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Keywords = flavonoid metabolism

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23 pages, 641 KB  
Article
Optimized Nutrition as a Driver of Cultivar-Specific Metabolic Plasticity in Sweet Basil
by Silvia Farkasová, Lucia Urbanová, Jana Lakatošová, Ivona Jančo, Eva Ivanišová, Ivana Mezeyová and Miroslav Šlosár
Agriculture 2026, 16(13), 1387; https://doi.org/10.3390/agriculture16131387 (registering DOI) - 25 Jun 2026
Abstract
Sweet basil is a medicinal herb valued for its culinary and therapeutic applications, primarily due to its secondary metabolite content. Therefore, optimizing its cultivation is essential for growers seeking to improve both the quality and nutritional value of the plants. Two cultivars of [...] Read more.
Sweet basil is a medicinal herb valued for its culinary and therapeutic applications, primarily due to its secondary metabolite content. Therefore, optimizing its cultivation is essential for growers seeking to improve both the quality and nutritional value of the plants. Two cultivars of Ocimum basilicum L., ‘Lettuce Leaf’ (LL) and ‘Purple Opal’ (PO), were evaluated under various nutritional regimes (mineral, organic, and organo-mineral). The assessment included measurements of total protein, fat, and ash content, as well as total polyphenol levels, phenolic acid content, and antioxidant activity. HPLC analysis was performed to evaluate the composition of selected phenolic and chlorogenic acids, flavonoids, and catechins. Additionally, mineral content was analyzed using OES-ICP. Gene expression of key genes involved in the phenylpropanoid pathway (PAL, C4H, 4Cl, CAD, and CVOMT) and the transcription factor OscWRKY1 was analyzed through RT-qPCR. The key findings indicated that the nutritional variants significantly impacted both primary and secondary metabolism in the assessed plants. Additionally, there was a significant (p < 0.05) cultivar-specific response to the different nutritional variants. The results suggest that the optimal nutritional strategy may vary depending on the target metabolite. Variant 4 was associated with the most favorable overall response in basil, including increased protein levels, higher total polyphenol content, and a balanced mineral composition. However, variant 5 showed the highest antioxidant activity for both cultivars. Rutin and protocatechuic acid were detected only in PO, and cryptochlorogenic acid was detected only in LL. A marked varietal difference was observed in gallocatechin content, with the LL variety containing more than fourfold higher levels than the PP variety. The results of RT-qPCR were fluctuating and strongly dependent on the cultivar. Full article
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20 pages, 2210 KB  
Article
Comprehensive Phytochemical Characterization and Quality Evaluation of Taxillus chinensis via Integrated Widely Targeted Metabolomics, HPLC Fingerprinting, and Multi-Component Quantification
by Zhouwei Li, Hongfei Wei, Jiahui Wu, Qiyuan Yang, Jiemei Liang, Xiaoxun Wang and Li Li
Metabolites 2026, 16(7), 446; https://doi.org/10.3390/metabo16070446 (registering DOI) - 25 Jun 2026
Abstract
Background/Objectives: This study aims to establish a systematic phytochemical characterization and quality evaluation method to systematically evaluate the influence of multiple factors on the chemical composition of Taxillus chinensis, thereby providing a scientific basis for its development, utilization, and quality control standards. [...] Read more.
Background/Objectives: This study aims to establish a systematic phytochemical characterization and quality evaluation method to systematically evaluate the influence of multiple factors on the chemical composition of Taxillus chinensis, thereby providing a scientific basis for its development, utilization, and quality control standards. Methods: To ensure a targeted and representative metabolic screening, six representative batches covering the major geographical origins and host plants were selected for initial metabolomic profiling. An integrated analytical approach combining UPLC-MS/MS-based widely targeted metabolomics, HPLC fingerprinting, and multi-component quantitative analysis with multivariate statistical analysis was employed. Results: Significant quality variations were identified across the samples. Metabolomics results indicated that while chemical component types were qualitatively consistent across growth conditions, their contents varied significantly. Unique differential metabolites clustered according to specific geographical origins or host plants. KEGG pathway analysis revealed that geographical origin primarily regulated phenylpropanoid biosynthesis, whereas host differences mainly influenced flavonoid and monoterpenoid biosynthesis. Furthermore, HPLC fingerprinting of 20 batches demonstrated similarities greater than 0.9, with 15 common peaks determined. Based on their high relative abundance, differential significance across samples, and documented pharmacological relevance to the herb’s traditional efficacy, six bioactive components—gallic acid, catechin, epicatechin, hyperoside, isoquercitrin, and quercitrin—were identified and quantified. Notably, samples originating from Wuzhou exhibited the highest total content of these components. Consistent with PCA and HCA results, gallic acid, hyperoside, isoquercitrin, and quercitrin were identified as potential markers driving quality differences. Conclusions: This integrated approach allows for a systematic analytical screening of Taxillus chinensis, clarifying chemical variations caused by environmental and biological factors, and supporting the standardization and comprehensive utilization of this medicinal plant. Full article
(This article belongs to the Topic Metabolomics in Plants)
5 pages, 637 KB  
Proceeding Paper
Quercetin Suppresses mRNA Expression of Fto and the TNF-α/NF-κB/NLRP3 Inflammasome Pathway in Hypothalamus of Diet-Induced Obese Rats
by Antonio Ávila-Guerrero, Ángel Miliar-García, Jorge Cornejo-Garrido, Alexis Alejandro García Rivero, Mercedes Uriyah Velázquez Romero and Aarón Domínguez López
Med. Sci. Forum 2026, 46(1), 4; https://doi.org/10.3390/msf2026046004 (registering DOI) - 25 Jun 2026
Abstract
Background: The NLRP3 inflammasome is a key driver of obesity-associated chronic low-grade inflammation, contributing to hypothalamic neuroinflammation and disruption of energy homeostasis. Quercetin, a bioactive flavonoid, has been proposed as a modulator of inflammatory and metabolic pathways, including the fat mass and obesity-associated [...] Read more.
Background: The NLRP3 inflammasome is a key driver of obesity-associated chronic low-grade inflammation, contributing to hypothalamic neuroinflammation and disruption of energy homeostasis. Quercetin, a bioactive flavonoid, has been proposed as a modulator of inflammatory and metabolic pathways, including the fat mass and obesity-associated gene (FTO). Objective: This study evaluated the effects of quercetin on hypothalamic mRNA expression of Fto and components of the TNF-α/NF-κB/NLRP3 pathway. Methodology: In a high-fat diet (HFD)-induced obesity model, male Wistar rats (n = 18) were divided into three groups: standard diet (SD), HFD, and HFD + Q (supplemented with quercetin 50 mg/kg/day for 12 weeks). Gene expression was analyzed by quantitative PCR using the 2−ΔΔCt method. Results: HFD significantly increased the expression of Fto and pro-inflammatory genes, including Tnf, Nlrp3, Casp1, Il1b, and Il18. Quercetin supplementation attenuated this upregulation, restoring expression levels toward baseline. Conclusions: These findings indicate that quercetin reduces hypothalamic neuroinflammation and modulates Fto expression, likely through inhibition of NF-κB signaling and suppression of NLRP3 inflammasome activation. Quercetin may represent a potential molecular modulator of obesity-associated neuroinflammatory processes. Full article
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19 pages, 62747 KB  
Article
Comparable Metabolic and Histopathological Observations of Enzymatic and Non-Enzymatic Thai Shallot Extracts in High-Fat Diet-Induced Obese Mice
by Artorn Anuduang, Jiraporn Laoung-on, Oranit Kraseasintra, Somdet Srichairatanakool, Kittipan Rerkasem, Sakaewan Ounjaijean and Kongsak Boonyapranai
Biology 2026, 15(13), 995; https://doi.org/10.3390/biology15130995 (registering DOI) - 24 Jun 2026
Abstract
Thai shallot (Allium cepa L. var. aggregatum) is rich in quercetin glycosides, which can be enzymatically hydrolyzed into aglycone forms with potentially higher bioavailability. However, whether this structural modification enhances metabolic efficacy in vivo remains unclear. This study aimed to compare [...] Read more.
Thai shallot (Allium cepa L. var. aggregatum) is rich in quercetin glycosides, which can be enzymatically hydrolyzed into aglycone forms with potentially higher bioavailability. However, whether this structural modification enhances metabolic efficacy in vivo remains unclear. This study aimed to compare the metabolic and histopathological effects of enzymatic (ESE) and non-enzymatic (NES) Thai shallot extracts in a high-fat diet (HFD)-induced obese mouse model. Male C57BL/6 mice were fed HFD for 12 weeks to induce obesity, followed by a 12-week treatment with NES or ESE (1000 and 2000 mg/kg/day). Metabolic parameters, lipid profiles, oxidative stress markers, hepatic enzyme activities, and histopathological changes were evaluated. Enzymatic hydrolysis significantly increased the proportion of quercetin aglycone without altering total quercetin content. Both NES and ESE improved fasting glucose, insulin resistance, lipid profiles, and oxidative stress markers compared with HFD controls. Histological examination showed attenuation of hepatic steatosis and preservation of tissue architecture in treated groups. However, no consistent superiority of ESE over NES was observed across metabolic or histopathological outcomes. Despite substantial modification of flavonoid composition, enzymatic processing did not enhance the measured metabolic efficacy of Thai shallot extract under the conditions tested. Because circulating quercetin and metabolite levels were not assessed, this finding should be interpreted as comparable metabolic efficacy rather than evidence of equivalent bioavailability. These findings suggest that factors beyond aglycone content may play a key role in determining biological activity, with implications for the development and cost-effectiveness of functional food products. Full article
(This article belongs to the Special Issue Recent Advances in Metabolic Disorders)
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19 pages, 1558 KB  
Article
Molecular Mechanism Study on the Color of Cosmos bipinnatus and Cosmos sulphureus
by Wentang Chen, Shutong Hou, Junnan Li, Mufan Yang, Fangliang Zhou, Xiaowen Lu, Mingyu Zhong, Chenxin Gao, Miao Qi, Zhiheng Li, Jiayi Zhang, Chunxian Yang and Lingjiang Zeng
Horticulturae 2026, 12(7), 771; https://doi.org/10.3390/horticulturae12070771 (registering DOI) - 24 Jun 2026
Abstract
Flavonoids are essential secondary metabolites that predominantly affect flower pigmentation in plants. Understanding the molecular mechanisms underlying flower color divergence is crucial for ornamental plant breeding. This study aimed to elucidate the factors responsible for the differences in color between white-petaled Cosmos bipinnatus [...] Read more.
Flavonoids are essential secondary metabolites that predominantly affect flower pigmentation in plants. Understanding the molecular mechanisms underlying flower color divergence is crucial for ornamental plant breeding. This study aimed to elucidate the factors responsible for the differences in color between white-petaled Cosmos bipinnatus and orange-petaled Cosmos sulphureus. We employed an integrated approach combining untargeted LC–MS/MS metabolomics and high-throughput transcriptome sequencing of fresh petals to analyze pigment composition and differential gene expression. Petal pigment extraction, total flavonoid quantification, and metabolomic profiling consistently revealed that differences in flavonoid abundance are responsible for flower color divergence between the two species. In contrast, carotenoids, previously considered potential contributors to flower coloration, were neither evident in the oil phase of the pigment extracts nor detected by metabolomic analysis. Flavonoid compounds accumulated at relatively high levels in the orange petals of C. sulphureus, reaching 11.36 times that of C. bipinnatus, contributing to its bright appearance. Transcriptomic analysis revealed differences in gene expression patterns between the two species, highlighting key candidate genes involved in the flavonoid biosynthesis pathway, such as chalcone synthase. These findings indicate that the orange coloration of C. sulphureus may be associated with CHS-regulated accumulation of naringenin chalcone and downstream compounds in the flavonoid metabolic pathway after CHS, providing valuable theoretical support for a deeper understanding of the causes underlying the differences in flower color between C. bipinnatus and the orange-petaled C. sulphureus. Full article
(This article belongs to the Special Issue Plant Secondary Metabolism and Its Applications in Horticulture)
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19 pages, 849 KB  
Review
From Pollen to Pathogen Defense: How Pollen Chemical Quality Impacts Deformed Wing Virus Infection and Survival in Honey Bees
by Richard García Domínguez, María D. López-Belchí, Nolberto Arismendi and Marisol Vargas
Viruses 2026, 18(7), 695; https://doi.org/10.3390/v18070695 (registering DOI) - 24 Jun 2026
Viewed by 45
Abstract
Pollen constitutes the primary source of proteins, amino acids, lipids, sterols, vitamins, and minerals for honey bees. However, not all pollen types provide the same resources or have the same biological value. Its chemical composition changes according to botanical origin, geographic location, and [...] Read more.
Pollen constitutes the primary source of proteins, amino acids, lipids, sterols, vitamins, and minerals for honey bees. However, not all pollen types provide the same resources or have the same biological value. Its chemical composition changes according to botanical origin, geographic location, and environmental conditions. This variability can influence metabolism, the immune system, oxidative balance, and the ability to resist or tolerate infections. This article examines the available evidence on the relationship between pollen chemical quality and the dynamics of Deformed Wing Virus (DWV) infection in Apis mellifera. The analysis is approached from molecular, physiological, ecological, and seasonal perspectives. Current findings suggest that more diverse and higher-quality pollen diets are generally associated with greater colony survival and improved health status, although their effects on viral load are more heterogeneous and context-dependent. In some studies, pollen intake is linked to a reduction in DWV, whereas in others viral loads remain stable or even increase despite improvements in survival, physiological condition, or colony performance. These differences suggest that pollen may act not only by enhancing resistance to the virus but also by increasing tolerance to infection-associated damage. The potential role of pollen bioactive compounds, particularly flavonoids and phenolic acids, is also discussed. Nevertheless, evidence of direct antiviral action of these compounds in bees remains limited, as many proposed mechanisms derive from other organisms. This synthesis provides an integrative perspective on pollen nutrition and its relevance for colony resilience against viral infections. Full article
(This article belongs to the Section Invertebrate Viruses)
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25 pages, 3780 KB  
Article
Non-Targeted Metabolomic Analyses Provide Insights into Exogenous Trehalose-Mediated Heat Stress Tolerance in Tea Plants (Camellia sinensis L.)
by Xiaohui Chen, Ziwei Zhou, Fang Wang, Chufei Liu, Rongzhao Lin and Shizhong Zheng
Plants 2026, 15(13), 1938; https://doi.org/10.3390/plants15131938 (registering DOI) - 23 Jun 2026
Viewed by 70
Abstract
Global warming exacerbates high-temperature stress, disturbing the growth, metabolic homeostasis and quality formation of tea plants (Camellia sinensis L.). Trehalose, a multifunctional osmolyte, can enhance abiotic stress tolerance, but its systematic metabolic mechanism against heat damage in tea remains unclear. Here, we [...] Read more.
Global warming exacerbates high-temperature stress, disturbing the growth, metabolic homeostasis and quality formation of tea plants (Camellia sinensis L.). Trehalose, a multifunctional osmolyte, can enhance abiotic stress tolerance, but its systematic metabolic mechanism against heat damage in tea remains unclear. Here, we applied integrated gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) non-targeted metabolomics to compare control (CK), heat-stressed (T), and trehalose-treated heat-stressed (TT) tea leaves. We identified 163 differential volatile metabolites in GC-MS and 1619 differential non-volatile metabolites in LC-MS. Metabolite classification showed that organic oxygen compounds dominated differential volatile metabolites, while lipids and lipid-like molecules dominated differential non-volatile metabolites. The Kyoto Encyclopedia of Genes and Genomes enrichment showed that alanine, aspartate and glutamate metabolism, arginine biosynthesis, aminoacyl-tRNA biosynthesis, and flavone and flavonol biosynthesis were core shared pathways. Quantitatively, exogenous trehalose under heat stress significantly increased carbohydrate accumulation, restored lipid homeostasis, and elevated alanine, arginine, and related intermediates, thereby maintaining carbon–nitrogen balance. Trehalose also remodeled the amino acid substrate pool for aminoacyl-tRNA biosynthesis. In flavonoid metabolism, trehalose enhanced high-antioxidant flavonoid aglycones while reducing most glycosides and inhibiting excessive hydroxylation of flavonols. Although total flavonoid content decreased in TT relative to T, this reflected alleviated oxidative damage and reduced dependence on flavonoid-based defense. Combined with total amino acid and flavonoid quantifications, we conclude that exogenous trehalose enhances tea plant thermotolerance by coordinately regulating primary amino acid metabolism and secondary flavonoid metabolism. These findings provide a theoretical basis for using trehalose in heat-resistance cultivation and quality improvement of tea plants. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
20 pages, 19634 KB  
Article
AI-Integrated Multi-Target Validation of Coreopsis tinctoria Polyphenols as a Functional Food Ingredient Against Diabetic Nephropathy
by Dilinare Abdurehman, Xueying Lu, Yindengzhi Guoruoluo, Geyu Liu, Jun Li, Tao Wu, Xuelei Xin and Haji Akber Aisa
Foods 2026, 15(13), 2257; https://doi.org/10.3390/foods15132257 (registering DOI) - 23 Jun 2026
Viewed by 144
Abstract
Diabetic nephropathy (DN) is a severe diabetic complication with substantial clinical burden. The complex pathogenesis of DN has hindered the development of targeted therapies, creating an urgent need to develop novel strategies that directly address its underlying inflammatory and fibrotic mechanisms. Coreopsis tinctoria [...] Read more.
Diabetic nephropathy (DN) is a severe diabetic complication with substantial clinical burden. The complex pathogenesis of DN has hindered the development of targeted therapies, creating an urgent need to develop novel strategies that directly address its underlying inflammatory and fibrotic mechanisms. Coreopsis tinctoria (CE) is an edible plant rich in polyphenols, but its mechanism against DN remains understood. An integrated framework combining network pharmacology and machine learning was developed to prioritize active polyphenols and their targets. A multi-layer perceptron classifier, trained on 3.16 million compound–target pairs from Binding DB, predicted interactions between 36 CE polyphenols and 12,030 DN-associated genes. The top 100 targets were subjected to KEGG enrichment analysis, and the identified pathways were validated in a high-fat diet/STZ-induced DN rat model. The MLP model achieved superior performance (AUC-ROC = 0.9219, AP = 0.9592). Five lead polyphenols (flavonoids/chalcones) showed high predicted activity. KEGG analysis revealed enrichment in PI3K-Akt, calcium signaling, metabolic pathways, and cellular senescence. In vivo, CE treatment (150–600 mg/kg/day) dose-dependently improved glucose/lipid metabolism and renal function, and ameliorated histopathological damage, including glomerular hypertrophy, fibrosis, and mesangial expansion. Mechanistically, CE suppressed NFκB/TGFβ/Smad signaling, restored PPARγ and Nrf2/HO-1/FoxO1 antioxidant defenses, and inhibited apoptosis via Bcl-2/Bax regulation. CE exerts multi-target renoprotective effects through coordinated modulation of metabolic, inflammatory, fibrotic, and antioxidant pathways, supporting its potential as a functional food ingredient for DN management. Full article
(This article belongs to the Section Food Nutrition)
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19 pages, 27299 KB  
Article
Distinct Preservation Strategies of Red and Yellow Onions Under Low-Temperature Storage Revealed by Integrated Metabolomics
by Chenghai Shan, Hongmei Di, Xuena Yu, Wenyou Zhang, Lin Yang, Xuan Dong, Deping Wu and Bo Sun
Horticulturae 2026, 12(7), 766; https://doi.org/10.3390/horticulturae12070766 (registering DOI) - 23 Jun 2026
Viewed by 180
Abstract
The effects of ambient storage (A), cold storage (C), and frozen storage (F) on the quality, metabolomic characteristics, and sulfur-related aroma of red onion ‘Kewei Red 10’ (R10) and yellow onion ‘Kewei Yellow 14’ (Y14) were investigated using integrated non-targeted and volatile metabolomics. [...] Read more.
The effects of ambient storage (A), cold storage (C), and frozen storage (F) on the quality, metabolomic characteristics, and sulfur-related aroma of red onion ‘Kewei Red 10’ (R10) and yellow onion ‘Kewei Yellow 14’ (Y14) were investigated using integrated non-targeted and volatile metabolomics. Ambient storage accelerated shrinkage, firmness loss, and sensory deterioration in both cultivars, whereas low-temperature storage effectively delayed quality decline. R10 exhibited better tolerance to frozen storage, while Y14 performed better under cold storage. Metabolomic analysis revealed that amino acids and lipid-related metabolites were closely associated with onion senescence in both cultivars. In contrast, flavonoids were enriched in preservation-associated subclasses in R10, whereas organic acids and their derivatives were more strongly associated with delayed senescence in Y14. Volatile metabolomic analysis identified sulfur compounds and heterocyclic sulfur compounds as the major contributors to onion aroma. Sulfur-related volatiles showed distinct cultivar-dependent accumulation patterns, with many sulfur compounds accumulating prominently in ambient-stored R10-A, whereas cold-stored Y14-C maintained relatively higher levels of characteristic onion-like aroma compounds. These findings demonstrate distinct metabolic adaptation strategies between red and yellow onions during storage and suggest that cultivar-specific storage conditions are required to optimize both shelf life and flavor quality. Full article
(This article belongs to the Section Postharvest Biology, Quality, Safety, and Technology)
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18 pages, 3759 KB  
Article
Screening of Aphid-Resistant Faba Bean Germplasm and Identification of Key Physiological and Biochemical Indicators Associated with Aphid Resistance
by Taijun Fang, Changcai Teng, Ziyan Wen, Luchao Bai and Yujiao Liu
Agronomy 2026, 16(13), 1214; https://doi.org/10.3390/agronomy16131214 (registering DOI) - 23 Jun 2026
Viewed by 147
Abstract
Aphis craccivora is a major piercing–sucking insect pest in faba bean (Vicia faba L.) production and severely restricts yield and quality. To identify aphid-resistant genetic resources and clarify the key physiological and biochemical mechanisms underlying resistance and susceptibility, 937 faba bean germplasm [...] Read more.
Aphis craccivora is a major piercing–sucking insect pest in faba bean (Vicia faba L.) production and severely restricts yield and quality. To identify aphid-resistant genetic resources and clarify the key physiological and biochemical mechanisms underlying resistance and susceptibility, 937 faba bean germplasm accessions were evaluated using a stepwise strategy comprising natural field screening, precise net-house re-screening, laboratory validation based on aphid life-table parameters, and physiological and biochemical characterization of representative resistant and susceptible accessions. After final laboratory validation, three resistant and three susceptible accessions were selected and subjected to aphid feeding for 0 h (CK), 36 h, and 72 h. Eleven physiological and biochemical traits were dynamically analyzed, including the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and phenylalanine ammonia-lyase (PAL), as well as the contents of soluble protein, soluble sugar, free amino acids, tannins, total phenolics, flavonoids, and lignin. Three stable aphid-resistant accessions were ultimately identified. Laboratory life-table analysis showed that the net reproductive rate of aphids on resistant accessions was significantly lower than that on susceptible accessions, with R0 decreasing from 53.63 to 25.08, representing a reduction of 53.2%. The intrinsic rate of increase decreased by 26.7%, whereas the mean generation time increased by 10.7%, confirming the reliability of the screening results. Physiological and biochemical analyses showed that aphid feeding induced significant and time-dependent increases in SOD, POD, CAT, and PAL activities and in tannin, total phenolic, flavonoid, and lignin contents in resistant accessions, whereas these defense responses were weak in susceptible accessions. In contrast, susceptible accessions showed abnormal accumulation of soluble sugars and free amino acids, whereas resistant accessions maintained these nutrients at low levels. Lignin exhibited both constitutive and inducible defense characteristics in resistant accessions and emerged as a prominent candidate indicator for aphid resistance in faba bean. This study establishes an effective technical pipeline for screening aphid-resistant faba bean germplasm and reveals a coordinated defense network involving antioxidant enzymes, phenylpropanoid metabolism, secondary metabolites, and physical barriers. These findings provide elite parental germplasm and theoretical support for aphid-resistance breeding in faba bean. Full article
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30 pages, 3672 KB  
Review
Autophagy Stress Responses in Localized Prostate Cancer: A Flux-Aware Framework for Disease-Relevant Interpretation
by Zaira Edith Hernández-Ramírez, Enoc Mariano Cortés Malagón, Jonathan Puente-Rivera and Javier Flores-Estrada
Cells 2026, 15(13), 1134; https://doi.org/10.3390/cells15131134 (registering DOI) - 23 Jun 2026
Viewed by 184
Abstract
Autophagy-associated readouts in localized prostate cancer cannot be interpreted based on LC3, p62/SQSTM1, or LC3 puncta alone. In line with the concept of autophagy as a stress-response system, this review proposes a flux-aware, organelle-centered framework for assigning biological meaning to autophagy-related changes under [...] Read more.
Autophagy-associated readouts in localized prostate cancer cannot be interpreted based on LC3, p62/SQSTM1, or LC3 puncta alone. In line with the concept of autophagy as a stress-response system, this review proposes a flux-aware, organelle-centered framework for assigning biological meaning to autophagy-related changes under disease-relevant stress. The framework integrates oxidative burden, lysosomal competence, selective autophagy, mitophagy, ferritinophagy, p62/SQSTM1-NRF2 signaling, ferroptosis-aware controls, and disease-stage context to distinguish four interpretive states: homeostatic quality control, adaptive tumor survival, blocked clearance, and stress-overload vulnerability. Flavonoid-associated responses are used as stress-test examples because they expose recurrent limitations in the field, including supraphysiologic exposures, limited metabolite realism, static-marker inflation, and insufficient assessment of lysosomal function. However, the framework is not restricted to dietary compounds; it applies to metabolic, pharmacological, inflammatory, androgen-related, radiation-associated, or therapy-induced perturbations in which autophagy-associated markers are altered without resolution of flux or organelle function. By linking autophagosome formation, cargo turnover, lysosomal acidification, redox buffering, and phenotype-level endpoints, this review defines a practical evidence hierarchy for interpreting autophagy in localized prostate cancer and for prioritizing translational vulnerabilities arising from organelle crosstalk. This contribution is primarily conceptual and is operationalized methodologically through flux-based evaluation criteria and translationally through disease-window-specific study-design recommendations. Full article
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20 pages, 4517 KB  
Article
Dracocephalum moldavica L. Flavonoids Alleviate Doxorubicin-Induced Cardiotoxicity by Activating the AMPK/PGC1αPathway to Preserve Mitochondrial Homeostasis
by Ruifang Zheng, Yanwen Du, Shoubao Wang, Wenling Su, Kaderyea Kader, Lijuan Zhang, Zihan Wang, Diwei Liu, Jianguo Xing, Shifeng Chu and Ming Xu
Int. J. Mol. Sci. 2026, 27(13), 5641; https://doi.org/10.3390/ijms27135641 (registering DOI) - 23 Jun 2026
Viewed by 76
Abstract
Doxorubicin (DOX) is a potent chemotherapeutic drug, whose clinical application is largely restricted by dose-dependent cardiotoxicity (DIC). Dracocephalum moldavica L. is a classic medicinal and edible plant with obvious cardiovascular protective effects; however, the role of its total flavonoids (TFDM) in DIC remains [...] Read more.
Doxorubicin (DOX) is a potent chemotherapeutic drug, whose clinical application is largely restricted by dose-dependent cardiotoxicity (DIC). Dracocephalum moldavica L. is a classic medicinal and edible plant with obvious cardiovascular protective effects; however, the role of its total flavonoids (TFDM) in DIC remains unclear. This study explored the cardioprotective effect of TFDM on DOX-induced myocardial injury and its mechanism related to mitochondrial quality control. We established in vivo and in vitro DIC models and adopted echocardiography, detection of cardiac injury and oxidative stress indicators, transmission electron microscopy, mitochondrial functional assessment and Western blotting, with AMPK knockdown performed for mechanism verification. Results showed that TFDM effectively improved cardiac function, reduced myocardial oxidative stress and apoptosis, and maintained mitochondrial ultrastructure and energy metabolism. TFDM activated the AMPK/PGC1α signaling axis to facilitate mitochondrial biogenesis, and AMPK silencing eliminated the protective effect of TFDM. In conclusion, AMPK/PGC-1α pathway is a primary key pathway involved in TFDM’s protective effects, which provides an experimental basis for the development of Dracocephalum moldavica L. as a functional food and adjuvant agent against DIC. Full article
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28 pages, 10095 KB  
Review
Gymnema sylvestre as a Multi-Target Antidiabetic Agent: Mechanistic Insights and Metabolic Regulation
by Sedef Ziyanok-Demirtas and Irem Serin
Int. J. Mol. Sci. 2026, 27(12), 5609; https://doi.org/10.3390/ijms27125609 (registering DOI) - 22 Jun 2026
Viewed by 109
Abstract
Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high [...] Read more.
Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article
(This article belongs to the Special Issue Molecular Mechanism of Diabetes and Its Complications)
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17 pages, 2452 KB  
Article
Overexpression of the Lavender LaDXS2-2 Gene in Tobacco Modulates the MEP Pathway to Improve Photosynthetic Efficiency and Alter Primary Metabolism: Evidence from Integrated Omics Analyses
by Xinyue Tang, Mingyang Sun, Qichen He, Liping Yang, Lingna Chen and Yongkun Chen
Horticulturae 2026, 12(6), 753; https://doi.org/10.3390/horticulturae12060753 (registering DOI) - 20 Jun 2026
Viewed by 348
Abstract
1-Deoxy-D-xylulose-5-phosphate synthase (DXS) serves as the initial rate-limiting enzyme in the methylerythritol phosphate (MEP) pathway, governing the biosynthesis of precursors for photosynthetic pigments and terpenoids. In this study, the LaDXS2-2 gene was cloned and functionally characterized in lavender (Lavandula angustifolia). The [...] Read more.
1-Deoxy-D-xylulose-5-phosphate synthase (DXS) serves as the initial rate-limiting enzyme in the methylerythritol phosphate (MEP) pathway, governing the biosynthesis of precursors for photosynthetic pigments and terpenoids. In this study, the LaDXS2-2 gene was cloned and functionally characterized in lavender (Lavandula angustifolia). The full-length coding sequence (CDS) of LaDXS2-2 spans 2178 base pairs, encoding a protein of 725 amino acids. Phylogenetic analysis revealed that LaDXS2-2 is most closely related to the DXS from Salvia miltiorrhiza. Expression profiling demonstrated that LaDXS2-2 was highly expressed in flower buds, and its transcript levels were significantly upregulated (p < 0.05) in response to ethephon, high light intensity, and low temperature, while exhibiting tissue-specific responses to gibberellin application. Subcellular localization assays confirmed LaDXS2-2 is targeted to the chloroplast. Heterologous overexpression of LaDXS2-2 in tobacco resulted in a marked increase in photosynthetic pigment content, enhanced the actual photochemical efficiency of photosystem II [Y(II)], and reduced non-photochemical quenching (NPQ). Integrated transcriptomic and metabolomic analyses further revealed that LaDXS2-2 overexpression activated the diterpenoid biosynthesis pathway and upregulated amino acid metabolism as well as the TCA cycle, while competitively suppressing phenylpropanoid and flavonoid biosynthesis pathways. These findings indicate that LaDXS2-2 not only enhances photosynthetic efficiency by promoting the synthesis of photosynthetic pigments but also suggests a potential role in influencing primary carbon and nitrogen metabolism, as inferred from transcriptomic and metabolomic data. This functionality may ultimately influence plant growth and metabolic homeostasis. Overall, this study provides a theoretical foundation for the synergistic improvement of photosynthetic efficiency and secondary metabolism in crops. Full article
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Article
Targeted Metabolite and Gene Expression Analysis of Anthocyanin and Kaempferol Glycoside Accumulation in Peach Accessions with Contrasting Flesh and Skin Pigmentation
by Weifeng Chen, Dan Tang, Jia Huang, Yu Yang and Liangbo Zhang
Foods 2026, 15(12), 2225; https://doi.org/10.3390/foods15122225 (registering DOI) - 20 Jun 2026
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Abstract
Peach (Prunus persica) fruit pigmentation is largely associated with anthocyanin accumulation, whereas colorless flavonols such as kaempferol glycosides may reflect alternative use of shared flavonoid precursors. To examine the relationship between anthocyanin and selected kaempferol glycoside accumulation, we analyzed 15 peach [...] Read more.
Peach (Prunus persica) fruit pigmentation is largely associated with anthocyanin accumulation, whereas colorless flavonols such as kaempferol glycosides may reflect alternative use of shared flavonoid precursors. To examine the relationship between anthocyanin and selected kaempferol glycoside accumulation, we analyzed 15 peach accessions classified by red, white, or yellow flesh pigmentation. Skin color was quantified using the a*/b* ratio, where a* represents redness/greenness and b* represents yellowness/blueness. Red-fleshed accessions showed higher skin a*/b* values and accumulated higher levels of total anthocyanins, particularly cyanidin-3-glucoside, than white and yellow accessions. In contrast, kaempferol-3-rhamnoside preferentially accumulated in white-fleshed accessions. Expression analysis of flavonoid pathway genes showed that dihydroflavonol 4-reductase (PpDFR) was more highly expressed in red accessions, whereas flavonol synthase (PpFLS) was more highly expressed in white accessions; chalcone synthase (PpCHS), flavanone 3-hydroxylase (PpF3H), flavonoid 3′-hydroxylase (PpF3′H), and anthocyanidin synthase (PpANS) showed no significant differences among color groups. Heterologous overexpression of PpF3′H in Arabidopsis thaliana, a well-characterized model plant for flavonoid biosynthesis, was associated with increased seed anthocyanin accumulation and a lower kaempferol-to-quercetin ratio, supporting its catalytic capacity to influence flavonoid composition in an exogenous system. Overall, these results indicate that differential anthocyanin and selected kaempferol glycoside accumulation in peach is associated with the relative expression patterns of branch-related flavonoid genes, particularly PpDFR and PpFLS. This study provides targeted metabolic and transcriptional evidence for understanding peach flesh and skin pigmentation and provides mechanistic insight into flavonoid branch competition linking gene expression patterns with metabolite allocation, and identifies candidate genes for improving fruit color and flavonoid-related nutritional quality. Full article
(This article belongs to the Section Plant Foods)
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