Rhoifolin, baicalein 5,6-dimethyl ether and agathisflavone prevent amnesia induced in scopolamine zebrafish (Danio rerio) model by increasing the mRNA expression of bdnf, npy, egr-1, nfr2α, and creb1 genes.

The increasing attention towards age-related diseases has generated significant interest in the concept of cognitive dysfunction associated with Alzheimer's disease (AD). Certain limitations are associated with the current therapies, and flavonoids have been reported to exhibit multiple biological activities and anti-AD effects in several AD models owing to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties. In this study, we performed an initial in silico predictions of the pharmacokinetic properties of three flavonoids (rhoifolin, baicalein 5,6-dimethyl ether and agathisflavone). Subsequently, we evaluated the antiamnesic and antioxidant potential of flavonoids in concentrations of 1, 3, and 5 µg/L in scopolamine (100 µM)-induced amnesic zebrafish (Danio rerio) model. Zebrafish behavior was analyzed by novel tank diving test (NTT), Y-maze, and novel object recognition test (NOR). Acetylcholinesterase (AChE) activity, brain antioxidant status and the expression of bdnf, npy, egr1, nrf2α, creb1 genes, and CREB-1 protein level was measured to elucidate the underlying mechanism of action. Our flavonoids improved memory and decreased anxiety-like behavior of scopolamine-induced amnesia in zebrafish. Also, the studied flavonoids reduced AChE activity and brain oxidative stress and upregulated the gene expression, collectively contributing to neuroprotective properties. The results of our study add new perspectives on the properties of flavonoids to regulate the evolution of neurodegenerative diseases, especially AD, by modulating the expression of genes involved in the regulation of synaptic plasticity, axonal growth, and guidance, sympathetic and vagal transmission, the antioxidant response and cell proliferation and growth.

Stress resistance, antiaging, and neuroprotective activities of baicalein 5,6-dimethyl ether and Alnus rugosa extract in Caenorhabditis elegans model.

The leaf extract of Alnus rugosa (AR) together with the isolated compound baicalein 5,6-dimethyl ether (BME) were investigated for their antioxidant, radical scavenging, antiaging, and neuroprotective properties using the Caenorhabditis elegans model. The stress resistance and antiaging potential of AR and BME were assessed in wild-type N2 and transgenic C. elegans strains CF1553, TJ356, and BA17. Transgenic CL4176 expressing the human amyloid-beta peptide (Aß) was used as a model for Aß toxicity, whereas transgenic AM141 expressing polyQ aggregates was employed as a model for Huntington's disease. An in silico molecular docking study using Discovery Studio 4.5 was performed to elucidate the putative binding mode of BME to the active sites of Daf-2 protein, involved in longevity and oxidative stress resistance in C. elegans. BME and AR significantly delayed the appearance of oxidative stress markers in wild-type N2 and transgenic strains TJ356 and CF1553, affecting the DAF-16/FOXO transcription factor subcellular distribution and inducing expression of the sod-3 antioxidative gene. Pretreatment with AR significantly reduced the aging marker lipofuscin accumulation in BA17 worms, its effect was greater than that of epigallocatechin gallate, suggesting a potential antiaging effect. Neuroprotective effects of AR and BME were confirmed in AM141 transgenic worms, inducing a significant reduction in the score of polyQ40::GFP aggregates. Moreover, BME (25 µg/mL) resulted in a significant delay in Aß-induced paralysis in CL4176 worms. In silico molecular modeling revealed that BME exhibited good fitting scores within the active sites of the Daf-2 protein. AR and BME exert beneficial effects in the modulation of age-related markers and attenuation of neurotoxicity in neurodegenerative disorders. Hence, AR and BME could be recognized as promising antioxidant and neuroprotective natural drug candidates that could be included in neuro-nutraceuticals.

Acremochlorin S and other prenylated chlorophenol antimicrobial metabolites from the fungus Acremonium sp. Strain MNA-F-1.

Chemical prospection for the mycelial extract of the fungus Acremonium sp. Strain MNA-F-1, derived from the inner tissue of anise roots (Pimpnella anisum L., family Apiaceae), led to the isolation and characterization of one previously undescribed natural product, acremochlorin S (1), together with five related derivatives (2-6) and an alkaloidal metabolite, ilicicolin H (7). Structure elucidation of the isolated compounds was determined through comprehensive 1D/2D NMR spectroscopic analyses and HR-ESI-MS measurements. The absolute configuration of acremochlorin S (1) was concluded based on the comparison of its experimental and calculated electronic circular dichroism (ECD) spectra implementing Time-dependent density functional theory (TDDFT). All isolated compounds were assessed for their antibacterial activity against Staphylococcus aureus, Escherichia coli and Mycobacterium tuberculosis, where several compounds revealed potent activities against tested Gram-positive strains.

The underrepresented quinolinone alkaloids in genera Penicillium and Aspergillus: structure, biology, and biosynthetic machinery.

Quinolone alkaloids are N-heterocycles with extensive structural diversity, mainly derived from in fungi from anthranilic acid and amino acids as precursors with a wide range of biological activities as antifungal, antimicrobial, anti-inflammatory, and insecticidal activities. The quinolone basic skeleton comprised of either 2-quinolones or 4-quinolones generated more than one hundred compounds. Several reviews discussed quinolones; particularly, the fluoroquinolones, yet few studies tackled natural quinolones. Many of these quinolones were not assayed for their antimicrobial potential despite their unique stereospecificity, which can supersede synthetic quinolones if their discovery is coupled with OMICS techniques, biochemical and molecular strategies as heterologous expression to maximize their yield. Herein, we conducted a comprehensive review of the quinolone's family in Aspergillus and Penicillium species, the exclusive producers of quinolones whether they are soil, endophytic or marine derived highlighting their isolation, chemical structures, pharmacological effects, structure activity relationships if any, and biosynthetic machinery. We believe that our initiative will pave the way for further development of natural quinolones as future antimicrobial agents.

Hepatoprotective activity of medicinal plants, their phytochemistry, and safety concerns: a systematic review.

Medicinal plants and their derivatives represent a promising reservoir of remedies for various ailments. Especially secondary metabolites of these plants, including alkaloids, flavonoids, phenolic compounds, terpenoids, steroids, saponins, tannins, and anthraquinones, play crucial roles in hepatoprotection. Studies have identified several prominent phytoconstituents, such as silymarin, quercetin, luteolin, glycyrrhizin, curcumin, gallic acid, chebulic acid, catechin, aloin, emodin, liquiritin, liquiritigenin, cudraflavone B, and karaviloside, as effective agents for addressing hepatotoxicity. The mechanisms underlying their efficacy include antioxidant, anti-inflammatory, free radical scavenging, and the ability to block oxidative stress, cytokine production, and stabilize liver cell membranes. The application of natural products derived from medicinal plants in treating liver injuries is rooted in their efficacy, cost-effectiveness, and safety profile, contributing to their popularity. Many studies, encompassing in vitro, in vivo, preclinical, and clinical investigations, have demonstrated that the extracts of medicinal plants mitigate chemical-induced liver damage using animal models. However, intensive research efforts regarding the safety, regulatory standard, and quality control issues for using medicinal plants as hepatoprotective agents remain the strong task of scholars. The primary focus of this systematic review is to analyze the current state of the literature regarding treating liver ailments using extracts from medicinal plants, examining their phytochemical composition, and addressing associated safety considerations.

Hibiscus schizopetalus boosts wound healing via restoring redox balance and hindering inflammatory responses in rats: Insights on metabolome profiling and molecular docking.

Hibiscus species (Malvaceae) possess a plethora of appealing pharmacological activities with an extended history of customary use in diverse medical conditions. The present study aimed at comparing the metabolomic analyses of three Hibiscus species native to Egypt, namely H. tiliaceus, H. schizopetalus extract (HSE), and H. rosa-sinensis, alongside identifying a promising natural wound healing candidate. Chemical profiling of the leaf extracts was achieved via UPLC-ESI/MS/MS-guided analysis that resulted in the tentative identification of a total of 48 secondary metabolites pertaining to phenolic acids, flavonoids, anthocyanins, fatty acids, and fatty amides. Remarkably, in vitro studies revealed that HSE exhibited the topmost wound healing activity. Subsequently, HSE was formulated into hydro- and nanogel (1% w/v) formulations for further assessing its efficacy in the wound excision model. HSE-nanogel demonstrated a significant in vivo wound contraction activity alongside improving histopathological abnormalities. Mechanistically, HSE-nanogel upregulated the wound antioxidant status through increasing the levels of reduced glutathione (GSH) and catalase activity. Moreover, HSE-nanogel suppressed the wound inflammatory responses by diminishing the expressions of NF-ĸB, TNF-α, and IL-6. Molecular docking studies were performed on HSE's major constituents using CDOCKER, which further supported the in vivo findings. Collectively, HSE nanogel exhibits notable aptitude as a wound-healing agent, warranting further clinical appraisal.

Moringa oleifera flowers: insights into their aroma chemistry, anti-inflammatory, antioxidant, and enzyme inhibitory properties.

BACKGROUND: Moringa oleifera is a highly nutritious plant widely used in traditional medicine. RESULTS: The aroma constituents present in the fresh flowers of M. oleifera versus the hydrodistilled oil and hexane extract were studied using GC-MS. Aldehydes were the major class detected in the fresh flowers (64.75%) with E-2-hexenal being the predominant component constituting > 50%. Alkane hydrocarbons, monoterpenes, and aldehydes constituted > 50% of the hydrodistilled oil, while alkane hydrocarbons exclusively constitute up to 65.48% of the hexane extract with heptacosane being the major component (46.2%). The cytotoxicity of the hexane extract was assessed on RAW 264.7 macrophages using the MTT assay which revealed no significant cytotoxicity at concentrations of 1 µg/mL and displayed IC50 value at 398.53 µg/mL as compared to celecoxib (anti-inflammatory drug) with IC50 value at 274.55 µg/ml. The hexane extract of Moringa flowers displayed good anti-inflammatory activity through suppression of NO, IL-6, and TNF-α in lipopolysaccharide-induced RAW 264.7 macrophages. The total phenolic and flavonoid content in the hexane extract was found to be 12.51 ± 0.28 mg GAE/g extract and 0.16 ± 0.01 mg RuE/g extract, respectively. It displayed moderate antioxidant activity as indicated by the in vitro DPPH, ABTS, CUPRAC, FRAP, and phosphomolybdenum (PBA) assays. No metal chelating properties were observed for the extract. The enzyme inhibitory potential of the hexane extract was evaluated on acetyl- and butyrylcholinesterases (for neuroprotective assessment), α-amylase and α-glucosidase (for antihyperglycemic assessment), and tyrosinase (for dermoprotective assessment) revealing promising results on cholinesterases, tyrosinase, and α-glucosidase. CONCLUSION: Our findings suggested that M. oleifera leaves can be considered as a multidirectional ingredient for preparing functional applications.

Comparative metabolomics study on the secondary metabolites of the red alga, Corallina officinalis and its associated endosymbiotic fungi.

Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).

The impact of seasonal variation on the composition of the volatile oil of Polyalthia suberosa (Roxb.) Thwaites leaves and evaluation of its acetylcholinesterase inhibitory activity.

BACKGROUND: Polyalthia suberosa (Roxb.) Thwaites (Annonaceae) is a medicinal plant that has been reported for its various pharmacological potentials, such as its anti-inflammatory, analgesic, antioxidant, and neuropharmacological activities. This study aimed to analyze the leaf essential oils of P. suberosa (PSLO) collected in different seasons, to evaluate the acetylcholinesterase inhibitory activity, and to corroborate the obtained results via in-silico molecular docking studies. METHODS: The leaf essential oils of P. suberosa collected in different seasons were analyzed separately by GC/MS. The acetylcholinesterase inhibitory activity of the leaves oil was assessed via colorimetric assay. In-silico molecular docking studies were elucidated by virtual docking of the main compounds identified in P. suberosa leaf essential oil to the active sites in human acetylcholinesterase crystal structure. RESULTS: A total of 125 compounds were identified where D-limonene (0.07 - 24.7%), α-copaene (2.25 - 15.49%), E-ß-caryophyllene (5.17 - 14.42%), 24-noroleana-3,12-diene (12.92%), ß-pinene (0.14 - 8.59%), and α-humulene (2.49-6.9%) were the most abundant components. Results showed a noteworthy influence of the collection season on the chemical composition and yield of the volatile oils. The tested oil adequately inhibited acetylcholinesterase enzyme with an IC50 value of 91.94 µg/mL. Additionally, in-silico molecular docking unveiled that palmitic acid, phytol, p-cymene, and caryophyllene oxide demonstrated the highest fitting scores within the active sites of human acetylcholinesterase enzyme. CONCLUSIONS: From these findings, it is concluded that P. suberosa leaf oil should be evaluated as a food supplement for enhancing memory.

Role of Nutraceuticals in Obesity Management: A Mechanism and Prospective Supported by Molecular Docking Studies.

Obesity and its comorbidities represent a major health problem worldwide. Treatment by reducing food intake and physical activity interventions has limited success especially with elderly people with chronic diseases. Nutraceuticals are naturally originated and successfully used for their physiological and nutritional benefit in health care. They might be alternative means to help lose weight and reduce obesity-associated metabolic disorders with the improvement of health, delay the aging process, prevention of chronic diseases, increase of life expectancy, or support to the structure or function of the body. The current study enumerates the inherent role of nutraceuticals in the management of obesity and its related comorbidities. The study is supported with the molecular docking studies discussing the mechanism of action. An attempt to optimize the role of nutraceuticals is made in this article in addition to widen the scope of its use in this chronic worldwide disease.

Genus Curcuma: chemical and ethnopharmacological role in aging process.

Aging or senescence is part of human life development with many effects on the physical, mental, and physiological aspects which may lead to age-related deterioration in many organs. Genus Curcuma family Zingieraceae represents one of the well-studied and medically important genera with more than eighty species. The genus is reported to contain different classes of biologically active compounds that are mainly presented in diphenylheptanoids, diphenylpentanoids, diphenylalkanoids, phenylpropene derivatives, alkaloids, flavonoids, chromones, terpenoids, phenolic acids and volatile constituents. Rhizomes and roots of such species are rich with main phytoconstituents viz. curcumin, demethoxycurcumin and bis-demethoxycurcumin. A wide variety of biological activities were demonstrated for different extracts and essential oils of genus Curcuma members including antioxidant, anti-inflammatory, cytotoxic and neuroprotective. Thus, making them as an excellent safe source for nutraceutical products and as a continuous promising area of research on lead compounds that may help in the slowing down of the aging process especially the neurologic and mental deterioration that are usually experienced upon aging. In this review different species of the genus Curcuma were summarized with their phytochemical and biological activities highlighting their role as antiaging agents. The data were collected from different search engines viz. Pubmed®, Google Scholar®, Scopus® and Web of Science® limiting the search to the period between 2003 up till now.

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.

Comparative metabolic study of the chloroform fraction of three Cystoseira species based on UPLC/ESI/MS analysis and biological activities.

This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The results revealed the identification of 19, 20 and 11 metabolites in C. myrica, C. trinodis, and C. tamariscifolia, respectively mainly terpenoids, flavonoids, phenolic acids and fatty acids. Also, an in vitro antioxidant study using FRAP and DPPH assays was conducted where the chloroform fraction of C. trinodis displayed the highest antioxidant activity in both assays, which would be attributed to its highest total phenolics and total flavonoids. Besides, the investigation of COX-1, α-glucosidase and α-amylase inhibitory activities were performed. Regarding C. trinodis, it showed the strongest inhibitory activity towards COX-1. Moreover, it showed potent inhibitory activity towards α-glucosidase and α-amylase enzymes. According to the molecular docking studies, the major compounds characterised showed efficient binding to the active sites of the target enzymes.

Eremophila purpurascens: Anti-oxidant, Anti-hyperglycemic, and Hepatoprotective Potential of Its Polyphenolic Rich Leaf Extract and Its LC-ESI-MS/MS Chemical Characterization and Standardization.

The genus Eremophila, despite comprising more than 250 species, has scarce literature studies that could be traced concerning the chemical profile and bioactivity of Eremophila purpurascens. The current study targets the investigation of the in vitro and in vivo anti-oxidant, anti-hyperglycemic, and hepatoprotective potential of the polyphenol-rich leaf extract of E. purpurascens (EP). EP showed promising total anti-oxidant capacity with IC50 values of 106 and 114 µg/mL in 2,2'-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) and diphenyl-1-picrylhydrazyl (DPPH) assays, respectively, with total anti-oxidant capacities of 331, 245, and 1767 µmol/g in ABTS, DPPH, and ferric reducing anti-oxidant power assays, respectively. In HepG2 cells, pre-treated with CCl4, a dose of 100 µg/mL EP ameliorated the reduced superoxide dismutase and glutathione levels and total anti-oxidant capacity with values of 312.5 U/mL, 15.47 mg/dL, and 1.03 nmol/mL, respectively. In vitro anti-diabetic evaluation using 3T3-L1 adipocyte culture showed that at a dose of 30 µg/mL, the EP extract elicited a 6.3% decrease in the concentration of glucose (22.4 mmol/L), showing significant amelioration with regard to pioglitazone and insulin. EP also demonstrated elevated serum insulin by 77.78% with a marked reduction in fasting blood glucose level by 64.55% relative to the streptozotocin diabetic rats in vivo. EP also relieved the liver stress markers both in vitro in CCl4 and in vivo in tamoxifen (TAM) models. EP markedly decreased TAM toxicity, as demonstrated by the decline in the liver stress markers, ALT and AST, by 36.1 and 51.1%, respectively. It also relieved the oxidative stress triggered by TAM, as revealed by the reduction in the levels of TBARs and TNF-α by 21.4 and 40%, respectively. Liquid chromatography electrospray ionization mass spectrometry of EP revealed a total of twelve peaks belonging to phenylpropanoids, lignans, and phenolics, where verbascoside and pinoresinol-4-O-ß-d-glucoside represented the most abundant secondary metabolites. The docking experiment showed that tri-O-galloyl-hexoside had the best fitting within the NADPH oxidase active sites with binding energy (ΔG = -81.12 kcal/mol). Thus, the plant can be of beneficial value in the control of hyperglycemia in diabetic patients, besides its prophylactic potential against hepatic complications.

Antimicrobial activities of metabolites isolated from endophytic Aspergillus flavus of Sarcophyton ehrenbergi supported by in-silico study and NMR spectroscopy.

BACKGROUND: Endophytic Aspergillus species produce countless valuable bioactive secondary metabolites. In the current study, Aspergillus flavus an endophyte from the soft coral Sarcophyton ehrenbergi was chemically explored and the extracted phytoconstituents were subsequently evaluated for antimicrobial activity. This is accomplished by employing nuclear magnetic resonance (NMR) spectroscopy and computational techniques. Additionally, An in vitro anticancer analysis of A. flavus total extract against breast cancer cells (MCF-7) was investigated. RESULT: Six compounds were separated from the crude alcohol extract of the endophytic Aspergillus flavus out of which anhydro-mevalonolactone was reported for the first time. The anti-fungal and anti-Helicobacter pylori properties of two distinct compounds (Scopularides A and B) were assessed. Additionally, computational research was done to identify the binding mechanisms for all compounds. Both the compounds were found to be active against H. pylori with minimum inhibitory concentration (MIC) values ranging from 7.81 to 15.63 µg/ mL as compared with clarithromycin 1.95 µg/ mL. Scopularides A was potent against both Candida albicans and Aspergillus niger with MIC values ranging from 3.9 to 31.25 µg/ mL, while scopularides B only inhibits Candida albicans with MIC value of 15.63 µg/ mL and weak inhibitory activity against A. niger (MIC = 125 µg/ mL). Furthermore, cytotoxic activity showed a significant effect (IC50: 30.46 mg/mL) against MCF-7 cells. CONCLUSION: Our findings report that cytotoxic activity and molecular docking support the antimicrobial activity of Aspergillus flavus, which could be a promising alternative source as a potential antimicrobial agent.

Insights into the Role of Erythrina corallodendron L. in Alzheimer's Disease: in Vitro and in Silico Approach.

Alzheimer's disease (AD) is a major health problem. Cholinergic transmission is greatly affected in AD. Phytochemical investigation of the alkaloid rich fraction (AF) of Erythrina corallodendron L leaves resulted in isolation of five known alkaloids: erysodine, erythrinine, 8-oxoerythrinine, erysovine N-oxide and erythrinine N-oxide. In this study, eysovine N-oxide was reported for the second time in nature. AF was assayed for cholinesterase inhibition at the concentration of 100 µg mL-1 . AF showed a higher percent inhibition for butyrylcholinesterase enzyme (BuChE) (83.28 %) compared to acetylcholinesterase enzyme (AChE) (64.64 %). The isolated alkaloids were also assayed for their anti-BuChE effect. In-silico docking study was done for the isolated compounds at the binding sites of AChE and BuChE to determine their binding pattern and interactions, also molecular dynamics were estimated for the compound displaying the best fit for AChE and BuChE. In addition, ADME parameters and toxicity were predicted for the isolated alkaloids compared to donepezil.

Austalide derivative from marine-derived Aspergillus sp. and evaluation of its cytotoxic and ADME/TOPKAT properties.

In-depth chemical investigation of an ethyl acetate extract of Aspergillus sp. isolated from the soft coral Sinularia species resulted in the isolation of one new meroterpenoid, austalide Z (1), one known austalide W (2), six known prenylated indole diketopiperazine alkaloids (3-8), and phthalic acid and its ethyl derivative (9-10). The structures were established by means of 1D and 2D NMR (one- and two-dimensional nuclear magnetic resonance) experiments supported by UV analysis and ESI-MS (electrospray ionization mass spectrometry). In vitro cytotoxic evaluation was performed against the Caco-2 cancer cell line using the MTT assay, which showed that the examined compounds had weak to moderate activities, with the new meroterpenoid austalide Z (1) displaying an IC50 value of 51.6 µg mL-1. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) predication performed in silico showed that most of the isolated compounds possessed reasonable pharmacokinetic, pharmacodynamic, and toxicity properties. Thus, it can be concluded that Aspergillus sp. could act as a source of drug leads for cancer prevention with promising pharmacokinetic and pharmacodynamic properties and thus could be incorporated in pharmaceutical dosage forms.

Analyses of Elaeocarpus sphaericus Extract for Antioxidant, Antiproliferative and Gene Repression Activities against HIF-1α and VEGF.

The study presents antioxidant, phytochemical, anti-proliferative, and gene repression activities against Hypoxia-inducible factor (HIF-1) alpha and Vascular endothelial growth factor (VEGF) of Elaeocarpus sphaericus extract. Elaeocarpus sphaericus dried and crushed plant leaves were extracted using water and methanol by ASE (Accelerated Solvent Extraction) method. Total phenolic content (TPC) and total flavonoid content (TFC) were used to measure the extracts' phytochemical activity (TFC). Antioxidant potential of the extracts was measured through DPPH, ABTS, FRAP, and TRP. Methanolic extract of the leaves of E. sphaericus has shown a higher amount of TPC (94.666±4.040 mg/gm GAE) and TFC value (172.33±3.21 mg/gm RE). The antioxidant properties of extracts in the yeast model (Drug Rescue assay) showed promising results. Ascorbic acid, gallic acid, hesperidin, and quercetin were found in the aqueous and methanolic extracts of E. sphaericus at varying amounts, according to a densiometric chromatogram generated by HPTLC analysis. Methanolic extract of E. sphaericus (10 mg/ml) has shown good antimicrobial potential against all bacterial strains used in the study except E. coli. The anticancer activity of the extract in HeLa cell lines ranged from 77.94±1.03 % to 66.85±1.95 %, while it ranged from 52.83±2.57 % to 5.44 % in Vero cell lines at varying concentration (1000 µg/ml-31.2 µg/ml). A promising effect of extract was observed on the expression activity of HIF-1 and VEGF gene through RT-PCR assay.

Comparative GC-MS Analysis of Fresh and Dried Curcuma Essential Oils with Insights into Their Antioxidant and Enzyme Inhibitory Activities.

Species belonging to the Zingiberaceae family are of high nutritional, industrial, and medicinal values. In this study, we investigated the effect of processing steps (fresh vs. dried milled rhizomes) and extraction methodologies (hydrodistillation vs. hexane extraction) of curcuma essential oil on its chemical content (using GC-MS analysis), its antioxidant behavior (using in vitro assays such as DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelation), and its enzyme inhibitory activities (on tyrosinase, acetylcholinesterase, butylcholinesterase, α-amylase, and α-glucosidase) supported by multivariate analysis, in silico studies, and molecular dynamics. The GC-MS investigations revealed a high degree of similarity in the chemical profile of fresh hydrodistilled and hexane-extracted essential oils with tumerone and curlone being the major metabolites. The extraction techniques affected the concentrations of other minor constituents such as terpinolene, caryophylla-4(12), 8(13)-dien-5α-ol, and neo-intermedeol, which were almost exclusively detected in the hydrodistilled fresh essential oil; however, zingiberene and ß-sesquiphellandrene were predominant in the hexane-extracted fresh essential oil. In the dried curcuma rhizomes, tumerone and curlone contents were significantly reduced, with the former being detected only in the hydrodistilled essential oil while the latter was doubly concentrated in the hexane-derived oil. Constituents such as D-limonene and caryophyllene oxide represented ca. 29% of the dried hydrodistilled essential oil, while ar-turmerone was detected only in the dried hydrodistilled and hexane-extracted essential oils, representing ca. 16% and 26% of the essential oil composition, respectively. These variations in the essential oil chemical content have subsequently affected its antioxidant properties and enzyme inhibitory activities. In silico investigations showed that hydrophobic interactions and hydrogen bonding were the characteristic binding modes of the bioactive metabolites to their respective targets. Molecular dynamics revealed the stability of the ligand-target complex over time. From the current study we conclude that fresh hexane-extracted essential oil showed the best radical scavenging properties, and fresh rhizomes in general display better enzyme inhibitory activity regardless of the extraction technique.

A comprehensive review on the medicinally valuable endosymbiotic fungi Penicillium chrysogenum.

Recently, it has been shown that metabolites derived from endosymbiotic fungi attracted high attention, since plenty of them have promising pharmaceutical applications. The variation of metabolic pathways in fungi is considered an optimistic source for lead compounds. Among these classes are terpenoids, alkaloids, polyketides, and steroids, which have proved several pharmacological activities, including antitumor, antimicrobial, anti-inflammatory, and antiviral actions. This review concludes the major isolated compounds from different strains of Penicillium chrysogenum during the period 2013-2023, together with their reported pharmacological activities. From literature surveys, 277 compounds have been identified from P. chrysogenum, which has been isolated as an endosymbiotic fungus from different host organisms, with specific attention paid to those showing marked biological activities that could be useful in the pharmaceutical industry in the future. This review represents documentation for a valuable reference for promising pharmaceutical applications or further needed studies on P. chrysogenum.