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The foremost target of the current work was to formulate and optimize a novel bergamot essential oil (BEO) loaded nano-phytosomes (NPs) and then combine it with spironolactone (SP) in order to clinically compare the efficiency of both formulations against acne vulgaris. The BEO-loaded NPs formulations were fabricated by the thin-film hydration and optimized by 32 factorial design. NPs' assessments were conducted by measuring entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In addition, the selected BEO-NPs formulation was further combined with SP and then examined for morphology employing transmission electron microscopy and three months storage stability. Both BEO-loaded NPs selected formula and its combination with SP (BEO-NPs-SP) were investigated clinically for their effect against acne vulgaris after an appropriate in silico study. The optimum BEO-NPs-SP showed PS of 300.40 ± 22.56 nm, PDI of 0.571 ± 0.16, EE% of 87.89 ± 4.14%, and an acceptable ZP value of −29.7 ± 1.54 mV. Molecular modeling simulations showed the beneficial role of BEO constituents as supportive/connecting platforms for favored anchoring of SP on the Phosphatidylcholine (PC) interface. Clinical studies revealed significant improvement in the therapeutic response of BEO-loaded NPs that were combined with SP over BEO-NPs alone. In conclusion, the results proved the ability to utilize NPs as a successful nanovesicle for topical BEO delivery as well as the superior synergistic effect when combined with SP in combating acne vulgaris. [ABSTRACT FROM AUTHOR]

This study aimed to assess the potential of Lactuca serriola (Asteraceae) seed n-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where n-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially n-hexane extract (400 mg/kg)—which showed 456.14%—increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, L. serriola enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of L. serriola seeds. [ABSTRACT FROM AUTHOR]

Drought is among the most common abiotic stresses that significantly influence plants' growth and metabolic activities. In this study, Eriocephalus africanus L. (Asteraceae) was exposed to three levels of drought stress (irrigation with 75, 50, and 25% field capacity), together with foliar spraying of a plant hormone, salicylic acid (1, 2, and 3 mM SA), to observe the effect of drought stress and SA on its secondary metabolites. These growing conditions efficiently affected its total flavonoid and polyphenol contents (TFC and TPC, respectively). TFC and TPC increased by 53% and 35%, respectively, in stressed plants. Consequently, the radical scavenging activity improved by 140%. UPLC-ESI-MS/MS profiles of the extracts of control and stressed plants were assessed. Among identified polyphenols, 3,4-dicaffeoylquinic acid predominated in both samples, although it was detected in a greater percentage of stressed plants. Essential oils hydro-distilled from the plants showed a higher yield (1.05 ± 0.03% v/w) in stressed plants. Artemisia ketone prevailed in all oil samples' GC/MS chromatograms, with a higher yield (42%) recorded in stressed plants. In conclusion, drought stress and SA spraying triggered the production of phenolic and essential oil components and increased the radical scavenging activity of E. africanus. Thus, agricultural conditions are optimized to provide a continuous supply of plant materials with appropriate amounts of bioactive constituents for economic industrialization. [ABSTRACT FROM AUTHOR]

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC50 = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC50 = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents. [ABSTRACT FROM AUTHOR]

Saussurea hypoleuca belongs to the family Asteraceae, which has previously shown hepatoprotective, anticancer, and antioxidant activity. This study aimed to evaluate the antihyperglycemic and antihyperlipidemic activity of its root methanol extract and various fractions for the first time. This was performed using alloxan-induced diabetes in the rat model for both short, and long-term periods using different administration doses. Different biochemical parameters were studied and further consolidated by histopathological examination and in silico molecular modeling. The results showed that in the long-term study, at a dose of 400 mg/kg b.wt, the ethyl acetate fraction caused a pronounced reduction in fasting blood glucose level (FBG) and glycated hemoglobin (HbA1c) by 77.2% and 36.8%, respectively, compared to the diabetic group. This was confirmed by the histopathological examination of the animals' pancreatic sections. The ethyl acetate fraction also showed a reduction in total cholesterol (TC), total glycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels. It improved kidney and liver functions, causing a reduction in aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), urea, and creatinine levels. This is mainly attributed to its richness in secondary metabolites. Molecular docking showed that all the tested compounds showed certain inhibitory potential towards human α-glucosidase (HAG) and ATP citrate lyase (ACL). Thus, Saussurea hypoleuca roots can help in the management of hyperglycemia, hyperlipidemia, and hepatic and kidney dysfunction. [ABSTRACT FROM AUTHOR]

This study presents a comparison between two mistletoe plants—P. acacia and P. curviflorus—regarding their total phenolic contents and antioxidant and anticancer activities. P. curviflorus exhibited a higher total phenolics content (340.62 ± 19.46 mg GAE/g extract), and demonstrated higher DPPH free radical scavenging activity (IC50 = 48.28 ± 3.41µg/mL), stronger reducing power (1.43 ± 0.54 mMol Fe+2/g) for ferric ions, and a greater total antioxidant capacity (41.89 ± 3.15 mg GAE/g) compared to P. acacia. The cytotoxic effects of P. acacia and P. curviflorus methanol extracts were examined on lung (A549), prostate (PC-3), ovarian (A2780) and breast (MDA-MB-231) cancer cells. The highest anticancer potential for the two extracts was observed on PC-3 prostate cancer cells, where P. curviflorus exhibited more pronounced antiproliferative activity (IC50 = 25.83 μg/mL) than P. acacia (IC50 = 34.12 μg/mL). In addition, both of the tested extracts arrested the cell cycle at the Pre-G1 and G1 phases, and induced apoptosis. However, P. curviflorus extract possessed the highest apoptotic effect, mediated by the upregulation of p53, Bax, and caspase-3, 8 and 9, and the downregulation of Bcl-2 expression. In the pursuit to link the chemical diversity of P. curviflorus with the exhibited bioactivities, its metabolomic profiling was achieved by the LC-ESI-TOF-MS/MS technique. This permitted the tentative identification of several phenolics—chiefly flavonoid derivatives, beside some triterpenes and sterols—in the P. curviflorus extract. Furthermore, all of the metabolites in P. curviflorus and P. acacia were inspected for their binding modes towards both CDK-2 and EGFR proteins using molecular docking studies in an attempt to understand the superiority of P. curviflorus over P. acacia regarding their antiproliferative effect on PC-3 cancer cells. Docking studies supported our experimental results; with all of this taken together, P. curviflorus could be regarded as a potential prospect for the development of chemotherapeutics for prostate cancer. [ABSTRACT FROM AUTHOR]

The development of bacterial resistance to traditional antibiotics constitutes an emerging public health issue. Promising approaches have been innovated to conquer bacterial resistance, and targeting bacterial virulence is one of these approaches. Bacterial virulence mitigation offers several merits, as antivirulence agents do not affect the growth of bacteria and hence do not induce bacteria to develop resistance. In this direction, numerous drugs have been repurposed as antivirulence agents prior to their clinical use alone or in combination with traditional antibiotics. Quorum sensing (QS) plays a key role in controlling bacterial virulence. In the current study, dipeptidase inhibitor-4 (DPI-4) antidiabetic gliptins were screened for their antivirulence and anti-quorum sensing (anti-QS) activities against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. Upon assessing their antibiofilm activities, the ten tested gliptins significantly diminished biofilm formation. In particular, sitagliptin exhibited the most efficient antibiofilm activity, so it was chosen as a representative of all gliptins to further investigate its antivirulence activity. Sitagliptin significantly protected mice from P. aeruginosa and S. aureus pathogenesis. Furthermore, sitagliptin downregulated QS-encoding genes in P. aeruginosa and S. aureus. To test the anti-QS activities of gliptins, a detailed molecular docking study was conducted to evaluate the gliptins' binding affinities to P. aeruginosa and S. aureus QS receptors, which helped explain the anti-QS activities of gliptins, particularly sitagliptin and omarigliptin. In conclusion, this study evaluates the possible antivirulence and anti-QS activities of gliptins that could be promising novel candidates for the treatment of aggressive Gram-negative or -positive bacterial infections either alone or as adjuvants to other antibiotics. [ABSTRACT FROM AUTHOR]