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Keywords = Morus alba L.

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24 pages, 37052 KB  
Article
Prediction of Targets and Mechanisms of Top Ten Core “Food–Medicine Homologous Traditional Chinese Medicines” in Delaying Vascular Aging: An Integrative Computational Study
by Yiling Bai, Qian Liu, Qing Zhou, Pengyang Xiao and Lina Xia
Pharmaceuticals 2026, 19(1), 131; https://doi.org/10.3390/ph19010131 - 12 Jan 2026
Viewed by 95
Abstract
Background and Objectives: Many “food–medicine homologous traditional Chinese medicines (TCMs)” have been shown to delay vascular aging. In this study, we will select “food–medicine homologous TCMs” with the most potential to delay human-origin vascular aging and predict their core targets and mechanisms. [...] Read more.
Background and Objectives: Many “food–medicine homologous traditional Chinese medicines (TCMs)” have been shown to delay vascular aging. In this study, we will select “food–medicine homologous TCMs” with the most potential to delay human-origin vascular aging and predict their core targets and mechanisms. Methods: Human-origin vascular-aging-related genes were screened from the NCBI and Aging Atlas databases. Candidate “food–medicine homologous TCMs” were initially filtered by constructing a protein–protein interaction network, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Key targets were validated in the Gene Expression Omnibus database and further screened by least absolute shrinkage and a selection operator. Finally, molecular docking and molecular dynamics simulations identified core targets. Results: Ten core “food–medicine homologous TCMs” with potential to delay human-derived vascular aging were identified: Crocus Sativus L., Glycyrrhiza uralensis Fisch., Chrysanthemum morifolium Ramat., Astragalus membranaceus (Fisch.) Bunge, Sophora japonica L., Hippophae rhamnoides L., Portulaca oleracea L., Lonicera japonica Thunb., Citrus aurantium L. var. amara Engl., and Morus alba L. Further analysis indicated that β-Carotene within these core “food–medicine homologous TCMs” may represent a potential active component targeting matrix metalloproteinase-1, with its action potentially linked to the interleukin-17 signaling pathway. The present study highlights the new hypothesis that immunosenescence (Th17/IL-17) is involved in vascular aging, suggesting that the top ten core “food–medicine homologous TCMs” may delay vascular aging by regulating immune cell function. Conclusions: The top ten “food–medicine homologous TCMs” provide potential candidates for functional products that delay vascular aging and provide computationally predicted mechanistic insights and a scientific basis for novel therapies. Full article
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13 pages, 1222 KB  
Article
Whole-Plant Trait Integration Underpins High Leaf Biomass Productivity in a Modern Mulberry (Morus alba L.) Cultivar
by Bingjie Tu, Nan Xu, Juexian Dong and Wenhui Bao
Horticulturae 2026, 12(1), 67; https://doi.org/10.3390/horticulturae12010067 - 6 Jan 2026
Viewed by 173
Abstract
Understanding yield improvement in horticultural systems depends on elucidating how multiple plant traits operate in concert to sustain productivity. Mulberry (Morus alba L.) provides a suitable model for examining such whole-plant integration. Under cold-region field conditions, a modern high-yield cultivar (‘Nongsang 14’) [...] Read more.
Understanding yield improvement in horticultural systems depends on elucidating how multiple plant traits operate in concert to sustain productivity. Mulberry (Morus alba L.) provides a suitable model for examining such whole-plant integration. Under cold-region field conditions, a modern high-yield cultivar (‘Nongsang 14’) was compared with a traditional cultivar (‘Lusang 1’). Measurements encompassed canopy architecture, biomass allocation between roots and shoots, leaf economic traits, and gas-exchange parameters, allowing trait coordination to be evaluated across structural and physiological dimensions. Multivariate profiling—Principal Component Analysis (PCA) and correlation networks—was used to characterise phenotypic integration. The modern cultivar’s superior productivity emerged as a coordinated “acquisitive” trait syndrome. This strategy couples a larger canopy (higher LAI) and nitrogen-rich foliage (higher LNC) with greater stomatal conductance (Gs), operating together with reduced root-to-shoot allocation. These features form a tightly connected network where structural investment and physiological upregulation are synchronised to maximise carbon gain. These findings provide a whole-plant framework for interpreting high productivity, offering guidance for breeding programmes that target trait integration rather than single-trait optimisation. Full article
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19 pages, 306 KB  
Article
In Vitro and In Situ Evaluation of White Mulberry (Morus alba) Pomace and Leaf: Fermentation Kinetics, Digestibility, and Potential as Alternative Ruminant Feed Sources
by Zekeriya Safa İnanç and Huzur Derya Arik
Fermentation 2025, 11(12), 692; https://doi.org/10.3390/fermentation11120692 - 12 Dec 2025
Viewed by 517
Abstract
Mulberry (Morus alba) by-products represent underutilized feed resources with potential for ruminant nutrition. This study evaluated the rumen fermentation kinetics and rumen digestibility of dried mulberry pomace (MP) and leaf (ML) to determine optimal inclusion strategies in dairy cattle diets. Mulberry [...] Read more.
Mulberry (Morus alba) by-products represent underutilized feed resources with potential for ruminant nutrition. This study evaluated the rumen fermentation kinetics and rumen digestibility of dried mulberry pomace (MP) and leaf (ML) to determine optimal inclusion strategies in dairy cattle diets. Mulberry pomace (MP) and mulberry leaf (ML) were sun-dried and incorporated at 50% substitution levels into total mixed rations (TMR) with varying concentrations (30%, 35%, 40%, 45%, and 50%) of neutral detergent fiber (NDF). This created ten treatment groups: 30NP through 50NP (pomace-supplemented, where the number represents basal TMR NDF%) and 30NL through 50NL (leaf-supplemented), plus control groups containing only MP or ML and five basal TMR controls (30N through 50N). Rumen fluid was collected from two non-lactating Holstein cows fitted with ruminal cannulas. Chemical analysis revealed that ML contained 19% crude protein and 27.4% NDF, while MP contained 14.9% crude protein and 35.8% NDF. The highest gas production was observed in the 45NP (43.20 mL) and 50NL (43.50 mL) groups. Results demonstrated that MP achieved optimal fermentation when combined with 40–45% NDF TMR (maximum total volatile fatty acid (VFA): 88.86 mmol/L in 40NP at 48 h), whereas ML performed best with 45% NDF TMR (45NL: 88.03 mmol/L total VFA), indicating these as the most promising treatment combinations for ruminant feeding systems pending in vivo validation. Acetate proportions were higher in ML groups (84–96%), while propionate ratios were elevated in MP groups. Both materials maintained optimal ruminal pH (6.2–6.8). In vitro NDF digestibility was significantly higher for ML, with differences increasing from 2.97% at 2 h to 16.44% at 240 h. In situ degradation of MP was nearly complete at 48 h, while ML reached maximum degradation at 24 h. These findings indicate the potential of MP and ML as valuable alternative feed sources for ruminants, particularly in TMRs containing 40–45% NDF. Full article
(This article belongs to the Special Issue Ruminal Fermentation: 2nd Edition)
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19 pages, 3542 KB  
Article
Regional Variation in Mulberry Leaf Metabolites: A Combined Metabolomic and Environmental Analysis of Biosynthetic Drivers
by Yao Zhou, Meiqi Li, Jinpeng Zhao, Lixia Yang, Fengxia Li, Jingtian Xu, Jingtian Chen, Yinyin Chen, Dongbei Xu, Dongju Feng, Wei Wu and Kai Hou
Metabolites 2025, 15(11), 728; https://doi.org/10.3390/metabo15110728 - 6 Nov 2025
Cited by 1 | Viewed by 670
Abstract
Background: Morus alba L. (family Moraceae) is widely cultivated across the world and is well-known for its medicinal and nutritional value, especially its leaves. This study investigates the regional variation in mulberry leaf metabolites, focusing on alkaloids and flavonoids, and explores the [...] Read more.
Background: Morus alba L. (family Moraceae) is widely cultivated across the world and is well-known for its medicinal and nutritional value, especially its leaves. This study investigates the regional variation in mulberry leaf metabolites, focusing on alkaloids and flavonoids, and explores the influence of climatic and environmental factors on their biosynthesis using an integrated metabolomic and environmental analysis. Mulberry leaves, known for their medicinal and nutritional value, were collected from six regions across China, including Sichuan, Xinjiang, and Tibet. Methods: Untargeted metabolomics via UHPLC-MS was conducted. Differential metabolites were identified through multivariate analysis and annotated using the KEGG database. Redundancy analysis was used to link metabolite profiles with climatic data. Results: Mulberry leaves from six Chinese regions showed significant variation in total flavonoid content (TFC), total polyphenol content (TPC), and 1-Deoxynojirmycin (DNJ), with Tibet having the highest TFC and TPC, and Panzhihua the highest DNJ. Metabolomic analysis identified 3794 metabolites, revealing distinct regional clustering. A total of 79 differential metabolites were identified, which are enriched in pathways such as galactose metabolism and phenylalanine biosynthesis. Environmental factors, especially bio3, bio10, bio2, bio5, and bio20, strongly influenced metabolite profiles. Conclusions: The biosynthesis and accumulation of secondary metabolites in mulberry leaves are significantly influenced by region-specific environmental factors, particularly temperature, precipitation, and light. The identified differential metabolites are mainly enriched in galactose metabolism, arginine, and proline metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. These pathways are closely associated with plant stress responses and the synthesis of secondary metabolites. The pronounced regional differences in metabolite profiles underscore the critical role of environmental factors in determining the chemical composition of mulberry leaves. This research provides valuable insights into the influence of climatic factors affecting the chemical composition of plants. It lays a theoretical foundation for the quality assessment and grading of mulberry leaves, providing scientific guidance for their targeted cultivation and utilization. Full article
(This article belongs to the Section Plant Metabolism)
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20 pages, 10204 KB  
Article
Synergistic Effects of Anthocyanin-Enriched Morus alba L. Extract and Vitamin C: Promising Nutraceutical Ingredients in Functional Food Development for Neuroprotection
by Nootchanat Mairuae, Jinatta Jittiwat, Kwanjit Apaijit, Parinya Noisa, Gang Bai, Yuanyuan Hou and Nut Palachai
Foods 2025, 14(21), 3630; https://doi.org/10.3390/foods14213630 - 24 Oct 2025
Viewed by 767
Abstract
Oxidative stress-induced mitochondrial dysfunction and apoptosis are critical factors in the pathogenesis of neurodegenerative diseases. This study investigated the synergistic neuroprotective effects of anthocyanin-enriched Morus alba L. extract combined with vitamin C (MAC) against hydrogen peroxide (H2O2)-induced oxidative stress [...] Read more.
Oxidative stress-induced mitochondrial dysfunction and apoptosis are critical factors in the pathogenesis of neurodegenerative diseases. This study investigated the synergistic neuroprotective effects of anthocyanin-enriched Morus alba L. extract combined with vitamin C (MAC) against hydrogen peroxide (H2O2)-induced oxidative stress in SH-SY5Y neuronal cells. Exposure to H2O2 triggered excessive reactive oxygen species (ROS) production and apoptosis, whereas treatment with MAC markedly alleviated these effects. Biochemical analyses revealed that MAC significantly reduced malondialdehyde (MDA) and enhanced the activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), thereby contributing to improved redox balance. Furthermore, MAC modulated apoptosis-related signaling by upregulating extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), while downregulating the pro-apoptotic protein Bcl-2-associated X (BAX) and cleaved caspase-3. Collectively, these findings demonstrate that MAC acts synergistically as a promising nutraceutical ingredient, supporting the development of functional foods for the prevention or mitigation of oxidative stress-related neurodegenerative disorders. Full article
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24 pages, 5386 KB  
Article
Kuwanon A Targeted YWHAB in Hepatocellular Carcinoma Cells to Inhibit the Raf/MEK/ERK Signaling Pathway
by Jingyang Xu, Hongbo Chang, Yongzhao Wang, Yi Du, Liping Zhong and Hongjuan Cui
Cells 2025, 14(19), 1487; https://doi.org/10.3390/cells14191487 - 23 Sep 2025
Viewed by 908
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and the lung is one of the most frequent metastatic sites for HCC. In this study, we aimed to identify a mild active substance in Morus alba L. that can inhibit [...] Read more.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and the lung is one of the most frequent metastatic sites for HCC. In this study, we aimed to identify a mild active substance in Morus alba L. that can inhibit the pulmonary metastasis of HCC and reduce the drug resistance of clinical therapies. Further deepen the understanding of the anti-cancer functions of the mulberry active substances. In this study, we have screened and identified a flavonoid compound extracted from the root bark of the Morus alba L. named Kuwanon A (KA). Our research demonstrated that KA directly targeted the YWHAB (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta) and mediated its dimer dissociation. Thereby inhibiting the MAPK pathway and affecting downstream biological functions, including cell cycle arrest and migration/invasion inhibition. The experiment results proved that KA could inhibit the proliferation and metastasis of highly metastatic HCC cells both in vitro and in vivo. Additionally, when KA was combined with the clinical drug sorafenib, it exhibited a synergistic effect in inhibiting HCC cell proliferation, migration, and invasion. In conclusion, KA demonstrated a favorable anti-tumor effect in HCC cells. Full article
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20 pages, 4041 KB  
Article
Response of Rhizosphere Microenvironment of Mulberry (Morus alba L.) to Different Cultivars
by Chuanjie Chen, Haiyang Zhang, Xiaoyan Liang, Meng Li and Yinyu Gu
Microorganisms 2025, 13(9), 2157; https://doi.org/10.3390/microorganisms13092157 - 16 Sep 2025
Viewed by 813
Abstract
Soil microbiomes have a crucial role in mulberry development; however, the correlation between the mulberry genotype and rhizosphere microenvironment has not been explored. The rhizosphere microbial community structure and function of rizhosphere bacteria and fungi in five mulberry cultivars and their interaction with [...] Read more.
Soil microbiomes have a crucial role in mulberry development; however, the correlation between the mulberry genotype and rhizosphere microenvironment has not been explored. The rhizosphere microbial community structure and function of rizhosphere bacteria and fungi in five mulberry cultivars and their interaction with soil chemical properties and agronomic traits were analyzed using Illumina-based sequencing. We demonstrated that the composition, structure, and assembly processes of rhizosphere bacteria and fungi exhibited significant differences among mulberry cultivars, and their response to soil chemical traits and leaf yield also varies. The correlations in the bacterial communities were more complex than in the fungal communities among the five cultivars. During the assembly process, bacteria were more stable than fungi. Penicillium and Phytophthora showed a positive correlation with leaf yield and were significantly enriched in the Canghai 12 rhizosphere soil, which exhibited the highest leaf production. Bacillus was a bacterium that showed a significant positive correlation with leaf yield. The saprotrophs exhibited the largest guild in terms of operational taxonomic unit richness. This research indicated that the mulberry genotype is one of the dominant factors in rhizosphere microorganism recruitment and assembly. These findings provide new insights into the complex microbial community soil–plant interaction and probiotic screening. Full article
(This article belongs to the Section Plant Microbe Interactions)
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31 pages, 9126 KB  
Article
Integrated Phytochemical Profiling, GC-MS Characterization, and In Silico, In Vitro Evaluation of Synergistic Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Morus alba Bark and Pinus densiflora Extracts with Methyl Gallate
by Muhammad Aleem Abbas, Ga-Yeong Lee, Syed Al Jawad Sayem, Seung-Jin Lee and Seung-Chun Park
Antioxidants 2025, 14(9), 1114; https://doi.org/10.3390/antiox14091114 - 13 Sep 2025
Cited by 1 | Viewed by 1990
Abstract
The growing challenge of antibiotic resistance and inflammation-related disorders calls for safe, multi-target therapeutic strategies. Morus alba (MOAL) and Pinus densiflora (PIDE) are known for their medicinal properties, yet their combined potential with methyl gallate (MG) has not been fully explored. In this [...] Read more.
The growing challenge of antibiotic resistance and inflammation-related disorders calls for safe, multi-target therapeutic strategies. Morus alba (MOAL) and Pinus densiflora (PIDE) are known for their medicinal properties, yet their combined potential with methyl gallate (MG) has not been fully explored. In this study, the phytochemical composition of MOAL and PIDE was characterized using GC–MS, and their combined antimicrobial, antioxidant, and anti-inflammatory activities were evaluated. Hydroethanolic extracts were prepared and assessed for antioxidant activity (DPPH assay), antibacterial activity (disk diffusion, MIC, time kill), and nitric oxide (NO) suppression in Lipopolysaccharide (LPS)-stimulated macrophages, alongside MTT cytotoxicity screening. MOAL exhibited a higher extraction efficiency, reaching 500 mg/mL at 4 h, whereas Pinus achieved 450 mg/mL at the same time point. Both exhibited a diverse and abundant phytochemical profile. The optimized blend (MOAL:PIDE:MG, 1:1:0.1) demonstrated significantly enhanced bioactivity, with over 90% DPPH scavenging with the low IC50 value (66.62 mg/mL), potent inhibition of both Gram-positive and Gram-negative bacteria, and the strongest effect against Staphylococcus aureus (264 μg/mL). Time-kill assays confirmed rapid bactericidal action, and NO production was reduced by approximately 75% without cytotoxicity. Molecular docking identified a lead multi-target compound exhibiting strong binding affinities to COX-2, TNF-α, and Keap1, supporting its observed anti-inflammatory and antioxidant potential. These findings highlight the promise of synergistic phytochemical formulations as broad-spectrum, multifunctional therapeutic candidates, supporting further in vivo and clinical validation. Full article
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38 pages, 7697 KB  
Article
Local Climate and Cultivation Practice Shape Total Protein and Phenolic Content of Mulberry (Morus sp.) Leaves in Sub-Mediterranean and Sub-Pannonian Regions of Slovenia
by Špela Jelen, Martin Kozmos, Jan Senekovič, Danijel Ivajnšič, Silvia Cappellozza and Andreja Urbanek Krajnc
Horticulturae 2025, 11(9), 1096; https://doi.org/10.3390/horticulturae11091096 - 10 Sep 2025
Viewed by 1502
Abstract
Mulberry (Morus sp.) trees, traditionally cultivated for their leaves used in sericulture, have recently gained recognition for their adaptability and valuable ecosystem services. The biochemical composition of mulberry leaves varies both qualitatively and quantitatively, depending on genotype, environmental conditions, and cultivation practices. [...] Read more.
Mulberry (Morus sp.) trees, traditionally cultivated for their leaves used in sericulture, have recently gained recognition for their adaptability and valuable ecosystem services. The biochemical composition of mulberry leaves varies both qualitatively and quantitatively, depending on genotype, environmental conditions, and cultivation practices. This study aimed to (1) identify differences in old local white (M. alba L.) and black mulberry (M. nigra L.) leaves, (2) perform a chemotype analysis of monitored local varieties, and (3) evaluate the influence of selected bioclimatic factors and pruning practices on the biochemical composition of leaves of white mulberry trees across Slovenian mesoregions. Black mulberry exhibited a higher phenolic content, particularly caffeoylquinic acid derivatives (16.05 mg/g dry weight (DW)), while white mulberry contained more quercetin glycosides (6.04 mg/g DW). Ward’s clustering identified three chemotypes, two of which had elevated protein and hydroxycinnamic acid levels, making them particularly suitable for silkworm feeding. Considering pruning practices of white mulberries, we determined significantly increased protein contents in yearly pruned trees (187.24 mg/g DW). Principal component analysis revealed interactions between bioclimatic, morphological, and biochemical factors, distinctly separating mulberries from the Sub-Mediterranean and Sub-Pannonian macroregions. White mulberries from Sub-Pannonian regions accumulated more caffeoylquinic acids in leaves under lower precipitation and total insolation, while those from Sub-Mediterranean regions exhibited higher kaempferol derivatives due to photo-thermal stress. These findings highlight the influence of climate and pruning on mulberry biochemical diversity and adaptation. Full article
(This article belongs to the Special Issue Horticulture from an Ecological Perspective)
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18 pages, 797 KB  
Review
Phytochemical Composition, Bioactive Compounds, and Antidiabetic Potential of Four Medicinal Plants Native to the UAE: Capparis spinosa, Citrullus colocynthis, Morus alba, and Rhazya stricta
by Seham M. Al Raish, Razan S. Almasri, Alaa S. Bedir and Aya A. Elkahwagy
Biology 2025, 14(9), 1146; https://doi.org/10.3390/biology14091146 - 30 Aug 2025
Viewed by 2741
Abstract
This review highlights the significant therapeutic properties of four indigenous plants in the United Arab Emirates. These include Capparis spinosa L. (family: Capparaceae), commonly known as caper and locally referred to as Kabir; Citrullus colocynthis (L) Schrad. (family: Cucurbitaceae), known in English as [...] Read more.
This review highlights the significant therapeutic properties of four indigenous plants in the United Arab Emirates. These include Capparis spinosa L. (family: Capparaceae), commonly known as caper and locally referred to as Kabir; Citrullus colocynthis (L) Schrad. (family: Cucurbitaceae), known in English as bitter apple and locally as Alhanzal; Morus alba L. (family: Moraceae), referred to as white mulberry and locally named Firsad; and Rhazya stricta Decne. (family: Apocynaceae), commonly called harmal-e-shami and known locally as Alhi-rimi. These species are traditionally used for various ethnobotanical purposes and are important components of the region’s flora, such as managing diabetes and associated metabolic disorders. These plants contain diverse bioactive compounds with notable pharmacological activities. For example, caper exhibits antidiabetic effects through flavonoids such as quercetin and kaempferol, which enhance insulin sensitivity and lower blood glucose levels. Bitter apple is rich in cucurbitacins and alkaloids that lower glycated hemoglobin and support pancreatic β-cell function. White mulberry contains chlorogenic acid, rutin, and 1-deoxynojirimycin, which improve glucose uptake, inhibit α-glucosidase, and reduce oxidative stress. Harmal-e-shami exhibits variable antidiabetic activity, including dipeptidyl peptidase-IV inhibition and enhancement of glucagon-like peptide-1 secretion, which is influenced by the type and dosage of the extract. Despite these promising effects, challenges remain in standardization, phytochemical variability, and clinical validation. This review underscores the therapeutic potential of these plants and recommends further research for their integration into sustainable, plant-based diabetes management strategies. Full article
(This article belongs to the Special Issue Plant Natural Products: Mechanisms of Action for Promoting Health)
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23 pages, 4402 KB  
Article
Elucidating Key Components and Mechanisms Underlying the Synergistic Anti-Type 2 Diabetes Effect of Morus alba L. and Siraitia grosvenorii Combination: An Integrated In Vitro Enzymology, Untargeted Metabolomics, and Network Pharmacology Approach
by Fang He, Shenglan Su, Ruihan Song, Yan Li, Luyan Zou, Zongjun Li, Yu Xiao, Aixiang Hou, Ke Li and Yuanliang Wang
Antioxidants 2025, 14(9), 1065; https://doi.org/10.3390/antiox14091065 - 29 Aug 2025
Cited by 3 | Viewed by 1197
Abstract
Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for [...] Read more.
Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for T2DM intervention. We evaluated the in vitro inhibitory activities of MLSG, ML, and SG on α-amylase and α-glucosidase, alongside antioxidant capacity assessments through DPPH/ABTS radical scavenging, reducing power, and FRAP assays. Bioactive metabolites were identified using non-targeted metabolomics, while core targets and pathways were predicted using network pharmacology and validated through molecular docking. The results reveal MLSG’s significantly enhanced inhibition of α-amylase (IC50 = 14.06 mg/mL) and α-glucosidase (IC50 = 0.02 mg/mL) compared to individual extracts, exhibiting 1.3–15.5-fold higher potency with synergistic effects (combination index < 1). MLSG also showed improved antioxidant capacity, outperforming SG in DPPH/ABTS+ scavenging and reducing power (p < 0.05), and surpassing ML in ABTS+ scavenging, reducing power, and FRAP values (p < 0.05). Metabolomics identified 26 MLSG-derived metabolites with anti-T2DM potential, and network analysis pinpointed 26 active components primarily targeting STAT3, AKT1, PIK3CA, EGFR, and MAPK1 to regulate T2DM pathways. Molecular docking confirmed strong binding affinities between these components and core targets. Collectively, MLSG exerts potent synergistic anti-T2DM effects through dual-enzyme inhibition, elevated antioxidant activity, and multi-target pathway regulation, providing a solid foundation for developing MLSG as functional food ingredients. Full article
(This article belongs to the Special Issue Potential Health Benefits of Dietary Antioxidants)
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22 pages, 6284 KB  
Article
Integrative Evidence on Mulberry Extract for Modulating Metabolic Risk Factors Associated with Vascular Dementia
by Jui-Ting Yu, Chen-Pi Li, Yao Hsiao, Kuan-Po Cheng and Ru-Yin Tsai
Int. J. Mol. Sci. 2025, 26(17), 8380; https://doi.org/10.3390/ijms26178380 - 28 Aug 2025
Viewed by 3546
Abstract
Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. [...] Read more.
Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. Recent research has identified a connection between metabolic syndrome and cognitive disorders such as mild cognitive impairment and vascular dementia (VaD). Mulberry (Morus alba L.) is a natural source of bioactive compounds with antioxidant, anti-inflammatory, and lipid-regulating properties. This meta-analysis assessed the potential of mulberry extract as an adjunctive treatment for metabolic risk factors linked to vascular dementia. We systematically reviewed randomized controlled trials (RCTs) published up to May 2025 that compared mulberry extract to placebo or standard care in adults with metabolic disorders. Fifteen trials including 1202 participants met the inclusion criteria. The primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, low-density lipoprotein cholesterol (LDL), triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers. Aspartate aminotransferase (AST) improved, whereas alanine aminotransferase (ALT) showed no significant change. Subgroup analyses revealed that greater benefits were associated with shorter treatment durations and doses below 500 milligrams per day. Furthermore, extracts from different parts of the mulberry plant showed varying effects on lipid and glucose metabolism. None of the included trials directly measured cognitive or neurovascular outcomes, so any potential neurovascular protection is inferred from changes in metabolic and inflammatory markers rather than demonstrated. In summary, these findings suggest that mulberry extract may be a promising complementary approach for managing metabolic risk factors in people at risk for VaD. However, further large-scale and rigorously designed studies are required to confirm its clinical benefits and to identify the most effective preparations. Full article
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23 pages, 13740 KB  
Article
Mulberroside A: A Multi-Target Neuroprotective Agent in Alzheimer’s Disease via Cholinergic Restoration and PI3K/AKT Pathway Activation
by Jin Li, Jiawen Wang, Yaodong Li, Jingyi Guo, Ziliang Jin, Shourong Qiao, Yunxia Zhang, Guoyin Li, Huazhen Liu and Changjing Wu
Biology 2025, 14(9), 1114; https://doi.org/10.3390/biology14091114 - 22 Aug 2025
Viewed by 977
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)—a bioactive glycoside from Morus alba [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, with current therapies offering only limited symptomatic relief and lacking disease-modifying efficacy. Addressing this critical therapeutic gap, natural multi-target compounds like mulberroside A (MsA)—a bioactive glycoside from Morus alba L.—present promising alternatives. This study investigated MsA’s neuroprotective potential using scopolamine-induced AD-like mice and N2a/APP695swe cells. In vivo, MsA significantly ameliorated cognitive deficits and neuronal loss, concurrently enhancing cholinergic neurotransmission through increased acetylcholine levels and inhibited acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) activities. MsA also upregulated neurotrophic factors (BDNF, CREB) in critical brain regions. In vitro, MsA restored cholinergic function, mitigated oxidative stress, and crucially reduced amyloid-β (Aβ) production by dual regulation of APP processing: promoting the non-amyloidogenic pathway via ADAM10 upregulation and inhibiting the amyloidogenic pathway via suppression of BACE1 and γ-secretase components. Mechanistically, these multi-target benefits were mediated by MsA’s activation of the PI3K/AKT pathway, which triggered downstream inhibitory phosphorylation of GSK3β—directly reduced tau hyperphosphorylation—and activation of CREB/BDNF signaling. Collectively, our findings demonstrate that MsA confers comprehensive neuroprotection against AD pathology by simultaneously targeting cholinergic dysfunction, oxidative stress, Aβ accumulation, tau phosphorylation, and impaired neurotrophic signaling, highlighting its strong therapeutic candidacy. Full article
(This article belongs to the Section Neuroscience)
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16 pages, 2650 KB  
Article
Inhibition of Tyrosinase and Melanogenesis by a White Mulberry Fruit Extract
by Nuttawadee Prasawang, Nareerat Sutjarit, Athisri Sitthipunya, Prasit Suwannalert, Wutarak Monsuwan and Nisamanee Charoenchon
Int. J. Mol. Sci. 2025, 26(15), 7589; https://doi.org/10.3390/ijms26157589 - 6 Aug 2025
Cited by 2 | Viewed by 3559
Abstract
Ultraviolet B (UVB) radiation is a key factor in the overproduction of melanin in the skin. Melanocytes produce melanin through melanogenesis to protect the skin from UVB radiation-induced damage. However, excessive melanogenesis can lead to hyperpigmentation and increase the risk of malignant melanoma. [...] Read more.
Ultraviolet B (UVB) radiation is a key factor in the overproduction of melanin in the skin. Melanocytes produce melanin through melanogenesis to protect the skin from UVB radiation-induced damage. However, excessive melanogenesis can lead to hyperpigmentation and increase the risk of malignant melanoma. Tyrosinase is the rate-limiting enzyme in melanogenesis; it catalyzes the oxidation of tyrosine to 3,4-dihydroxy-L-phenylalanine and subsequently to dopaquinone. Thus, inhibiting tyrosinase is a promising strategy for preventing melanogenesis and skin hyperpigmentation. White mulberry (Morus alba L.) is rich in antioxidants, and mulberry fruit extracts have been used as cosmetic skin-lightening agents. However, data on the capacity of mulberry fruit extracts to inhibit tyrosinase under UVB radiation-induced melanogenic conditions remain scarce, especially in an in vivo model. In this study, we evaluated the effects of a mulberry crude extract (MCE) on UVB radiation-induced melanogenesis in B16F10 melanoma cells and zebrafish embryos. The MCE significantly reduced tyrosinase activity and melanogenesis in a dose-dependent manner without inducing cytotoxicity. These effects are likely attributable to the antioxidant constituents of the extract. Our findings highlight the potential of this MCE as an effective tyrosinase inhibitor for the prevention of UVB radiation-induced skin hyperpigmentation. Full article
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Article
Influence of Morus alba Leaves Extract on Human Erythrocytes
by Stefano Putaggio, Annamaria Russo, Giuseppe Tancredi Patanè, Antonella Calderaro, Santa Cirmi, Ivana Verboso, Giuseppina Laganà, Silvana Ficarra, Davide Barreca, Françisco Raymo and Ester Tellone
Biology 2025, 14(8), 1005; https://doi.org/10.3390/biology14081005 - 5 Aug 2025
Viewed by 1153
Abstract
Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect [...] Read more.
Morus alba L. (MA) is a member of the Moraceae family, known as “white mulberry”. Due to the high levels of bioactive compounds, mulberry plants can be considered a good source of nutrients and antioxidant compounds. Our study aims to analyze the effect of MA extract leaves on erythrocytes, focusing on its action on metabolism and membrane integrity. The choice of erythrocytes as a study model is based on their metabolic simplicity and their easy availability. Cell viability, following exposure of the cells to the extract, was evaluated by hemolysis, methemoglobin, caspase 3 activity and flow cytofluorimetric analysis; in addition, the effect of the pretreatment with the MA was detected after incubation of erythrocytes with different stressors. The impact on cell metabolism was evaluated by measuring anion flux kinetics, ATP levels and phosphatase activity. The results obtained show a peculiar (double) effect of the extract, which, on the one hand, probably by exploiting its component with antioxidant properties, protects the cell membrane by accumulating on the bilayer. On the other hand, the alteration of anion exchange could lead to the triggering of apoptosis and consequent cell death. The hypotheses, although excluded by our data, all point toward a beneficial and protective action of the extract on the health and vitality of RBCs. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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