Search Results (1,365)

Neurodegenerative diseases (NDs) encompass a group of chronic conditions, characterized by neuronal losses in large areas of the brain, leading to cognitive and behavioral impairments. Alzheimer’s Disease (AD), the most common form of dementia, is a progressive ND, characterized by the accumulation of amyloid β and tau protein, entails cognitive decline, neuroinflammation, mitochondrial dysfunction, and blood–brain barrier impairment, with oxidative stress playing a critical role in its pathogenesis. To date, the available pharmacotherapy has shown limited efficacy, and multitarget activity of plant-derived neuroprotective bioactive compounds is currently in focus. This review synthesizes experimental evidence regarding Ocimum species with neuroprotective potential in AD, particularly Ocimum sanctum and Ocimum basilicum. These plants are rich in bioactive compounds including polyphenols, flavonoids, essential oils, and triterpenoids that synergistically scavenge reactive oxygen/nitrogen species, upregulate endogenous antioxidant enzymes (SOD, CAT, and GPx), and reduce lipid peroxidation. Furthermore, these extracts have demonstrated the ability to decrease β-amyloid accumulation and tau protein levels, key pathological features of AD. Even though additional research is required to fully assess their potential as therapeutic agents for NDs, by diving into the specific mechanisms through which they improve neurodegenerative processes, important steps can be made towards this endpoint. Full article

Development of paclitaxel-induced neuropathic pain (PINP) during chemotherapy may lead to paclitaxel discontinuation, potentially compromising effective anticancer therapy. PINP can manifest as allodynia. One recently discovered key factor in paclitaxel-induced mechanical allodynia (PIMA) pathogenesis is the elevated activity of monoacylglycerol lipase (MAGL), an enzyme that metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG). Thus, inhibiting MAGL serves as a potential analgesic target. Notoginsenoside R1 (NGR1), a metabolite of Panax notoginseng, has shown promise in reducing oxidative stress and neuronal apoptosis in nerve injury models. However, its effects on PIMA and MAGL activity have not yet been explored. This study is a proof-of-concept preclinical study investigating the antiallodynic effects of NGR1 on PIMA in female BALB/c mice and also examining its effect on MAGL activity. The effect of treatment of mice with NGR1 intraperitoneally on the development of PIMA was evaluated. Molecular docking using CB-Dock2 compared the binding energies to MAGL of NGR1 and pristimerin, a triterpene MAGL inhibitor. The effects of NGR1 on human recombinant MAGL activity, as well as the MAGL activity in mice paw skin tissues, were assessed using MAGL inhibitor screening and MAGL activity assay kits, respectively. NGR1 prevented the development of PIMA in a dose-dependent manner. The docking scores showed that NGR1 has a good affinity for MAGL (−7.8 kcal/mol, binding energy) but less affinity than pristimerin (−10.3 kcal/mol). NGR1 inhibited the human recombinant MAGL activity in a reversible and concentration-dependent manner, although the inhibition was in a reverse order. Treatment of mice with NGR1 showed a non-significant trend in reducing the paclitaxel-induced increase in MAGL activity in the paw skin. This study shows for the first time that NGR1 prevents the development of PIMA and suggests that NGR1 has affinity for and inhibits human recombinant MAGL activity with a paradoxical inhibition pattern. More mechanistic studies are needed to fully elucidate the molecular mechanisms of NGR1 in preventing PIMA. Full article

The aim of this study was to investigate the metabolites in Aspergillus subramanianii 1901NT-1.40.2 extract using UPLC-MS, isolate and elucidate the structure of individual compounds, and study the antimicrobial and cytotoxic activities of the isolated compounds. The structures of two previously unreported ergostane triterpenoid aspersubrin A (1) and pyrazine alkaloid ochramide E (2) were established using NMR and HR ESI-MS. The absolute configuration of 1 was determined using quantum chemical calculations. Moreover, the known polyketides sclerolide (3) and sclerin (4); the indolediterpene alkaloid 10,23-dihydro-24,25-dehydroaflavinine (5); the bis-indolyl benzenoid alkaloids kumbicin D (6), asterriquinol D dimethyl ether (7), petromurin C (8); and the cyclopentenedione asterredione (9) were isolated. The effects of compounds 3-9 on the growth and biofilm formation of the yeast-like fungus Candida albicans and the bacteria Staphylococcus aureus and Escherichia coli were investigated. Compounds 5 and 6 inhibited C. albicans growth and biofilm formation at an IC₅₀ of 7–10 µM. Moreover, the effects of compounds 3-9 on non-cancerous H9c2 cardiomyocytes, HaCaT keratinocytes, MCF-10A breast epithelial cells, and breast cancer MCF-7 and MDA-MB-231 cells were also investigated. Compound 8 (10 µM) significantly decreased the viability of MCF-7 cells, inhibited colony formation, and arrested cell cycle progression and proliferation in monolayer culture. Moreover, 8 significantly decreased the area of MCF-7 3D spheroids by approximately 30%. A competitive test with 4-hydroxytamoxyfen and molecular docking showed that estrogen receptors (ERβ more than ERα) were involved in the anticancer effect of petromurin C (8). Full article

Antrodia camphorata (AC), a medicinal fungus native to Taiwan, contains bioactive compounds such as triterpenoids with anticancer properties. However, their high lipophilicity results in poor aqueous solubility and limited bioavailability, restricting their therapeutic application. To address this issue, a nanoparticle-based delivery system was developed using chitosan, alginate, and hyaluronic acid to encapsulate AC extracts. AC-loaded nanoparticles (AC-NPs) with a particle size less than 100 nm improved drug solubility and facilitated intracellular accumulation. Assessment of cytotoxicity revealed that AC-NPs significantly and more effectively suppressed the growth of breast cancer cells than free AC extracts. After 72 h, IC₅₀ values for MDA-MB-231 (triple-negative) and MCF-7 (estrogen receptor-positive) were 46.9 and 75.6 μg/mL, respectively, with greater sensitivity observed in MDA-MB-231 cells. AC-NPs exhibited minimal toxicity toward normal mammary epithelial cells (NMuMG), indicating good biocompatibility. Fluorescently labeled AC-NPs showed rapid, time-dependent uptake in both cancer cell lines. Particularly, MDA-MB-231 cells exhibited rapid internalization, whereas MCF-7 cells likely benefited from hyaluronic acid-mediated targeting of CD44 receptors. In conclusion, AC-NPs enhanced the solubility, cellular uptake, and anticancer efficacy of AC while maintaining biocompatibility, thereby suggesting their robust potential as nanocarrier platforms for breast cancer therapy. Full article

Background/Objectives: Anaerobic gut fungi (Neocallimastigomycota) are biotechnologically relevant, lignocellulose-degrading microbes with under-explored biosynthetic potential for secondary metabolites. Untargeted metabolomic profiling with gas chromatography–mass spectrometry (GC-MS) was applied to two gut fungal strains, Anaeromyces robustus and Caecomyces churrovis, to establish a foundational metabolomic dataset to identify metabolites and provide insights into gut fungal metabolic capabilities. Methods: Gut fungi were cultured anaerobically in rumen-fluid-based media with a soluble substrate (cellobiose), and metabolites were extracted using the Metabolite, Protein, and Lipid Extraction (MPLEx) method, enabling metabolomic and proteomic analysis from the same cell samples. Samples were derivatized and analyzed via GC-MS, followed by compound identification by spectral matching to reference databases, molecular networking, and statistical analyses. Results: Distinct metabolites were identified between A. robustus and C. churrovis, including 2,3-dihydroxyisovaleric acid produced by A. robustus and maltotriitol, maltotriose, and melibiose produced by C. churrovis. C. churrovis may polymerize maltotriose to form an extracellular polysaccharide, like pullulan. GC-MS profiling potentially captured sufficiently volatile products of proteomically detected, putative non-ribosomal peptide synthetases and polyketide synthases of A. robustus and C. churrovis. The triterpene squalene and triterpenoid tetrahymanol were putatively identified in A. robustus and C. churrovis. Their conserved, predicted biosynthetic genes—squalene synthase and squalene tetrahymanol cyclase—were identified in A. robustus, C. churrovis, and other anaerobic gut fungal genera. Conclusions: This study provides a foundational, untargeted metabolomic dataset to unmask gut fungal metabolic pathways and biosynthetic potential and to prioritize future efforts for compound isolation and identification. Full article

Haloxylon articulatum is traditionally used for treating infections, digestive issues, and oxidative stress. Despite its ethnopharmacological relevance, its phytochemistry and biological activities, particularly in Iraq, are underexplored. This study investigated the phytochemical composition of H. articulatum extracts and evaluated their antioxidant and anti-Helicobacter pylori activities, supported by molecular docking and in silico ADMET analysis. Methanol/water and ethyl acetate extracts from roots and aerial parts were analyzed using LC-HRMS/MS. Antioxidant capacity was measured via DPPH assay, and anti-H. pylori activity was assessed using broth microdilution. Molecular docking targeted bacterial isoleucyl-tRNA synthetase, and ADMET predictions were carried out with SwissADME and ADMETlab. Phytochemical profiling identified 32 compounds, including phenolamides, flavonoids, alkaloids, and triterpenoid glycosides. Root extracts exhibited stronger antioxidant and antibacterial effects than aerial parts. Ethyl acetate extracts were inactive. Phenolamides, N-caffeoyltyramine, and sinapoyltyramine, present in the extract, showed significant activity (MICs = 54 ± 0.92 and 74 ± 1.05 µg/mL). Docking supported their strong binding to the target enzyme. ADMET results indicated good oral bioavailability and low toxicity. This study is the first to report the anti-H. pylori activity of H. articulatum and to characterize its Iraqi chemotype through advanced metabolomics. The findings highlight the plant’s potential as a source of multifunctional phytochemicals with antioxidant and antibacterial applications, warranting further preclinical development and toxicological investigation. Full article

Liver fibrosis remains difficult to treat, in part because many hepatoprotective triterpenoids suffer from poor oral bioavailability and lack of optimized delivery formats. Ganoderma amboinense is a rare “antler” reishi species long valued in Eastern traditions yet scarcely studied for its phytochemical and pharmacological potential. Here, we report the first investigation of an ethanol-extracted G. amboinense sublingual dripping pill formulation (GDP) in a carbon-tetrachloride (CCl₄)–induced mouse model of liver fibrosis. Mice treated with GDP at one- and five-times the human equivalent dose were compared to groups receiving unprocessed G. amboinense powder (GP) or purified ganoderic acid A (GA-A). GDP significantly prevented CCl₄-induced weight loss and hepatomegaly, normalizing liver-to-body weight ratios and serum AST/ALT activities (p < 0.05). Histological evaluation showed that GDP markedly reduced hepatocellular necrosis and collagen deposition, restoring tissue architecture. Furthermore, GDP suppressed hepatic expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, COX-2) and profibrotic markers (TGF-β1, CTGF, α-SMA) to levels comparable with or superior to GA-A. These results demonstrate that a dripping pill dosage form can effectively deliver G. amboinense triterpenoids and unlock their hepatoprotective activity, supporting further development of GDP as a novel liver-support nutraceutical. Full article

Antrodia cinnamomea is a fungus endemic to Taiwan that exhibits various medicinal properties, including anti-cancer and anti-inflammatory effects, many of which stem from its unique triterpenoids. Studies on A. cinnamomea generally focus on the red phenotype, while only a handful of studies on its naturally-occurring mutant white phenotype exist. This study investigated the effect of two different culture types (solid-state dish culture and submerged flask culture) and three carbon sources (glucose, maltose, and sucrose) on the mycelial dry weight and triterpenoid content of red (AC) and white (W) strains of A. cinnamomea. The concentrations of eight key triterpenoid compounds were also determined to compare triterpenoid profiles. Biomass accumulation under solid-state culture was more than two-fold for the W strain than for the AC strain. In submerged culture mycelial biomass was not significantly different between strains. Total triterpenoid content was 29%, 88%, and 134% greater in the AC strain than the W strain under submerged culture with glucose, maltose, and sucrose, respectively. Similarly, triterpenoid content of solid-state-cultured fungus increased by 10% with glucose and 53% with maltose. Although both strains responded similarly to each carbon source with regards to mycelial dry weight, their triterpenoid profiles differed in solid-state culture. Five of the eight key compounds were detected in the solid-state culture of the AC strain (antcin A, antcin B, antcin C, antcin K, and DMMB) and four were detected in the submerged culture (antcin A, antcin B, antcin K, and DMMB). The concentration of individual triterpenoid compounds was up to 100 times greater in the solid-state culture than in the submerged culture. None of the eight key compounds were found in the W strain. This study indicates that the triterpenoid profile of in vitro cultured white A. cinnamomea differs from red strains, and that further investigation of their metabolomic profiles is required. Full article

Traditional Douchiba (DCB), a bacterial-type fermented soybean condiment, suffers from pronounced bitterness and limited functional attributes, hindering its broader application. To address these challenges, this study innovatively compounded matured Bacillus subtilis-fermented adlay (BFA) with DCB at varying ratios to develop a fermented adlay-DCB seasoning (FADS). Key physicochemical, nutritional, functional, and sensory parameters were systematically analyzed, and a multidimensional quality evaluation system was established via the Entropy Method for composite scoring. Results revealed that BFA integration enhanced the brightness and increased the content of total triterpenoid (by 16-fold) and γ-aminobutyric acid (by 9-fold) in FADS. Notably, electronic tongue analysis demonstrated that BFA significantly reduced the bitterness, after-bitterness, and saltiness intensities of DCB, achieving maximum reductions of 90.12% for bitterness and 87.63% for after-bitterness. Meanwhile, GC-MS profiling identified 89 volatile compounds, with pyrazines, alcohols, and acids as the primary volatile components in FADS. Additionally, the S4 sample (the BFA:DCB ratio = 6:4) achieved the highest composite score (0.64), with pyrazines contributing 0.13 points to the evaluation. In summary, BFA not only significantly mitigated bitterness in DCB but also substantially enhanced its bioactive properties. The results offer a scientific basis for the flavor improvement of fermented seasonings. Full article

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

Polyscias fruticosa (L.) Harms, a Southeast Asian medicinal plant of the Araliaceae family, has gained increasing attention due to its rich phytochemical profile and potential pharmacological applications. This review provides an up-to-date synthesis of biotechnological strategies and chemical investigations related to this species. In vitro propagation methods, including somatic embryogenesis, adventitious root, and cell suspension cultures, are discussed with emphasis on elicitation and bioreactor systems to enhance the production of secondary metabolites. Phytochemical analyses using gas chromatography–mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) have identified over 120 metabolites, including triterpenoid saponins, polyphenols, sterols, volatile terpenoids, polyacetylenes, and fatty acids. Several compounds, such as tocopherols, conjugated linoleic acids, and alismol, were identified for the first time in the genus. These constituents exhibit antioxidant, anti-inflammatory, antimicrobial, antidiabetic, anticancer, and neuroprotective activities, with selected saponins (e.g., chikusetsusaponin IVa, Polyscias fruticosa saponin [PFS], zingibroside R1) showing confirmed molecular mechanisms of action. The combination of biotechnological tools with phytochemical and pharmacological evaluation supports P. fruticosa as a promising candidate for further functional, therapeutic, and nutraceutical development. This review also identifies knowledge gaps related to compound characterization and mechanistic studies, suggesting future directions for interdisciplinary research. Full article

Background: Liuwei Dihuang Pills, a classic traditional Chinese medicine formula, has been widely used in clinical practice for its multiple pharmacological effects. However, the systematic characterization and identification of its chemical constituents, especially the aqueous decoction, remain insufficient, which hinders in-depth research on its pharmacodynamic material basis. Thus, there is an urgent need for a comprehensive analysis of its chemical components using advanced analytical techniques. Methods: After screening chromatographic columns, the ACQUITY UPLC™ HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was selected. The column temperature was set to 40 °C, and the mobile phase consisted of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B). A gradient elution program was adopted, and the separation was completed within 20 min. Ultra-high performance liquid chromatography–Orbitrap mass spectrometry (UPLC-Orbitrap-MS) combined with a self-established information database was used for the analysis. Results: A total of 80 compounds were tentatively identified, including 13 monoterpenoids, 6 phenolic acids, 16 iridoids, 11 flavonoids, 25 triterpenoids, and 9 other types. Triterpenoids are mainly derived from Poria cocos and Alisma orientale; iridoids are mainly from Rehmannia glutinosa; monoterpenoids are mainly from Moutan Cortex; and flavonoids are mainly from Dioscorea opposita. Among them, monoterpenoids, iridoids, and triterpenoids are important pharmacodynamic components. The cleavage pathways of typical compounds (such as pachymic acid, catalpol, oxidized paeoniflorin, and puerarin) are clear, and their mass spectral fragment characteristics are consistent with the literature reports. Conclusions: Through UPLC-Orbitrap-MS technology and systematic optimization of conditions, this study significantly improved the coverage of chemical component identification in Liuwei Dihuang Pills, providing a comprehensive reference for the research on its pharmacodynamic substances. However, challenges remain in the identification of trace components and isomers. In the future, analytical methods will be further improved by combining technologies such as ion mobility mass spectrometry or multi-dimensional liquid chromatography. Full article

In this report, we describe the synthesis of a compound derived from the natural compound celastrol, which is connected to a phthalimide moiety via an ester linkage. The compound was fully characterized by proton (¹H), carbon-13 (¹³C), heteronuclear single-quantum coherence (HSQC), and distortionless enhancement by polarization transfer (DEPT) NMR. Ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared (FTIR), and elementary analysis were also performed. Full article

Cucurbitacin B (CuB), a tetracyclic triterpenoid compound isolated from Cucurbitaceae plants, exhibits inhibitory effects on various tumor cells (e.g., liver, gastric, and colorectal cancer cells). Since the 1970s–1980s, cucurbitacin tablets containing CuB have been used as an adjuvant therapy for chronic hepatitis and primary liver cancer. CuB exerts anticancer effects through multiple mechanisms: inducing apoptosis, cell cycle arrest (G2/M or S phase), autophagy, and cytoskeleton disruption; inhibiting migration, invasion, and angiogenesis (via VEGF/FAK/MMP-9 and Wnt/β-catenin pathways); regulating metabolic reprogramming and immune responses; inducing pyroptosis, ferroptosis, and epigenetic changes; and reversing tumor drug resistance. These effects are associated with signaling pathways like JAK/STAT, PI3K/Akt/mTOR, and FOXM1-KIF20A. To improve its application potential, strategies such as structural modification (e.g., NO donor conjugation), combination therapy (with gemcitabine or cisplatin), and nanomaterial-based delivery (e.g., liposomes and exosome-mimicking nanoparticles) have been developed to enhance efficacy, reduce toxicity, and improve bioavailability. CuB shows broad-spectrum anticancer activity, but further research is needed to clarify the mechanisms underlying its cell-specific sensitivity and interactions with the immune system. This review systematically summarizes the physicochemical properties, anticancer mechanisms, and strategies for applying CuB and suggests future research directions, providing references for scientific research and clinical translation. Full article

Aralia chinensis L. has shown potential in breast cancer treatment, yet its pharmacodynamically active components and mechanisms remain undefined. To systematically identify the bioactive constituents absorbed into the bloodstream and elucidate their multi-target mechanisms against breast cancer, we employed ultra-high-performance liquid chromatography in conjunction with Q Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) alongside serum pharmacochemistry to analyze the chemical constituents of total saponins derived from A. chinensis (TSAC) and to identify the blood-absorbed prototypes in a rat model. Network pharmacology predicted targets and pathways of serum prototypes, validated by molecular docking and in vitro experiments. We identified 38 triterpenoid saponins, 3 steroidal saponins, and 8 triterpenoids in TSAC, with 22 prototype compounds detected in serum. An integrative analysis encompassing 486 compound targets and 1747 genes associated with breast cancer elucidated critical pathways, notably the PI3K-Akt signaling pathway and resistance mechanisms to EGFR tyrosine kinase inhibitors. Molecular docking confirmed strong binding of araloside A and elatoside L to SRC, PIK3R1, PIK3CA, STAT3, and EGFR. In MCF-7 cells, TSAC suppressed proliferation and migration while downregulating Src, PI3K, and EGFR expression at the gene and protein levels. This study successfully identified TSAC’s serum-absorbed bioactive components and demonstrated their anti-breast cancer effects via multi-target mechanisms involving the Src/PI3K/EGFR axis, providing a crucial pharmacological foundation for developing A. chinensis-derived breast cancer therapies. Full article