Socio-demographical Profile of 7285 SARS-Cov-2 Positive Early Cases; Comparison with National Four Epidemic Waves.

Background: Objectives were to investigate aspects of the COVID-19 epidemics via testing the individuals who were referred to Aramesh Medical Laboratory in Tehran and to integrate the molecular results with epidemiological data since the beginning of the epidemic. Methods: In this cross-sectional Study 77528 outpatients were referred to Aramesh Medical laboratory by physicians for the diagnosis of SARS-CoV-2 infection between March 2019 and May 2021. Viral acid nucleic extracted from nasal and throat specimens and subsequently amplified using Reverse Transcriptase Real-Time PCR. Laboratory data including Ct values compared with epidemic peaks of COVID-19 countrywide. Statistical Analysis was done by SPSS 21 Software. Results: 14312 (18.46%) tested positive.36.5% of the positive cases were in the 30 to 39 years old age group. The positive result rate was significantly different based on months, ranging from 6% to 28%, compatible with four recognized epidemic peaks encompassing the end of March through the first week of April (first epidemic peak), from June to July 2020 (second epidemic peak), October until mid of November 2020 (third epidemic wave) followed by the end of April to May 2021 (until the end period of study, in the middle of 4th peak). In 37.8% of cases, the Ct value was between 21 and 28. Two separate trends were seen for Ct ≤ 25 and Ct ≤ 20 for the first and fourth epidemic peaks, respectively. There was an association between the number of total monthly positive results and total deaths in the country, especially with the second to third peaks (in the course of summer 2020) and fourth epidemic peak. Conclusion: It might be useful to consider laboratory admission rates as an indicator for changes in the epidemic level in the country to continue the SARS-CoV-2 surveillance in accordance with public decision-makers.

A Review of the Phytochemistry and Antimicrobial Properties of Origanum vulgare L. and Subspecies.

Origanum vulgare L. (O. vulgare) is an important medicinal herb of the family Lamiaceae. In the current study, we explained the critical evaluation of traditional uses, the phytochemistry and the antimicrobial properties of O. vulgare and its subspecies, with a focus on the mechanisms of actions of the most important phytochemicals from O. vulgare subspecies. The most important phytochemicals of O. vulgare are volatile (essential oil) and non-volatile phenolic compounds (phenolic acids & flavonoids). The constituents of the O. vulgare essential oil (EO) include high percentages of thymol and carvacrol with excellent antimicrobial activity alone or in combination with other antibiotics. Interesting results have been reported the remarkable antimicrobial activities of infusion or tea products of O. vulgare with a high amount of EO against multidrug-resistant bacterial and fungal microorganism (such as Escherichia coli, Staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa). The most important antibacterial mechanisms of O. vulgare are enzyme inhibition, efflux pump inhibition, ATP depletion, biofilm formation inhibition and cytoplasmic membrane damage. The antimicrobial activity of the hirtum subspecies has been confirmed in different in-vitro and in-vivo studies. The present review confirms the clinical and preclinical research showing the O. vulgare and its subspecies antimicrobial effects.

Effects of phytochemicals on macrophage cholesterol efflux capacity: Impact on atherosclerosis.

High-density lipoprotein cholesterol (HDL) is the major promoter of reverse cholesterol transport and efflux of excess cellular cholesterol. The functions of HDL, such as cholesterol efflux, are associated with cardiovascular disease rather than HDL levels. We have reviewed the evidence base on the major classes of phytochemicals, including polyphenols, alkaloids, carotenoids, phytosterols, and fatty acids, and their effects on macrophage cholesterol efflux and its major pathways. Phytochemicals show the potential to improve the efficiency of each of these pathways. The findings are mainly in preclinical studies, and more clinical research is warranted in this area to develop novel clinical applications.

Histone Deacetylase Inhibitory and Cytotoxic Activities of the Constituents from the Roots of Sophora Pachycarpa.

Four prenylated flavonoids, including isosophoranone, sophoraflavanone G, alopecurone J, alopecurone P, and a resveratrol derivative HPD (2-(4-hydroxyphenyl)-2,3-dihydrobenzo[b] furan-3,4,6-triol), were isolated from the roots of Sophora pachycarpa. The cytotoxic activity of obtained compounds was evaluated against A2780, A549, HeLa, and HCT116 human cancer cell lines. We also evaluated their histone deacetylase (HDAC) inhibitory activities. Of all compounds tested, alopecurone J was the most active with IC50 values in the range of 9.97-30.91 µM against four cancer cell lines with potent pan-HDAC inhibitory activity (IC50 = 0.08-3.85 µM). Molecular docking experiments of these compounds with HDAC8 displayed potential selective HDAC inhibitory. Molecular docking data showed consistent results in the in-vitro experiments with high selectivity towards HDAC8. The Resveratrol group plays an essential role in HDAC inhibition.

Histone deacetylase inhibitory and cytotoxic activities of the constituents from the roots of three species of Ferula.

OBJECTIVES: Histone deacetylase inhibitory and cytotoxic activities of 18 naturally occuring terpenoids (ferutinin, stylosin, tschimgine and guaiol), coumarins (umbelliprenin, farnesiferone B, conferone, feselol, ligupersin A, conferdione, conferoside) and sulfur-containing derivatives (latisulfies A-E, persicasulphides A and C) from the roots of three species of Ferula (Ferula latisecta, Ferula ovina and Ferula flabelliloba) were evaluated. MATERIALS AND METHODS: The cytotoxic activity of compounds was evaluated against human cancer cell lines (HeLa, HCT116, A2780 and A549) by AlamarBlue® assay using vorinostat as the positive control. On the other hand, we aimed to evaluate their inhibitory activities against pan-HDAC. RESULTS: The methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography. Further purification by preparative thin-layer chromatography (PTLC) and semipreparative RP-HPLC yielded twelve known compounds (1-12). This is the first report on the isolation of guaiol (1), persicasulphide C (3) and conferoside (10) from the roots of F. flabelliloba. Six compounds including persicasulfide A, conferone, feselol, latisufide C, conferoside and ferutinin showed cytotoxic activity with IC50 values in the range of 11.61-49.40 µM against cancer cells and pan-HDAC inhibitory activity with IC50 values in the range of 1.06-35.27 µM. CONCLUSION: Results indicated that persicasulfide A (2), conferone (6) and feselol (7) showed moderate cytotoxicity with IC50 values in the range of 11.76-39.24 µM against cancer cells and potent pan-HDAC inhibitory activity with IC50 values in the range of 1.06-10.73 µM. Conferone was more active than others with a higher potency for HDAC inhibition (1.06- 1.17 µM).

A qHNMR method for simultaneous quantification of terpenoids from Ferula ovina (Boiss.) Boiss roots.

Ferula ovina (Boiss.) Boiss is one of the most important endemic medicinal plants in Iran, which has three main terpenoid compounds including ferutinin, stylosin and tschimgine. Ferutinin is the strongest natural phytoestrogen that has agonistic activity on estrogen receptors, particularly α-receptors. To determine the amount of ferutinin in F. ovina roots, we firstly used HPLC-UV method. In the HPLC method, the resolution of ferutinin from the two other compounds, stylosin and tshimgine, was poor. Therefore, we decided to use qHNMR method for simultaneous quantification of ferutinin, stylosin and tshimgine in the plant roots. Quantitative 1H-NMR (qHNMR) was carried out based on the relative ratio of signal integration of each compound [(H-1 for tschimgine (δH 4.94-5.03), OCH3 for stylosin (δH 3.8), and H-9 for ferutinin (δH 5.58)] to certain amount of the internal standard dimethyl sulfone (DMSO2). The qHNMR method showed good precision (intra-day RSD ≤ 2.31%, inter-day RSD ≤ 2.72%), linearity (in the ranges of 1.3-10.41, 1.2-9.7 and 1.1-9.02 mg/mL with correlation coefficients at 0.9991), repeatability (RSD ≤ 2.99%) and stability (RSD ≤ 2.4%) for the quantification of the compounds. This work confirmed that qHNMR represents a feasible alternative to high-performance liquid chromatography based methods for simultaneous quantification of ingredients in plant extracts.

Absolute configuration and anti-cancer effect of prenylated flavonoids and flavonostilbenes from Sophora pachycarpa: Possible involvement of Wnt signaling pathway.

A new prenylated flavonostilbene, namely, alopecurone P together with three known compounds sophoraflavanone G, 2-(4-hydroxyphenyl)-2,3-dihydrobenzo[b]furan-3,4,6-triol and alopecurone J were characterized from the roots of Sophora pachycarpa. The absolute configuration of alopecurones J and P were characterized by comparison of experimental electronic circular dichroism (ECD) spectroscopy and simulated data using time-dependent density functional theory (TDDFT) for possible stereoisomers. The cytotoxic properties of isolated compounds have also been evaluated on two breast cancer cell lines (MCF-7 and MDA-MB-231) and normal cell line (NIH/3T3) using AlamarBlue®, flowcytometry and western blot assays. Alopecurone J and P showed cytotoxic effect on MCF-7 cell line through Wnt signaling pathway. It seems that the presence of lavandulyl substitution in C-8 position of flavanone structure increased the cytotoxic effect.

Biologically active prenylated flavonoids from the genus Sophora and their structure-activity relationship-A review.

The genus Sophora (Fabaceae) has been used in traditional medicine for years. Prenylated flavonoids are one of the constituents of Sophora species that play important roles in their biological properties. Different classes of prenylated flavonoids are produced by Sophora spp. including prenylated flavonol (e.g., sophoflavescenol), prenylated flavanone (e.g., sophoraflavanone G), prenylated flavonostilbene (e.g., alopecurones A and B), and prenylated chalcone (kuraridin). Prenylated flavonoids have a more lipophilic structure, which leads to its high affinity to the cell membranes and enhancement of the biological activity, which includes cytotoxicity, antibacterial, anti-inflammatory, and estrogenic activities. However, it is reported that prenylation decreases the plasma absorption but increases the tissue accumulation. The presence of the prenyl or lavandulyl groups on C8 position of flavonoids plays an important role in the biological activity. It seems that prenylated flavonoids have the potential to be developed as new drugs or supplements for human health.

Sulfur-containing compounds from the roots of Ferula latisecta and their cytotoxic activities.

Five new sulfur-containing compounds, with a new geometry (cis) of the propenyl moiety, and five known compounds were isolated from the roots of Ferula latisecta. The structures of these compounds, were elucidated on the basis of spectroscopic data including 1D and 2D NMR experiments and HRMS. All of the isolated compounds were tested against A2780, A549, HeLa, and HCT116 human cancer cell lines and some of them showed moderate cytotoxic activities.

Evaluation of phytochemicals, antioxidant and burn wound healing activities of Cucurbita moschata Duchesne fruit peel.

OBJECTIVES: Cucurbita moschata Duchesne (pumpkin) is a well-known plant with several pharmacological effects. The aim of the present study was to assess burn wound healing activity of C. moschata peel extract (CE). Also, standardized CE was assessed for antioxidant activity and antibacterial effects against major pathogens of burns. MATERIALS AND METHODS: Healing properties of topical preparation of 10% and 20% concentrations of CE were assessed on second degree burn in rats during a 14-day period as well as histological studies, total antioxidant power, lipid peroxidation and total thiol content of skin tissue samples. RESULTS: Radical scavenging IC50 and ferric-reducing antioxidant power value were 4.015±0.20 mg/ml and 142.63±2.65 mmol Fe2+/g, respectively. Total mucilage content was 13.8%. The optimal results were obtained by 20% CE that showed 90.80±5.86 % wound closure and tissue repair as well as significant reduction of tissue oxidative stress biomarkers. Histological analyses confirmed wound healing activity of pumpkin peel extract. CONCLUSION: Considering the high mucilage content of the plant, providing a moist environment for wound, C. moschata peel extract could be a natural remedy for treatment of burns. Further clinical studies are suggested to confirm C. moschata peel extract as a wound healing agent.

Cytotoxic and apoptogenic properties of three isolated diterpenoids from Salvia chorassanica through bioassay-guided fractionation.

Bioassay-guided fractionation of Salvia chorassanica Bunge roots for the first time led to the isolation of taxodione, ferruginol and 6-hydroxysalvinolone. Cytotoxic studies revealed that all compounds exhibited high cytotoxic activity against apoptosis-proficient HL-60 and apoptosis-resistant K562 cells, with IC50 values ranging from 7.7 to 60.3 µM with much less cytotoxic effects on normal human lymphocytes. Sub-G1 peak in flow cytometry histogram of treated cells by S. chorassanica and all pure compounds in comparison with control was induced and DNA fragmentation confirmed the cytotoxicity and apoptosis. Taxodione, ferruginol and 6-hydroxysalvinolone (2.5 and 5.0 µM) also enhanced expression of the pro-apoptotic protein Bax, cleaved caspase-3 and cleaved PARP after treatment for 48 h. Collectively, these findings suggest cytotoxic and apoptotic effectiveness of taxodione, ferruginol and 6-hydroxysalvinolone against the leukemic K562 and HL-60 cancer cells.