Oxindole and Benzoxazinone Alkaloids from the Seeds of Persea americana (Avocado) and Their SIRT1 Stimulatory Activity.

Persea americana Mill. (Lauraceae), commonly known as avocado, is a well-known food because of its nutrition and health benefits. The seeds of avocado are major byproducts, and thus their phytochemicals and bioactivities have been of interest for study. The chemical components of avocado seeds were investigated by using UPLC-qTOF-MS/MS-based molecular networking, resulting in the isolation of seven new oxindole alkaloids (1-7) and two new benzoxazinone alkaloids (8 and 9). The chemical structures of the isolated compounds were identified by the analysis of NMR data in combination with computational approaches, including NMR and ECD calculations. Bioactivities of the isolated compounds toward silent information regulation 2 homologue-1 (SIRT1) in HEK293 cells were assessed. The results showed that compound 1 had the most potent effect on SIRT1 activation with an elevated NAD+/NADH ratio with potential for further investigation as an anti-aging agent.

Investigating individual intention to make money: can motivation of wealth be a socio-economic leverage?

Wealth is an indicator of individual well-being. Increasing wealth is a pathway to achieving socio-economic development. Thus, it is imperative to shed light on factors that induce individual intention to increase wealth. This study investigates the effects of perception of wealth, perception of the rich, and behavioral control on personal intention to make money. A stratified sampling method was employed to obtain a sample of 991 respondents from Northern, Central, and Southern Vietnam who were invited to participate in a structured questionnaire survey in 2021. We utilized the Confirmatory Factor Analysis to validate the proposed model and tested the hypotheses using the Partial Least Squared-SEM. Empirical results highlight that individual behavioral control, explicit perception of the rich, and perception of wealth are essential determinants of individual intention to make money. Interestingly, motivation of wealth positively moderates the relationship between the perception of wealth and personal intention to make money. In addition, post-Covid-19 opportunities positively moderate two-pair relationships: perception of wealth-individual intention to make money and explicit perception of the rich-individual intention to make money. Insights from this study imply appropriate policies for the government to enhance the inspiration of people to work harder, leading to sustainable development.

Cyclohumulanoid Sesquiterpenes Induced by the Noncompetitive Coculture of Phellinus orientoasiaticus and Xylodon flaviporus.

Microbial cocultivation has been applied as a strategy to induce the biosynthesis of specialized metabolites. However, most previous studies have focused on competitive interactions between test strains. During our LC-MS-based chemical screening of randomized cocultures of Basidiomycetous fungi, we discovered that the coculture of Phellinus orientoasiaticus (Hymenochaetaceae) and Xylodon flaviporus (Schizoporaceae) induces multiple metabolites, although they did not show any competitive morphology. Targeted isolation yielded three new sesquiterpenes (1-3) along with five known analogues (4-8). The structures of the isolates were determined by MS and NMR experiments as well as electronic circular dichroism analysis. LC-MS analysis suggested that cyclohumulanoids of illudane-, sterpurane-, and tremulane-type scaffolds (1-7) were produced by P. orientoasiaticus, whereas a drimane-type sesquiterpene (8) was produced by X. flaviporus. None of the isolates exhibited antifungal activity or cytotoxicity, and compounds 1-7 exhibited NO production of LPS-treated RAW276.4 cells in a range of 15.9% to 38.0% at 100 µM.

Melicopteline A-E, Unusual Cyclopeptide Alkaloids with Antiviral Activity against Influenza A Virus from Melicope pteleifolia.

In the search for antiviral cyclopeptides against influenza A virus, five unprecedented Caryophyllaceae-type cyclopeptides (1-5) were isolated from the leaves of Melicope pteleifolia. Their chemical structures and absolute configurations were unambiguously determined by means of advanced Marfey's analysis and comprehensive spectroscopic analyses including two-dimensional nuclear magnetic resonance and MS/MS fragmentation. Interestingly, compounds 3-5 contain an unusual heterocycle, a 3a-hydroxypyrroloindole moiety, which was biosynthetically formed by a nucleophilic cyclization from the least abundant amino acid, tryptophan, precursor and has aroused a great interest in the aspect of chemical diversity and biological activity. All isolates (1-5) were evaluated for their protective effects against influenza A viruses H1N1 and H9N2 in MDCK cells. All isolated cyclopeptides exhibited strong anti-influenza activity, especially against H1N1. Compound 3 showed the most potent CPE inhibition effect, which was stronger than that of the positive control ribavirin against H1N1, with an EC50 (µM) of 2.57 ± 0.45 along with higher selectivity.

Rugonidines A-F, Diastereomeric 1,6-Dioxa-7,9-diazaspiro[4.5]dec-7-en-8-amines from the Leaves of Alchornea rugosa.

Rugonidines A-F (1-6), three pairs of novel configurationally semistable diastereomers featuring an unprecedented 1,6-dioxa-7,9-diazaspiro[4.5]dec-7-en-8-amine scaffold, were isolated from Alchornea rugosa based on MS/MS-based molecular networking analysis. Their structures were elucidated by NMR spectroscopy in combination with quantum-chemical calculations. Compounds 1-3 showed a significant increase in glucose uptake level in differentiated 3T3-L1 adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent-tagged glucose probe.

Oleanane Triterpenoids from the Leaves of Gymnema inodorum and Their Insulin Mimetic Activities.

During an effort to find insulin mimetic compounds, the leaves of Gymnema inodorum were shown to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation on a 70% ethanol extract of G. inodorum was applied to yield two new (1 and 2) and two known (8 and 9) oleanane triterpenoids with a methyl anthranilate moiety together with five further new oleanane triterpenoids (3-7). The chemical structures of all isolates were determined based on their spectroscopic data, including IR, UV, NMR, and mass spectrometric analysis. The isolated compounds (1-9) were determined for their stimulatory activities on glucose uptake in differentiated 3T3-L1 adipocyte cells using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent-tagged glucose probe. Three compounds (3, 5, and 9) showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Chemicals with a methyl anthranilate moiety have been considered as crucial contributors of flavor odor in foods, and quantitative analysis showed the content of compound 8 to be 0.90 ± 0.01 mg/g of the total extract. These results suggest that the leaves of G. inodorum have the potential to be used as an antidiabetic functional food or tea.

Neuroprotective Effects of Triterpenoids from Camellia japonica against Amyloid ß-Induced Neuronal Damage.

Alzheimer's disease (AD), a neurocognitive impairment affecting human mental capacity, is related to the accumulation of amyloid-ß peptide (Aß) and the hyperphosphorylation of tau protein. In addition to modern therapies approved for AD treatment, natural products with antioxidant and anti-inflammatory properties have been studied for their potential to prevent AD pathogenesis. Six new noroleanane triterpenoids from the fruit peels of Camellia japonica were isolated, and their structures were determined by diverse spectroscopic methods. The neuroprotective effects of the six new compounds were tested against Aß-induced neurotoxicity and neuroinflammation in mouse hippocampal and microglial cells. In the model of HT22-transfected cells, compounds 1-4 showed strongly neuroprotective effects via antioxidant response element gene activation and decreased the level of glutamate uptake. Compounds 1-4 also appeared to have strong inhibitory effects on NO production in Aß1-42-transfected BV2 microglial cells. A docking simulation study was used to explain the inhibitory effects of compounds 1-4 on ß-secretase 1 (BACE1). Noroleanane triterpenoids 1-4 had potential neuroprotective and anti-inflammatory effects against Aß-induced neuronal damage. The structure-activity relationships of the 30 oleanane triterpenoids from C. japonica were assessed in a model of Aß1-42-transfected HT22 cells.

Development of a Building Block Strategy to Target the Classification, Identification, and Metabolite Profiling of Oleanane Triterpenoids in Gymnema sylvestre Using UHPLC-qTOF/MS.

The major class of bioactive metabolites in Gymnema sylvestre, a popular Ayurvedic medicinal plant for the treatment of diabetes mellitus, is oleanane triterpenoids. In this study, a targeted, biosynthesis-inspired approach using UHPLC-qTOF/MS was implemented to elucidate the whole chemical profile of this plant for the standardization of the Vietnamese G. sylvestre variety. The known compounds were first determined to identify the building blocks of the biosynthetic intermediates and the construction rules for synthesizing oleanane triterpenoids in the plant. These blocks were recombined to build a virtual library of all reasonable compounds consistent with the deduced construction rules. Various techniques, including relative mass defect filtering, multiple key ion analysis, mass fragmentation analysis, and comparison with standard references, were applied to determine the presence of these predicted compounds. Conventional isolation and structure elucidation of six of the new compounds were carried out to identify the new building blocks and validate the assignments. Consequently, 119 peaks were quickly assigned to oleanane triterpenoids, and among them, 77 peaks were predicted to be new compounds based on their molecular formulas and mass fragmentation patterns. All the identified metabolites were then classified into different layers to analyze their logical relationships, and a multilayered chemical profile of the oleanane triterpenoids was constructed. This new approach is expected to be practical for characterizing structures of modular secondary metabolites, such as triterpenoid saponins, and for proposing biosynthetic relationships among compounds of the same class of metabolites in medicinal plants.

Dereplication by High-Performance Liquid Chromatography (HPLC) with Quadrupole-Time-of-Flight Mass Spectroscopy (qTOF-MS) and Antiviral Activities of Phlorotannins from Ecklonia cava.

Ecklonia cava is edible seaweed that is found in Asian countries, such as Japan and Korea; and, its major components include fucoidan and phlorotannins. Phlorotannins that are isolated from E. cava are well-known to have an antioxidant effect and strong antiviral activity against porcine epidemic diarrhea virus (PEDV), which has a high mortality rate in piglets. In this study, the bioactive components were determined based on two different approaches: (i) bio-guided isolation using the antiviral activity against the H1N1 viral strain, which is a representative influenza virus that originates from swine and (ii) high-resolution mass spectrometry-based dereplication, including relative mass defects (RMDs) and HPLC-qTOFMS fragmentation analysis. The EC70 fraction showed the strongest antiviral activity and contained thirteen phlorotannins, which were predicted by dereplication. Ten compounds were directly isolated from E. cava extract and then identified. Moreover, the dereplication method allowed for the discovery of two new phlorotannins. The structures of these two isolated compounds were elucidated using NMR techniques and HPLC-qTOFMS fragmentation analysis. In addition, molecular modelling was applied to determine the absolute configurations of the two new compounds. The antiviral activities of seven major phlorotannins in active fraction were evaluated against two influenza A viral strains (H1N1 and H9N2). Six of the compounds showed moderate to strong effects on both of the viruses and phlorofucofuroeckol A (12), which showed an EC50 value of 13.48 ± 1.93 µM, is a potential active antiviral component of E. cava.

BM-BronchoLC - A rich bronchoscopy dataset for anatomical landmarks and lung cancer lesion recognition.

Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.

Unique guanidine-conjugated catechins from the leaves of Alchornea rugosa and their autophagy modulating activity.

Natural guanidines, molecules that contain the guanidine moiety, are structurally unique and often exhibit potent biological activities. A phytochemical investigation of the leaves of Alchornea rugosa (Lour.) Müll.Arg. by MS/MS-based molecular networking revealed eight undescribed guanidine-flavanol conjugates named rugonines A-H. The chemical structures of the isolated compounds were comprehensively elucidated by NMR spectroscopy, HRESIMS, and circular dichroism (CD) analysis. All isolated compounds were tested for autophagosome formation in HEK293 cells stably expressing GFP-LC3. The results revealed that compounds rugonines D-G showed potential autophagy inhibitory activity.

Linderanidins A-F: Rare oligomeric flavonoids with an unusual C-3-C-4 linkage from the roots of Lindera erythrocarpa and their inhibitory activities on autophagy.

Autophagy is a crucial process for maintaining cellular homeostasis by degrading and recycling unnecessary or damaged cellular components. In the process of exploring autophagy regulators in plants, unique nine oligomeric flavonoids linked by the bonding of C-3 and C-4, consisting of three pairs of biflavonoids, linderanidins A-C [(+)-1/(-)-1, (+)-2/(-)-2, and (+)-3/(-)-3], and three trimeric A-type proanthocyanidins, linderanidins D-F (4-6), were isolated from the roots of Lindera erythrocarpa. The structures and absolute configurations of these compounds were determined using various techniques, such as 1D and 2D NMR, mass spectrometry, X-ray crystallography, and electronic circular dichroism. All isolates were evaluated for their ability to regulate autophagy, and compounds (±)-1-(±)-3, (-)-1-(-)-3, (+)-1-(+)-3 and 4 were found to inhibit autophagy by blocking the fusion process between autophagosome and lysosome in HEK293 cells. This study suggests that unique oligomeric flavonoids possessing a C-3-C-4 linkage derived from the roots of L. erythrocarpa are potent autophagy inhibitors.

Chemical constituents with senolytic activity from the stems of Limacia scandens.

While screening senotherapeutics from natural products, seven undescribed chemicals, two syringylglycerol derivatives, two cyclopeptides, one tigliane analogue, and two chromone derivatives, as well as six known compounds were isolated from the stems of Limacia scandens. The structures of compounds were elucidated through spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and CD data. All compounds were tested in replicative senescent human dermal fibroblasts (HDFs) to determine their potential as senotherapeutic agents to specifically target senescent cells. One tigliane and two chromones derivatives showed senolytic activity, indicating that senescent cells were selectively removed. Especially, 2-{2-[(3'-O-ß-d-glucopyranosyl)phenyl]ethyl}chromone is expected to be a potential senotherapeutics by inducing HDF death, inhibiting the activity of senescence-associated ß-galactosidase (SA-ß-gal) and expressing senescence-associated secretory phenotype (SASP) factors.

Metabolite Profiling of Allium hookeri Leaves Using UHPLC-qTOF-MS/MS and the Senomorphic Activity of Phenolamides.

The plant Allium hookeri, a member of the Allium genus, has a rich history of culinary and medicinal use. Recent studies have unveiled its potent antioxidant and anti-inflammatory properties. While research on A. hookeri has demonstrated its neuroprotective and anti-neuroinflammatory effects, the specific bioactive compounds responsible for these effects remain unidentified in prior research. This study utilized an untargeted metabolomic approach, employing HRESI-qTOF MS/MS-based molecular networking, to comprehensively profile the chemical composition of metabolites in A. hookeri and identify new compounds within the plant. As a result, ten compounds, comprising one novel flavonoid (2) and nine known compounds (1 and 3-10), were isolated and identified through NMR analysis. The inhibitory effects of all isolated compounds on the senescent cell-associated secretory phenotype (SASP), which is pivotal in neuroprotective actions, were evaluated. Biological activity testing revealed N-trans-feruloyltyramine (7) to be the most potent compound, effectively inhibiting SASP markers and contributing to the senomorphic activities of A. hookeri. These findings underscore the potential of phenolamides from A. hookeri as a promising source of bioactive compounds for mitigating senescence-associated diseases.

Insulin-mimetic activity of 23-glycosyl oleanane triterpenoids isolated from Gymnema latifolium.

Chemical investigation of the plant Gymnema latifolium led to the isolation of seven undescribed 23-glycosyl oleanane triterpenoids, gymlatinosides GLF1-GLF7, and two known compounds, gymnemosides D and E. The structures of the isolated compounds were elucidated using diverse spectroscopic methods. The extract of G. latifolium and all isolated compounds significantly enhanced 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) uptake into 3T3-L1 adipocytes at 20 µM. Among them, gymlatinosides GLF2 and gymlatinosides GLF4 showed particularly potent stimulatory effects on glucose uptake in a dose-dependent manner. Further investigation revealed that gymlatinosides GLF2 at 20 µM upregulated the expression of phosphorylated AMPK (p-AMPK). The results suggested that gymlatinosides GLF2 may enhance glucose uptake via regulating the AMPK signaling pathway.

Chemical constituents of the culture broth of Dentipellis fragilis and their anti-inflammatory activities.

Seven undescribed compounds, dentipellinones A‒D (1, 2, 5, and 6), dentipellinol (3), methoxyerinaceolactone B (4), and erinaceolactomer A (7), were isolated from the culture broth of Dentipellis fragilis. Chemical structures of these isolated compounds were determined by analyses of 1D and 2D-NMR and MS data in comparison with data reported in the literature. Absolute configurations of 1‒7 were also determined by Electronic Circular Dichroism calculations. The isolated compounds were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokines levels in LPS-stimulated RAW264.7 cells. Compounds 5 and 7 were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokine levels in LPS-stimulated RAW264.7 cells. They exhibited inhibitory effects on LPS-induced NO production in a dose-dependent manner, and significantly reduced the levels of inflammatory-related cytokines such as IL-1ß and IL-6. TNF-α was not involved in the anti-inflammatory effects of these compounds. Finally, compounds 5 and 7 showed significant anti-inflammatory effects.

Sesquiterpene lactone and its unique proaporphine hybrids from Magnolia grandiflora L. and their anti-inflammatory activity.

Two undescribed sesquiterpene lactone-proaporphine hybrid skeletons, two undescribed sesquiterpenes, and four known compounds were isolated from the aerial part of Magnolia grandiflora L. The structures of isolated compounds were unambiguously determined based on the interpretation of a combination of NMR spectroscopy, HRESIMS, DP4+ probability calculation of carbon data, X-ray crystallographic analyses, and ECD calculation. The isolated compounds were investigated for their anti-inflammatory activity against nitric oxide production and the protein expression of COX-2 in LPS-stimulated RAW 264.7 cells.

Heliciopsides A-E, Unusual Macrocyclic and Phenolic Glycosides from the Leaves of Heliciopsis terminalis and Their Stimulation of Glucose Uptake.

Ten phenolic constituents, including three new macrocyclic glycosides (1-3), a new phenolic glycoside (5), a new biphenyl glycoside (6), and five known compounds (4, 7-10), were isolated from a 70% MeOH extract of the leaves of Heliciopsis terminalis by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-guided molecular networking. The chemical structures of new compounds 1-3, 5 and 6 were established based on comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS techniques. All isolated compounds (1-10) were evaluated for their stimulation of glucose uptake in differentiated 3T3-L1 adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent glucose analog. Compounds 3, 6 and 8 showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Among them, compounds 3 and 6 activated the AMPK signaling pathway in differentiated C2C12 myoblasts.

Meroterpenoids from the leaves of Psidium guajava (guava) cultivated in Korea using MS/MS-based molecular networking.

MS/MS-based molecular networking showed differences in the chemical profiles, especially the terpenoid-coupled-phloroglucinol clusters, of Psidium guajava grown in Jeju Island of South Korea ("Jejuguava"), Vietnam and China. A chemical investigation of the 95% EtOH extract of Jejuguava leaves revealed meroterpenoids characterized by a dihydropyran ring junction between an acylphloroglucinol structure and terpenoid, and named jejuguajavones A-J (1-10). Compounds (±)-8-(±)-10 are racemic mixtures that were separated using a chiral HPLC column. The chemical structures of all the isolated compounds (1-10) were determined by analyzing the spectroscopic data and performing electronic circular dichroism calculations. Among the isolates, compounds 1-4 exhibit inhibitory activity against the protein tyrosine phosphatase 1B (PTP1B) enzyme, and this result was confirmed by molecular docking simulations.