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26 pages, 6743 KiB  
Review
Nudibranchs as Sources of Marine Natural Products with Antitumor Activity: A Comprehensive Review
by Máximo Servillera, Mercedes Peña, Laura Cabeza, Héctor J. Pula, Jose Prados and Consolación Melguizo
Mar. Drugs 2025, 23(8), 319; https://doi.org/10.3390/md23080319 (registering DOI) - 3 Aug 2025
Abstract
Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as [...] Read more.
Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)
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16 pages, 3158 KiB  
Article
Comparative Metabolomics Analysis of Four Pineapple (Ananas comosus L. Merr) Varieties with Different Fruit Quality
by Ping Zheng, Jiahao Wu, Denglin Li, Shiyu Xie, Xinkai Cai, Qiang Xiao, Jing Wang, Qinglong Yao, Shengzhen Chen, Ruoyu Liu, Yuqin Liang, Yangmei Zhang, Biao Deng, Yuan Qin and Xiaomei Wang
Plants 2025, 14(15), 2400; https://doi.org/10.3390/plants14152400 (registering DOI) - 3 Aug 2025
Abstract
Understanding the metabolic characteristics of pineapple varieties is crucial for market expansion and diversity. This study performed comparative metabolomic analysis on the “Comte de Paris” (BL) and three Taiwan-introduced varieties: “Tainong No. 11” (XS), “Tainong No. 23” (MG), and “Tainong No. 13” (DM). [...] Read more.
Understanding the metabolic characteristics of pineapple varieties is crucial for market expansion and diversity. This study performed comparative metabolomic analysis on the “Comte de Paris” (BL) and three Taiwan-introduced varieties: “Tainong No. 11” (XS), “Tainong No. 23” (MG), and “Tainong No. 13” (DM). A total of 551 metabolites were identified across the four varieties, with 231 metabolites exhibiting no significant differences between all varieties. This included major sugars such as sucrose, glucose, and fructose, as well as key acids like citric, malic, and quinic acids, indicating that the in-season maturing fruits of different pineapple varieties can all achieve good sugar–acid accumulation under suitable conditions. The differentially accumulated metabolites (DAMs) that were identified among the four varieties all primarily belonged to several major subclasses, including phenolic acids, flavonoids, amino acids and derivatives, and alkaloids, but the preferentially accumulated metabolites in each variety varied greatly. Specifically, branched-chain amino acids (L-leucine, L-isoleucine, and L-valine) and many DAMs in the flavonoid, phenolic acid, lignan, and coumarin categories were most abundant in MG, which might contribute to its distinct and enriched flavor and nutritional value. XS, meanwhile, exhibited a notable accumulation of aromatic amino acids (L-phenylalanine, L-tryptophan), various phenolic acids, and many lignans and coumarins, which may be related to its unique flavor profile. In DM, the dominant accumulation of jasmonic acid might contribute to its greater adaptability to low temperatures during autumn and winter, allowing off-season fruits to maintain good quality. The main cultivar BL exhibited the highest accumulation of L-ascorbic acid and many relatively abundant flavonoids, making it a good choice for antioxidant benefits. These findings offer valuable insights for promoting different varieties and advancing metabolome-based pineapple improvement programs. Full article
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25 pages, 1802 KiB  
Article
HPLC-ESI-HRMS/MS-Based Metabolite Profiling and Bioactivity Assessment of Catharanthus roseus
by Soniya Joshi, Chen Huo, Rabin Budhathoki, Anita Gurung, Salyan Bhattarai, Khaga Raj Sharma, Ki Hyun Kim and Niranjan Parajuli
Plants 2025, 14(15), 2395; https://doi.org/10.3390/plants14152395 (registering DOI) - 2 Aug 2025
Abstract
A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate [...] Read more.
A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate antimicrobial activity, and limited cytotoxicity in both the brine shrimp lethality assay and MTT assay against HeLa and A549 cell lines. High-performance liquid chromatography–electrospray ionization–high-resolution tandem mass spectrometry (HPLC-ESI-HRMS/MS) analysis led to the annotation of 34 metabolites, primarily alkaloids. These included 23 indole alkaloids, two fatty acids, two pentacyclic triterpenoids, one amino acid, four porphyrin derivatives, one glyceride, and one chlorin derivative. Notably, two metabolites—2,3-dihydroxypropyl 9,12,15-octadecatrienoate and (10S)-hydroxypheophorbide A—were identified for the first time in C. roseus. Furthermore, Global Natural Products Social Molecular Networking (GNPS) analysis revealed 18 additional metabolites, including epoxypheophorbide A, 11,12-dehydroursolic acid lactone, and 20-isocatharanthine. These findings highlight the diverse secondary metabolite profile of C. roseus and support its potential as a source of bioactive compounds for therapeutic development. Full article
19 pages, 993 KiB  
Article
Antibacterial Properties of Submerged Cultivated Fomitopsis pinicola, Targeting Gram-Negative Pathogens, Including Borrelia burgdorferi
by Olga Bragina, Maria Kuhtinskaja, Vladimir Elisashvili, Mikheil Asatiani and Maria Kulp
Sci 2025, 7(3), 104; https://doi.org/10.3390/sci7030104 (registering DOI) - 2 Aug 2025
Abstract
The rise in multidrug-resistant bacterial strains and persistent infections such as Lyme disease caused by Borrelia burgdorferi highlights the need for novel antimicrobial agents. The present study explores the antioxidant, antibacterial, and cytotoxic properties of extracts from submerged mycelial biomass of Fomitopsis pinicola [...] Read more.
The rise in multidrug-resistant bacterial strains and persistent infections such as Lyme disease caused by Borrelia burgdorferi highlights the need for novel antimicrobial agents. The present study explores the antioxidant, antibacterial, and cytotoxic properties of extracts from submerged mycelial biomass of Fomitopsis pinicola, cultivated in synthetic and lignocellulosic media. Four extracts were obtained using hot water and 80% ethanol. The provided analysis of extracts confirmed the presence of various bioactive compounds, including flavonoids, alkaloids, and polyphenols. All extracts showed dose-dependent antioxidant activity (IC50: 1.9–6.7 mg/mL). Antibacterial tests revealed that Klebsiella pneumoniae was most sensitive, with the L2 extract producing the largest inhibition zone (15.33 ± 0.47 mm), while the strongest bactericidal effect was observed against Acinetobacter baumannii (MBC as low as 0.5 mg/mL for L1). Notably, all extracts significantly reduced the viability of stationary-phase B. burgdorferi cells, with L2 reducing viability to 42 ± 2% at 5 mg/mL, and decreased biofilm mass, especially with S2. Cytotoxicity assays showed minimal effects on NIH 3T3 cells, with slight toxicity in HEK 293 cells for S2 and L1. These results suggest that F. pinicola extracts, particularly ethanolic L2 and S2, may offer promising natural antimicrobial and antioxidant agents for managing resistant infections. Full article
(This article belongs to the Section Biology Research and Life Sciences)
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16 pages, 1632 KiB  
Article
Meloidogyne incognita Significantly Alters the Cucumber Root Metabolome and Enriches Differential Accumulated Metabolites Regulating Nematode Chemotaxis and Infection
by Naicun Chen, Qianqian Sun, Zhiqun Chen and Xu Zhang
Horticulturae 2025, 11(8), 892; https://doi.org/10.3390/horticulturae11080892 (registering DOI) - 1 Aug 2025
Abstract
Root-knot nematode (Meloidogyne incognita) is a globally destructive plant-parasitic nematode that severely impedes the sustainable production of horticultural crops. Metabolic reprogramming in plant roots represents the host response to M. incognita infection that can also be exploited by the nematode to [...] Read more.
Root-knot nematode (Meloidogyne incognita) is a globally destructive plant-parasitic nematode that severely impedes the sustainable production of horticultural crops. Metabolic reprogramming in plant roots represents the host response to M. incognita infection that can also be exploited by the nematode to facilitate its parasitism. In this study, untargeted metabolomics was employed to analyze metabolic changes in cucumber roots following nematode inoculation, with the goal of identifying differentially accumulated metabolites that may influence M. incognita behavior. Metabolomic analysis revealed that M. incognita significantly altered the cucumber root metabolome, triggering an accumulation of lipids and organic acids and enriching biotic stress-related pathways such as alkaloid biosynthesis and linoleic acid metabolism. Among differentially accumulated metabolites, myristic acid and hexadecanal were selected for further study due to their potential roles in nematode inhibition. In vitro assays demonstrated that both metabolites suppressed egg hatching and reduced infectivity of M. incognita, while pot experiments indicated a correlation between their application and reduced root gall formation. Chemotaxis assays further revealed that both metabolites exerted repellent effects on the chemotactic migration of M. incognita J2 and suppressed the transcriptional expression of two motility-and feeding-related neuropeptides, Mi-flp-1 and Mi-flp-18. In conclusion, this study demonstrates the significant potential of differentially accumulated metabolites induced by M. incognita infection for nematode disease control, achieved by interfering with nematode chemotaxis and subsequent infection. This work also provides deeper insights into the metabolomic mechanisms underlying the cucumber-M. incognita interaction. Full article
(This article belongs to the Special Issue 10th Anniversary of Horticulturae—Recent Outcomes and Perspectives)
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15 pages, 2979 KiB  
Article
A Metabolomics Exploration of Young Lotus Seeds Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging
by Ying Chen, Xiaomeng Xu and Chunping Tang
Molecules 2025, 30(15), 3242; https://doi.org/10.3390/molecules30153242 (registering DOI) - 1 Aug 2025
Abstract
Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. [...] Read more.
Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. To investigate the “homologous plants with different effects” phenomenon in traditional Chinese medicine, this study established a Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) method. This study employed immature lotus seeds as the experimental material, diverging from the mature seeds conventionally used. Conductive double-sided tape was employed for sample preparation, and complete longitudinal sections of the seeds were obtained, followed by MALDI-MSI analysis to identify and visualize the spatial distribution of characteristic secondary metabolites within the entire seeds. The results unveiled the diversity of metabolites in lotus seeds and their differential distribution across tissues, with pronounced distinctions in the plumule. A total of 152 metabolites spanning 13 categories were identified in lotus seeds, with 134, 89, 51, and 98 metabolites discerned in the pericarp, seed coat, cotyledon, and plumule, respectively. Strikingly, young lotus seeds were devoid of liensinine/isoliensinine and neferine, the dominant alkaloids of mature lotus seed plumule, revealing an early-stage alkaloid profile that sharply contrasts with the well-documented abundance found in mature seeds and has rarely been reported. We further propose a biosynthetic pathway to explain the presence of the detected benzylisoquinoline and the absence of the undetected bisbenzylisoquinoline alkaloids in this study. These findings present the first comprehensive metabolic atlas of immature lotus seeds, systematically exposing the pronounced chemical divergence from their mature counterparts, and thus lays a metabolomic foundation for dissecting the spatiotemporal mechanisms underlying the nutritional and medicinal value of lotus seeds. Full article
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12 pages, 1435 KiB  
Article
Amino Acid Analysis and Cytotoxicity Study of Iraqi Ocimum basilicum Plant
by Omar Hussein Ahmed
Molecules 2025, 30(15), 3232; https://doi.org/10.3390/molecules30153232 (registering DOI) - 1 Aug 2025
Viewed by 21
Abstract
Background: This paper deals with the detection of amino acid composition of Iraqi Ocimum basilicum (basil) leaves and evaluation of the cytotoxic effects of the plant leaf extract on human colorectal cancer cells. Methods: Leaves of Ocimum basilicum were collected from Iraq in [...] Read more.
Background: This paper deals with the detection of amino acid composition of Iraqi Ocimum basilicum (basil) leaves and evaluation of the cytotoxic effects of the plant leaf extract on human colorectal cancer cells. Methods: Leaves of Ocimum basilicum were collected from Iraq in November 2024. After drying and powdering, the plant material went through cold methanol extraction. Initial phytochemical screening was conducted to identify the presence of alkaloids, flavonoids, coumarins, and terpenoids. Amino acid analysis was completed by an amino acid analyzer with fluorescence detection. The cytotoxic effect was evaluated via the MTT assay on HRT-18 cell lines. Morphological changes were further tested using dual Propidium Iodide/Acridine Orange assay fluorescent staining. Results: Seventeen amino acids were detected in the plant extract. The extract showed dose-dependent cytotoxic effects on HRT-18 cells, with significant reduction in cell viability at concentrations of more than 25 µg/mL. Morphological alterations of membrane blebbing and cell shrinkage were observed, suggesting apoptotic activity. The IC50 value confirmed strong cytotoxic potential. Conclusions: The extract of Ocimum basilicum leaf cultivated in Iraq shows a rich amino acid profile and significant cytotoxic activity against colorectal cancer cells that highlights its potential effect as a natural source of anticancer compounds. Full article
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21 pages, 3036 KiB  
Article
Histological Features Detected for Separation of the Edible Leaves of Allium ursinum L. from the Poisonous Leaves of Convallaria majalis L. and Colchicum autumnale L
by Márta M-Hamvas, Angéla Tótik, Csongor Freytag, Attila Gáspár, Amina Nouar, Tamás Garda and Csaba Máthé
Plants 2025, 14(15), 2377; https://doi.org/10.3390/plants14152377 (registering DOI) - 1 Aug 2025
Viewed by 27
Abstract
Allium ursinum (wild garlic) has long been collected and consumed as food and medicine in the north temperate zone, where its popularity is growing. Colchicum autumnale and Convallaria majalis contain toxic alkaloids. Their habitats overlap, and without flowers, their vegetative organs are similar. [...] Read more.
Allium ursinum (wild garlic) has long been collected and consumed as food and medicine in the north temperate zone, where its popularity is growing. Colchicum autumnale and Convallaria majalis contain toxic alkaloids. Their habitats overlap, and without flowers, their vegetative organs are similar. Confusing the leaves of Colchicum or Convallaria with the leaves of wild garlic has repeatedly led to serious human and animal poisonings. Our goal was to find a histological characteristic that makes the separation of these leaves clear. We compared the anatomy of foliage leaves of these three species grown in the same garden (Debrecen, Hungary, Central Europe). We used a bright-field microscope to characterize the transversal sections of leaves. Cell types of epidermises were compared based on peels and different impressions. We established some significant differences in the histology of leaves. The adaxial peels of Allium consist of only “long” cells without stomata, but the abaxial ones show “long”, “short” and “T” cells with wavy cell walls as a peculiarity, and stomata. Convallaria and Colchicum leaves are amphystomatic, but in the case of Allium, they are hypostomatic. These traits were confirmed with herbarium specimens. Our results help to clearly identify these species even in mixed, dried plant material and may be used for diagnostic purposes. Full article
32 pages, 2108 KiB  
Review
Phytochemical Composition and Multifunctional Applications of Ricinus communis L.: Insights into Therapeutic, Pharmacological, and Industrial Potential
by Tokologo Prudence Ramothloa, Nqobile Monate Mkolo, Mmei Cheryl Motshudi, Mukhethwa Michael Mphephu, Mmamudi Anna Makhafola and Clarissa Marcelle Naidoo
Molecules 2025, 30(15), 3214; https://doi.org/10.3390/molecules30153214 (registering DOI) - 31 Jul 2025
Viewed by 230
Abstract
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its [...] Read more.
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its terminal panicle-like inflorescences bear monoecious flowers, and its seeds are enclosed in prickly capsules. Throughout its various parts, R. communis harbours a diverse array of bioactive compounds. Leaves contain tannins, which exhibit astringent and antimicrobial properties, and alkaloids like ricinine, known for anti-inflammatory properties, as well as flavonoids like rutin, offering antioxidant and antibacterial properties. Roots contain ellagitannins, lupeol, and indole-3-acetic acid, known for anti-inflammatory and liver-protective effects. Seeds are renowned for ricin, ricinine, and phenolic compounds crucial for industrial applications such as biodegradable polymers. Pharmacologically, it demonstrates antioxidant effects from flavonoids and tannins, confirmed through minimum inhibitory concentration (MIC) assays for antibacterial activity. It shows potential in managing diabetes via insulin signalling pathways and exhibits anti-inflammatory properties by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, it has anti-fertility effects and potential anticancer activity against cancer stem cells. This review aims to summarize Ricinus communis’s botanical properties, therapeutic uses, chemical composition, pharmacological effects, and industrial applications. Integrating the current knowledge offers insights into future research directions, emphasizing the plant’s diverse roles in agriculture, medicine, and industry. Full article
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34 pages, 954 KiB  
Review
Insights into the Activities and Usefulness of Deoxynojirimycin and Morus alba: A Comprehensive Review
by Angela Fulvia Tricase, Maria Maddalena Cavalluzzi, Alessia Catalano, Michela De Bellis, Annalisa De Palma, Giovanna Basile, Maria Stefania Sinicropi and Giovanni Lentini
Molecules 2025, 30(15), 3213; https://doi.org/10.3390/molecules30153213 (registering DOI) - 31 Jul 2025
Viewed by 312
Abstract
Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, [...] Read more.
Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for this compound. However, DNJ has not been approved as a food supplement until now. Several studies, also in clinics, are carried out on Morus spp. containing DNJ. Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Some spurious studies have been conducted on Reducose® and Glubloc™, two products that contain DNJ and Morus alba, respectively. However, mulberry allergy, including respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria, may be observed. This review aims to explore a crucial and timely question: how DNJ exerts its biological effects and what role it may play in therapeutic applications. We provide a comprehensive summary of the current understanding of DNJ’s pharmacological potential and the methods used for its production. We also report recent developments in clinical studies on Morus alba, Reducose® and Glubloc™. Full article
(This article belongs to the Section Organic Chemistry)
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35 pages, 2638 KiB  
Review
Genetic Divergence and Functional Significance of Bioactive Compounds in Rice and Barley: Implications for Biofortification and Human Health
by Essam ElShamey, Jiazhen Yang, Xiaomeng Yang, Md. Mahmudul Hasan, Tao Yang and Yawen Zeng
Int. J. Mol. Sci. 2025, 26(15), 7374; https://doi.org/10.3390/ijms26157374 (registering DOI) - 30 Jul 2025
Viewed by 107
Abstract
The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) [...] Read more.
The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) and barley (Hordeum vulgare) are key dietary staples with distinct genetic architectures influencing the biosynthesis and accumulation of these bioactive compounds. In this study, we explore the interaction and divergence of gene loci associated with GABA, RS, and alkaloid pathways in rice and barley, leveraging comparative genomics to identify conserved and species-specific regulatory mechanisms. We highlight key quantitative trait loci (QTLs) and candidate genes, such as GAD (glutamate decarboxylase) for GABA synthesis, SSIIa and GBSS for RS formation, and alkaloid biosynthesis genes including CYP80G2. Additionally, we discuss the health implications of these functional components, including their roles in reducing hypertension, managing diabetes, and exhibiting neuroprotective effects. Understanding the genetic differences between rice and barley in accumulating these compounds can guide biofortification strategies to enhance nutritional quality in cereal crops, ultimately benefiting human health and dietary outcomes. Full article
(This article belongs to the Special Issue Molecular Insight into Plant Bioactive Compounds)
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17 pages, 2627 KiB  
Article
Cuscohygrine and Hygrine as Biomarkers for Coca Leaf Chewing: Analytical Challenges in GC-MS Detection and Implications for the Differentiation of Cocaine Use in Forensic Toxicology
by Nélida C. Rubio, Iván Alvarez-Freire, Pamela Cabarcos-Fernández, María J. Tabernero-Duque, Inés Sánchez-Sellero, Antonio Moreda-Piñeiro, Pilar Bermejo-Barrera and Ana M. Bermejo-Barrera
Separations 2025, 12(8), 201; https://doi.org/10.3390/separations12080201 - 30 Jul 2025
Viewed by 134
Abstract
Cuscohygrine (CUS) and hygrine (HYG) are pyrrolidine alkaloids proposed as biomarkers of coca leaf consumption, a culturally accepted practice in some Latin American countries. Differentiating legal coca use from illicit cocaine consumption holds forensic importance. While LC-MS/MS is preferred, GC-MS remains widely used [...] Read more.
Cuscohygrine (CUS) and hygrine (HYG) are pyrrolidine alkaloids proposed as biomarkers of coca leaf consumption, a culturally accepted practice in some Latin American countries. Differentiating legal coca use from illicit cocaine consumption holds forensic importance. While LC-MS/MS is preferred, GC-MS remains widely used in Latin American toxicology labs due to accessibility. This study critically evaluates the analytical limitations of GC-MS for detecting CUS and HYG in biological matrices. Key parameters—injector temperature (180–290 °C), injection mode (split/splitless), solvent, liner condition, and matrix—were systematically studied. GC-MS showed significant limitations: low-abundance, non-specific fragments (m/z 42, 84, 98, 140) failed to meet the identification criteria in SIM mode. Thermal degradation of CUS to HYG and CUS-d6 to HYG-d3 was observed, especially with splitless injection and aged liners. Matrix effects produced signal enhancement ranging from +29% to +316%, meaning that analyte responses in biological samples were significantly higher than in neat standards, likely due to reduced degradation or adsorption. Although deuterated internal standards (CUS-d6) partially corrected signal variability and matrix enhancement, these corrections were not sufficient to overcome the fundamental limitations of GC-MS, including poor ion specificity and compound instability. These findings support the need for LC-MS/MS-based approaches for reliable alkaloid detection and question the suitability of GC-MS for CUS analysis in forensic toxicology contexts. Full article
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49 pages, 3170 KiB  
Review
Nano-Phytomedicine: Harnessing Plant-Derived Phytochemicals in Nanocarriers for Targeted Human Health Applications
by Nargish Parvin, Mohammad Aslam, Sang Woo Joo and Tapas Kumar Mandal
Molecules 2025, 30(15), 3177; https://doi.org/10.3390/molecules30153177 - 29 Jul 2025
Viewed by 201
Abstract
Phytochemicals from medicinal plants offer significant therapeutic benefits, yet their clinical utility is often limited by poor solubility, instability, and low bioavailability. Nanotechnology presents a transformative approach to overcome these challenges by encapsulating phytochemicals in nanocarriers that enhance stability, targeted delivery, and controlled [...] Read more.
Phytochemicals from medicinal plants offer significant therapeutic benefits, yet their clinical utility is often limited by poor solubility, instability, and low bioavailability. Nanotechnology presents a transformative approach to overcome these challenges by encapsulating phytochemicals in nanocarriers that enhance stability, targeted delivery, and controlled release. This review highlights major classes of phytochemicals such as polyphenols, flavonoids, and alkaloids and explores various nanocarrier systems including liposomes, polymeric nanoparticles, and hybrid platforms. It also discusses their mechanisms of action, improved pharmacokinetics, and disease-specific targeting. Further, the review examines clinical advancements, regulatory considerations, and emerging innovations such as smart nanocarriers, AI-driven formulation, and sustainable manufacturing. Nano-phytomedicine offers a promising path toward safer, more effective, and personalized therapies, bridging traditional herbal knowledge with modern biomedical technology. Full article
(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)
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28 pages, 5315 KiB  
Article
Integrated Transcriptome and Metabolome Analysis Provides Insights into the Low-Temperature Response in Sweet Potato (Ipomoea batatas L.)
by Zhenlei Liu, Jiaquan Pan, Sitong Liu, Zitong Yang, Huan Zhang, Tao Yu and Shaozhen He
Genes 2025, 16(8), 899; https://doi.org/10.3390/genes16080899 - 28 Jul 2025
Viewed by 292
Abstract
Background/Objectives: Sweet potato is a tropical and subtropical crop and its growth and yield are susceptible to low-temperature stress. However, the molecular mechanisms underlying the low temperature stress of sweetpotato are unknown. Methods: In this work, combined transcriptome and metabolism analysis was employed [...] Read more.
Background/Objectives: Sweet potato is a tropical and subtropical crop and its growth and yield are susceptible to low-temperature stress. However, the molecular mechanisms underlying the low temperature stress of sweetpotato are unknown. Methods: In this work, combined transcriptome and metabolism analysis was employed to investigate the low-temperature responses of two sweet potato cultivars, namely, the low-temperature-resistant cultivar “X33” and the low-temperature-sensitive cultivar “W7”. Results: The differentially expressed metabolites (DEMs) of X33 at different time stages clustered in five profiles, while they clustered in four profiles of W7 with significant differences. Differentially expressed genes (DEGs) in X33 and W7 at different time points clustered in five profiles. More DEGs exhibited continuous or persistent positive responses to low-temperature stress in X33 than in W7. There were 1918 continuously upregulated genes and 6410 persistent upregulated genes in X33, whereas 1781 and 5804 were found in W7, respectively. Core genes involved in Ca2+ signaling, MAPK cascades, the reactive oxygen species (ROS) signaling pathway, and transcription factor families (including bHLH, NAC, and WRKY) may play significant roles in response to low temperature in sweet potato. Thirty-one common differentially expressed metabolites (DEMs) were identified in the two cultivars in response to low temperature. The KEGG analysis of these common DEMs mainly belonged to isoquinoline alkaloid biosynthesis, phosphonate and phosphinate metabolism, flavonoid biosynthesis, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, ABC transporters, and glycerophospholipid metabolism. Five DEMs with identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected for correlation analysis. KEGG enrichment analysis showed that the carbohydrate metabolism, phenylpropanoid metabolism, and glutathione metabolism pathways were significantly enriched and played vital roles in low-temperature resistance in sweet potato. Conclusions: These findings contribute to a deeper understanding of the molecular mechanisms underlying plant cold tolerance and offer targets for molecular breeding efforts to enhance low-temperature resistance. Full article
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15 pages, 2504 KiB  
Review
The Madangamines: Synthetic Strategies Toward Architecturally Complex Alkaloids
by Valentina Ríos, Cristian Maulen, Claudio Parra and Ben Bradshaw
Mar. Drugs 2025, 23(8), 301; https://doi.org/10.3390/md23080301 - 28 Jul 2025
Viewed by 264
Abstract
Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven [...] Read more.
Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses—covering five of the six members—have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A–E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field. Full article
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