Six New Phenylpropanoid Derivatives from Chemically Converted Extract of Alpinia galanga (L.) and Their Antiparasitic Activities

Chemical conversion of the extract of natural resources is a very attractive way to expand the chemical space to discover bioactive compounds. In order to search for new medicines to treat parasitic diseases that cause high morbidity and mortality in affected countries in the world, the ethyl acetate extract from the rhizome of Alpinia galanga (L.) has been chemically converted by epoxidation using dioxirane generated in situ. The biological activity of chemically converted extract (CCE) of A. galanga (L.) significantly increased the activity against Leishmania major up to 82.6 ± 6.2 % at 25 μg/mL (whereas 2.7 ± 0.8% for the original extract). By bioassay-guided fractionation, new phenylpropanoids (1–6) and four known compounds, hydroquinone (7), 4-hydroxy(4-hydroxyphenyl)methoxy)benzaldehyde (8), isocoumarin cis 4-hydroxymelein (9), and (2S,3S,6R,7R,9S,10S)-humulene triepoxide (10) were isolated from CCE. The structures of isolated compounds were determined by spectroscopic analyses of 1D and 2D NMR, IR, and MS spectra. The most active compound was hydroquinone (7) with IC₅₀ = 0.37 ± 1.37 μg/mL as a substantial active principle of CCE. In addition, the new phenylpropanoid 2 (IC₅₀ = 27.8 ± 0.34 μg/mL) also showed significant activity against L. major compared to the positive control miltefosine (IC₅₀ = 7.47 ± 0.3 μg/mL). The activities of the isolated compounds were also evaluated against Plasmodium falciparum, Trypanosoma brucei gambisense and Trypanosoma brucei rhodeisense. Interestingly, compound 2 was selectively active against trypanosomes with potent activity. To the best of our knowledge, this is the first report on the bioactive “unnatural” natural products from the crude extract of A. galanga (L.) by chemical conversion and on its activities against causal pathogens of leishmaniasis, trypanosomiasis, and malaria.     

Optimization of Ultrasound-Assisted Cellulase Extraction from Nymphaea hybrid Flower and Biological Activities: Antioxidant Activity,Protective Effect against ROS Oxidative Damage in HaCaT Cells and Inhibition of Melanin Production in B16 Cells

In this study, ultrasonic-assisted cellulase extraction (UCE) was applied to extract flavonoids and polyphenols from the Nymphaea hybrid flower. The extraction conditions were optimized using the response surface method (RSM) coupled with a Box-Behnken design. The crude extract of Nymphaea hybrid (NHE) was further purified using AB-8 macroporous resins, and the purified extract (NHEP) was characterized by FTIR and HPLC. In vitro activity determination by chemical method showed that NHEP displayed strong free radical scavenging abilities against the DPPH and ABTS radicals, good reduction power, and hyaluronidase inhibition. The cell viability by CCK-8 assays showed that NHEP had no significant cytotoxicity for B16 and HaCaT cells when the concentration was below 100 μg/mL and 120 μg/mL, respectively. NHEP with a concentration of 20–160 μg/mL can more effectively reduce the ROS level in H₂O₂ damaged HaCaT cells compared with 10 μg/mL of VC. The 40 μg/mL of NHEP had similar activity against intracellular melanin production in the B16 melanoma cells compared with 20 μg/mL Kojic acid. Good activities of antioxidation, whitening and protective effect against H₂O₂-induced oxidative damage promote the potential for NHEP as a functional raw material in the field of cosmetics and medicine.     

Phytochemical Composition,Antioxidant Activity,and Enzyme Inhibitory Activities (α-Glucosidase,Xanthine Oxidase,and Acetylcholinesterase) of Musella lasiocarpa

In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their α-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH· scavenging ability, ABTS·⁺ scavenging ability, and α-glucosidase inhibitory activity with the IC₅₀ values of 22.17, 12.10, and 125.66 μg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO₄/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC₅₀ = 10.11 μg/mL), and the best xanthine oxidase inhibitory ability (IC₅₀ = 5.23 μg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 μg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications.     

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant,Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂) were found to be IC₅₀ = 66.16 μg/mL and 76.05 μg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC₅₀ = 64.91 μg/mL) and Caco-2 (IC₅₀ = 83.98 μg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products.     

In Vitro Phenotypic Activity and In Silico Analysis of Natural Products from Brazilian Biodiversity on Trypanosoma cruzi

Chagas disease (CD) affects more than 6 million people worldwide. The available treatment is far from ideal, creating a demand for new alternative therapies. Botanical diversity provides a wide range of novel potential therapeutic scaffolds. Presently, our aim was to evaluate the mammalian host toxicity and anti-Trypanosoma cruzi activity of botanic natural products including extracts, fractions and purified compounds obtained from Brazilian flora. In this study, 36 samples of extracts and fractions and eight pure compounds obtained from seven plant species were evaluated. The fraction dichloromethane from Aureliana fasciculata var. fasciculata (AFfPD) and the crude extract of Piper tectoniifolium (PTFrE) showed promising trypanosomicidal activity. AFfPD and PTFrE presented EC₅₀ values 10.7 ± 2.8 μg/mL and 12.85 ± 1.52 μg/mL against intracellular forms (Tulahuen strain), respectively. Additionally, both were active upon bloodstream trypomastigotes (Y strain), exhibiting EC₅₀ 2.2 ± 1.0 μg/mL and 38.8 ± 2.1 μg/mL for AFfPD and PTFrE, respectively. Importantly, AFfPD is about five-fold more potent than Benznidazole (Bz), the reference drug for CD, also reaching lower EC₉₀ value (7.92 ± 2.2 μg/mL) as compared to Bz (23.3 ± 0.6 μg/mL). Besides, anti-parasitic effect of eight purified botanic substances was also investigated. Aurelianolide A and B (compounds 1 and 2) from A. fasciculata and compound 8 from P. tuberculatum displayed the best trypanosomicidal effect. Compounds 1, 2 and 8 showed EC₅₀ of 4.6 ± 1.3 μM, 1.6 ± 0.4 μM and 8.1 ± 0.9 μM, respectively against intracellular forms. In addition, in silico analysis of these three biomolecules was performed to predict parameters of absorption, distribution, metabolism and excretion. The studied compounds presented similar ADMET profile as Bz, without presenting mutagenicity and hepatotoxicity aspects as predicted for Bz. Our findings indicate that these natural products have promising anti-T. cruzi effect and may represent new scaffolds for future lead optimization.     

Analysis of a “3-(Naphthalen-1-ylimino)indolin-2-one” Compound and Its Antimicrobial Assessment Using Lipid-Based Self-Nanoemulsifying Formulations

In recent years, indole derivatives have acquired conspicuous significance due to their wide spectrum of biological activities—antibacterial, antiviral, and anticonvulsant. This compound is derived from naturally grown plants. Therefore, synthesis of a novel “3-(Naphthalen-1-ylimino)indolin-2-one” compound (2) and its analysis using UPLC systems along with antimicrobial assessment was the aim of the current study. Isatin was used as a parent drug for synthesizing compound (2). Liquid Chromatographic analysis was performed using a C18 BEH column (1.7 μm 2.1 × 50 mm) by UPLC systems. Degradation studies were carried out to see whether acid, base, thermal, and oxidizing agents had any impact on the synthesized molecule in stress conditions (100 °C). A lipid-based self-nanoemulsifying formulation was developed and selectivity, specificity, recovery, accuracy, and precision were measured as part of the UPLC system’s validation process. Antimicrobial studies were conducted using gram-positive and gram-negative bacteria. The standard samples were run with a concentration range of 5.0–100.0 μg/mL using the isocratic mobile phase comprising of methanol/water (70/30 %v/v) at 234 nm; good linearity (R² = 0.9998) was found. The lower limits of detection (LOD) and quantitation (LOQ) of the method were found to be 0.81 μg/mL and 2.5 μg/mL, respectively. The coefficients of variation were found to be less than 2%. The antimicrobial study suggests that compound (2) has a substantial growth effect against gram-negative bacteria. It was successfully synthesized and applied to measure the concentrations in lipid-based dosage form, along with potent antimicrobial activities.     

Cytotoxic and apoptotic effects of Hypericum androsaemum on prostate adenocarcinoma (PC-3) and hepatocellular carcinoma (Hep G2) cell lines with identification of secondary metabolites by LC-HRMS

The study aims to determine the secondary metabolites of Hypericum androsaemum L. extracts by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and investigate the antioxidant and cytotoxic activities of the plant. Cytotoxic activity was evaluated by MTT assay, and apoptosis induction abilities on human prostate adenocarcinoma (PC-3), and hepatocellular carcinoma (Hep G2) cell lines. Accordingly, major secondary metabolites were found as hederagenin (762 ± 70.10 μg/g) in the leaves dichloromethane (LD), herniarin (167 ± 1.50 μg/g) in fruit dichloromethane (FD), (-)-epicatechin (6538 ± 235.36 μg/g) in the leaves methanol (LM), (-)-epigallocatechin gallate (758 ± 20.46 μg/g) in the fruit methanol (FM), and caffeic acid (370 ± 8.88 μg/g) in the fruit water (FW), and (3313 ± 79.51 μg/g) in the leaves water (LW) extracts. LM exerted strong antioxidant activity in DPPH free (IC₅₀ 10.94 ± 0.08 μg/mL), and ABTS cation radicals scavenging (IC₅₀ 9.09 ± 0.05 μg/mL) activities. FM exhibited cytotoxic activity with IC₅₀ values of 73.23 ± 3.06 µg/mL and 31.64 ± 2.75 µg/mL on PC-3 and Hep G2 cell lines, respectively. Being the richest extract in terms of quillaic acid (630 ± 18.9 μg/g), which is a well-known cytotoxic triterpenoid with proven apoptosis induction ability on different cells, FM extract showed apoptosis induction activity with 64.75% on PC-3 cells at 50 μg/mL concentration. The study provides promising results about the potential of Hypericum androsaemum on cancer prevention.     

Phenolic compounds,essential oil composition,and antioxidant activity of Angelica purpurascens (Avé-Lall.) Gill

In this study, methanol extracts (MEs) and essential oil (EO) of Angelica purpurascens (Avé-Lall.) Gill obtained from different parts (root, stem, leaf, and seed) were evaluated in terms of antioxidant activity, total phenolics, compositions of phenolic compound, and essential oil with the methods of 2,2-azino-bis(3ethylbenzo-thiazoline-6-sulfonic acid (ABTS•⁺), 2,2-diphenyl-1-picrylhydrazil (DPPH•) radical scavenging activities, and ferric reducing/antioxidant power (FRAP), the Folin–Ciocalteu, liquid chromatography−tandem mass spectrometry (LC−MS/MS), and gas chromatography-mass spectrometry (GC−MS), respectively. The root extract of A. purpurascens exhibited the highest ABTS•⁺, DPPH•, and FRAP activities (IC₅₀: 0.05 ± 0.0001 mg/mL, IC₅₀: 0.06 ± 0.002 mg/mL, 821.04 ± 15.96 µM TEAC (Trolox equivalent antioxidant capacity), respectively). Moreover, EO of A. purpurascens root displayed DPPH• scavenging activity (IC₅₀: 2.95 ± 0.084 mg/mL). The root extract had the highest total phenolic content (438.75 ± 16.39 GAE (gallic acid equivalent), µg/mL)). Twenty compounds were identified by LC−MS/MS. The most abundant phenolics were ferulic acid (244.39 ± 15.64 μg/g extract), benzoic acid (138.18 ± 8.84 μg/g extract), oleuropein (78.04 ± 4.99 μg/g extract), and rutin (31.21 ± 2.00 μg/g extract) in seed, stem, root, and leaf extracts, respectively. According to the GC−MS analysis, the major components were determined as α-bisabolol (22.93%), cubebol (14.39%), α-pinene (11.63%), and α-limonene (9.41%) among 29 compounds. Consequently, the MEs and EO of A. purpurascens can be used as a natural antioxidant source.     

Metabolomic Profiling and Antioxidant Activities of Breonadia salicina Using 1H-NMR and UPLC-QTOF-MS Analysis

Breonadia salicina (Vahl) Hepper and J.R.I. Wood is widely used in South Africa and some other African countries for treatment of various infectious diseases such as diarrhea, fevers, cancer, diabetes and malaria. However, little is known about the active constituents associated with the biological activities. This study is aimed at exploring the metabolomics profile and antioxidant constituents of B. salicina. The chemical profiles of the leaf, stem bark and root of B. salicina were comprehensively characterized using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The antioxidant activities of the crude extracts, fractions and pure compounds were determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging and reducing power assays. A total of 25 compounds were tentatively identified using the UPLC-QTOF-MS. Furthermore, the ¹H-NMR fingerprint revealed that the different parts of plant had differences and similarities among the different crude extracts and fractions. The crude extracts and fractions of the root, stem bark and leaf showed the presence of α-glucose, β-glucose, glucose and fructose. However, catechin was not found in the stem bark crude extracts but was found in the fractions of the stem bark. Lupeol was present only in the root crude extract and fractions of the stem bark. Furthermore, 5-O-caffeoylquinic acid was identified in the methanol leaf extract and its respective fractions, while the crude extracts and fractions from the root and dichloromethane leaf revealed the presence of hexadecane. Column chromatography and preparative thin-layer chromatography were used to isolate kaempferol 3-O-(2″-O-galloyl)-glucuronide, lupeol, d-galactopyranose, bodinioside Q, 5-O-caffeoylquinic acid, sucrose, hexadecane and palmitic acid. The crude methanol stem bark showed the highest antioxidant activity in the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity with an IC₅₀ value of 41.7263 ± 7.6401 μg/mL, whereas the root crude extract had the highest reducing power activity with an IC_0.5 value of 0.1481 ± 0.1441 μg/mL. Furthermore, the ¹H-NMR and UPLC-QTOF-MS profiles showed the presence of hydroxycinnamic acids, polyphenols and flavonoids. According to a literature survey, these phytochemicals have been reported to display antioxidant activities. Therefore, the identified hydroxycinnamic acid (caffeic acid), polyphenol (ellagic acid) and flavonoids (catechin and (epi) gallocatechin) significantly contribute to the antioxidant activity of the different parts of plant of B. salicina. The results obtained in this study provides information about the phytochemistry and phytochemical compositions of Breonadia salicina, confirming that the species is promising in obtaining constituents with medicinal potential primarily antioxidant potential.     

Trichilianones A-D,Novel Cyclopropane-Type Limonoids from Trichilia adolfi

The fractionation of an ethanol extract of the bark of Trichilia adolfi yielded four novel limonoids (trichilinones A-D, 1–4), with five fused rings and related to the hortiolide-type limonoids. Starting with an ε-lactone, which is α,β-unsaturated in trichilinones A and D (1 and 4), attached to a tetrahydrofuran ring that is connected to an unusual bicyclo [5.1.0] hexane system, joined with a cyclopentanone with a 3-furanyl substituent [(2-oxo)-furan-(5H)-3-yl in trichilinone D (4)], the four compounds isolated display a new 7/5/3/5/5 limonoid ring system. Their structures were established based on extensive analysis of NMR spectroscopic data. As the crude extract possessed anti-leishmanial properties, the compounds were assayed for cytotoxic and anti-parasitic activities in vitro in murine macrophages cells (Raw 264.7) and leishmania promastigotes (L. amazoniensis and L. braziliensis), respectively. The compounds showed moderate cytotoxicity (approximately 70 μg/mL), but are not responsible for the leishmanicidal effect of the extract.     

LC-HRMS Profiling and Antidiabetic,Anticholinergic, and Antioxidant Activities of Aerial Parts of Kınkor (Ferulago stellata)

Kınkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kınkor (Ferulago stellata), some putative antioxidant methods such as DPPH· scavenging activity, ABTS^•+ scavenging activity, ferric ions (Fe³⁺) reduction method, cupric ions (Cu²⁺) reducing capacity, and ferrous ions (Fe²⁺)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and α-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kınkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kınkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kınkor (Ferulago stellata) demonstrated IC₅₀ values of 1.772 μg/mL against acetylcholinesterase (AChE), 33.56 ± 2.96 μg/mL against α-glycosidase, and 0.639 μg/mL against α-amylase enzyme respectively.     

Identification of Dipeptidyl Peptidase-4 and α-Amylase Inhibitors from Melicope glabra (Blume) T. G. Hartley (Rutaceae) Using Liquid Chromatography Tandem Mass Spectrometry,In Vitro and In Silico Methods

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of M. glabra based on dipeptidyl peptidase-4 (DPP-4) and α-Amylase inhibitory activity assays. The chloroform extract of the leaves was found to be most active towards inhibition of DPP-4 and α-Amylase with IC₅₀ of 169.40 μg/mL and 303.64 μg/mL, respectively. Bioassay-guided fractionation of the leaves’ chloroform extract revealed fraction 4 (CF4) as the most active fraction (DPP-4 IC₅₀: 128.35 μg/mL; α-Amylase IC₅₀: 170.19 μg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol (1), swermirin (2), methyl 3,4,5-trimethoxycinnamate (3), renifolin (4), 4′,5,6,7-tetramethoxy-flavone (5), isorhamnetin (6), quercetagetin-3,4′-dimethyl ether (7), 5,3′,4′-trihydroxy-6,7-dimethoxy-flavone (8), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (9) as the major components. The computational study suggested that (8) and (7) were the most potent DPP-4 and α-Amylase inhibitors based on their lower binding affinities and extensive interactions with critical amino acid residues of the respective enzymes. The binding affinity of (8) with DPP-4 (−8.1 kcal/mol) was comparable to that of sitagliptin (−8.6 kcal/mol) while the binding affinity of (7) with α-Amylase (−8.6 kcal/mol) was better than acarbose (−6.9 kcal/mol). These findings highlight the phytochemical profile and potential antidiabetic compounds from M. glabra that may work as an alternative treatment for diabetes.     

Chemical Profiling,Bioactivity Evaluation and the Discovery of a Novel Biopigment Produced by Penicillium purpurogenum CBS 113139

Biobased pigments are environmentally friendly alternatives to synthetic variants with an increased market demand. Production of pigments via fermentation is a promising process, yet optimization of the production yield and rate is crucial. Herein, we evaluated the potential of Penicillium purpurogenum to produce biobased pigments. Optimum sugar concentration was 30 g/L and optimum C:N ratio was 36:1 resulting in the production of 4.1–4.5 AU (namely Pigment Complex A). Supplementation with ammonium nitrate resulted in the production of 4.1–4.9 AU (namely Pigment Complex B). Pigments showed excellent pH stability. The major biopigments in Pigment Complex A were N-threonyl-rubropunctamin or the acid form of PP-R (red pigment), N-GABA-PP-V (violet pigment), PP-O (orange pigment) and monascorubrin. In Pigment Complex B, a novel biopigment annotated as N-GLA-PP-V was identified. Its basic structure contains a polyketide azaphilone with the same carboxyl-monascorubramine base structure as PP-V (violet pigment) and γ-carboxyglutamic acid (GLA). The pigments were not cytotoxic up to 250 μg/mL.     

Bioactive Polyketide and Diketopiperazine Derivatives from the Mangrove-Sediment-Derived Fungus Aspergillus sp. SCSIO41407

Ten polyketide derivatives (1–10), including a new natural product named (E)-2,4-dihydroxy-3-methyl-6-(2-oxopent-3-en-1-yl) benzaldehyde (1), and five known diketopiperazines (11–15), were isolated from the mangrove-sediment-derived fungus Aspergillus sp. SCSIO41407. The structures of 1–15 were determined via NMR and MS spectroscopic analysis. In a variety of bioactivity screening, 3 showed weak cytotoxicity against the A549 cell line, and 2 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 3, 5, and 6 showed inhibition against acetylcholinesterase (AChE) with IC₅₀ values of 23.9, 39.9, and 18.6 μM. Compounds 11, 12, and 14 exhibited obvious inhibitory activities of lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) with IC₅₀ values of 19.2, 20.9, and 8.7 μM, and they also suppressed RANKL-induced osteoclast differentiation in bone marrow macrophages cells (BMMCs), with the concentration of 5 μM. In silico molecular docking with AChE and NF-κB p65 protein were also performed to understand the inhibitory activities, and 1, 11–14 showed obvious protein/ligand-binding effects to the NF-κB p65 protein.     

Asperflaloids A and B from Aspergillus flavipes DZ-3, an Endophytic Fungus of Eucommia ulmoides Oliver

The fungus strain DZ-3 was isolated from twigs of the well-known medicinal plant Eucommia ulmoides Oliver and identified as Aspergillus flavipes. Two new alkaloids, named asperflaloids A and B (1 and 2), together with 10 known compounds (3–12) were obtained from the EtOAc extract of the strain. Interestingly, the alkaloids 1–4 with different frameworks are characterized by the presence of the same anthranilic acid residue. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of asperflaloids A and B was resolved by quantum chemistry calculation. All compounds were screened for their inhibitions against α-glucosidase and the antioxidant capacities. The results were that compound 3 had an IC₅₀ value of 750.8 μM toward α-glucosidase, and the phenol compounds 7 and 8 exhibited potent antioxidant capacities with IC₅₀ values 14.4 and 27.1 μM respectively.     

Evaluation of the In Vitro Antiparasitic Effect of the Essential Oil of Cymbopogon winterianus and Its Chemical Composition Analysis

Cymbopogon winterianus, known as “citronella grass”, is an important aromatic and medicinal tropical herbaceous plant. The essential oil of C. winterianus (EOCw) is popularly used to play an important role in improving human health due to its potential as a bioactive component. The present study aimed to identify the components of the essential oil of C. winterianus and verify its leishmanicidal and trypanocidal potential, as well as the cytotoxicity in mammalian cells, in vitro. The EOCw had geraniol (42.13%), citronellal (17.31%), and citronellol (16.91%) as major constituents. The essential oil only exhibited significant cytotoxicity in mammalian fibroblasts at concentrations greater than 250 μg/mL, while regarding antipromastigote and antiepimastigote activities, they presented values considered clinically relevant, since both had LC₅₀ < 62.5 μg/mL. It can be concluded that this is a pioneer study on the potential of the essential oil of C. winterianus and its use against the parasites T. cruzi and L. brasiliensis, and its importance is also based on this fact. Additionally, according to the results, C. winterianus was effective in presenting values of clinical relevance and low toxicity and, therefore, an indicator of popular use.     

Bioactive PKS–NRPS Alkaloids from the Plant-Derived Endophytic Fungus Xylaria arbuscula

A novel hybrid PKS–NRPS alkaloid, xylarialoid A (1), containing a 13-membered macrocyclic moiety and [5,5,6] fused tricarbocyclic rings, together with ten known cytochalasins (2–11), was isolated from a plant-derived endophytic fungus, Xylaria arbuscula. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculation. Compounds 1–3 and 10 exhibited significant antitumor activities against A549 and Hep G2 cell lines, with IC₅₀ values of 3.6–19.6 μM. In addition, compound 1 showed potent anti-inflammatory activity against LPS-induced nitric oxide (NO) production in macrophage RAW 264.7 cells (IC₅₀, 6.6 μM).     

Anticancer,Anticoagulant, Antioxidant and Antimicrobial Activities of Thevetia peruviana Latex with Molecular Docking of Antimicrobial and Anticancer Activities

Natural origin molecules represent reliable and excellent sources to overcome some medicinal problems. The study of anticancer, anticoagulant, and antimicrobial activities of Thevetia peruviana latex were the aim of the current research. An investigation using high-performance liquid chromatography (HPLC) revealed that the major content of the flavonoids are rutin (11.45 µg/mL), quersestin (7.15 µg/mL), naringin (5.25 µg/mL), and hisperdin (6.07 µg/mL), while phenolic had chlorogenic (12.39 µg/mL), syringenic (7.45 µg/mL), and ferulic (5.07 µg/mL) acids in latex of T. peruviana. Via 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging, the experiment demonstrated that latex had a potent antioxidant activity with the IC₅₀ 43.9 µg/mL for scavenging DPPH. Hemolysis inhibition was 58.5% at 1000 µg/mL of latex compared with 91.0% at 200 µg/mL of indomethacin as positive control. Negligible anticoagulant properties of latex were reported where the recorded time was 11.9 s of prothrombin time (PT) and 29.2 s of the activated partial thromboplastin time (APTT) at 25 µg/mL, compared with the same concentration of heparin (PT 94.6 s and APPT 117.7 s). The anticancer potential of latex was recorded against PC-3 (97.11% toxicity) and MCF-7 (96.23% toxicity) at 1000 μg/mL with IC₅₀ 48.26 μg/mL and 40.31 µg/mL, respectively. Disc diffusion assessment for antimicrobial activity recorded that the most sensitive tested microorganisms to latex were Bacillus subtilis followed by Escherichia coli, with an inhibition zone (IZ) of 31 mm with minimum inhibitory concentration (MIC) (10.2 μg/mL) and 30 mm (MIC, 12.51 μg/mL), respectively. Moreover, Candida albicans was sensitive (IZ, 28 mm) to latex, unlike black fungus (Mucor circinelloides). TEM examination exhibited ultrastructure changes in cell walls and cell membranes of Staphylococcus aureus and Pseudomonas aeruginosa treated with latex. Energy scores of the molecular docking of chlorogenic acid with E. coli DNA (7C7N), and Rutin with human prostate-specific antigen (3QUM) and breast cancer-associated protein (1JNX), result in excellent harmony with the experimental results. The outcome of research recommended that the latex is rich in constituents and considered a promising source that contributes to fighting cancer and pathogenic microorganisms.     

Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.

Englerophytum magalismontanum, a medicinal plant with ethnopharmacology use, has a dearth of information regarding its antidiabetic properties. This study evaluated the crude methanol leaf extract of E. magalismontanum and its fractions for total phenolic content, antioxidant activity, and digestive enzymes (α-amylase and α-glucosidase) inhibitory activity using standard methods. The total phenolic content (56.53 ± 1.94 mg GAE/g dry extract) and DPPH Trolox antioxidant equivalent (TAE) (1.51 ± 0.66 µg/mL) of the methanol fraction were the highest among the fractions. The IC₅₀ values of the methanol fraction against α-amylase (10.76 ± 1.33 µg/mL) and α-glucosidase (12.25 ± 1.05 µg/mL) activities were also high. Being the most active, the methanol fraction was subjected to bio-assay guided column chromatography-based enzyme inhibition to obtain a pure compound. The phenolic compound isolated and identified as naringenin inhibited α-amylase and α-glucosidase with IC₅₀ of 5.81 ± 2.14 µg/mL and 4.77 ± 2.99 µg/mL, respectively. This is the first study to isolate naringenin from E. magalismontanum extract. The molecular docking and molecular dynamics studies demonstrated naringenin as a promising lead compound in comparison to acarbose for the treatment of diabetes through the inhibition of α-glucosidase activity.     

An Insight into Kiwiberry Leaf Valorization: Phenolic Composition,Bioactivity and Health Benefits

During kiwiberry production, different by-products are generated, including leaves that are removed to increase the fruit’s solar exposure. The aim of this work was to extract bioactive compounds from kiwiberry leaf by employing microwave-assisted extraction (MAE). Compatible food solvents (water and ethanol) were employed. The alcoholic extract contained the highest phenolic and flavonoid contents (629.48 mg of gallic acid equivalents (GAE) per gram of plant material on dry weight (dw) (GAE/g dw) and 136.81 mg of catechin equivalents per gram of plant material on dw (CAE/g dw), respectively). Oppositely, the hydroalcoholic extract achieved the highest antioxidant activity and scavenging activity against reactive oxygen and nitrogen species (IC₅₀ = 29.10 μg/mL for O₂^•−, IC₅₀ = 1.87 μg/mL for HOCl and IC₅₀ = 1.18 μg/mL for ^•NO). The phenolic profile showed the presence of caffeoylquinic acids, proanthocyanidin, and quercetin in all samples. However, caffeoylquinic acids and quercetin were detected in higher amounts in the alcoholic extract, while proanthocyanidins were prevalent in the hydroalcoholic extract. No adverse effects were observed on Caco-2 viability, while the highest concentration (1000 µg/mL) of hydroalcoholic and alcoholic extracts conducted to a decrease of HT29-MTX viability. These results highlight the MAE potentialities to extract bioactive compounds from kiwiberry leaf.