Search Results (393)

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Mauritia flexuosa, commonly known as “canangucha,” holds significant nutritional and economic value in the Amazon region. While its pulp is widely utilized in local food products, the seed or kernel is largely underutilized. This study investigated the proximal and phytochemical composition of M. flexuosa, alongside its biological properties, specifically focusing on the hypoglycemic activity of an ethanolic extract from M. flexuosa seeds (MFSs). Proximal analysis revealed that MFSs are a notable source of crude fiber (28.4%) and a moderate source of protein (9.1%). Phytochemical screening indicated a high total polyphenol content (123.4 mg gallic acid equivalents/100 mg dry weight) and substantial antiradical capacity against the ABTS radical (IC₅₀ = 171.86 µg/mL). Notably, MFS ethanolic extracts exhibited significant in vitro antihyperglycemic activity via inhibiting α-amylase and α-glucosidase enzymes, demonstrating comparable inhibition to acarbose at higher concentrations. This hypoglycemic effect was further corroborated in an in vivo rat model with induced diabetes, where the administration of 100 mg/kg of MFS ethanolic extract significantly reduced blood glucose levels compared to the diabetic control group (p < 0.05). A moderate antihypertensive effect was observed at a concentration of 150 mg/kg, correlating with ACE inhibition. High-performance liquid chromatography–mass spectrometry (UHPLC-ESI-HRMS) analysis of the seed extract identified phenolic compounds including ellagic, p-coumaric, and chlorogenic acids, as well as flavonoids such as quercetin, myricetin, and epicatechin. This study provides the first evidence of the hypoglycemic activity of MFSs, offering valuable insights into their phytochemistry and potential therapeutic applications. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

Dietary advanced glycation end-products (dAGEs) contained in high-sugar/fat and ultra-processed foods of the “Western diet” (WD) pattern predispose to several diseases by altering protein function or increasing oxidative stress and inflammation via RAGE (receptor for advanced glycation end-products). Although elevated endogenous AGEs are associated with loss of muscle mass and functionality (i.e., muscle wasting; MW), the impact of dAGEs on MW has not been elucidated. Here, we show that the most common dAGEs or their precursor, methylglyoxal (MGO), induce C2C12 myotube atrophy as endogenous AGE-derived BSA. ROS production, mitochondrial dysfunction, mitophagy, ubiquitin–proteasome activation, and inhibition of myogenic potential are common atrophying mechanisms used by MGO and AGE-BSA. Although of different origins, ROS are mainly responsible for AGE-induced myotube atrophy. However, while AGE-BSA activates the RAGE-myogenin axis, reduces anabolic mTOR, and causes mitochondrial damage, MGO induces glycolytic stress and STAT3 activation without affecting RAGE expression. Among thirty selected natural compounds, Vaccinium macrocarpon (VM), Camellia sinensis, and chlorophyll showed a surprising ability in counteracting in vitro AGE formation. However, only the standardized VM, containing anti-glycative metabolites as revealed by UHPLC-HRMS analysis, abrogates AGE-induced myotube atrophy. Collectively, our data suggest that WD-linked dAGE consumption predisposes to MW, which might be restricted by VM food supplements. Full article

Plant secondary metabolites regulate plant growth and serve as valuable pharmaceutical resources. Napier grass (Pennisetum purpureum Schumach.), a Poaceae species, shows potential as a functional food. In this study, we employed high-resolution mass spectrometry combined with a data-independent acquisition (DIA) strategy for the untargeted detection of anthocyanins, a group of secondary metabolites, in napier grass. Clear MS² fragmentation patterns were observed for anthocyanins, characterized by diagnostic aglycone signals and sequential losses of hexosyl (C₆H₁₀O₅), deoxyhexosyl (C₆H₁₀O₄), pentosyl (C₅H₈O₄), and p-coumaroyl groups (C₉H₈O₃). Based on matching with authentic standards and an in-house database, ten anthocyanins were identified, seven of which were newly reported in napier grass. In a single-laboratory validation analysis, both absolute and semi-quantitative results reliably reflected the specific distribution of metabolites across different cultivars and plant organs. The purple cultivar (TS5) exhibited the highest anthocyanin content, with the cyanidin 3-O-glucoside content reaching 5.0 ± 0.5 mg/g, whereas the green cultivar (TS2), despite its less pigmented appearance, contained substantial amounts of malvidin 3-O-arabinoside (0.7 ± <0.1 mg/g). Flavonoid profiling revealed that monoglycosylated anthocyanins were the dominant forms in floral tissues. These findings shed light on napier grass metabolism and support future Poaceae breeding and functional food development. Full article

Arugula leaves (Diplotaxis tenuifolia L. and Eruca sativa L.) are a must-have ingredient in ready-to-eat salads, as they are prized for their appearance, taste, and flavor. The nutraceutical properties of this leafy vegetable are attributed to the presence of valuable secondary metabolites, such as phenolic acids and glucosinolates. Using UHPLC-Q-Orbitrap HRMS analysis and ion chromatography, we characterized the content of phenolic acids, glucosinolates, nitrates, and organic acids in organic arugula [Diplotaxis tenuifolia (L.) DC] and evaluated how the foliar application of three different non-microbial biostimulants (a seaweed extract, a vegetable protein hydrolysate, and a tropical plant extract) modulated the expression of these. Although the application of vegetable protein hydrolysate increased, compared to control plants, the nitrate content, the application of the same biostimulant increased the total content of glucosinolates and phenolic acid derivatives by 5.2 and 17.2%. Specifically, the foliar application of the plant-based biostimulant hydrolyzed protein significantly increased the content of glucoerucin (+22.9%), glucocheirolin (+76.8%), and ferulic acid (+94.1%). The highest values of flavonoid derivatives (173.03 μg g⁻¹ dw) were recorded from plants subjected to the exogenous application of seaweed extract. The results obtained underscore how biostimulants, depending on their origin and composition, can be exploited not only to improve agronomic performance but also to enhance the nutraceutical content of vegetables, guaranteeing end consumers a product with premium quality characteristics. Full article

Background: Hydroxyl and amino compounds play a significant role in defining the flavor and quality of sauce-flavor Baijiu, yet their comprehensive analysis remains challenging due to limitations in detection sensitivity. In this study, we developed a novel bromine isotope labeling approach combined with ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to achieve high-coverage profiling of these compounds in sauce-flavor Baijiu. Methods: The method employs 5-bromonicotinoyl chloride (BrNC) for rapid (30 s) and mild (room temperature) labeling of hydroxyl and amino functional groups, utilizing bromine’s natural isotopic pattern (Δm/z = 1.998 Da) for efficient screening. Annotation was performed hierarchically at five confidence levels by integrating retention time, accurate mass, and MS/MS spectra. Results: A total of 309 hydroxyl and amino compounds, including flavor substances (e.g., tyrosol and phenethyl alcohol) and bioactive compounds (e.g., 3-phenyllactic acid), were identified in sauce-flavor Baijiu. The method exhibited excellent analytical performance, with wide linearity (1–4 orders of magnitude), precision (RSD < 18.3%), and stability (RSD < 15% over 48 h). When applied to sauce-flavor Baijiu samples of different grades, distinct compositional patterns were observed: premium-grade products showed greater metabolite diversity and higher contents of bioactive compounds, whereas lower-grade samples exhibited elevated concentrations of acidic flavor compounds. Conclusions: These results demonstrate that the established method is efficient for the comprehensive analysis of hydroxyl and amino compounds in complex food matrices. The findings provide valuable insights for quality control and flavor modulation in sauce-flavor Baijiu production. Full article

Colonization of plant tissues by bacterial endophytes might lead to qualitative and quantitative changes in secondary metabolites (SMs). In this work, in vitro co-culture experiments were performed using cell suspensions of the medicinal plant Alkanna tinctoria and eight of its bacterial endophytes. An untargeted metabolomics approach using Ultra-High-Performance Liquid Chromatography High-Resolution Mass Spectrometry (UHPLC-HRMS) was employed to investigate plant–microbe interactions. Hierarchical clustering analysis and principal component analysis highlighted significant modifications of specific regulation patterns in SM production, caused by bacterial endophytes. The annotation step lead to the identification of 32 stimulated compounds in A. tinctoria cell suspensions. Among them, 3′-hydroxy-14-hydroxyshikonofuran H (5), 8′-decarboxy-rosmarinic acid (18), 8‴-decarboxy-salvianolic B (23), 8″-8‴-didecarboxy-salvianolic acid B (26) were putatively identified for the first time. Our findings highlight that employing selected microbial inoculants under controlled conditions can be an effective strategy for enhancing or stimulating the production of specific high-value metabolites. Full article

Background/Objectives: One of the plants found in Indonesian forests that has potential as an herbal medicine is andaliman (Zanthoxylum acanthopodium DC.). The fruit of Z. acanthopodium contains phenolic compounds that are known to modulate the immune response. The purpose of this study is to determine the extract profile and immunomodulatory activity of Z. acanthopodium fruit and to develop a soft capsule formulation of the extract in the form of emulsion, which stabilizes and acts as an immunomodulatory candidate. Methods: Extract profiling was conducted by liquid chromatography UHPLC–HRMS, and the predicted molecular structure was then used to search for the name of the compound using the mzcloud database. Immunomodulatory activity of the extract and its emulsion was assessed using a lymphocyte viability assay. The extract emulsion to be encapsulated as a soft capsule was developed by employing different types of oil and solubilizer in the oil phase, and a water phase containing the extract and two types of emulsifiers. Results: The chemical composition of andaliman extract was analyzed, including total phenolic content (4%), total flavonoid content (0.35%), and quercetin content (0.13%). Based on LC-HRMS analysis, eleven compounds derived from the ethanolic extract of andaliman were identified as potential immunomodulatory agents. The F3.3F formulation, which contains 30% MCT oil phase with solubilizer lauroyl-PEG-32 glycerides and a water phase with 35% Polysorbat (Tween) 80 emulsifier, provided the most stability. This stability is attributed to the presence of the Tween 80 emulsifier, which has superior wetting and washing functions, strong detergency, and good emulsifying properties compared to the PEG emulsifier used in formulation F3.3E. The survival rates in the lymphocyte cell viability test results indicate that treatment with andaliman extract (173.697% at 15.625 ppm; 174.923% at 31.25 ppm; 168.457% at 62.5 ppm) was better than treatment with kojic acid (144.375% at 15.625 ppm; 137.891% at 31.25 ppm; 146.345% at 62.5 ppm), used as the immunomodulatory agent standard. Conclusions: This study highlights the potential of andaliman extract as an immunomodulatory agent to be developed as an emulsion in a soft capsule. Full article

The current study evaluated the anticonvulsant properties of ethanolic extracts from Morus alba, Angelica archangelica, Passiflora incarnata, and Valeriana officinalis using integrated phytochemical, in vivo, biochemical, and computational approaches. Phytochemical analysis by UHPLC-HRMS/MS revealed the presence of various bioactive compounds, notably flavonoids such as isorhamnetin, quercetin, and kaempferol. In an electroshock-induced seizure model, Morus alba extract (MAE, 100 mg/kg) demonstrated significant anticonvulsant effects, reducing both seizure duration and incidence, likely mediated by flavonoid interactions with GABA-A and 5-HT3A receptors, as suggested by target prediction and molecular docking analyses. The extracts of Angelica archangelica (AAE, 100 mg/kg) and Passiflora incarnata (PIE, 50 mg/kg) exhibited moderate, non-significant anticonvulsant activities. At the same time, Valeriana officinalis (VOE, 50 mg/kg) displayed considerable antioxidant and anti-inflammatory properties but limited seizure protection. All extracts significantly reduced brain inflammation markers (TNF-α) and enhanced antioxidant defenses, as indicated by total thiols. Molecular docking further supported the interaction of key phytochemicals, including naringenin and chlorogenic acid, with human and mouse 5-HT3A receptors. Overall, Morus alba extract exhibited promising therapeutic potential for epilepsy management, warranting further investigation into chronic seizure models and optimized dosing strategies. Full article

Asparagus (Asparagus officinalis L.) is widely recognized for its nutritional and functional properties, attributed to its rich content of polyphenols and antioxidant compounds. However, the content of compounds that remains bioaccessible following typical domestic preparation and digestion remains unclear. This study assessed the polyphenolic profile and antioxidant capacity of the edible portion of two A. officinalis cultivars (Placoseps and Darlise), harvested in different seasons, in edible form, cooked (using boiling on an induction cooktop), and cooked-digested extracts. Rutin emerged as the most abundant in all analyzed samples; its concentration in the edible part reached 1770.72 in Placoseps and 995.20 mg/kg in Darlise. Cooking increased rutin content in April-harvested asparagus to 1966.00 in Placoseps and 2042.44 mg/kg in Darlise, reflecting an increase of more than 2.5-fold compared to the respective values observed at the earlier harvest. Despite the substantial reduction in bioactive compounds observed during in vitro gastrointestinal digestion, a total of 146.95 to 454.58 mg/kg of bioaccessible compounds remaining available for potential intestinal absorption after digestion across both cultivars and harvest periods. These results provide a greater understanding of the behavior of polyphenol-rich vegetables and underscore the importance of simulating gastrointestinal processes when assessing the health-promoting potential of bioactive compounds. Full article

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques. Methods: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay. Results: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response. Conclusions: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria. Full article

Essential oils are complex mixtures of apolar components, mainly phenylpropanoids, monoterpenes, and sesquiterpenes. Vetiver (Vetiveria zizanioides (L.) Nash) is a non-endemic grass in several tropical regions, widely used for slope stabilization and erosion control because of its long and deep roots that help to bind the soil together, preventing landslides and soil loss. From these roots, vetiver essential oil is obtained, which is extracted and produced worldwide and highly valued for its diverse range of bioactive substances used by the cosmetics and perfume industries. These substances, present in a very complex mixture, are difficult to isolate. Zizanoic acid is a very rare substance in nature and also very interesting because of the biological properties already described. In the present study, zizanoic acid was selectively isolated with 84–87% purity from vetiver commercial essential oils, in which it was present at less than 10%, using KOH-impregnated silica gel column chromatography alone. The experiments were monitored using GC-MS and UHPLC-HRMS, and the isolated substances (zizanoic and valerenic acids) were further determined by NMR experiments. The whole methodology and analytical approach proved to be very efficient for natural product complex mixture analysis and also very selective, allowing for a distinct capacity to recover carboxylic acids from complex biological samples. Full article

Milk lipids are fundamental to the nutritional quality, functional properties, and processing behavior of dairy products. In this study, we employed an untargeted lipidomics approach based on ultra-high-performance liquid chromatography coupled with ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to systematically characterize the lipid profiles of ten milk types from eight animal species, including camel, mare, donkey, goat, buffalo, yak, Jersey, and Holstein. A total of 640 lipid species were identified, spanning triglycerides (TGs), phospholipids (PLs), sphingolipids (SPs), ceramides (Cer), wax esters (WEs), and other subclasses. A statistical analysis revealed significant differences in lipid types and abundances among the milk samples. Camel milk exhibited the highest lipid diversity, with notable enrichment in phospholipids and sphingolipids, conferring superior emulsifying properties and stability. Mare milk was rich in polyunsaturated fatty acids (PUFAs), such as linoleic acid and alpha-linolenic acid, making it ideal for developing health-focused dairy products. Despite having the lowest total lipid content, donkey milk was enriched in cholesterol esters and PUFA, suitable for low-fat functional dairy products. Goat milk featured a balanced lipid composition with higher levels of medium-chain fatty acids (MCFAs), promoting digestibility. Buffalo milk was characterized by high TG and wax ester (WE) levels, offering high energy density and suitability for rich dairy products. Yak milk contained higher levels of ceramides (Cer) and saturated fatty acids, reflecting adaptations to high-altitude environments. Jersey milk and Holstein milk displayed similar lipid profiles, with stable compositions suitable for versatile dairy product development. Principal component analysis (PCA), hierarchical clustering, and volcano plot analyses further confirmed species-specific lipidomic signatures and revealed several potential lipid biomarkers, such as LPC (O-16:0) in Hongyuan yak milk, suggesting applications in geographical indication (GI) traceability. This study offers a comprehensive lipidomic landscape across diverse milk sources, providing molecular insights to guide the development of tailored, functional, and regionally branded dairy products. Full article