The Cytotoxic Activity and Metabolic Profiling of Hyptis rhomboidea Mart. et Gal.

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography-mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC50 values ranging from 15.8 to 40.0 µg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph-mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties.

An advanced metabolomic approach on grape skins untangles cultivar preferences by Drosophila suzukii for oviposition.

Insects' host preferences are regulated by multiple factors whose interactions are only partly understood. Here we make use of an in-depth, untargeted metabolomic approach combining molecular networking (MN) and supervised Analysis of variance Multiblock Orthogonal Partial Least Squares (AMOPLS) to untangle egg-laying preferences of Drosophila suzukii, an invasive, highly polyphagous and destructive fruit pest originating from Southeast Asia. Based on behavioural experiments in the laboratory as well as field observation, we selected eight genetically related Vitis vinifera cultivars (e.g., Ancellotta, Galotta, Gamaret, Gamay, Gamay précoce, Garanoir, Mara and Reichensteiner) exhibiting significant differences in their susceptibility toward D. suzukii. The two most and the two least attractive red cultivars were chosen for further metabolomic analyses of their grape skins. The combination of MN and statistical AMOPLS findings with semi-quantitative detection information enabled us to identify flavonoids as interesting markers for differences in the attractiveness of the four studied grape cultivars towards D. suzukii. Overall, dihydroflavonols were accumulated in unattractive grape cultivars, while attractive grape cultivars were richer in flavonols. Crucially, both dihydroflavonols and flavonols were abundant metabolites in the semi-quantitative analysis of the extracted molecules from the grape skin. We discuss how these two flavonoid classes might influence the egg-laying behaviour of D. suzukii females and how they could serve as potential markers for D. suzukii infestations in grapes that can be potentially extended to other fruits. We believe that our novel, integrated analytical approach could also be applied to the study of other biological relationships characterised by multiple evolving parameters.

Toward the apoplast metabolome: Establishing a leaf apoplast collection approach suitable for metabolomics analysis.

The leaf apoplast contains several compounds that play important roles in the regulation of different physiological processes in plants. However, this compartment has been neglected in several experimental and modelling studies, which is mostly associated to the difficulty to collect apoplast washing fluid (AWF) in sufficient amount for metabolomics analysis and as free as possible from symplastic contamination. Here, we established an approach based in an infiltration-centrifugation technique that use little leaf material but allows sufficient AWF collection for gas chromatography mass spectrometry (GC-MS)-based metabolomics analysis in both tobacco and Arabidopsis. Up to 54 metabolites were annotated in leaf and apoplast samples from both species using either 20% (v/v) methanol (20% MeOH) or distilled deionized water (ddH2O) as infiltration fluids. The use of 20% MeOH increased the yield of the AWF collected but also the level of symplastic contamination, especially in Arabidopsis. We propose a correction factor and recommend the use of multiple markers such as MDH activity, protein content and conductivity measurements to verify the level of symplastic contamination in MeOH-based protocols. Neither the concentration of sugars nor the level of primary metabolites differed between apoplast samples extracted with ddH2O or 20% MeOH. This indicates that ddH2O can be preferentially used, given that it is a non-toxic and highly accessible infiltration fluid. The infiltration-centrifugation-based approach established here uses little leaf material and ddH2O as infiltration fluid, being suitable for GC-MS-based metabolomics analysis in tobacco and Arabidopsis, with great possibility to be extended for other plant species and tissues.

Gastric Cancer and Intestinal Metaplasia: Differential Metabolic Landscapes and New Pathways to Diagnosis.

Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC.

Serum Metabolites as Potential Markers and Predictors of Depression-like Behavior and Effective Fluoxetine Treatment in Chronically Socially Isolated Rats.

Metabolic perturbation has been associated with depression. An untargeted metabolomics approach using liquid chromatography-high resolution mass spectrometry was employed to detect and measure the rat serum metabolic changes following chronic social isolation (CSIS), an animal model of depression, and effective antidepressant fluoxetine (Flx) treatment. Univariate and multivariate statistics were used for metabolic data analysis and differentially expressed metabolites (DEMs) determination. Potential markers and predictive metabolites of CSIS-induced depressive-like behavior and Flx efficacy in CSIS were evaluated by the receiver operating characteristic (ROC) curve, and machine learning (ML) algorithms, such as support vector machine with linear kernel (SVM-LK) and random forest (RF). Upregulated choline following CSIS may represent a potential marker of depressive-like behavior. Succinate, stachydrine, guanidinoacetate, kynurenic acid, and 7-methylguanine were revealed as potential markers of effective Flx treatment in CSIS rats. RF yielded better accuracy than SVM-LK (98.50% vs. 85.70%, respectively) in predicting Flx efficacy in CSIS vs. CSIS, however, it performed almost identically in classifying CSIS vs. control (75.83% and 75%, respectively). Obtained DEMs combined with ROC curve and ML algorithms provide a research strategy for assessing potential markers or predictive metabolites for the designation or classification of stress-induced depressive phenotype and mode of drug action.

An Efficient Integrated Strategy for Comprehensive Metabolite Profiling of Sakurasosaponin from Aegiceras corniculatum in Rats.

OBJECTIVE: Sakurasosaponin, a primary bioactive saponin from Aegiceras corniculatum, shows potential as an anti-cancer agent. However, there is a lack of information on its in vivo metabolism. This study aims to profile the in vivo metabolites of sakurasosaponin in rat feces, urine, and plasma after oral administration. An efficient strategy using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was developed, which combined metabolic prediction, multiple mass defects filtering, and highresolution extracted ion chromatograms for rapid and systematic analysis. METHODS: Firstly, a theoretical list of metabolites for sakurasosaponin was developed. This was done by considering the metabolic pathways of saponins. Next, the multiple mass defects filtering method was employed to identify potential metabolites in feces and urine, using the unique metabolites of sakurasosaponin as multiple mass defects filtering templates. Subsequently, a high-resolution extracted ion chromatogram was used to quickly determine the metabolites in rat plasma post-identification in feces and urine. Lastly, the analysis of accurate mass, typical neutral loss, and diagnostic ion of the candidate metabolites was carried out to confirm their structural elucidation, and metabolic pathways of sakurasosaponin in vivo were also proposed. RESULTS: In total, 30 metabolites were provisionally identified in feces, urine, and plasma. Analysis of metabolic pathways revealed isomerization, deglycosylation, oxidation, hydroxylation, sulfate conjugation, glucuronide conjugation, and other related reactions as the primary biotransformation reactions of sakurasosaponin in vivo. CONCLUSION: The findings demonstrate that the designed research strategy effectively minimizes matrix interference, prevents the omission of low-concentration metabolites, and serves as a foundation for the discovery of active metabolites of sakurasosaponin.

Mycobolome of Phialomyces macrosporus across OSMAC-based assorted culture media.

The fungus Phialomyces macrosporus was cultured using the One Strain Many Compounds (OSMAC) strategies to evaluate its metabolome. Variations in the nutrient culture media, culture regime, and cultivation parameters can significantly influence fungal extract quantity and chemical diversity. This study aimed to explore the mycobolome of P. macrosporus in five different culture media and two different cultivation conditions using NMR-based metabolomics. Principal component analysis (PCA) of 1H NMR spectra revealed clear differentiation between these samples, highlighting the rice dextrose agar medium (RDA) and potato dextrose broth (PDB) as standard complex media for conducting a fungal metabolite screening program.

Biochemical characterisation of a cassava (Manihot esculenta crantz) diversity panel for post-harvest physiological deterioration; metabolite involvement and environmental influence.

Cassava (Manihot esculenta Crantz) produces edible roots, a major carbohydrate source feeding more than 800 million people in Africa, Latin America, Oceania and Asia. Post-harvest physiological deterioration (PPD) renders harvested cassava roots unpalatable and unmarketable. Decades of research on PPD have elucidated several genetic, enzymatic and metabolic processes involved. Breeding populations were established to enable verification of robust biomarkers for PPD resistance. For comparison, these PPD populations have been cultivated concurrently with diversity population for carotenoid (ß-carotene) content. Results highlighted a significant variation of the chemotypes due to environmental factors. Less than 3% of the detected molecular features showed consistent trends between the two harvest years and were putatively identified as phenylpropanoid derived compounds (e.g. caffeoyl rutinoside). The data corroborated that ∼20 µg ß-carotene/g DW can reduced the PPD response of the cassava roots to a score of ∼1. Correlation analysis showed a significant correlation of ß-carotene content at harvest to PPD response (R2 -0.55). However, the decrease of ß-carotene over storage was not significantly correlated to initial content or PPD response. Volatile analysis observed changes of apocarotenoids derived from ß-carotene, lipid oxidation products (alkanes, alcohols and carbonyls and esters) and terpenes. The majority of these volatiles (>90%) showed no significant correlation to ß-carotene or PPD. Observed data indicated an increase (∼2-fold) of alkanes in varieties with ß-carotene >10 µg/g DW and a decrease (∼60%) in varieties with less ß-carotene. Fatty acid methyl esters with a chain length > C9 were detected solely after storage and show lower levels in varieties with higher ß-carotene content. In combination with correlation values to PPD (R2 ∼0.3; P-value >0.05), the data indicated a more efficient ROS quenching mechanism in PPD resistant varieties.

Comparative study for metabolomics, antioxidant activity, and molecular docking simulation of the newly bred Korean red rice accessions.

This study analyzed the metabolite profiles and antioxidant capacities of two waxy and non-waxy Korean red rice accessions newly bred. Fifteen phenolic compounds were detected in the rice samples. Accession1 had high fatty acids, phytosterols, and vitamin E; accession3 had high vitamin E and phytosterol; and accession4 had a high total flavonoid. The correlation analysis findings from this study validated the positive association between all the metabolites and antioxidant activity. in silico results revealed that protocatechuic acid had a docking score of -9.541, followed by luteolin, quercetin, and caffeic acid, all of which had significant docking scores and a significant number of contacts. Similarly, molecular dynamics simulations showed that phytochemicals had root mean square deviation values of <2.8 Å with Keap 1, indicating better stability. This study provides valuable insights into potential directions for future investigations and improvements in the functional qualities of other colored rice varieties.

Comprehensive metabolome characterization of leaves, internodes, and aerial roots of Vanilla planifolia by untargeted LC-MS and GC × GC-MS.

INTRODUCTION: Untargeted metabolomics is a powerful tool that provides strategies for gaining a systematic understanding of quantitative changes in the levels of metabolites, especially when combining different metabolomic platforms. Vanilla is one of the world's most popular flavors originating from cured pods of the orchid Vanilla planifolia. However, only a few studies have investigated the metabolome of V. planifolia, and no LC-MS or GC-MS metabolomics studies with respect to leaves have been performed. OBJECTIVE: The aim of the study was to comprehensively characterize the metabolome of different organs (leaves, internodes, and aerial roots) of V. planifolia. MATERIAL AND METHODS: Characterization of the metabolome was achieved using two complementary platforms (GC × GC-MS, LC-QToF-MS), and metabolite identification was based on a comparison with in-house databases or curated external spectral libraries. RESULTS: In total, 127 metabolites could be identified with high certainty (confidence level 1 or 2) including sugars, amino acids, fatty acids, organic acids, and amines/amides but also secondary metabolites such as vanillin-related metabolites, flavonoids, and terpenoids. Ninty-eight metabolites showed significantly different intensities between the plant organs. Most strikingly, aglycons of flavonoids and vanillin-related metabolites were elevated in aerial roots, whereas its O-glycoside forms tended to be higher in leaves and/or internodes. This suggests that the more bioactive aglycones may accumulate where preferably needed, e.g. for defense against pathogens. CONCLUSION: The results derived from the study substantially expand the knowledge regarding the vanilla metabolome forming a valuable basis for more targeted investigations in future studies, e.g. towards an optimization of vanilla plant cultivation.

Systematic metabolomics study in the serum and urine of a mouse model of Fabry disease.

Background: Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD. Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA). Results: A total of 27 and 23 metabolites from the serum and urine of Fabry mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice. Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.

Salvadora persica leaves: phytochemical profile and in vitro-inhibitory activity on inflammatory mediators implicated in periodontal disease.

CONTEXT: Virtually all parts of Salvadora persica L. (Salvadoraceae) are used in traditional medicine. The twigs and leaves are used for oral health, but leaves are far less investigated. OBJECTIVE: This study assesses the oral health-promoting potential of S. persica leaves with emphasis on anti-inflammatory and antiproliferative effects and provides an in depth-characterization of their metabolite profile. MATERIALS AND METHODS: Hot-water and methanolic S. persica leaf extracts (1, 10, and 100 µg/mL) and their major constituents (5, 10, and 50 µM), were subjected to cellular assays on IL-8 and TNFα release in LPS-stimulated human neutrophils, NO-release in LPS/IFNγ stimulated mouse macrophages, and proliferation of HNO97 human tongue carcinoma cells. Metabolite profiling was performed by UHPLC-HRMS analysis. Major constituents were isolated and structurally elucidated. RESULTS AND DISCUSSION: Both extracts showed pronounced anti-inflammatory activity in LPS-stimulated neutrophils. Major identified compound classes were flavonoid glycosides, the glucosinolate glucotropaeolin, phenyl- and benzylglycoside sulfates, and megastigmane glycosylsulfates, the latter ones identified for the first time in S. persica. Glucotropaeolin strongly inhibited the release of IL-8 and TNF-α (13.3 ± 2.0 and 22.7 ± 2.6% of the release of stimulated control cells at 50 µM), while some flavonoids and 3-(3'-O-sulfo-ß-d-glucopyranosyloxy)-7,8-dihydro-ß-ionone, a newly isolated megastigmane glycosylsulfate, were moderately active. Benzylisothiocyanate, which is likely formed from glucotropaeolin during traditional application of S. persica, showed considerable antiproliferative activity (IC50 in HNO97 cells: 10.19 ± 0.72 µM) besides strongly inhibiting IL-8 and TNFα release. CONCLUSIONS: Glucotropaeolin and benzylisothiocyanate are likely implicated in the oral health-promoting effects of S. persica leaves. The chemistry and pharmacology of the newly identified megastigmane glycosylsulfates should be further evaluated.

Mycotoxin contamination in moldy slices of bread is mostly limited to the immediate vicinity of the visible infestation.

Bread is an important staple food that is susceptible to spoilage, making it one of the most wasted foods. To determine the safety of partially moldy bread, five types of bread were inoculated with common mold species. After incubation, the metabolite profile was determined in and under the inoculation spot, as well as at a lateral distance of 3 cm from the moldy spot. The result showed that the metabolites were exclusively concentrated in the inoculation area and directly below the inoculation area. The only exception was citrinin, a mycotoxin produced by Penicillia such as Penicillium citrinum, which was detected in almost all tested bread areas when inoculated with the corresponding strains. The results of our study suggest that the removal of moldy parts may be a solution to reduce food waste if the remaining bread is to be used, for example for insect farming to produce animal feed.

Metabolomics and anti-inflammatory activity of Commiphora madagascariensis jacq. leaves extract using in vitro and in vivo models.

C. madagascariensis, an unexplored species of Burseraceae is used by local population for the management of inflammation and throat pain. The disease alleviation by this plant could be due to the presence of rich repository of active compounds with various pharmacological importances. In this study, therefore, the profiling of metabolites and isolation of active compounds of C. madagascariensis was performed. Furthermore, the ethanol, ethyl acetate extracts and a selected active compound was subjected for in vitro and in vivo anti-inflammatory activities. Metabolomic analysis identified and quantified 116 metabolites from leaves, young stem and gum-resins of C. madagascariensis (Burseraceae) followed by multivariate PCA analysis. NMR, GC-MS and HPLC were used to analyze primary and secondary metabolites. Subsequently, five main isolated compounds were identified as trimethoxy tetrahydrobenzo dioxolo isochromene (TTDI), butyl phenol, butyl propionate phenol, germacrone and ß-elemenone. Amongst them, TTDI was found to be a novel compound. Hence, a process was developed to obtain the enriched fraction of TTDI in ethanol and ethyl acetate extracts of leaves. Furthermore, TTDI and extracts were subjected for their in vitro anti-inflammatory activity in LPS sensitized murine splenocytes. The results showed that TTDI and both extracts significantly suppressed the levels of pro-inflammatorycytokines (TNF-α, IFN-γ). Interestingly, the suppression of pro-inflammatory cytokines was evenmore significant by the similar concentration of TTDI when compared with colchicine. However, the level of anti-inflammatory cytokine (IL-10) was found to be unchanged. Additionally, in vivo anti-inflammatory study revealed a significant reduction in carrageenan induced paw edema by TTDI and both the extracts. In the docking study, TTDI was more active than colchicine with strong binding affinity to COX-2, PLA2, and 5ß reductase. Our results highlighted that the presence of metabolites with medicinal and nutraceutical importance in C. madagascariensis, could provide opportunities for the development of a new plant-based therapeutics for inflammation.

Explainable AI to Facilitate Understanding of Neural Network-Based Metabolite Profiling Using NMR Spectroscopy.

Neural networks (NNs) are emerging as a rapid and scalable method for quantifying metabolites directly from nuclear magnetic resonance (NMR) spectra, but the nonlinear nature of NNs precludes understanding of how a model makes predictions. This study implements an explainable artificial intelligence algorithm called integrated gradients (IG) to elucidate which regions of input spectra are the most important for the quantification of specific analytes. The approach is first validated in simulated mixture spectra of eight aqueous metabolites and then investigated in experimentally acquired lipid spectra of a reference standard mixture and a murine hepatic extract. The IG method revealed that, like a human spectroscopist, NNs recognize and quantify analytes based on an analyte's respective resonance line-shapes, amplitudes, and frequencies. NNs can compensate for peak overlap and prioritize specific resonances most important for concentration determination. Further, we show how modifying a NN training dataset can affect how a model makes decisions, and we provide examples of how this approach can be used to de-bug issues with model performance. Overall, results show that the IG technique facilitates a visual and quantitative understanding of how model inputs relate to model outputs, potentially making NNs a more attractive option for targeted and automated NMR-based metabolomics.

Black Goji Berry (Lycium ruthenicum) Juice Fermented with Lactobacillus rhamnosus GG Enhances Inhibitory Activity against Dipeptidyl Peptidase-IV and Key Steps of Lipid Digestion and Absorption.

With the global increase in hyperglycemia and hyperlipidemia, there is an urgent need to explore dietary interventions targeting the inhibition of dipeptidyl peptidase-IV (DPP-IV) and lipid digestion and absorption. This study investigated how Lactobacillus rhamnosus GG (LGG) affects various aspects of black goji berry (BGB) (Lycium ruthenicum Murr.) juice, including changes in physicochemical and functional properties, as well as microbiological and sensory attributes. Throughout the fermentation process with 2.5-10% (w/v) BGB, significantly improved probiotic viability, lactic acid production, and decreased sugar content. While total flavonoids increase, anthocyanins decrease, with no discernible change in antioxidant activities. Metabolite profiling reveals elevated phenolic compounds post-fermentation. Regarding the inhibition of lipid digestion and absorption, fermented BGB exhibits improved bile acid binding, and disrupted cholesterol micellization by approximately threefold compared to non-fermented BGB, while also increasing pancreatic lipase inhibitory activity. Furthermore, a decrease in cholesterol uptake was observed in Caco-2 cells treated with fermented BGB (0.5 mg/mL), with a maximum reduction of 16.94%. Fermented BGB also shows more potent DPP-IV inhibition. Sensory attributes are significantly improved in fermented BGB samples. These findings highlight the potential of BGB as a bioactive resource and a promising non-dairy carrier for LGG, enhancing its anti-hyperglycemic and anti-hyperlipidemic properties.

Sustainable Agrochemical Exploitation of Ligurian Aromatic Plant Ecotypes.

The characterization of local improved varieties as well as the reduction of synthetic chemical fertilizers are sustainable approaches in the vision of a new precision Farming. Aim of our study was to improve the geographical characterization of local ecotypes and to identify peculiar features of new crops in terms of bioactive compounds. NMR and LC-MS metabolite profiling approaches followed by multivariate data analysis were applied to characterize local rosemary and garlic ecotypes. With the aim of applying for a protected designation of origin, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify representative sensory quality indicators for Vessalico garlic and rosemary "Eretto Liguria" local ecotypes, Variable Influence on Projections (VIP) values of OPLS-DA indicated six metabolites as quality indicators for Vessalico garlic and sixteen metabolites as quality indicators for rosemary "Eretto Liguria". Finally, to discover and utilize new ecotypes in a sustainable way, Vessalico garlic extracts antiviral activity, previously evaluated against Tomato brown rugose fruit virus (ToBRFV), a Tobamovirus affecting tomato crops, was extended to Pepino mosaic virus (PepMV) with positive results.

Chemo-profiling and exploring therapeutic potential of Momordica dioica Roxb. ex Willd. for managing metabolic related disorders: In-vitro studies, and docking based approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Momordica dioica Roxb. ex Willd. (M. dioica Roxb.) a nutritious and therapeutic property rich crop of Cucurbitaceae plant family. In various folklore medicine including Ayurveda fruits are used to treat several metabolic related disorders i.e., hyperglycemia, hyperlipidemia, diabetes, obesity etc. Furthermore, traditionally it is used to treat fever, inflammation, ulcer, skin diseases, haemorrhoids, hypertension and also employed as cardioprotective, hepatoprotective, analgesic, diuretic. AIM OF THE STUDY: This study focuses to explore the therapeutic potential of Momordica dioica Roxb. ex Willd. through in-vitro and in-silico approach for managing hyperlipidemia, hyperglycemia and related metabolic disorders along with its phytochemical profiling for quality evaluation and validation of traditional claim. MATERIALS AND METHODS: The present study was carried out on hydroalcohol extract of dried leaf and fruit of Momordica dioica. In-vitro antioxidant potential using DPPH and Nitric oxide scavenging assay along with in-vitro enzyme inhibitory potential against α-amylase, α-glucosidase, and pancreatic lipase enzymes was studied. The bioactive metabolites were identified from the most potent bioactive extract by analysis with LC-QTOF-MS and also studied their role to lessen the metabolic related disorder through in-silico approaches. RESULTS: The results confirmed that the fruit extract is more active to possess antioxidant and prominent enzyme inhibition potential compared to the leaf. Sixteen identified metabolites in M. dioica Roxb. fruits may be responsible for the therapeutic potential related to metabolic related disorder. The in-silico study of the identified phytomolecules against α-amylase, α-glucosidase and pancreatic lipase showed significant docking scores ranging from -9.8 to -5.5, -8.3 to -4.8 and -8.3 to -6 respectively. CONCLUSION: The current study illustrated that M. dioica Roxb., a traditionally important plant is potential against metabolic related disorders. Phytocomponents present in the fruit extract may be responsible for antioxidant as well as the enzymes' inhibitory potential. Thus, fruits of M. dioica Roxb. will be useful as alternative therapeutics for treatment of hyperlipidemia, hyperglycemia and related metabolic disorders.

Comparative metabolite analysis of Piper sarmentosum organs approached by LC-MS-based metabolic profiling.

Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia, offering both health and culinary benefits. In this study the secondary metabolites in different organs of P. sarmentosum were identified and their relative abundances were characterized. The metabolic profiles of leaves, roots, stems and fruits were comprehensively investigated by liquid chromatography high-resolution mass spectrometry (LC-HR-MS) and the data subsequently analyzed using multivariate statistical methods. Manual interpretation of the tandem mass spectrometric (MS/MS) fragmentation patterns revealed the presence of 154 tentatively identified metabolites, mostly represented by alkaloids and flavonoids. Principle component analysis and hierarchical clustering indicated the predominant occurrence of flavonoids, lignans and phenyl propanoids in leaves, aporphines in stems, piperamides in fruits and lignan-amides in roots. Overall, this study provides extensive data on the metabolite composition of P. sarmentosum, supplying useful information for bioactive compounds discovery and patterns of their preferential biosynthesis or storage in specific organs. This can be used to optimize production and harvesting as well as to maximize the plant's economic value as herbal medicine or in food applications.

UPLC-qTOF-MS phytochemical profile of Commiphora gileadensis leaf extract via integrated ultrasonic-microwave-assisted technique and synthesis of silver nanoparticles for enhanced antibacterial properties.

The utilization of metallic nanoparticles in bio-nanofabrication holds significant potential in the field of applied research. The current study applied and compared integrated ultrasonic-microwave-assisted extraction (US/MICE), ultrasonic extraction (USE), microwave-assisted extraction (MICE), and maceration (MAE) to extract total phenolic content (TPC). In addition, the study examined the antioxidant activity of Commiphora gileadensis (Cg) leaf. The results demonstrated that the TPC of US/MICE exhibited the maximum value at 59.34 ± 0.007 mg GAE/g DM. Furthermore, at a concentration of 10 µg/mL, TPC displayed a significant scavenging effect on DPPH (56.69 %), with an EC50 (6.48 µg/mL). Comprehensive metabolite profiling of the extract using UPLC-qTOF-MS/MS was performed to identify active agents. A total of 64 chromatographic peaks were found, out of which 60 were annotated. The most prevalent classes of metabolites found were polyphenols (including flavonoids and lignans), organic compounds and their derivatives, amides and amines, terpenes, and fatty acid derivatives. Transmission electron microscopy (TEM) revealed the aggregate size of the synthesized nanoparticles and the spherical shape of C. gileadensis-mediated silver nanoparticles (Cg-AgNPs). The nanoparticles had a particle size ranging from 7.7 to 42.9 nm. The Cg-AgNPs exhibited more inhibition zones against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cg-extract, AgNPs, and Cg-AgNPs were also tested. This study demonstrated the feasibility of using combined ultrasonic-microwave-assisted extraction to separate and extract chemicals from C. gileadensis on a large scale. These compounds have potential use in the pharmaceutical industry. Combining antibacterial and biocompatible properties in materials is vital for designing new materials for biomedical applications. Additionally, the results showed that the biocompatibility of the Ag-NPs using C. gileadensis extracts demonstrated outstanding antibacterial properties.