Search

Ecklonia cava and its major compound dieckol, both natural marine products, possess antioxidant, anti-inflammatory, and metabolic-regulating effects. Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is transmitted by mosquitoes and causes serious illnesses in humans. This study aimed to evaluate the anti-ZIKV potential of Ecklonia cava and dieckol. The antiviral activity of Ecklonia cava extract (ECE), prepared with 80% ethanol, was assessed in ZIKV-infected Vero E6 cells through MTT assay, plaque assay, and quantitative polymerase chain reaction (qPCR), demonstrating no cytotoxicity and a significant reduction in viral titers and ZIKV mRNA levels. In addition, ECE decreased the expression of tumor necrosis factor-α and interferon-induced protein with tetratricopeptide repeats in the ZIKV-infected cells. Dieckol, the primary active compound in ECE, exhibited potent anti-ZIKV activity, with a half maximal inhibitory concentration (IC50), value of 4.8 µM. In silico molecular docking analysis revealed that dieckol forms stable complexes with key ZIKV proteins, including the envelope, NS2B/NS3, and RNA-dependent RNA polymerase (RdRp) protein, exhibiting high binding energies of −438.09 kcal/mol, −1040.51 kcal/mol, and −1043.40 kcal/mol, respectively. Overall, our findings suggest that ECE and dieckol are promising candidates for the development of anti-ZIKV agents. [ABSTRACT FROM AUTHOR]

Abstract The genus Primula holds great importance as a source of traditional remedies in various folk medicine systems. In the present study, we investigated the chemical composition and biological properties of different extracts (ethyl acetate, ethanol, ethanol/water, and water) of aerial parts and rhizomes of Primula vulgaris. To determine the chemical profile, the extracts were analyzed using ultrahigh performance liquid chromatography‐high‐resolution mass spectrometry (UHPLC‐HRMS) technique and flavonoids were a major group in this profile. The antioxidant capacity was demonstrated by in vitro chemical tests and in general the ethanol/water extract was found to be the most potent. Enzyme inhibition was studied against various enzymes and ethanol and ethanol/water extracts were more active than others. To assess the anti‐inflammatory potential of the extracts at the molecular level, human dermal fibroblasts (HDF) were treated with lipopolysaccharide (LPS). In vitro experiments showed that the levels of nuclear factor kappa B (NFKB), receptor for advanced glycation endproducts (RAGE), activator protein‐1 (AP‐1), interleukin 6 (IL‐6), interleukin 17 (IL‐17) and tumor necrosis factor (TNF)‐alpha were significantly reduced after treatment with the tested extracts. In addition, the extracts showed an inhibitory effect on the enzymes collagenase, elastase, and hyaluronidase, which are involved in the inflammatory process and destabilization of the extracellular matrix (ECM). P. vulgaris has been observed to modulate matrix metalloproteinase (MMP) synthesis by decreasing the concentration of cellular reactive oxygen species (ROS) during LPS‐induced inflammation. This study also examined the molecular binding and dynamic behavior of various enzymes and proteins associated with skin and infections using ligands derived from the tested extracts. Simulations with AutoDock Vina V1.1.2 and GROMACS 2023.1 showed that isoquercetin in particular showed superior performance in interactions with hyaluronidase. These findings are important for the development of potential therapeutic strategies for skin health and infection control. In summary, P. vulgaris can be considered as an important source of natural bioactive compounds for the development of effective health‐promoting applications in nutraceuticals, pharmaceuticals, and cosmetics

The antihyperglycemic activity of ethanolic extract from Annona cherimola Miller (EEAch) and its products were evaluated using in vivo and in silico assays. An α-glucosidase inhibition was evaluated with oral sucrose tolerance tests (OSTT) and molecular docking studies using acarbose as the control. SGLT1 inhibition was evaluated with an oral glucose tolerance test (OGTT) and molecular docking studies using canagliflozin as the control. Among all products tested, EEAc, the aqueous residual fraction (AcRFr), rutin, and myricetin reduced the hyperglycemia in DM2 mice. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak such as the control drugs. In the molecular docking studies, rutin showed more affinity in inhibiting α-glucosidase enzymes and myricetin in inhibiting the SGLT1 cotransporter, showing ∆G values of −6.03 and −3.32 kcal/mol−1, respectively, in α-glucosidase enzymes. In the case of the SGLT1 cotransporter, molecular docking showed ∆G values of 22.82 and −7.89 in rutin and myricetin, respectively. This research sorts in vivo and in silico pharmacological studies regarding the use of A. cherimola leaves as a source for the development of new potential antidiabetic agents for T2D control, such as flavonoids rutin and myricetin. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies. [ABSTRACT FROM AUTHOR]

Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: Drug-induced phospholipidosis is a side effect for which drug candidates can be screened in the drug discovery phase. The numerous in silico models that have been developed as a first line of screening are based on the characteristic physicochemical properties of phospholipidosis-inducing drugs, e.g. high log P and pK b values. However, applying these models on a predominantly high lipophilic, basic CNS chemistry results in a high false positive rate and consequently in a wrong classification of a large number of valuable drug candidates. Here, we tested 33 CNS-compounds (24 in vivo negative and 9 in vivo positive phospholipidosis-inducers) in our in house developed in vitro phospholipidosis screening assay () and compared its predictivity with the outcome of three different, well established in silico prediction models. Our in vitro assay demonstrates an increased specificity of 79% over the in silico models (29%). Moreover, by considering the proposed plasma concentration at the efficacious dose we can show a clear correlation between the in vitro and in vivo occurrence of phospholipidosis, improving the specificity of prediction to 96%. Through its high predictive value, the in vitro low throughput assay is thus preferred above high throughput in silico assays, characterized by a high false positive rate. [Copyright &y& Elsevier]

Approximately 20% industrial water pollution comes from textile dyeing process, with Azo dyes being a major problem in this scenario and requiring new forms of efficient treatment. Effluent treatments using the Advanced Oxidation Processes (AOP) are justified by the potential of application in the dyed effluent treatments once they can change the Azo dye chemical structure. Thus, this study aimed to evaluate the toxicity and mutagenic capacity of a synthetic effluent containing Amido Black 10B (AB10B) azo dye before treatment with AOP, named Gross Synthetic Effluent (GSE), and after the AOP, named Treated Synthetic Effluent (TSE). Daphnia magna and Allium cepa tests were used to evaluate acute toxicity effects and chromosomal mutagenesis, respectively. The Salmonella /microsome assay was performed to evaluate gene mutations. In silico assays were also performed aiming to identify the mutagenic and carcinogenic potential of the degradation byproducts of AB10B. There was 100% immobility to D. magna after 24 h and 48 h of treatments with TSE, showing EC 50 values around 5%, whereas GSE did not show acute toxicity. However, GSE induced chromosomal mutations in A. cepa test. Both GSE and TSE were not able to induce gene mutations in S. typhimurium strains. These effects can be associated with two byproducts generated with the cleavage of the azo bonds of AB10B, 4-nitroaniline and -2-7-triamino-8-hydroxy-3-6-naphthalinedisulfate (TAHNDS). In conclusion, AOP is an efficient method to reduce the mutagenicity of synthetic effluent containing AB10B and additional methods should be applied aiming to reduce the toxicity. • Amido Black 10B shows potential mutagenicity and carcinogenicity in silico models. • Advanced Oxidation Process decreases the mutagenicity of synthetic effluent. • Byproducts from Amido Black 10B might increase the toxicity of treated effluent. [ABSTRACT FROM AUTHOR]