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24 pages, 2907 KB  
Review
Plant Immune Elicitors for Postharvest Fruit Preservation: Multifunctional Benefits, Emerging Secreted Protein Elicitors, and Future Perspectives
by Donghai Xie, Chan Xu, Juanni Yao and Yulin Cheng
Int. J. Mol. Sci. 2026, 27(17), 7699; https://doi.org/10.3390/ijms27177699 (registering DOI) - 28 Aug 2026
Abstract
Fruits contain abundant diverse nutrients and are an essential component of the human diet. Postharvest pathogens cause severe fruit decay and even mycotoxin contamination, leading to enormous economic losses and food safety risks worldwide. Plants have evolved an intricate immune system to counter [...] Read more.
Fruits contain abundant diverse nutrients and are an essential component of the human diet. Postharvest pathogens cause severe fruit decay and even mycotoxin contamination, leading to enormous economic losses and food safety risks worldwide. Plants have evolved an intricate immune system to counter pathogen attacks, and plant immune elicitors, particularly biogenic elicitors, offer a promising approach for eco-friendly plant disease management. Although mechanistic studies of plant immunity have largely focused on leaf tissues, considerable progress has been made in the application of immune elicitors for controlling postharvest fruit diseases. In this review, we categorize the main types of plant immune elicitors for postharvest disease control, and highlight that certain elicitors possess multifunctional benefits, including improving fruit quality and enhancing fruit abiotic stress tolerance. Meanwhile, we summarize the molecular mechanisms of newly identified secreted protein elicitors. Finally, we outline a roadmap that combines high-throughput screening with artificial intelligence to accelerate the discovery of novel secreted protein elicitors and their plant receptors, while critically assessing translational barriers to their commercial application in fruit preservation. Full article
(This article belongs to the Section Biochemistry)
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30 pages, 20899 KB  
Article
Genome-Wide Analysis of Triticum aestivum Root Meristem Growth Factor (RGF) Gene Family Highlights TaRGF5 as a Putative Component of Root-Associated Signaling
by Hala B. Khalil, Haidar A. Alsahoud, Abdulrahman Darwish Mostafa, Fatimah A. Alhassan, Norah Al-helal and Shinya Ikeno
Int. J. Mol. Sci. 2026, 27(17), 7616; https://doi.org/10.3390/ijms27177616 - 25 Aug 2026
Viewed by 177
Abstract
Wheat (Triticum aestivum), a key global crop, faces rising drought stress that limits root growth and water uptake. Root meristem growth factors (RGFs) are small peptides that regulate root stem cell maintenance, meristem activity, and lateral root formation in model plants, [...] Read more.
Wheat (Triticum aestivum), a key global crop, faces rising drought stress that limits root growth and water uptake. Root meristem growth factors (RGFs) are small peptides that regulate root stem cell maintenance, meristem activity, and lateral root formation in model plants, yet the RGF gene family remains unexplored in wheat. Here, we performed a comprehensive genome-wide analysis of the TaRGF gene family, identifying 15 genes distributed across the A, B, and D subgenomes and classified into five homeologous groups (TaRGF1TaRGF5), predominantly located on chromosomes 2 and 6. All TaRGFs contained a characteristic RGF motif, with dibasic cleavage sites and Asp–Tyr motifs indicating conserved maturation mechanisms. Based on the phylogenetic analysis, the TaRGF5 homeologs showed the highest similarity to Arabidopsis thaliana RGF5. Tested RNA-seq data revealed predominantly root-enriched expression for all TaRGF genes, with TaRGF5 exhibiting the most root-preferential and downregulation under drought stress. Quantitative real-time PCR (qRT-PCR) confirmed that drought stress suppressed the expression of TaRGF5A, TaRGF5B, and TaRGF5D in roots of wheat cultivar Sids-13 across all time points, unlike the higher accumulation seen in controls. Promoter analysis predicted a unique BES1 transcription factor binding site exclusively in TaRGF5B, linking brassinosteroid signaling to peptide-mediated root regulation. Structural modeling and molecular docking predicted an interaction between wheat TaRGF5 homeologs and root growth factor-insensitive receptor kinase (TaRGI3), characterized by conserved sulfotyrosine-mediated binding and favorable interaction energetics. Based on this characterization of the wheat RGF gene family, particularly the potential role of TaRGF5 in root development and drought-adaptation signaling, we propose targeting this gene for functional analysis to improve wheat resilience under water-limited conditions. Full article
(This article belongs to the Special Issue Omics-Driven Advances in Plant Abiotic Stress Tolerance)
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35 pages, 3623 KB  
Review
Ethnobotanical Uses and Phytochemical, Pharmacological, Behavioral, and Toxicological Effects of Montanoa Species Used by Pre-Columbian Mesoamerican Cultures for Anxiety and Depression
by Juan Francisco Rodríguez-Landa, María de Jesús Rovirosa-Hernández, Francisco García-Orduña, Gabriel Guillén-Ruiz, Jonathan Cueto-Escobedo, Frank Pulido-Criollo, Oscar Jerónimo Olmos-Vázquez and Ana Karen Limón-Vázquez
Molecules 2026, 31(17), 2972; https://doi.org/10.3390/molecules31172972 - 25 Aug 2026
Viewed by 397
Abstract
Ancient cultures have long studied plants for medicinal use. Today, multidisciplinary research focuses on re-evaluating these plants to discover drugs for treating various diseases, including psychiatric disorders. Pre-Columbian Mesoamerican cultures described three plants (Montanoa tomentosa, Montanoa frutescens, and Montanoa grandiflora [...] Read more.
Ancient cultures have long studied plants for medicinal use. Today, multidisciplinary research focuses on re-evaluating these plants to discover drugs for treating various diseases, including psychiatric disorders. Pre-Columbian Mesoamerican cultures described three plants (Montanoa tomentosa, Montanoa frutescens, and Montanoa grandiflora) for treating both anxiety and depression disorders, which were called cihuapahtli in Nahuatl. This narrative review describes and analyzes the ethnobotanical use and phytochemical, pharmacological, behavioral, and toxicological effects of cihuapahtli, which can contribute to the discovery of anxiolytic and antidepressant drugs. The results show a significant advance in identifying bioactive phytochemicals, including triterpenes, diterpenes, monoterpenes, and sesquiterpenes, as well as sterols, flavonoids, and alkaloids. In particular, the mechanism of action underlying their anxiolytic and antidepressant effects involves the activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus, as well as that of the GABAergic system by targeting GABAA receptors. The three Montanoa species have the potential to help us develop anxiolytic and antidepressant drugs; however, future studies are still required to evaluate toxicity, dose standardization, possible variability in plant-derived compounds, pharmacokinetic parameters, and pharmacological interactions. Only then will preclinical evidence be sufficiently robust to justify translational studies evaluating the safety and efficacy of these plant extracts for the development of anxiolytic and antidepressant phytomedicines. Full article
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18 pages, 13584 KB  
Article
Novel Lytic Agrobacterium Bacteriophage Miki Representing a New Genus
by Anna D. Tokmakova, Anna A. Lukianova, Mikhail M. Shneider, Ilia A. Putilov, Ekaterina S. Elkina, Maria S. Filatova, Anna D. Burtseva, Konstantin M. Boyko, Yuliya V. Mikhailova, Andrey A. Shelenkov, Peter V. Evseev and Konstantin A. Miroshnikov
Viruses 2026, 18(9), 927; https://doi.org/10.3390/v18090927 - 22 Aug 2026
Viewed by 313
Abstract
Rhizogenic Agrobacterium (Rhizobium) spp. are causative agents of hairy root disease (HRD), a major threat to hydroponic crop production worldwide. The use of specific bacteriophages is considered a prospective approach to control the development of HRD in greenhouses. A combination of [...] Read more.
Rhizogenic Agrobacterium (Rhizobium) spp. are causative agents of hairy root disease (HRD), a major threat to hydroponic crop production worldwide. The use of specific bacteriophages is considered a prospective approach to control the development of HRD in greenhouses. A combination of diverse bacteriophages is a key step to overcome potential phage resistance in the pathogen. In this study, a novel lytic bacteriophage, named Miki, was identified and characterized for its antibacterial potential against a rhizogenic Agrobacterium sp. strain circulating in greenhouses in Central Russia. High-throughput sequencing revealed a 63,458 bp double-stranded DNA genome (G + C content 53%), with 117 predicted coding sequences, considering Miki as a lytic candidate phage for plant protection. Electron microscopy of phage Miki shows a morphology unusual for Agrobacterium phages, and phylogenetic analysis attributes it as a representative of a previously undescribed taxon at least at the genus level. The paper presents a detailed analysis of the genome and structural proteome of phage Miki, including in silico predictions and modeling of receptor-binding proteins, including central and proximal fibers resembling the adsorption apparatus of Escherichia phage T5. Full article
(This article belongs to the Special Issue Bacteriophage-Based Biocontrol in Agriculture, 3rd Edition)
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16 pages, 926 KB  
Review
Kava (Piper methysticum G. Forst) for Substance Use Disorders: A Review of Mechanism, Pharmacology, Clinical Evidence, and Therapeutic Potential
by Jason Krehl, Jessica Nissi Mamallapalli, Chengguo Xing and Oliver Grundmann
Nutrients 2026, 18(17), 2747; https://doi.org/10.3390/nu18172747 - 22 Aug 2026
Viewed by 333
Abstract
Substance use disorders (SUDs) remain a major public health concern and contribute substantially to compromised quality of life, mortality, and healthcare burden. In the United States alone, millions of individuals are affected by alcohol use disorder (AUD), tobacco use disorder (TUD), and opioid [...] Read more.
Substance use disorders (SUDs) remain a major public health concern and contribute substantially to compromised quality of life, mortality, and healthcare burden. In the United States alone, millions of individuals are affected by alcohol use disorder (AUD), tobacco use disorder (TUD), and opioid use disorder (OUD), with many cases complicated by co-existing anxiety and stress-related disorders. Piper methysticum G. Forst (kava), a traditional South Pacific plant preparation, has gained attention for its anxiolytic, sedative, and sleep-promoting properties. Its pharmacological effects are primarily attributed to a set of lipophilic compounds known as kavalactones, which have been reported to modulate GABAA receptor activity, dopaminergic and adrenergic signaling pathways, monoamine oxidase-B activity, cannabinoid receptor type 1 activity, and voltage-gated ion channels. Peer-reviewed literature was identified through searches of PubMed, NIH resources, and other scientific databases using terms related to kava, kavalactones, addiction, anxiety, stress, insomnia, and SUDs. Both clinical and preclinical studies were reviewed, including investigations of neurotransmitter systems and addiction-related signaling pathways. The current literature suggests that the strongest rationale for kava use exists in AUD, where anxiety and stress are established contributors to relapse. Evidence supporting kava use in TUD and OUD is largely theoretical, while concerns regarding hepatotoxicity, cytochrome P450 interactions, product variability, and additive risk remain important barriers to its clinical application. In summary, current evidence does not support kava as a replacement for established therapies, while its unique pharmacological profile warrants further investigation as a potential adjunctive treatment for withdrawal and relapse in SUDs. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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20 pages, 10841 KB  
Article
Multiple BnaSOBIR1-Associated Receptor-like Proteins Contribute to Enhanced Resistance to Sclerotinia sclerotiorum in Brassica napus L. (Oilseed Rape)
by Chenghuizi Yang, Liying Ma, Jieying Nong and Shitou Xia
Plants 2026, 15(16), 2545; https://doi.org/10.3390/plants15162545 - 21 Aug 2026
Viewed by 197
Abstract
As a major fungal pathogen of Brassica napus, Sclerotinia sclerotiorum causes significant yield reductions worldwide. Receptor-like proteins (RLPs) are essential components of plant immunity, but the functions of many RLPs in B. napus still remain unclear. In this study, three BnaSOBIR1-interacting leucine-rich [...] Read more.
As a major fungal pathogen of Brassica napus, Sclerotinia sclerotiorum causes significant yield reductions worldwide. Receptor-like proteins (RLPs) are essential components of plant immunity, but the functions of many RLPs in B. napus still remain unclear. In this study, three BnaSOBIR1-interacting leucine-rich repeat RLPs (LRR-RLPs), named BnaRLP-G13-2, BnaRLP-G13-3, and BnaRLP-G13-4, were identified by yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Promoter analysis revealed diverse cis-acting elements involved in stress and phytohormone responses. Overexpression of these genes significantly improved resistance to S. sclerotiorum in both Arabidopsis thaliana and B. napus. Consistently, BnaRLP-G13-2/3/4 restored disease resistance and NLP-induced ROS production in the rlp23-1 mutant. Furthermore, BiFC assays suggested an association between BnaRLP-G13-2/3/4 and Ssnlp24SsNEP2-associated perception, although direct biochemical binding remains to be demonstrated. These findings advance the understanding of BnaSOBIR1-associated BnaRLP-G13-2/3/4-mediated immunity and provide new insights into enhancing disease resistance in oilseed crops. Full article
(This article belongs to the Special Issue Phytohormones: Methodologies, Mechanisms and Applications)
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18 pages, 3665 KB  
Review
Pectin Structural Dynamics: Developmental and Evolutionary Perspectives
by Zúñiga-Sánchez Esther, Corral-Castrejón Estela and Gamboa-deBuen Alicia
Plants 2026, 15(16), 2531; https://doi.org/10.3390/plants15162531 - 21 Aug 2026
Viewed by 240
Abstract
Plant cell walls play a crucial role in plant development and evolution. This structure is primarily composed of proteins and polysaccharides, including cellulose, hemicellulose, and pectins. Homogalacturonan (HG), the most abundant pectin in the primary cell wall, is synthesized by α -1,4-D-GALACTURONOSYLTRANSFERASE (GAUT) [...] Read more.
Plant cell walls play a crucial role in plant development and evolution. This structure is primarily composed of proteins and polysaccharides, including cellulose, hemicellulose, and pectins. Homogalacturonan (HG), the most abundant pectin in the primary cell wall, is synthesized by α -1,4-D-GALACTURONOSYLTRANSFERASE (GAUT) enzymes, methylesterified, and subsequently secreted into the apoplast. The dynamics of pectin methylesterification is regulated by enzymes such as PECTIN METHYLESTERASES (PMEs) and PECTIN METHYLESTERASE INHIBITORS (PMEIs). Across plant evolution and development, different cell types display distinct domains of pectin methylesterification. The binding of de-methylesterified pectins to the Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) proteins and RAPID ALKALINIZATION FACTOR (RALF) peptides is involved in pectin signaling and cell wall integrity maintenance during developmental processes. While phylogenetic studies highlight molecular innovations in pectin metabolism, functional studies remain scarce outside of angiosperms. Furthermore, the explicit role of de-methylesterified pectin in coupling cell wall structure to intracellular signaling has only been demonstrated in angiosperms. Comparative functional studies addressing key evolutionary transitions will ultimately reveal how pectin metabolism has contributed to morphological innovations across plant evolution. Full article
(This article belongs to the Section Plant Development and Morphogenesis)
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34 pages, 1398 KB  
Review
The Role of Anti-Inflammatory Nutrition in Metabolic Syndrome and Cardiometabolic Diseases
by Cristina-Sorina Cătană, Monica Mihaela Marta, Denisa Popa and Eleonora Dronca
Nutrients 2026, 18(16), 2732; https://doi.org/10.3390/nu18162732 - 21 Aug 2026
Viewed by 287
Abstract
Background: Metabolic syndrome is closely linked to chronic systemic inflammation and intestinal dysbiosis. Anti-inflammatory nutrition is an approach based on the interaction between dietary intake, chronic low-grade inflammation, and the pathophysiological mechanisms of metabolic syndrome and cardiometabolic diseases. This narrative review evaluates [...] Read more.
Background: Metabolic syndrome is closely linked to chronic systemic inflammation and intestinal dysbiosis. Anti-inflammatory nutrition is an approach based on the interaction between dietary intake, chronic low-grade inflammation, and the pathophysiological mechanisms of metabolic syndrome and cardiometabolic diseases. This narrative review evaluates the impact of plant-based dietary models, including vegan and modified Mediterranean variants, on key metabolic and inflammatory parameters. Methods: Literature data published in PubMed, Science Direct, Scopus, and Google Scholar between 2017 and 2026 were used to evaluate the relation between diet, inflammation, and cardiometabolic diseases. We focused on multiple biomarkers, including inflammatory, metabolic, and oxidative-stress indicators measured by standardized laboratory methods to estimate the overall relationship between diet and chronic inflammation. Results: Dietary indices such as eADI-17 allow quantification of the inflammatory potential of anti-inflammatory nutrition and correlate with biomarkers such as hsCRP, IL-6, and soluble TNF receptors. Conclusions: Integrated nutritional strategies that combine plant-based models, temporal control of meals, and microbiota-directed interventions provide efficient support by improving endothelial dysfunction, the thrombotic profile, and chronic inflammation. Full article
(This article belongs to the Special Issue Nutritional Biomarkers: Implication for Health)
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19 pages, 2308 KB  
Review
Pelargonium graveolens L’Hér. in Traditional and Contemporary Medicine: Phytochemistry, Pharmacology, and Molecular Mechanisms
by Kamil Bukowiec, Mateusz Sroka, Agata Pałkiewicz, Bartłomiej Warzecha, Agnieszka Stasik, Piotr Szpak and Julita Kulbacka
Appl. Sci. 2026, 16(16), 8161; https://doi.org/10.3390/app16168161 - 16 Aug 2026
Viewed by 259
Abstract
Pelargonium graveolens L’Hér. is a widely distributed aromatic plant that has been utilized in traditional medicine for an extended period. It is currently experiencing a surge in popularity in modern phytotherapy. The ethnopharmacological uses of this species include treatment of respiratory tract infections, [...] Read more.
Pelargonium graveolens L’Hér. is a widely distributed aromatic plant that has been utilized in traditional medicine for an extended period. It is currently experiencing a surge in popularity in modern phytotherapy. The ethnopharmacological uses of this species include treatment of respiratory tract infections, digestive disorders, and analgesia. The plant’s multifaceted biological activity is attributed to the presence of monoterpenes, such as citronellol and geraniol, as well as non-volatile polyphenolic fractions and organic acids. Research has demonstrated the efficacy of PGEO (P. graveolens essential oil) in mitigating inflammation, a phenomenon attributable to the suppression of NF-κB and MAPK signaling pathways, as well as the inhibition of inflammatory mediators such as histamine, prostaglandins (PGs), and nitric oxide (NO). Furthermore, a broad spectrum of antimicrobial activity has been demonstrated against pathogens such as MRSA and Mycobacterium tuberculosis, whilst myricetin derivatives have been shown to enable the effective eradication of bacterial biofilms. It is also noteworthy that the oil’s components can reduce ACE2 receptor expression, indicating their potential to inhibit SARS-CoV-2 infection. Active compounds, such as geraniol, have been shown to modulate metabolic processes through interaction with LXR and FXR nuclear receptors. In addition, these compounds have been observed to exhibit spasmolytic effects within the gastrointestinal tract by blocking calcium channels. The influence on the HPA axis and the GABAergic system provides a scientific rationale for the plant’s traditional use in reducing stress and anxiety. Nevertheless, variations in chemical composition, determined by geographical origin, and an insufficient number of rigorous clinical data hinder the full medical implementation of this plant. It is imperative that further standardization of extracts and their verification in clinical trials is undertaken. Full article
(This article belongs to the Special Issue Biological Activities of Plant Extracts and Their Applications)
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22 pages, 7079 KB  
Article
Water Deficit and Methyl Jasmonate Enhance the Antiplatelet Potential of Blueberries Through Changes in Selected Phenolic Compounds
by Carlos Vasquez-Rojas, Lyanne Rodríguez, Daniel Bustos, Valentina Jara-Villacura, Cristian Balbontín, Gabriela Urra, Ricardo E. Hernández, Evelyn Villagra, Daniel Laporte, Carolina Parra-Palma, Patricio Ramos, Eduardo Fuentes and Luis Morales-Quintana
Int. J. Mol. Sci. 2026, 27(16), 7306; https://doi.org/10.3390/ijms27167306 - 16 Aug 2026
Viewed by 201
Abstract
Agronomic modulation of secondary metabolism may influence not only crop resilience but also the biological activity of fruit-derived phytochemicals. In this study, we evaluated the impact of exogenous methyl jasmonate (MeJA) application under contrasting water regimes on the selected phenolic compounds and vascular [...] Read more.
Agronomic modulation of secondary metabolism may influence not only crop resilience but also the biological activity of fruit-derived phytochemicals. In this study, we evaluated the impact of exogenous methyl jasmonate (MeJA) application under contrasting water regimes on the selected phenolic compounds and vascular bioactivity of Vaccinium corymbosum L. cv. Legacy. Antioxidant capacity was assessed by FRAP and DPPH assays, phytochemical composition was characterized by HPLC-DAD, and antiplatelet activity was evaluated through inhibition of TRAP-6–induced P-selectin (CD62P) expression in human platelets. Selected phenolic constituents were further examined using molecular docking and molecular dynamics simulations against a platelet receptor model. Although MeJA treatment altered the abundance of selected phenolic compounds identified by HPLC-DAD, total antioxidant capacity remained largely unchanged. Blueberry extracts significantly inhibited platelet activation in a concentration-dependent manner without cytotoxic effects, and antiplatelet potency was not strictly related to global antioxidant indices. Computational analyses revealed stable ligand–receptor interactions and favorable binding free energies for selected phenolics, providing a structural explanation for receptor-level modulation. These findings suggest that elicitor-driven responses in blueberries can influence platelet functional responses and highlight the importance of qualitative phytochemical composition in determining vascular bioactivity. This multiscale approach connects plant stress physiology, natural product chemistry, and human platelet biology, underscoring the translational relevance of agronomic strategies for nutraceutical functionality. Full article
(This article belongs to the Special Issue Bioactives from Natural Products)
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44 pages, 12565 KB  
Review
Anti-Androgenic Potential of Plant Extracts: Molecular Mechanisms, Synergistic Effects, and Nutritional Interventions
by Yijing Yang, Yong Pang, Jie Zhang and Li Ren
Molecules 2026, 31(16), 2849; https://doi.org/10.3390/molecules31162849 - 14 Aug 2026
Viewed by 234
Abstract
Androgen dysregulation impairs the homeostasis of the prostate, hair follicles, and ovaries, driving the pathogenesis of prostate cancer (PCa), benign prostatic hyperplasia (BPH), androgenetic alopecia (AGA), and polycystic ovary syndrome (PCOS). Current antiandrogen therapies are constrained by drug resistance, off-target toxicity, and limited [...] Read more.
Androgen dysregulation impairs the homeostasis of the prostate, hair follicles, and ovaries, driving the pathogenesis of prostate cancer (PCa), benign prostatic hyperplasia (BPH), androgenetic alopecia (AGA), and polycystic ovary syndrome (PCOS). Current antiandrogen therapies are constrained by drug resistance, off-target toxicity, and limited long-term efficacy. Plant extracts, enriched with bioactive constituents such as polyphenols, alkaloids, and flavonoids, represent promising multi-target candidates. Therefore, focusing on plant extracts—particularly those of dietary origin—this review summarized the mechanisms by which they regulate androgen-dependent and androgen-independent signaling pathways, and recent advances in nutritional interventions targeting androgen-responsive organs. Furthermore, it discussed the multi-component combined effects and factors affecting in vivo exposure of plant extracts, including metabolic transformation and tissue distribution, which may influence the anti-androgenic activity. In summary, anti-androgenic plant extracts primarily target androgen synthesis and AR signaling across various androgen disorder models, with crosstalk into cell growth and cycle, anti-inflammatory pathways, and regulation of growth factors. This multi-target regulation relies on the mixture effects of plant extracts. Future research should focus on three directions: extract standardization, clinical validation, and advanced delivery systems. Full article
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26 pages, 12863 KB  
Article
Exploring the Molecular Mechanism of Cinnamaldehyde Intervening in Ochratoxin A-Induced Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Comorbidity: An Integrated Approach Based on Network Pharmacology, Network Toxicology and Molecular Docking
by Mingli Shen, Qingping Shi, Shuang Gao, Beiyan Chen and Jieru Han
Pharmaceuticals 2026, 19(8), 1283; https://doi.org/10.3390/ph19081283 - 13 Aug 2026
Viewed by 265
Abstract
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it [...] Read more.
Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 3rd Edition)
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22 pages, 27189 KB  
Article
BMP2-Binding Caffeoylquinic Acids from Periploca forrestii Promote Osteoblast Differentiation via Smad Signaling Activation
by Minghong Dong, Xinyue Wang, Xiongwei Liu, Tingting Feng, Chang Liu and Ying Zhou
Biology 2026, 15(16), 1385; https://doi.org/10.3390/biology15161385 - 13 Aug 2026
Viewed by 254
Abstract
The BMP2-Smad signaling pathway serves as a central regulator of osteoblast differentiation and bone formation, rendering it a promising target for the discovery of osteogenic agents from natural sources. Nonetheless, direct BMP2-binding ligands derived from complex herbal extracts remain poorly characterized. In the [...] Read more.
The BMP2-Smad signaling pathway serves as a central regulator of osteoblast differentiation and bone formation, rendering it a promising target for the discovery of osteogenic agents from natural sources. Nonetheless, direct BMP2-binding ligands derived from complex herbal extracts remain poorly characterized. In the present study, surface plasmon resonance (SPR)-based target fishing against BMP2, in conjunction with UPLC-Q-TOF-MS identification, was employed to screen for bioactive ligands from Periploca forrestii, a traditional Miao medicinal plant used for bone-related conditions. Six caffeoylquinic acid derivatives, namely neochlorogenic acid (NCA), 3-O-caffeoyl-4-O-sinapoylquinic acid, chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC), were captured as direct BMP2-binding ligands. All six compounds promoted osteoblast differentiation and mineralization in MC3T3-E1 Subclone 14 cells, with IB displaying the strongest binding affinity and bioactivity. Mechanistically, IB failed to rescue the osteogenic suppression induced by the BMP type I receptor inhibitor LDN-193189, indicating its dependence on BMP signaling. In an LPS-induced inflammatory model, IB significantly reversed the downregulation of key proteins in the BMP2-Smad pathway (p-Smad1, Smad4, and Runx2) and osteogenic marker genes (Osterix, COL1A1, and OCN), demonstrating its capacity to restore osteogenic function under compromised conditions. Collectively, these findings establish that caffeoylquinic acid derivatives, particularly IB, function as BMP2-targeting osteogenic constituents of P. forrestii that activate BMP2-Smad signaling to promote osteoblast differentiation, thereby offering a pharmacological basis for the development of natural product-derived osteogenic agents. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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18 pages, 9167 KB  
Article
Evolution of Characteristic Aroma During Processing of Space-Induced Mutant Dahongpao Tea and the Preliminary Exploration of Its Olfactory Perception
by Junbin Gu, Shunxian Lin, Yuhua Wang, Yulin Wang, Miao Jia, Qi Zhang, Xiaoli Jia, Tingting Wang, Jianghua Ye and Haibin Wang
Foods 2026, 15(16), 2816; https://doi.org/10.3390/foods15162816 - 12 Aug 2026
Viewed by 226
Abstract
Space-induced mutation is a novel approach in tea plant breeding, but its effect on processing-induced aroma formation remains unclear. This study analyzed the dynamic changes in VOCs during the processing of space-induced mutants of Dahongpao tea. The results showed that processing significantly reshaped [...] Read more.
Space-induced mutation is a novel approach in tea plant breeding, but its effect on processing-induced aroma formation remains unclear. This study analyzed the dynamic changes in VOCs during the processing of space-induced mutants of Dahongpao tea. The results showed that processing significantly reshaped the VOC profile, with the fermentation stage exerting the greatest impact and terpenoids serving as the major contributors. Seven characteristic VOCs (α-phellandrene, β-phellandrene, d-sylvestrene, iso-geraniol, seudenone, hexyl benzene, and nerol) were identified and a transformation network linking floral, green, woody, almond, and fruity attributes was constructed. Molecular docking revealed that VOCs exhibiting green, woody and almond characteristics could form strong binding interactions with more than 100 olfactory receptors, whereas those with floral and fruity characteristics bound to fewer receptors. This finding indicates that during the processing, the first three odor characteristics may be perceived more prominently. Overall, this study provided a theoretical basis for the aroma evaluation of space-induced mutant tea. Full article
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Review
Natural Products Targeting Airway Inflammation and Mucus Hypersecretion: Molecular Mechanisms and Therapeutic Potential for Respiratory Health
by Sung-Gyu Lee, Jae-Ho Lee and Hyun Kang
Nutrients 2026, 18(16), 2599; https://doi.org/10.3390/nu18162599 - 8 Aug 2026
Viewed by 665
Abstract
Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis, and chronic bronchitis, are characterized by persistent airway inflammation and mucus hypersecretion, leading to airway remodeling and progressive pulmonary dysfunction. Although current therapies improve disease control, they often fail to [...] Read more.
Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis, and chronic bronchitis, are characterized by persistent airway inflammation and mucus hypersecretion, leading to airway remodeling and progressive pulmonary dysfunction. Although current therapies improve disease control, they often fail to adequately target the complex molecular mechanisms underlying chronic airway diseases and may cause adverse effects during long-term use. Natural products have therefore emerged as promising multitarget therapeutic agents because they simultaneously regulate oxidative stress, inflammatory signaling, epithelial dysfunction, and mucus production. Recent evidence demonstrates that marine-derived bioactive compounds and plant-derived phytochemicals modulate key signaling pathways, including nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Janus kinase/signal transducer and activator of transcription (JAK/STAT), the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and nuclear factor erythroid 2-related factor 2 (Nrf2), thereby suppressing airway inflammation, oxidative stress, goblet cell differentiation, and MUC5AC overexpression. Advances in nanoformulation, pulmonary drug delivery, multi-omics, artificial intelligence-assisted drug discovery, and network pharmacology are expected to accelerate clinical translation. Collectively, natural products represent promising candidates for the development of evidence-based functional foods, nutraceuticals, and novel therapeutic strategies for chronic respiratory diseases. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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