Metabolomic study of the estrogenic and anti-osteoporotic potential of Erythrina bidwillii leaf.

Erythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and gas chromatography-mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8-oxoerythraline (2), (+)-erythrinine (3), (+)-erythraline (4) and 8-oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti-osteoporotic, anti-hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF-7 cell lines. An in silico study of the isolated metabolites revealed that (+)-erythrinine (3) and 8-oxoerythrinine (5) exhibited the highest affinity for ERα and ERß, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials.

Phoenix dactylifera L.: An Overview of Phytochemical Constituents and Impact on Women's Health.

Phoenix dactylifera L. (date palm) is the most significant member of the palm family (Arecaceae), particularly in the Middle East and Arab World. It is a valuable source of both primary and secondary metabolites including sugars, amino acids, phenolic acids, flavonoids, proanthocyanidins, carotenoids, phytosterols, terpenes and sphingolipids, besides vitamins and minerals. Besides, it possesses a wide array of pharmacologic activities viz. immunomodulatory, antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, anti-mutagenic and anti-cancer activities, in addition to its positive effects on male and female fertility. Further research is still required to deeply understand its clinical implications, especially concerning women's health. Moreover, there are other Phoenix species that still need to be investigated to learn more about their undiscovered phytochemical components and biological activities.

HPLC and GC Characterization of Dicliptera bupleuroides Aerial Parts and Evaluation of Its Anti-Inflammatory Potential in Vitro, in silico and in Vivo Using Carrageenan and Formalin Induced Inflammation in Rat Models.

The current study aimed to evaluate the anti-inflammatory activity of Dicliptera bupleuroides Nees aerial parts methanol extract and its different fractions namely hexane, chloroform, ethyl acetate and butanol in vitro using cyclooxygenase inhibitory assay (COX-2). In vivo anti-inflammatory evaluation was performed using carrageenan and formalin induced inflammation in rat models followed by molecular docking. High performance liquid chromatography (HPLC) and gas chromatography coupled with mass chromatography (GC/MS) analyses were used for chemical analyses of the tested samples. The tested samples showed significant inhibition in COX-2 inhibitory assay where methanol extract (DBM) showed the highest inhibitory potential at 100 µg/mL estimated by 67.86 %. At a dose of 400 mg/kg, all of the examined samples showed pronounced results in carrageenan induced acute inflammation in rat model at 4th h interval with DBM showed the highest efficiency displaying 65.32 % inhibition as compared to the untreated rats. Formalin model was employed for seven days and DBM exhibited 65.33 % and 69.39 % inhibition at 200 and 400 mg/kg, respectively approaching that of the standard on the 7th day. HPLC revealed the presence of caffeic acid, gallic acid and sinapic acid, quercetin and myricetin in DBM. GC/MS analysis of its hexane fraction revealed the presence of 16 compounds belonging mainly to fatty acids and sterols that account for 85.26 % of the total detected compounds. Molecular docking showed that hexadecanoic acid followed by decanedioic acid and isopropyl myristate showed the best fitting within cyclooxygenase-II (COX-II) while nonacosane followed by hexatriacontane and isopropyl myristate revealed the most pronounced fitting within the 5-lipoxygenase (5-LOX) active sites. Absorption, metabolism, distribution and excretion and toxicity prediction (ADMET/ TOPKAT) concluded that most of the detected compounds showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties that could be further modified to be more suitable for incorporation in pharmaceutical dosage forms combating inflammation and its undesirable consequences.

A Comparative GC/MS Analysis of Citrus Essential Oils: Unveiling the Potential Benefits of Herb-Drug Interactions in Preventing Paracetamol-Induced Hepatotoxicity.

Our study aimed to test the potential of Citrus oils in protecting against paracetamol (PAR)-induced hepatotoxicity. The essential oils of Pineapple sweet orange (OO), Murcott mandarin (MO), Red grapefruit (GO), and Oval kumquat (KO) were investigated using gas chromatography coupled with mass spectrometry (GC/MS). Twenty-seven compounds were identified, with monoterpene hydrocarbons being abundant class. d-Limonene had the highest percentage (92.98 %, 92.82 %, 89.75 %, and 94.46 % in OO, MO, GO, and KO, respectively). Hierarchical cluster analysis (HCA) and principal components analysis (PCA) revealed that octanal, linalool, germacrene D, and d-limonene were the principal discriminatory metabolites that segregated the samples into three distinct clusters. In vitro antioxidant capacities were ranged from 1.2-12.27, 1.79-5.91, and 235.05-585.28 µM Trolox eq/mg oil for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic (ABTS), ferric-reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC), respectively. In vivo, citrus oils exhibited a significant reduction in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and nitric oxide (NO). Additionally, there was an increase in glutathione reductase (GSH), and the liver architecture was nearly normal. Molecular docking revealed that d-limonene exhibited a good inhibitory interaction with cytochrome P450 (CYP450) isoforms 1A2, 3A4, and 2E1, with binding energies of -6.17, -4.51, and -5.61 kcal/mol, respectively.

A perspective study of the possible impact of obeticholic acid against SARS-CoV-2 infection.

The causative agent of CoV disease 2019 is a new coronavirus CoV type 2, affecting the respiratory tract with severe manifestations (SARS-CoV-2). Covid-19 is mainly symptomless, with slight indications in about 85% of the affected cases. Many efforts were done to face this pandemic by testing different drugs and agents to make treatment protocols in different countries. However, the use of these proposed drugs is associated with the development of adverse events. Remarkably, the successive development of SARS-CoV-2 variants which could affect persons even they were vaccinated, prerequisite wide search to find efficient and safe agents to face SARS-CoV-2 infection. Obeticholic acid (OCA), which has anti-inflammatory effects, may efficiently treat Covid-19. Thus, the goal of this perspective study is to focus on the possible medicinal effectiveness in managing Covid-19. OCA is a powerful farnesoid X receptor (FXR) agonist possessing marked antiviral and anti-inflammatory effects. FXR is dysregulated in Covid-19 resulting in hyper-inflammation with concurrent occurrence of hypercytokinemia. Interestingly, OCA inhibits the reaction between this virus and angiotensin-converting enzyme type 2 (ACE2) receptors. FXR agonists control the expression of ACE2 and the inflammatory signaling pathways in this respiratory syndrome, which weakens the effects of Covid-19 disease and accompanied complications. Taken together, FXR agonists like OCA may reveal both direct and indirect impacts in the modulation of immune reaction in SARS-CoV-2 conditions. It is highly recommended to perform many investigations regarding different phases of the discovery of new drugs.

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors.

Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC50 determination against Aurora A and B kinases revealed the inhibition of both kinases with selectivity toward Aurora A. Two of the compounds, natural quinone naphthazarin (1) and a pseudo anthraquinone, 2-(chloromethyl)quinizarin (11), potently inhibited the proliferation of various cancer cell lines with IC50 values ranging from 0.16 ± 0.15 to 1.7 ± 0.06 and 0.15 ± 0.04 to 6.3 ± 1.8 µM, respectively. Treatment of cancer cells with these compounds for 24 h resulted in abrogated mitosis and apoptotic cell death. Direct binding of both the compounds with Aurora A kinase was also confirmed through STD NMR analysis. Docking studies predicted the binding of both compounds to the ATP binding pocket of Aurora A kinase. We have, therefore, identified quinones as Aurora kinase inhibitors that can serve as a lead for future drug discovery endeavors.

FTIR Characterization of Sulfated Polysaccharides Obtained from Macrocystis integrifolia Algae and Verification of Their Antiangiogenic and Immunomodulatory Potency In Vitro and In Vivo.

The aim of this study was to evaluate the antiangiogenic and immunomodulatory potential of sulfated polysaccharides from the marine algae Macrocystis integrifolia characterized by FTIR. The cytotoxicity of sulfated polysaccharides was evaluated using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay. Antiangiogenic activity was evaluated using the chicken chorioallantoic membrane (CAM) assay. Immunomodulatory activity was determined on macrophage functionality and allergic response. The results showed that sulfated polysaccharides significantly decreased angiogenesis in chicken chorioallantoic membranes (p < 0.05). Likewise, they inhibited in vivo chemotaxis and in vitro phagocytosis, the transcription process of genes that code the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and nitric oxide synthase-2 (NOS-2) and the nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), showing immunomodulatory properties on the allergic response, as well as an in vivo inhibitory effect in the ovalbumin-induced inflammatory allergy model (OVA) and inhibited lymphocyte proliferation specific to the OVA antigen in immunized mice. Finally, these compounds inhibited the histamine-induced skin reaction in rats, the production of immunoglobulin E (IgE) in mice, and the passive response to skin anaphylaxis in rats. Therefore, the results of this research showed the potential of these compounds to be a promising source for the development of antiangiogenic and immunomodulatory drugs.

Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease.

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of Mpro (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to PRD_002214 resulted in the election of sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, and 278). Then, results of molecular docking versus Mpro PDB ID: 6LU7 favored eight compounds (128, 130, 156, 180, 184, 203, 204, and 278) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds 130, 184, and 278, which exhibited the best binding modes against Mpro. MD tests revealed that luteoside C (130) has the greatest potential to inhibit SARS-CoV-2 main protease.

The Role of Cannabis sativa L. as a Source of Cannabinoids against Coronavirus 2 (SARS-CoV-2): An In Silico Study to Evaluate Their Activities and ADMET Properties.

Cannabis sativa L. is an annual herbaceous plant that belongs to the family Cannabinaceae. In this study, the potential use of forty-five cannabinoids, previously identified from Cannabis sativa to alleviate COVID-19 infection via prohibition of crucial SARS-CoV-2 proteins using molecular docking, was examined. In silico studies were performed on three vital enzymes that serve as principle therapeutic targets to prevent SARS-CoV-2 replication. These enzymes are the main protease SARS-CoV-2 MPro, papain-like protease SARS-CoV-2 PLpro and angiotensin-converting enzyme 2 (ACE2). Regarding SARS-CoV-2 MPro, cannabichromanon (32) showed the best fitting within its active centers, followed by cannabinolic acid (22) and cannabinol (21), displaying ∆G of -33.63, -23.24, and -21.60 kcal/mol, respectively. Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with ∆G values of -28.36, -22.81, and -19.89 kcal/mol. Furthermore, cannabichromanon (32), cannabinolic acid (22), and cannabinol (21) showed considerable fitting within the active sites of angiotensin-converting enzyme 2 (ACE2) evidenced by their significant ∆G values that were estimated as -41.77, -31.34, and -30.36 kcal/mol, respectively. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) evaluation was performed on the tested cannabinoids to further explore their pharmacokinetics, pharmacodynamics, and toxicity properties. The results indicated the considerable pharmacokinetic, pharmacodynamic, and toxicity properties of cannabinol (21), cannabinolic acid (22), cannabichromanon (32), and cannabicyclolic acid (41) that showed best fitting scores within the active sites of the tested enzymes. Multivariate data analysis revealed that cannabichromanon and cannabinolic acid showed a discriminant nature and hence can be incorporated in pharmaceutical dosage forms to alleviate COVID-19 infection.

Silviridoside: A New Triterpene Glycoside from Silene viridiflora with Promising Antioxidant and Enzyme Inhibitory Potential.

A new triterpene glycoside, silviridoside, was isolated from the aerial parts of Silene viridiflora (Caryophyllaceae) using different chromatographic techniques. The structure of silviridoside was comprehensively elucidated as 3-O-ß-D-galacturonopyranosyl-quillaic acid 28-O-ß-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-fucopyranosyl ester by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). Silviridoside showed promising antioxidant activity in different antioxidant assays such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) (2.32 mg TE/g), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (1.24 mg TE/g), cupric-reducing antioxidant capacity (CUPRAC) (9.59 mg TE/g), ferric-reducing antioxidant power (FRAP) (5.13 mg TE/g), phosphomolybdenum (PHD) (0.28 mmol TE/g), and metal-chelating (MCA) (6.62 mg EDTA/g) assays. It exhibited a good inhibitory potential on acetylcholinesterase (AChE) (2.52 mg GALAE/g), butyrylcholinesterase (BChE) (7.16 mg GALAE/g), α-amylase (0.19 mmol ACAE/g), α-glucosidase (1.21 mmol ACAE/g), and tyrosinase (38.83 mg KAE/g). An in silico evaluation of the pharmacodynamic, pharmacokinetic, and toxicity properties of silviridoside showed that the new compound exhibited reasonable pharmacodynamic and pharmacokinetic properties without any mutagenic effect, but slight toxicity. Thus, it could be concluded that silviridoside could act as a promising lead drug for pharmaceutical and nutraceutical developments to combat oxidative stress and various disorders, but a future optimization is necessary.

Lobularia libyca: Phytochemical Profiling, Antioxidant and Antimicrobial Activity Using In Vitro and In Silico Studies.

Lobularia libyca (L. libyca) is a traditional plant that is popular for its richness in phenolic compounds and flavonoids. The aim of this study was to comprehensively investigate the phytochemical profile by liquid chromatography, electrospray ionization and tandem mass spectrometry (LC-ESI-MS), the mineral contents and the biological properties of L. libyca methanol extract. L. libyca contains significant amounts of phenolic compounds and flavonoids. Thirteen compounds classified as flavonoids were identified. L. libyca is rich in nutrients such as Na, Fe and Ca. Moreover, the methanol extract of L. libyca showed significant antioxidant activity without cytotoxic activity on HCT116 cells (human colon cancer cell line) and HepG2 cells (human hepatoma), showing an inhibition zone of 13 mm in diameter. In silico studies showed that decanoic acid ethyl ester exhibited the best fit in ß-lactamase and DNA gyrase active sites; meanwhile, oleic acid showed the best fit in reductase binding sites. Thus, it can be concluded that L. libyca can serve as a beneficial nutraceutical agent, owing to its significant antioxidant and antibacterial potential and due to its richness in iron, calcium and potassium, which are essential for maintaining a healthy lifestyle.

Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.

Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3-8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9-11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted for all isolated compounds on crucial enzymes involved in the formation, progression and metastasis of cancer which included human cyclin-dependent kinase 2 (CDK-2), human DNA topoisomerase II (TOP-2) and matrix metalloproteinase 13 (MMP-13). Diorcinol (7), sulochrin (9) and monochlorosulochrin (10) displayed notable stability within the active pocket of CDK-2 with free binding energy (ΔG) equals to -25.72, -25.03 and -25.37 Kcal/mol, respectively whereas sulochrin (9) exerted the highest fitting score within MMP-13 active center (ΔG = -33.83 Kcal/mol). In vitro cytotoxic assessment using MTT assay showed that sulochrin (9) exhibited cytotoxic activity versus L5178Y mouse lymphoma cells with an IC50 value of 5.1 µM and inhibition of migration of MDA-MB 231 breast cancer cells at a concentration of 70 µM.

Bioactive Alkaloids from Genus Aspergillus: Mechanistic Interpretation of Their Antimicrobial and Potential SARS-CoV-2 Inhibitory Activity Using Molecular Modelling.

Genus Aspergillus represents a widely spread genus of fungi that is highly popular for possessing potent medicinal potential comprising mainly antimicrobial, cytotoxic and antioxidant properties. They are highly attributed to its richness by alkaloids, terpenes, steroids and polyketons. This review aimed to comprehensively explore the diverse alkaloids isolated and identified from different species of genus Aspergillus that were found to be associated with different marine organisms regarding their chemistry and biology. Around 174 alkaloid metabolites were reported, 66 of which showed important biological activities with respect to the tested biological activities mainly comprising antiviral, antibacterial, antifungal, cytotoxic, antioxidant and antifouling activities. Besides, in silico studies on different microbial proteins comprising DNA-gyrase, topoisomerase IV, dihydrofolate reductase, transcriptional regulator TcaR (protein), and aminoglycoside nucleotidyl transferase were done for sixteen alkaloids that showed anti-infective potential for better mechanistic interpretation of their probable mode of action. The inhibitory potential of compounds vs. Angiotensin-Converting Enzyme 2 (ACE2) as an important therapeutic target combating COVID-19 infection and its complication was also examined using molecular docking. Fumigatoside E showed the best fitting within the active sites of all the examined proteins. Thus, Aspergillus species isolated from marine organisms could afford bioactive entities combating infectious diseases.

Chemical constituents and gastro-protective potential of Pachira glabra leaves against ethanol-induced gastric ulcer in experimental rat model.

Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)-ß -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3'-O-ß-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)- ß -Dgalactoside (4), quercetin-3- O-ß -D-galactoside (5), 7-hydroxy maltol-3-O-ß-D-glucoside (6), maltol-3- O-ß -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.

Evaluation of The Antioxidant, Antimicrobial, and Anticancer Activities of Dicliptera bupleuroides Isolated Compounds Using In Vitro and In Silico Studies.

Phytochemical investigation of chloroform fraction (DBC) and ethyl acetate fraction (DBE) of D. bupleuroides (Acanthaceae) resulted in the isolation of ß-sitosterol (1) from DBC and vanillic acid (2) from DBE, which were first to be isolated from D. bupleuroides. ß-Sitosterol (1) exhibited substantial antioxidant activity (IC50 = 198.87 µg/mL), whereas vanillic acid (2) showed significant antioxidant power (IC50 = 92.68 µg/mL) employing 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical scavenging capacity assay. Both compounds showed pronounced antimicrobial activity using the agar disc diffusion method, particularly against fungi showing MIC values of 0.182 and 0.02 concerning Candida albicans, respectively, and 0.001 mg/mL regarding Penicillium notatum. They revealed considerable antibacterial activity with MIC values ranging between 0.467 and 0.809 mg/mL. Vanillic acid (2) exhibited substantial anticancer potential displaying 48.67% cell viability at a concentration of 100 µg/mL using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyl-2H-Tetrazolium Bromide) assay concerning HepG2 cell lines. These results were further consolidated by in silico studies on different enzymes, where vanillic acid displayed a high fitting score in the active pockets of DNA-gyrase, dihydrofolate reductase, aminoglycoside nucleotidyltransferase, and ß-lactamase. It also inhibited human cyclin-dependent kinase 2 (CDK-2) and DNA topoisomerase II, as revealed by the in silico studies. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) prediction showed that vanillic acid exhibited reasonable pharmacodynamic, pharmacokinetic, and toxicity properties and, thus, could perfectly together with D. bupleuroides crude extract be incorporated in pharmaceutical preparations to counteract cancer and microbial invasion, as well as oxidative stress. Thus, it is concluded that D. bupleroides could be a potential source of therapeutically active compounds, which would be helpful for the discovery of clinically effective and safe drugs.

Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies, and the Evaluation of Their ADMET Properties.

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes' potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol 2',3',4',7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-ß-d-xylopyranoside-(23R,24S)-16ß,23;16α,24-diepoxycycloart-25(26)-en-3ß,7ß-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (-7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.

Azaphilones from the Red Sea Fungus Aspergillus falconensis.

The marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Canyon at Dahab, Red Sea, yielded two new chlorinated azaphilones, falconensins O and P (1 and 2) in addition to four known azaphilone derivatives (3-6) following fermentation of the fungus on solid rice medium containing 3.5% NaCl. Replacing NaCl with 3.5% NaBr induced accumulation of three additional new azaphilones, falconensins Q-S (7-9) including two brominated derivatives (7 and 8) together with three known analogues (10-12). The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and HRESIMS data as well as by comparison with the literature. The absolute configuration of the azaphilone derivatives was established based on single-crystal X-ray diffraction analysis of 5, comparison of NMR data and optical rotations as well as on biogenetic considerations. Compounds 1, 3-9, and 11 showed NF-κB inhibitory activity against the triple negative breast cancer cell line MDA-MB-231 with IC50 values ranging from 11.9 to 72.0 µM.

In vivo antiulcer activity, phytochemical exploration, and molecular modelling of the polyphenolic-rich fraction of Crepis sancta extract.

Bioactivity-guided investigation of the methanol extract of Crepis sancta aerial parts, collected off Al-Tafilah, South Jordan, was applied, and in this study, the extract was explored for its phytochemical components and in vivo antiulcer activity. In addition, a docking study involving the purified compounds with the newly crystalized gastric proton pump (PDB # 5YLU) was performed. In-depth phytochemical investigation using the state-of-the-art chromatographic and analytical techniques was implemented resulting in the identification of two eudesmane-type sesquiterpenoids, 3-oxo-γ-costic acid (1) and its methyl ester (2) together with seven different methoxylated flavonols (3-9) as the extract's major components. The in vivo antiulcer study at three different doses (50, 100, and 200 mg/kg) against ethanol-induced gastric ulcer in male albino rats, compared to omeprazole (20 mg/kg) as a standard proton pump inhibitor antiulcer drug, revealed that the tested extract, at the middle and the highest doses, featured comparable or even superior activities relative to omeprazole as deduced from histopathological examination, in particular with regard to reducing inflammatory cell infiltration and ceasing mucosal haemorrhage. The tested extract revealed also a dose-dependent reduction in the volume and titrable acidity of the gastric juice together with a dose-dependent increase in the protective gastric mucin content which may explain the noticeable gastroprotective effect. Molecular modelling study of the isolated compounds showed a binding mode similar to the co-crystallized substrate vonoprazan in 5YLU which strengthens the importance of the tested extract as a potential natural remedy for treating gastric ulcer.

A Comprehensive Review of Bioactive Peptides from Marine Fungi and Their Biological Significance.

Fungal marine microorganisms are a valuable source of bioactive natural products. Fungal secondary metabolites mainly comprise alkaloids, terpenoids, peptides, polyketides, steroids, and lactones. Proteins and peptides from marine fungi show minimal human toxicity and less adverse effects comparable to synthetic drugs. This review summarizes the chemistry and the biological activities of peptides that were isolated and structurally elucidated from marine fungi. Relevant fungal genera including Acremonium, Ascotricha, Aspergillus, Asteromyces, Ceratodictyon, Clonostachys, Emericella, Exserohilum, Microsporum, Metarrhizium, Penicillium, Scytalidium, Simplicillium, Stachylidium, Talaromyces, Trichoderma, as well as Zygosporium were extensively reviewed. About 131 peptides were reported from these 17 genera and their structures were unambiguously determined using 1D and 2D NMR (one and two dimensional nuclear magnetic resonance) techniques in addition to HRMS (high resolution mass spectrometry). Marfey and Mosher reactions were used to confirm the identity of these compounds. About 53% of the isolated peptides exhibited cytotoxic, antimicrobial, and antiviral activity, meanwhile, few of them showed antidiabetic, lipid lowering, and anti-inflammatory activity. However 47% of the isolated peptides showed no activity with respect to the examined biological activity and thus required further in depth biological assessment. In conclusion, when searching for bioactive natural products, it is worth exploring more peptides of fungal origin and assessing their biological activities.

Study of the anti-allergic and anti-inflammatory activity of Brachychiton rupestris and Brachychiton discolor leaves (Malvaceae) using in vitro models.

BACKGROUND: Brachychiton rupestris and Brachychiton discolor (Malvaceae) are ornamental trees native to Australia. Some members of Brachychiton and its highly related genus, Sterculia, are employed in traditional medicine for itching, dermatitis and other skin diseases. However, scientific studies on these two genera are scarce. Aiming to reveal the scientific basis of the folk medicinal use of these plants, the cytotoxicity, anti-inflammatory and anti-allergic activities of Brachychiton rupestris and Brachychiton discolor leaves extracts and fractions were evaluated. Also, phytochemical investigation of B. rupestris was performed to identify the compounds exerting the biological effect. METHODS: Extracts as well as fractions of Brachychiton rupestris and Brachychiton discolor were tested for their cytotoxicity versus hepatoma HepG2, lung A549, and breast MDA-MB-231 cancer cell lines. Assessment of the anti-allergic activity was done using degranulation assay in RBL-2H3 mast cells. Anti-inflammatory effect was tested by measuring the suppression of superoxide anion production as well as elastase release in fMLF/CB-induced human neutrophils. Phytochemical investigation of the n-hexane, dichloromethane and ethyl acetate fractions of B. rupestris was done using different chromatographic and spectroscopic techniques. RESULTS: The tested samples showed no cytotoxicity towards the tested cell lines. The nonpolar fractions of both B. rupestris and B. discolor showed potent anti-allergic potency by inhibiting the release of ß-hexosaminidase. The dichloromethane fraction of both species exhibited the highest anti-inflammatory activity by suppressing superoxide anion generation and elastase release with IC50 values of 2.99 and 1.98 µg/mL, respectively for B. rupestris, and 0.78 and 1.57 µg/mL, respectively for B. discolor. Phytochemical investigation of various fractions of B. rupestris resulted in the isolation of ß-amyrin acetate (1), ß-sitosterol (2) and stigmasterol (3) from the n-hexane fraction. Scopoletin (4) and ß-sitosterol-3-O-ß-D-glucoside (5) were obtained from the dichloromethane fraction. Dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucoside (6) and dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucoside (7) were separated from the ethyl acetate fraction. Scopoletin (4) showed anti-allergic and anti-inflammatory activity. CONCLUSIONS: It was concluded that the nonpolar fractions of both Brachychiton species exhibited anti-allergic and anti-inflammatory activities.