetic properties. Hence, L. saligna can be considered a source of phytochemical compounds with remarkable activities, while further in vitro and in vivo studies are required to explore the main biological activities of this plant.

In silico Evaluation of ACE2 Inhibition by Prunus armeniaca L. and in vivo Toxicity Study.

BACKGROUND: SARS-CoV-2 is a virus that uses ACE2 to enter the host cell. AIMS AND OBJECTIVES: This study aimed to evaluate the in silico inhibitory activity of polyphenols from Prunus armeniaca (P. armeniaca) on angiotensin-converting enzyme 2 (ACE2). METHODS: The efficacy of phytocompounds from P. armeniaca in inhibiting ACE2 was tested through molecular docking and dynamic analyses. The toxicological analysis of P. armeniaca was also evaluated. RESULTS: A total of twenty polyphenols were docked against the ACE2 active site, and four compounds showed interesting profiles. In vivo acute toxicity study demonstrated that the aqueous extract of Prunus armeniaca was safe. CONCLUSION: Four compounds from Prunus armeniaca seem to exert an inhibitory potential of ACE2.

Preventive planning against mercury over-exposure among Moroccan dentists using multidimensional statistical methods.

BACKGROUND: Mercury used in dental amalgams constitutes a significant source of chronic exposure to this heavy metal among dentists. Thus, the safety of dental amalgam remains a controversial issue despite its long history of use. In Morocco, most studies about dental mercury were mainly focused on the environmental risk related to the management of mercury-contaminated waste. OBJECTIVE: In order to evaluate the occupational exposure to mercury among liberal dentists practicing in two Moroccan regions, a multidimensional statistical approach was used to analyze the collected data. The main objective was to help establishing a targeted prevention plan aiming to reduce the mercury exposure among Moroccan dentists. METHODS: Fifteen variables from 146 dentists were elected for a three-step classification procedure: a multiple correspondence analysis followed by a hierarchical ascendant clustering consolidated by the k-Means algorithm. RESULTS: Three homogenous clusters were identified. The most important one includes 57.5% of the population as well as the majority of the risky factors. The characterization of these clusters allows proposing concise guidelines for a targeted preventive plan. CONCLUSIONS: A real mercurial risk has been observed in the studied population. However, its impact on health as well as the efficiency of simple preventive recommendations remains to be unveiled.

Modeling Subjective Symptoms Related to Micro-Hydrargyrism in a Population of Moroccan Dentists.

BACKGROUND: The ability of mercury to deposit throughout the body and alter a wide range of molecular and cellular pathways results in a polymorphic and complex clinical phenotype with over 250 possible symptoms. However, some of them are recurrently cited as evoking chronic mercury poisoning. In this light, dentists users of dental amalgams are chronically exposed to mercury so that in-depth epidemiological investigations and adapted statistical methods are required to highlight adverse effects of this exposure. METHODS: In order to study the health impact of the occupational mercury exposure in a population of liberal dentists practicing in two Moroccan regions, a list of eighteen subjective symptoms commonly associated with micro-hydrargyrism was drawn up. Then, seven statisctical models adapted to count data were fitted. Finally, three methods were used to compare their relative performance in order to choose the most appropriate one. RESULTS: The adopted logical path, from the response variable selection till models' comparison, led us to lean towards quasi-Poisson regression as the best way to predict the number of symptoms declared by dentists according to mercury exposure. CONCLUSIONS: Interpretation of the selected model allowed us to conclude that the reduction of dental amalgam use allows the reduction of subjective symptoms related to mercury exposure.

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.