LC-qTOF-MS/MS phytochemical profiling of Tabebuia impetiginosa (Mart. Ex DC.) Standl. leaf and assessment of its neuroprotective potential in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia impetiginosa (Bignoniaceae) was traditionally used for memory enhancement and central nervous system (CNS) stimulation. AIM OF THE STUDY: This study aims to create a metabolic profile of the ethyl acetate fraction of T. impetiginosa (TEF) and investigate for the first time its neuroprotective potential on cyclophosphamide (CP)-induced chemobrain, validating its traditional use. MATERIALS AND METHODS: Metabolite profiling of TEF was performed using Liquid Chromatography coupled with Quadrupole Time of Flight-Mass/Mass Spectrometry (LC-qTOF-MS/MS). For the in vivo study, CP (200 mg/kg, i.p.) was administered to induce cognitive impairment in rats; TEF (30 mg/kg, p.o.) was administered throughout the 14 days of the experiment to assess its role in mitigating CP-induced neuronal deficits. Behavioral tests including locomotor, Y-maze, and passive avoidance tests were conducted. Additionally, biochemical markers such as reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and caspase-3 immunoexpression were assessed in the hippocampus area. RESULTS: Forty-four phytoconstituents were tentatively identified in TEF, mainly iridoids and organic acids. TEF showed significant memory enhancement as evidenced by the increase in step-through latency in the passive avoidance test by 1.5 folds and the increase in sequence alternation percentage (SAP) in the Y-maze test by 67.3%, as compared to CP-group. Moreover, it showed pronounced antioxidant and anti-inflammatory potentials evidenced by the significant elevation in reduced glutathione (GSH) levels by 80% and a pronounced decline in MDA and TNF-α levels by 24% and 45%, respectively relative to the CP group. TEF treatment restored normal hippocampal histological features and attenuated apoptotic caspase-3 expression by 70% compared to the CP group. CONCLUSIONS: TEF can act as a promising natural scaffold in managing the chemobrain induced by CP in cancer patients.

A comparative untargeted metabolomic analysis and assessment of antiplasmodial potential of nine Albizia species.

The genus Albizia is one of the richest genera in phenolics besides other classes of secondary metabolites including saponins, terpenes, and alkaloids with promising medicinal applications. In the current study, UHPLC-PDA-ESI-MS/MS-based metabolic profiling of leaves of Albizia lebbeck, Albizia julibrissin, Albizia odoratissima, Albizia procera, Albizia anthelmintica, Albizia guachapele, Albizia myriophylla, Albizia richardiana, and Albizia lucidior resulted in the tentative identification of 64 metabolites, mainly flavonoids, phenolic acids, saponins, and alkaloids. Some metabolites were identified in Albizia for the first time and could be used as species-specific chemotaxonomic markers, including: apigenin 7-O-dihydroferuloyl hexoside isomers, apigenin 7-O-pentosyl hexoside, quercetin 3-O-rutinoside 7-O-deoxyhexoside, quercetin 3,7-di-O-hexoside deoxyhexoside, quercetin 7-O-feruloyl hexoside, methyl myricetin 7-O-deoxyhexoside, kaempferol di-3-O-di-deoxyhexoside-7-O-hexoside, and kaempferol 3-O-neohesperidoside 7-O-hexoside. Comparative untargeted metabolomic analysis was undertaken to discriminate between species and provide a chemotaxonomic clue that can be used together with morphological and genetic analyses for more accurate classification within this genus. Moreover, the in vitro antiplasmodial activity was assessed and correlated to the metabolic profile of selected species. This was followed by a molecular docking study and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction of the identified budmunchiamine alkaloids, revealing promising interactions with the active site of lactate dehydrogenase of Plasmodium falciparum and good pharmacokinetics and pharmacodynamics, which could help in designing novel antimalarial drugs.

Unveiling the Antimicrobial and Larvicidal Potential of Butyrolactones and Orsellinic Acid Derivatives from the Morus alba-derived Fungus Aspergillus terreus via Integrated In vitro and In silico Approaches.

The emergence of multi-drug-resistant microbial strains spurred the search for antimicrobial agents; as a result, two distinct approaches were combined: four in vitro studies and four corresponding molecular docking investigations. Antituberculosis, anti-methicillin-resistant Staphylococcus aureus (anti-MRSA), antifungal, and larvicidal activities of the crude extract, two fractions, and seven isolated compounds from Aspergillus terreus derived from Morus alba roots were explored. The isolated compounds (5 butyrolactones and 2 orsellinic acid derivatives) showed potent to moderate antitubercular activity with MIC values ranging from 1.95 to 62.5 µg/mL (compared to isoniazid, 0.24 µg/mL) and promising anti-MRSA potential with inhibition zone diameters ranging from 8 to 25 mm. Additionally, the in silico study proved that the isolated compounds bind to the two corresponding proteins' active sites with high to moderate -(C-Docker interaction energies) and stable interactions. The isolated compounds displayed antifungal activities against different fungal strains at diverse degrees of activity, among them compound (8"S,9")-dihydroxy-dihydrobutyrolactone I eliciting the best antifungal activity. Meanwhile, all isolated compounds, fractions, and the crude extract demonstrated extremely selective potent to moderate activity against Cryptococcus neoformans. The isolated five butyrolactone derivatives could develop potential mosquito larvicidal agents as a result of promising docking outcomes in the larval enzyme carboxylesterase.

Cytotoxic and antimicrobial mycophenolic acid derivatives from an endophytic fungus Penicillium sp. MNP-HS-2 associated with Macrozamia communis.

Macrozamia communis and its associated endophytic fungi are untapped sources of bioactive metabolites with great potential for medicinal exploitation. Chemical investigation of the mycelial extract derived from an endophytic fungus Penicillium sp. MNP-HS-2 associated with M. communis fruit afforded four mycophenolic acid derivatives recognized as previously undescribed natural products (1-4), together with nine known metabolites (5-13). Chemical structures of isolated compounds were determined based on extensive spectroscopic analyses, including 1D/2D NMR and HRESIMS. The absolute stereochemistry of alternatain E (1) was unambiguously established by comparing its experimental and calculated time-dependent density functional theory electronic circular dichroism spectra (TDDFT-ECD). All isolated compounds were assessed for their antimicrobial and cytotoxic activities, where mycophenolic acid methyl ester (7), displayed significant cytotoxic activity against seven different cell lines with IC50 values in the low micromolar to nanomolar range. Mycophenolene A (3) exhibited significant antibacterial activity against Staphylococcus aureus (MIC = 2.1 µg/mL).

New Meroterpenoid Derivatives from the Pomegranate-Derived Endophytic Fungus Talaromyces purpureogenus.

In this study, we report the isolation of two new meroterpenoids, miniolutelide D (1) and miniolutelide E (13-epi-miniolutelide C) (2), along with two meroterpenoidal analogues (3 and 4) and two phenolic compounds (5 and 6) from the endophytic fungus Talaromyces purpureogenus derived from Punica granatum fruits. Their structures were elucidated using extensive MS, 1D, and 2D NMR spectroscopic analyses as well as by comparing with data in the literature. The absolute configurations of 1 and 2 were determined using TDDFT-ECD calculations. Antimicrobial activity was evaluated. Compound 5 displayed significant activity against methicillin-resistant Staphylococcus aureus strain ATCC 700699 and moderate activity against S. aureus strain ATCC 29213.

Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review.

Aspergillus terreus microorganism represents a promising prospective source for drug discovery since it is rich in diverse kinds of bioactive secondary metabolites. It contributed to many biotechnological applications and its metabolites are used in the synthesis of certain pharmaceuticals and food products, in addition to its useful uses in fermentation processes. There are about 346 compounds identified from marine and terrestrial-derived A. terreus from 1987 until 2022, 172 compounds of them proved a vast array of bioactivity. This review aimed to create an up-to-date comprehensive literature data of A. terreus's secondary metabolites classes supported by its different bioactivity data to be a scientific record for the next work in drug discovery.

Neuroprotective Effect of Artichoke-Based Nanoformulation in Sporadic Alzheimer's Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways.

The vast socio-economic impact of Alzheimer's disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol O-glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, ß-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste.

Chemical Composition, Antiaging Activities and Molecular Docking Studies of Essential Oils from Acca sellowiana (Feijoa).

This study aimed to investigate the chemical composition of essential oils isolated from Acca sellowiana (feijoa) leaves and stems and elaborate on their relevance as natural anti-aging, coupled with molecular-docking studies. The isolated oils were analysed using gas chromatography-mass spectrometry analysis and investigated for inhibitory effects against acetylcholinesterase, ß-secretase, collagenase, elastase and tyrosinase. Molecular-modelling study was performed using MOE-Dock program to evaluate binding interactions of major components with the above-mentioned targets. The leaf oil revealed the predominance of caryophyllene oxide (24.3 %), linalool (7.9 %), and spathulenol (6.6 %), while the stem oil was presented by caryophyllene oxide (38.1 %), α-zingiberene (10.1 %) and humulene oxide II (6.0 %). The stem oil expressed superior inhibitory activities against acetylcholinesterase (IC50 =0.15±0.01 µg/mL), ß-secretase (IC50 =3.99±0.23 µg/mL), collagenase (IC50 =408.10±20.80 µg/mL), elastase (IC50 =0.17±0.01 µg/mL) and tyrosinase (IC50 =8.45±0.40 µg/mL). The valuable binding interactions and docking scores were observed for caryophyllene oxide and α-zingiberene with acetylcholinesterase. Besides, α-zingibirene followed by linalool and τ-cadinol revealed tight fitting with collagenase and elastase. Additionally, linalool, spathulenol and τ-cadinol showed the best binding energy to tyrosinase. This study provides valuable scientific data on A. sellowiana as potential candidates for the development of natural antiaging formulations. The current study provided scientific evidence for the potential use of feijoa essential oils in antiaging formulations and as an adjuvant for the prophylaxis against Alzheimer disease.

Rosmarinus officinalis L. hexane extract: phytochemical analysis, nanoencapsulation, and in silico, in vitro, and in vivo anti-photoaging potential evaluation.

A shift towards natural anti-aging ingredients has spurred the research to valorize traditionally used plants. In this context, Rosmarinus officinalis L. was evaluated for its photoprotective, antioxidant, anti-inflammatory, and anti-wrinkling properties. GC/MS and LC-ESI-HRMS based phytochemical profiling of rosemary leaves hexane extract resulted in the identification of 47 and 31 compounds, respectively and revealed rich content in triterpenoids, monoterpenoids and phenolic diterpenes. In vitro assays confirmed the antioxidant, anti-aging, and wound healing potential of rosemary extract along with a good safety profile, encouraging further development. A systematic molecular modelling study was conducted to elucidate the mechanistic background of rosemary anti-aging properties through the inhibitory effects of its major constituents against key anti-aging targets viz. elastase, collagenase, and hyaluronidase. Development of rosemary extract lipid nanocapsules-based mucoadhesive gels was performed to improve skin contact, permeation, and bioavailability prior to in vivo testing. The developed formulae demonstrated small particle size (56.55-66.13 nm), homogenous distribution (PDI of 0.207-0.249), and negatively charged Zeta potential (- 13.4 to - 15.6). In UVB-irradiated rat model, topical rosemary hexane extract-loaded lipid nanocapsules-based gel provided photoprotection, restored the antioxidant biochemical state, improved epidermal and dermal histological features, and decreased the level of inflammatory and wrinkling markers. The use of rosemary hexane extract in anti-aging and photoprotective cosmeceuticals represents a safe, efficient, and cost-effective approach.

Use of radiographic and histologic scores to evaluate cats with idiopathic megacolon grouped based on the duration of their clinical signs.

Since the duration of clinical signs could be used to identify cases of chronic constipation, in addition, prolonged duration is often associated with irreversible changes. Thus, the main objective of this study was to determine whether the duration of clinical signs of idiopathic megacolon in cats affected their diagnosis and prognosis after treatment. Medical records of cats that either had confirmed megacolon for an unknown cause (cat patients) or with normal bowels (control cats) were reviewed. Cat patients were grouped based on the duration of their clinical signs (constipation/obstipation) to cats <6 months and ≥6 months. For all feline patients, abdominal radiographs (for colonic indexes) and resected colon specimens (for histology) were assessed vs. control cats. Treatment applied to cat patients was also evaluated. Cat patients were older (p = 0.0138) and had a higher maximum colon diameter (MCD; mean 41.25 vs. 21.67 mm, p < 0.0001) and MCD/L5L ratio (1.77 vs. 0.98, p < 0.0001) than controls. Compared to cats with <6 months, cats ≥6 months showed a higher MCD (43.78 vs. 37.12 mm, p < 0.0001) and MCD/L5L ratio (1.98 vs. 1.67, p < 0.0001). Histologically, increased thickness of the smooth muscularis mucosa (54.1 vs. 22.33 µm, p < 0.05), and inner circular (743.65 vs. 482.67 µm, p < 0.05) and outer longitudinal (570.68 vs. 330.33 µm, p < 0.05) smooth muscular layers of the muscularis externa was noted only in cat patients with ≥6 months compared to controls. Similarly, fewer ganglion cells (0.93 vs. 2.87, p < 0.005) and more necrotized myocytes (2.25 vs. 0.07, p < 0.005) were observed in cats with ≥6 months. In contrast to <6 months, the majority of cats (94.4%) with ≥6 months duration did not show any response to medical treatment and therefore underwent surgery with favorable results. In conclusion, this study suggests that the duration of clinical signs should be considered in conjunction with maximal colon scores to evaluate cats for idiopathic megacolon and determine the level of treatment. Functional abnormalities of the colonic smooth muscles may be a possible cause of idiopathic megacolon in cats.

Molecular and phytochemical variability among genus Albizia: a phylogenetic prospect for future breeding.

Fabaceae, the third-largest Angiosperm family, exhibits great morphological diversity with significantly high species diversification rate. Albizia, one of the largest genera of the legume family, possesses high ecological, economical and medicinal application prospects and displays a global distribution. The taxonomic classification among Albizia remains, however, unclear and has been subjected to changes. The resolution of phylogenetic relationships among members of genus Albizia is a priority. Nine Albizia species cultivated in Egypt; Albizia lebbeck, A. julibrissin, A. odoratissima, A. procera, A. anthelmintica, A. guachapele, A. myriophylla, A. richardiana and A. lucida were subjected to molecular classification via DNA fingerprinting techniques viz. Inter Simple Sequence Repeat (ISSR) and Start Codon Targeted polymorphism (SCoT) using ten primers, five for each technique. The total number of bands produced by ISSR and SCoT primers was 28 and 40, respectively. The percentage of polymorphism varied from 64.28% in ISSR to 67.50% in SCoT analysis. Additionally, chemotaxonomic analysis was implemented based on UV spectroscopic profiling and total phenolic content coupled to unsupervised chemometric tools; Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). Interspecific relationships were confirmed via molecular and phytochemical analyses between A. procera and A. guachapele; A. lebbeck and A. odoratissima; and A. julibrissin and A. lucida. The study reveals that chemotaxonomic data can reflect phylogenetic relationships among examined Albizia species and provides insights to the significance of utilizing the strengths of both molecular taxonomy and chemotaxonomy to resolve phylogenetic relationship among this genus which offers baseline for breeding programs. Future strategies to enrich taxonomic classification among Albizia includes extensive morphological characterization, DNA barcoding techniques and metabolomic profiling.

A comparative volatilomic characterization of Florence fennel from different locations: antiviral prospects.

The genus Foeniculum is known for its wide ethnobotanical use in the Mediterranean region. Herein, we explored the compositional differences of volatile oils and headspace aroma of Florence fennel (Foeniculum vulgare var. azoricum (Mill.) Thell.) based on its different organs and various geographical origins via gas chromatography coupled with mass spectrometry (GC-MS). Sixty-seven volatile components were detected with phenylpropenes and monoterpenes, including trans-anethole, limonene, α-pinene, trans-ß-ocimene, fenchyl acetate, and fenchone, as major constituents. Phenylpropenes were dominant in fennel hydro-distilled oils, whereas monoterpenes were dominant in most of the headspace aroma. The infraspecific variability was assessed using the unsupervised multivariate data analysis tools PCA and HCA, resulting in segregate clustering of accessions from different organs and locations with trans-anethole, limonene, trans-ß-ocimene, fenchone, myristicin, and apiole as major phytomarkers contributing to this segregation. The antiviral activities of samples against hepatitis A and C viruses were investigated using the plaque reduction assay, HAV 3C proteinase and HCV NS5B polymerase inhibitory assays with a percentage inhibition between 66% and 85% and IC50 values from 1.8 to 26.7 µg mL-1. In silico molecular docking scores in latter enzyme binding pockets revealed key allosteric interactions with trans-ß-ocimene and ß-fenchyl acetate showing the best Gibb's free energy. Florence fennel exhibited interesting new perspectives for medicinal and industrial applications.

A pilot study of Livin gene and Yes-associated protein 1 expression in hepatocellular carcinoma patients.

BACKGROUND: Livin gene and Yes-Associated Protein 1 (YAP1 (play a pivotal role in organ size control and tumorigenesis. AIM: In the present pilot study, we investigate the expression of Livin gene and YAP1 in hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) compared to other HCV patients and controls.Methods: the studied patients were divided into three groups 30 patients in each group in addition to 30 healthy subjects as a control group. Relative quantification of Livin gene and YAP-1 were assessed by quantitative Real Time RT-PCR (qPCR) in all studied patients and healthy controls. other laboratory investigations were done including complete blood count (CBC),international normalized ratio (INR) as well as liver function tests and tumor markers. RESULTS: Significant overexpression of Livin gene and YAP-1 was detected in HCC group followed by Hepatitis C Virus (HCV) untreated group then HCV treated group. The relative quantitation (RQ) of both genes showed positive correlation to the carcinoembryonic antigen (CEA) level and a significant relation was found between higher level of Livin and YAP1 genes and tumor size. The overall survival rate was low in those patients with high levels of Livin and YAP 1 genes so they were considered as indicators of a bad prognosis. CONCLUSION: There is overexpression of Livin gene and YAP1 in hepatocellular carcinoma patients. They can be used as indicators of bad prognosis of the disease pathway together with low survival rate.

Artemisinin nanoformulation suitable for intravenous injection: Preparation, characterization and antimalarial activities.

More than 40 years after its discovery, artemisinin has become the most promising antimalarial agent. However, no intravenous formulation is available due to its poor aqueous solubility. Here, we report the preparation, characterization, and in vitro and in vivo biological evaluation of biodegradable albumin-bound artemisinin nanoparticles. The nanoparticles were prepared by a combination of a bottom-up and a top-down processes and characterized by different spectroscopic techniques. The preparation process was optimized to develop a nanoformulation with the smallest possible diameter and good homogeneity suitable for intravenous injection enabling direct contact of artemisinin with infected erythrocytes. Chemically and physically stable artemisinin nanoparticles were obtained with excellent entrapment efficiency. In in vitro experiments, the artemisinin nanoformulation was interestingly more effective than non-formulated artemisinin. In Plasmodiumm falciparum-infected 'humanized' mice, the nanoparticles proved to be highly effective with 96% parasitemia inhibition at 10mg/kg/day, prolonging mean survival time without recrudescence. This nanoparticulate albumin-bound system allows the intravenous administration of artemisinin for the first time without harsh organic solvents or cosolvents with 100% bioavailability.

Albumin-bound nanoparticles of practically water-insoluble antimalarial lead greatly enhance its efficacy.

We recently showed that the indolone-N-oxides can be promising candidates for the treatment of chloroquine-resistant malaria. However, the in vivo assays have been hampered by the very poor aqueous solubility of these compounds resulting in poor and variable activity. Here, we describe the preparation, characterization and in vivo evaluation of biodegradable albumin-bound indolone-N-oxide nanoparticles. Nanoparticles were prepared by precipitation followed by high-pressure homogenization and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry and X-ray powder diffraction. The process was optimized to yield nanoparticles of controllable diameter with narrow size distribution suitable for intravenous administration, which guarantees direct drug contact with parasitized erythrocytes. Stable nanoparticles showed greatly enhanced dissolution rate (complete drug release within 30 min compared to 1.5% of pure drug) preserving the rapid antimalarial activity. The formulation achieved complete cure of Plasmodium berghei-infected mice at 25mg/kg with parasitemia inhibition (99.1%) comparable to that of artesunate and chloroquine and was remarkably more effective in prolonging survival time and inhibiting recrudescence. In 'humanized' mice infected with Plasmodium falciparum, the same dose proved to be highly effective: with parasitemia reduced by 97.5% and the mean survival time prolonged. This formulation can help advance the preclinical trials of indolone-N-oxides. Albumin-bound nanoparticles represent a new strategic approach to use this most abundant plasma protein to target malaria-infected erythrocytes.

Macrocyclic spermidine alkaloids from Androya decaryi L. Perrier.

Three new spermidine alkaloids and two known compounds were isolated from the leaves of Androya decaryi. Their structures were elucidated on the basis of their spectroscopic data (NMR and mass spectrometry), by X-Ray diffraction and by comparison with literature values. Evaluation of the in vitro antiplamosdial properties of the isolated compounds revealed they did not possess any significant activity.

Interactions between antimalarial indolone-N-oxide derivatives and human serum albumin.

The binding affinity of human serum albumin (HSA) to three antimalarial indolone-N-oxide derivatives, INODs, was investigated under simulated physiological conditions using fluorescence spectroscopy in combination with UV-vis absorption and circular dichroism (CD) spectroscopy. Analysis of fluorescence quenching data of HSA by these compounds at different temperatures using Stern-Volmer and Lineweaver-Burk methods revealed the formation of a ground state indolone-HSA complex with binding affinities of the order 10(4) M(-1). The thermodynamic parameters ΔG, ΔH, and ΔS, calculated at different temperatures, indicated that the binding reaction was endothermic and hydrophobic interactions play a major role in this association. The conformational changes of HSA were investigated qualitatively using synchronous fluorescence and quantitatively using CD. Site marker competitive experiments showed that the binding process took place primarily at site I (subdomain IIA) of HSA. The number of binding sites and the apparent binding constants were also studied in the presence of different ions.