Search Results (344)

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition that progressively impairs cognitive processes, particularly learning and memory. A key pathological feature of AD involves senile plaques mainly composed of β-amyloid (Aβ) peptides, generated via the amyloidogenic pathway from amyloid precursor protein (APP) through sequential β-secretase (BACE1) and γ-secretase cleavage, positioning BACE1 inhibition as a prime therapeutic target. In this study, we applied bioassay-guided fractionation of the butanol-soluble fraction from Dryopteris crassirhizoma rhizomes, previously reported to inhibit Aβ production, to isolate and characterize Aβ-lowering constituents. Through successive chromatographic steps, nine compounds were isolated and structurally classified into flavonoids, chromones, and phloroglucinols, including epicatechin (1), β-carboxymethyl-(-)-epicatechin (2), 7-methoxy-isobiflorin (3), biflorin (4), eriodictyol (5), noreugenin (6), phloroglucinols (butyrylphloroglucinol (7), 2-propionyl-4-methylphloroglucinol (8), and 2-butyryl-4-methylphloroglucinol (9) by comprehensive spectroscopic analysis (NMR, MS, UV, IR). These compounds were assessed for effects on sAPPβ and BACE1 (β-secretase) levels by Western blot, with Aβ production quantified via ELISA in a cellular AD model (APP-CHO cells). Compounds 5–9 significantly reduced sAPPβ and BACE1 expression while potently suppressing Aβ generation. These results demonstrate that diverse constituents from D. crassirhizoma rhizomes inhibited Aβ production through BACE1 suppression, highlighting their potential as natural lead compounds for AD prevention or therapy. Full article

Latex-producing plants harbor unique microbial communities that may play important roles in host defense; however, their diversity and biocontrol potential remain largely unexplored. Characterizing these communities provides opportunities to identify novel microbial-derived antifungal agents for sustainable crop protection. Bacterial strains were isolated from the latex of Alstonia scholaris (L.) R. Br. and identified using 16S rRNA gene sequencing. Antifungal activity was evaluated against four phytopathogens: Fusarium graminearum, Colletotrichum musae, Colletotrichum gloeosporioides, and Glomerella cingulata. Bioassay-guided fractionation, size-exclusion chromatography, SDS-PAGE, and LC-MS/MS were used to characterize antifungal proteins. Nine bacterial strains were isolated, including eight Bacillus spp. and one Enterococcus faecalis. Among them, Bacillus sp. AsL-2 exhibited the strongest broad-spectrum antifungal activity, inhibiting fungal growth by up to 80%. The antifungal activity of its crude extract remained stable over a wide temperature range. Further characterization identified a novel endo-β-1,3-1,4-glucanase enzyme (~23 kDa) as the major antifungal protein. This study reveals A. scholaris latex as an underexplored microbial niche and identifies Bacillus sp. AsL-2, affiliated with the B. velezensis–B. amyloliquefaciens species complex, as a promising biocontrol candidate. The identified antifungal enzyme represents a potential natural alternative to synthetic fungicides for sustainable agricultural disease management. Full article

Turmeric (Curcuma longa L., Zingiberaceae) is a widely consumed spice and functional food valued for its bioactive constituents. Using an activity-guided strategy, this study identified the dichloromethane fraction as the most potent anti-inflammatory fraction, exhibiting markedly stronger inhibition of reactive oxygen species (ROS) production than ibuprofen (IC₅₀ $\le$ 0.4 vs. 11.2 μg/mL). Bioassay-guided purification yielded bisacurone (1), didemethoxycurcumin (2), and β-turmerone (3), with compounds 1 and 2 reported here for the first time in this fraction. Among them, β-turmerone displayed the strongest anti-inflammatory activity (IC₅₀ = 4.7 μg/mL), consistent with in silico docking and molecular dynamics analyses, revealing greater binding affinity and complex stability with myeloperoxidase (ΔG_bind = −20.90 vs. −18.89 kcal/mol for ibuprofen). Gas chromatography–mass spectrometry (GC-MS) profiling revealed a phytochemical profile dominated by turmerones and curlone, correlating with the observed bioactivity. None of the fractions exhibited acute toxicity in brine shrimp lethality assays, indicating a favorable preliminary safety profile. Our findings demonstrate the value of activity-guided isolation combined with computational validation for identifying turmeric-derived bioactives with promising nutraceutical potential, warranting further in vivo evaluation. Full article

Plant fungal diseases pose a serious threat to crop production and safety, and natural products are one of the important directions for the development of new green fungicides. This study found that the extract of Murraya euchristifolia had significant antifungal activity, and a main antifungal coumarin (1) was isolated by bioassay-guided fractionation. The structure of 1 was identified by NMR and MS spectroscopic data as a fused bis-furan coumarin (microminutinin) which was first isolated from the Murraya genus and exhibited strong broad-spectrum antifungal activity against eight plant pathogenic fungi from different families and genera. The EC₅₀ value of 1 (11.33 μg/mL) against Pestalotiopsis theae (the most sensitive to 1) was slightly higher than that (7.03 μg/mL) of the positive drug (80% carbendazim WP), indicating that 1 has the potential to serve as a lead compound for botanical fungicides. The bioassay results against P. theae in vivo indicated that 1 also has the potential for field application. Scanning electron microscopy and optical microscopy revealed that 1 disrupted the morphological structure of mycelium, causing hyphae to twist, shrink, and even crack and severely reducing hyphal branching. Furthermore, propidium iodide staining proved that microminutinin destroyed the integrity of the cell membrane, causing leakage of cellular components. In addition, calcofluor white staining and chitin content changes illustrated that microminutinin disrupted the cell wall structure. This research provides compound sources and a theoretical basis for the development of botanical fungicides. Full article

Cadmium (Cd) is a recognized environmental contaminant, present in soil, water, and food, which has been reported to cause male reproductive damage in vivo and vitro. Selenium-enriched rapeseed flowering stalks exhibit protective effects against Cd-induced reproductive damage, yet the bioactive components and underlying mechanisms remain unclear. We optimized the process of obtaining the crude extract (CE) via single-factor experiments. Subsequent bioassay-guided fractionation identified the water extract (WE) as significantly more effective in alleviating Cd-induced cytotoxicity compared to the petroleum ether extract, ethyl acetate extract, and n-butanol extract. High-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS) analysis revealed that WE contained the highest contents of methylselenocysteine (MeSeCys) and selenocystine (SeCys₂) among four fractions. Both MeSeCys and SeCys₂ exhibited protective effects against Cd-induced cytotoxicity. To further elucidate the underlying mechanisms, network pharmacology, RNA-Seq, qPCR, and Western blotting analysis were employed. The results revealed that WE exhibited good free radical scavenging capabilities, and the protective mechanisms of WE, MeSeCys, and SeCys₂ against Cd-induced cytotoxicity were related to a reduction in oxidative damage, the inhibition of the ERK/p38 MAPK signaling pathway, and the suppression of cell cycle arrest, inflammation, and apoptosis triggered by Cd exposure. Collectively, these findings suggest that selenium-enriched rapeseed flowering stalks may serve as a promising dietary supplement in the prevention of Cd-induced reproductive toxicity. Full article

Despite the availability of effective vaccines, yellow fever outbreaks persist, highlighting the need for antiviral drugs. Background/Objectives: This study investigated Hippeastrum puniceum (Amaryllidaceae) as a potential source of antiviral compounds against wild-type yellow fever virus (wt-YFV). Methods/Results: The crude bulb extract of H. puniceum exhibited 58% protection against wt-YFV. Bioassay-guided fractionation of the extract by UHPLC-HRMS led to the annotation of six alkaloids (bulbisine, cathinone, trigonelline, tetrahydroharman-3-carboxylic acid, and 2,7-dimethoxyhomolycorine or 3-O-acetylnarcissidine) in active fractions, along with the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analyses predicted favorable pharmacokinetic and toxicological profiles, supporting their potential as drug candidates. Six of the annotated compounds were evaluated in vitro for cytotoxicity and antiviral activity against wt-YFV. However, none showed significant antiviral activity when tested individually, suggesting that the observed antiviral effect may result from synergistic interactions between two or more compounds within active fractions. Conclusions: Our results underscore the importance of further investigations in vitro, particularly assays exploring the synergy among the annotated compounds against YFV. The integration of bioassay-guided fractionation of active plant extracts with computational analyses emerges as a promising strategy for the discovery of natural products with therapeutic potential against yellow fever, a reemerging disease. Full article

Background: Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection. This disease is associated with an increased susceptibility to HIV and HPV infections. Currently, resistance to metronidazole (MTZ), the main drug used for treatment, has been reported in up to 9.6% of cases; additionally, the compound is also associated with adverse side effects. Therefore, it is urgent to identify new treatment options. Objective: In this study, we investigated for the first time the in vitro and in silico activity against T. vaginalis of betulin and stigmasterol isolated from Tagetes nelsonii Greenm, as well as their hemolytic activity. Methods: Plant specimen was collected in Chiapas, Mexico. Hexane and methanol extracts were prepared through sonication-assisted maceration. The antiprotozoal and hemolytic activities were evaluated in vitro against Trichomonas vaginalis trophozoites and human erythrocytes. The most active extract was fractionated using chromatographic techniques in a bioassay-guided study. The active metabolites were identified by ¹H and ¹³C-NMR spectroscopy, and their biological activity was further assessed in silico against lactate dehydrogenase (LDH), pyruvate ferredoxin oxidoreductase (PFOR) methionine gamma-lyase (MGL) and purine nucleoside phosphorylase (PNP) T. vaginalis enzymes. Results: Both triterpenes showed anti-trichomonal activity and no hemolytic activity at 100 µg/mL. Molecular docking studies predicted promising interactions of triterpenes with T. vaginalis drug target proteins, TvpFOR and TvLDH. Conclusions: Our results revealed that betulin and stigmasterol are potential molecules for the development of new trichomonacidal therapies against T. vaginalis. Full article

Dietary polyphenols are recognized as crucial modulators of gastrointestinal motility, holding therapeutic promise for conditions like irritable bowel syndrome, postoperative ileus, and functional dyspepsia. However, their reported effects are heterogeneous, ranging from spasmolytic to prokinetic. This review aims to clarify these inconsistencies by synthesizing experimental evidence on structure–activity relationships and underlying mechanisms. Relevant publications were identified in PubMed and Google Scholar using terms related to polyphenols and gastrointestinal motility. References were selected for relevance, and the narrative review integrates findings from in vitro, ex vivo, in vivo, and clinical studies. Across various experimental models, polyphenols function as multi-target modulators of gastrointestinal smooth muscle. The primary mechanisms identified involve the blockade of voltage-dependent L-type Ca²⁺ channels, activation of K⁺ channels (BK, K_ATP), and modulation of the NO/cGMP and cAMP/PKA pathways. Flavones and multiple flavonols consistently demonstrate spasmolytic activity via Ca²⁺ channel antagonism. In contrast, flavanones engage BK and K_ATP channels to induce membrane hyperpolarization. Complex extracts from plants like ginger and turmeric exhibit mixed pro- or antimotility effects, reflecting the diverse profiles of their constituent compounds. While robust ex vivo pharmacology and some in vivo and human data exist, a high degree of dataset heterogeneity and inconsistent reporting impedes direct translational efforts. Polyphenols are promising multi-mechanistic modulators of gastrointestinal motility with clear structure–activity patterns. To advance their clinical application, future research must focus on establishing standardized in vivo pharmacokinetics, conducting targeted structure–activity studies, employing bioassay-guided fractionation, and designing rigorous clinical trials. Full article

Francisella tularensis is a pathogenic bacterium and the causative agent of the disease tularemia. Because of the virulence of this bacterium and the potential for weaponization, the Centers for Disease Control and Prevention (CDC) has classified F. tularensis as a Category A Bioterrorism Agent. Therefore, the need for new treatments for tularemia is critical. In this work, we screened a cataloged library of natural extracts to identify those that inhibit the growth of F. tularensis only during infection of THP-1 monocyte cells. One of the most promising extracts identified in this screen was derived from Foeniculum vulgare (fennel). Using bioassay-guided fractionation, the fennel extract was fractionated, and the bioactive compound was isolated and structurally elucidated as the phenylpropanoid dillapiole. We subsequently confirmed that dillapiole alone could limit the replication of F. tularensis in infected THP-1 cells, but not outside of this infection model. Investigations on host responses suggested that dillapiole was not substantially augmenting the immunity of these THP-1 cells. We then investigated the potential virulence modulation activity of dillapiole. To test this hypothesis, RNA-seq analysis was carried out on F. tularensis bacteria that were treated with dillapiole. This showed that dillapiole caused a significant downregulation of genes controlled by the transcriptional regulators MglA and SspA, including those encoded in the Francisella pathogenicity island. Western blotting validated these findings as both IglA and IglC expression was diminished in F. tularensis LVS bacteria treated with dillapiole. Because dillapiole dampens the virulence gene expression of F. tularensis, we concluded that this compound has potential to be used as a novel therapeutic for tularemia with a unique mechanism of action. Full article

Tuberculosis (TB) is still a significant public health threat, with rising drug resistance and high incidence in multiple areas worldwide. In the search for novel antitubercular agents, this study explores the application of a bioactivity-guided molecular networking approach to identify bioactive compounds from seven plant species (Curatella americana, Davilla nitida, Dipteryx punctata, Indigofera suffruticosa, Quassia amara, Tetradenia riparia, and Zingiber zerumbet) collected in French Guiana. Using ultrasound-assisted extraction followed by liquid–liquid partitioning and UHPLC-HRMS/MS analysis, a library of 72 samples was tested against Mycobacterium tuberculosis. The non-polar fractions from Indigofera suffruticosa, Tetradenia riparia, and Zingiber zerumbet showed the highest activity. The integration of metabolomic and bioassay data on molecular networks allowed the prioritization and annotation of active compounds, revealing flavonoids as contributors to the antitubercular activity of the active samples. In addition, the use of computational tools such as GNPS, SIRIUS, and TIMA-R enabled dereplication and increased the confidence in the structural prediction of active metabolites. This approach demonstrated its potential in accelerating the identification of both known and novel bioactive compounds without requiring exhaustive isolation, offering a robust strategy for natural product-based drug development against TB. Full article

Background/Objectives: Tuberculosis (TB) remains one of the most pressing global health challenges, ranking among the leading infectious causes of mortality worldwide. Medicinal plants possess antimycobacterial potential, warranting the isolation and characterization of their bioactive compounds to address bacterial infections. The study aimed to determine five selected traditional medicinal plants’ in vitro antioxidant and antibacterial activities and the isolation of active phytoconstituents. Methods: Powdered leaf material was extracted using n-hexane, dichloromethane, acetone, methanol, and water. The quantity of phytochemicals and antioxidants was determined using colorimetric assay, The antimycobacterial activity and combination effects were determined using microbroth dilution assay. Cell viability was determined using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT reduction assay. Bioassay-guided fractionation was used to isolate bioactive compounds. Results: Polar solvents had high extraction yields, and all extracts had varying phytoconstituents. Active extracts were selected for fractionation and isolation of pure compounds using gradient elution column chromatography. Rhoicissus tridentata water extracts had the highest total phenolic (335.20 ± 8.26 mg GAE/g) and tannin (103.48 ± 7.36 mg GAE/g) content, while Rosmarinus officinalis (45.90 ± 11.04 mg QE/g) methanol extract had the highest total flavonoid. Ximenia caffra had promising antioxidant activity. R. officinalis had prominent antimycobacterial. Rhoicissus tridentata had the highest percentage cell viability. Two compounds were isolated, and they were active against Mycobacterium smegmatis with minimum inhibitory concentration values ranging from 0.125 to 0.25 mg/mL. Conclusions: The selected medicinal plants contain phytochemicals with antioxidant and antimycobacterial activities, supporting their pharmacokinetic studies and evaluation against Mycobacterium tuberculosis H37Rv. Full article

The present study investigates the antioxidant potential of the stem bark of Elaeocarpus floribundus Blume through an integrated approach involving phytochemical isolation, in vitro radical scavenging assays, ADMET-based safety profiling, and molecular docking. Bioassay-guided fractionation of the ethanolic extract into hexane, chloroform, and ethyl acetate fractions revealed the ethyl acetate fraction to possess the highest antioxidant activity, with an IC₅₀ value of 6.19 μg/mL in the DPPH assay, surpassing that of ascorbic acid (IC₅₀ = 9.74 μg/mL). Subsequent isolation and characterization from the ethyl acetate fraction of the stem bark yielded five known compounds from this plant part for the first time, including gallic acid and epigallocatechin gallate. Both compounds showed potent radical scavenging activity in vitro. Among these, gallic acid exhibited superior pharmacokinetic and safety profiles based on in silico ADMET predictions, no Lipinski’s rule violations, and no predicted toxicity. Molecular docking studies showed that gallic acid had high binding affinities for glutathione reductase (GR) and superoxide dismutase (SOD), exceeding those of their reference inhibitors. A docking analysis further revealed stable interactions with catalytically relevant residues, suggesting a stabilizing modulatory effect on redox homeostasis. These findings identify E. floribundus stem bark as a novel source of antioxidant compounds and highlight gallic acid as a promising therapeutic candidate for oxidative stress-related disorders. Full article

Abnormal skin pigmentation can cause significant esthetic concerns and impact quality of life. As melanin determines pigmentation, melanogenesis is a key target to manage pigmentation disorders. This study investigated the effects of extracts from the rhizome of Iris ×germanica L. var. florentina Dykes (often called Iris florentina L.) on melanogenesis. Active phytochemicals were identified by combining LC-MS-MS metabolic profiling with subsequent bioassay-directed fractionation of chromatographic eluent collected into 96-well plates. Fractions 41–43 increased melanin and contained germanaism B, providing evidence that it is a melanogenesis stimulator. In contrast, fractions 90–93 reduced melanin and contained iriflorental and iripallidal, identified as prospective melanogenesis inhibitors. To explore extract-based applications, the plant was subjected to ethanolic, chloroform, and supercritical carbon dioxide (SC-CO₂) extractions and tested in skin equivalent tissues. The ethanolic extract (rich in germanaism B) increased pigmentation, while the chloroform extract (higher in iriflorental and iripallidal) decreased it. The SC-CO₂ extract, with minimal germanaism B and enriched iriflorental and iripallidal, showed stronger depigmenting effect. This study is the first to report that rhizome of I. florentina contains phytochemicals with opposing effects on melanogenesis. Through different extraction processes, targeted extracts from a single botanical can address both hyper- and hypopigmentation, offering a novel approach to pigmentation modulation. Full article

Several natural products have been shown to display antiviral activity against the hepatitis B virus (HBV), among a number of other viruses. In a previous study, the hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest were tested on the hepatoma cell line HepG2.2.15, which constitutively produces HBV. One of the species that exerted inhibitory activity on HBV replication was Senna silvestris. The aim of this study was the bioassay-guided purification of the ethanol fraction of leaves of S. silvestris, which displayed the most significant inhibitory activity against HBV. After solvent extraction and two rounds of reverse-phase HPLC purification, NMR analysis identified salsolinol as the compound that may exert the desired antiviral activity. The purified compound exerted inhibition of both HBV DNA and core HBV DNA. Pure salsolinol obtained from a commercial source also displayed anti-HBV DNA inhibition, with an approximate MIC value of 12 µM. Although salsolinol is widely used in Chinese traditional medicine to treat congestive heart failure, it has also been associated with Parkinson’s disease. More studies are warranted to analyze the effect of changes in its chemical conformation, searching for potent antiviral, perhaps dual agents against HBV and HIV, with reduced toxicity. Full article

Plant genetics and chemotaxonomic analysis are considered key parameters in understanding evolution, plant diversity and adaptation. Korean Peninsula has a unique biogeographical landscape that supports various aromatic plant species, each with considerable ecological, ethnobotanical, and pharmacological significance. This review aims to provide a comprehensive overview of the chemotaxonomic traits, biological activities, phylogenetic relationships and potential applications of Korean aromatic plants, highlighting their significance in more accurate identification. Chemotaxonomic investigations employing techniques such as gas chromatography mass spectrometry, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy have enabled the identification of essential oils and specialized metabolites that serve as valuable taxonomic and diagnostic markers. These chemical traits play essential roles in species delimitation and in clarifying interspecific variation. The biological activities of selected taxa are reviewed, with emphasis on antimicrobial, antioxidant, anti-inflammatory, and cytotoxic effects, supported by bioassay-guided fractionation and compound isolation. In parallel, recent advances in phylogenetic reconstruction employing DNA barcoding, internal transcribed spacer regions, and chloroplast genes such as rbcL and matK are examined for their role in clarifying taxonomic uncertainties and inferring evolutionary lineages. Overall, the search period was from year 2001 to 2025 and total of 268 records were included in the study. By integrating phytochemical profiling, pharmacological evidence, and molecular systematics, this review highlights the multifaceted significance of Korean endemic aromatic plants. The conclusion highlights the importance of multidisciplinary approaches including metabolomics and phylogenomics in advancing our understanding of species diversity, evolutionary adaptation, and potential applications. Future research directions are proposed to support conservation efforts. Full article