Isolation and Structure Analysis of Chitin Obtained from Different Developmental Stages of the Mulberry Silkworm (Bombyx mori).

Chitin, a ubiquitous biopolymer, holds paramount scientific and economic significance. Historically, it has been primarily isolated from marine crustaceans. However, the surge in demand for chitin and the burgeoning interest in biopolymers have necessitated the exploration of alternative sources. Among these methods, the mulberry silkworm (Bombyx mori) has emerged as a particularly intriguing prospect. To isolate chitin from Bombyx mori, a chemical extraction methodology was employed. This process involved a series of meticulously orchestrated steps, including Folch extraction, demineralization, deproteinization, and decolorization. The resultant chitin was subjected to comprehensive analysis utilizing techniques such as attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), 13C nuclear magnetic resonance (NMR) spectroscopy, and wide-angle X-ray scattering (WAXS). The obtained results allow us to conclude that the Bombyx mori represents an attractive alternative source of α-chitin.

Pharmacokinetic studies, molecular docking, and molecular dynamics simulations of phytochemicals from Morus alba: a multi receptor approach for potential therapeutic agents in colorectal cancer.

This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.

Characterizations of White Mulberry, Sea-Buckthorn, Garlic, Lily of the Valley, Motherwort, and Hawthorn as Potential Candidates for Managing Cardiovascular Disease-In Vitro and Ex Vivo Animal Studies.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dysfunction. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, thromboembolism, and kidney and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta blockers, calcium inhibitors, ACE inhibitors, and anti-platelet drugs remains a second-line treatment after dietary interventions and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be effective and free from side effects, either taken together with or before the standard pharmacological intervention. Such herbal-originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea-buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (motherwort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and potential therapeutic option in the management of cardiovascular disorders.

The Effect of Phenolic-Rich Extracts of Rubus fruticosus, R. ulmifolius and Morus nigra on Oxidative Stress and Caco-2 Inhibition Growth.

Currently, a clear interest has been given to berries due to their richness in active metabolites, including anthocyanins and non-coloured phenolics. Therefore, the main aim of the present work is to investigate the phenolic profile, antioxidant abilities, and antiproliferative effects on normal human dermal fibroblasts (NHDF) and human colon carcinoma cell line (Caco-2) cells of phenolic-rich extracts from three red fruits highly appreciated by consumers: two species of blackberries (Rubus fruticosus and Rubus ulmifolius) and one species of mulberry (Morus nigra). A total of 19 different phenolics were identified and quantified by HPLC-DAD-ESI/MSn and HPLC-DAD, respectively. Focusing on the biological potential of the phenolic-rich extracts, all of them revealed notable scavenging abilities. Concerning the antiproliferative properties, R. fruticosus presented a cytotoxic selectivity for Caco-2 cells compared to NHDF cells. To deeper explore the biological potential, combinations with positive controls (ascorbic acid and 5-fluorouracil) were also conducted. Finally, the obtained data are another piece of evidence that the combination of phenolic-rich extracts from natural plants with positive controls may reduce clinical therapy costs and the possible toxicity of chemical drugs.

Molecular phylogeny and secondary structure analysis of hop stunt viroid (HSVd) associated with Mulberry (Morus alba) in India.

Hop stunt viroid (HSVd), a small, single stranded, circular, non-coding infectious RNA known to cause infection in various economically important crop plants. In the present investigation, a study was conducted in the southern part of Karnataka districts of India to detect the possible association of HSVd infection in mulberry plants. A total of 41 mulberry plants showing typical viroid-like symptoms along with asymptomatic samples were collected and screened using conventional Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) using a specific set of HSVd-Fw/ HSVd-Re primers. Out of 41 samples, the study confirmed the presence of HSVd in six samples of mulberry collected from Ramanagara (1 sample), Chikkaballapur (3 samples) and Doddaballapura (2 samples) regions with an expected HSVd amplicon size of ∼ 290-300 nucleotides. The mechanical transmission of HSVd was also confirmed on cucumber (cv. Suyo) seedlings through bioassay, which was reconfirmed by RT-PCR. The amplicons were cloned, sequenced, and the representative nucleotide sequences were deposited in the NCBI GenBank. Subsequently, molecular phylogenetic analysis showed that HSVd mulberry isolates from this study were most closely related to grapevine isolates, indicating a common origin. On the other hand, it was shown to belong to a different group from mulberry isolates so far reported from Iran, Italy, Lebanon, and China. The secondary structure analysis of HSVd mulberry Indian isolates exhibited substitutions in the terminal left, pathogenicity, and variable regions compared to those of the Indian grapevine isolates. As far as this study is concerned, HSVd was detected exclusively in some mulberry plants with viral-like symptoms, but the pathogenesis and symptom expression needs to be further investigated to establish the relationship between HSVd and the disease symptoms in the mulberry plants.

Investigating the molecular mechanism of Mori Cortex against osteosarcoma by bioinformatics analysis and in vitro experimental.

OBJECTIVE: To explore the therapeutic mechanism of Mori Cortex against osteosarcoma (OS), we conducted bioinformatics prediction followed by in vitro experimental validation. METHODS: Gene expression data from normal and OS tissues were obtained from the GEO database and underwent differential analysis. Active Mori Cortex components and target genes were extracted from the Traditional Chinese Medicine System Pharmacology database. By intersecting these targets with differentially expressed genes in OS, we identified potential drug action targets. Using the STRING database, a protein-protein interaction network was constructed. Subsequent analyses of these intersected genes, including Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, were performed using R software to elucidate biological processes, molecular functions, and cellular components, resulting in the simulation of signaling pathways. Molecular docking assessed the binding capacity of small molecules to signaling pathway targets. In vitro validations were conducted on U-2 OS cells. The CCK8 assay was used to determine drug-induced cytotoxicity in OS cells, and Western Blotting was employed to validate the expression of AKT, extracellular signal-regulated kinases (ERK), Survivin, and Cyclin D1 proteins. RESULTS: Through differential gene expression analysis between normal and OS tissues, we identified 12,364 differentially expressed genes. From the TCSMP database, 39 active components and 185 therapeutic targets related to OS were derived. The protein-protein interaction network indicated that AKT1, IL-6, JUN, VEGFA, and CASP3 might be central targets of Mori Cortex for OS. Molecular docking revealed that the active compound Morusin in Mori Cortex exhibits strong binding affinity to AKT and ERK. The CCK8 assay showed that Morusin significantly inhibits the viability of U-2 OS cells. Western Blot demonstrated a reduction in the p-AKT/AKT ratio, the p-ERK/ERK ratio, Survivin, and Cyclin D1. CONCLUSION: Mori Cortex may exert its therapeutic effects on OS through multiple cellular signaling pathways. Morusin, the active component of Mori Cortex, can inhibit cell cycle regulation and promote cell death in OS cells by targeting AKT/ERK pathway.

Mulberry Leaf-Derived Morin Activates ß-Catenin by Binding to Frizzled7 to Promote Intestinal Stem Cell Expansion upon Heat-Stable Enterotoxin b Injury.

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/ß-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated ß-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.

Exploitation of Aureobasidium pullulans NRRL Y-2311-1 xylanase in mulberry and rice flours-based gluten-free cookie formulation: Effects on dough properties and cookie characteristics.

Xylanases are mainly utilized in bakery industry for the hydrolysis of dietary fiber-based fractions. Their applications in gluten-free products have not been considered before. In the present study, the xylanase produced by Aureobasidium pullulans NRRL Y-2311-1 was utilized in a mulberry and rice flours-based gluten-free cookie formulation for the first time. Effects of various xylanase concentrations on gluten-free dough rheology and cookie characteristics were elucidated. Only rice flour-based cookie and only wheat flour-based cookie formulations were also prepared as comparison. Incorporation of xylanase into all cookie recipes resulted in softer cookie doughs with lower absolute stickiness. The hardness and absolute stickiness of the cookie doughs prepared by the mixture of mulberry and rice flours decreased by the addition of the enzyme into the formulation in a concentration-dependent manner. Enzyme concentrations above 100 U/100 g flour did not provide statistically significant further changes on gluten-free cookie doughs. Incorporation of xylanase into the cookie recipes resulted in increased baking loss and spread ratio in an enzyme concentration-dependent manner for all cookie types. Hardness values of both types of gluten-free cookies decreased by xylanase incorporation. Different effects on fracturability were observed depending on the cookie type and enzyme concentration. Enzyme concentration of 100 U/100 g flour provided mulberry and rice flours-based cookies with a more flexible and softer structure. No significant effects on color parameters of cookies were observed by xylanase incorporation.

Structure-function relationship and biological activity of polysaccharides from mulberry leaves: A review.

Mulberry (Latin name "Morus alba L.") is a perennial deciduous tree in the family of Moraceae, widely distributed around the world. In China, mulberry is mainly distributed in the south and the Yangtze River basin. Its leaves can be harvested 3-6 times a year, which has a great resource advantage. Mulberry leaves are regarded as the homology of medicine and food traditional Chinese medicine (TCM). Polysaccharides, as its main active ingredients, have various effects, such as antioxidant, hypoglycemic, hepatoprotective, and immunomodulatory. This review summarizes the research progress in the extraction, purification, structural characterization, and structure-function relationship of polysaccharides from mulberry leaves in the last decade, hoping to provide a reference for the subsequent development and market application of polysaccharides from mulberry leaves.

Safe utilization and remediation potential of the mulberry-silkworm system in heavy metal-contaminated lands: A review.

Mulberry cultivation and silkworm rearing hold a prominent position in the agricultural industries of many Asian countries, contributing to economic growth, sustainable development, and cultural heritage preservation. Applying the soil-mulberry-silkworm system (SMSS) to heavy metal (HM)-contaminated areas is significant economically, environmentally, and socially. The ultimate goal of this paper is to review the main research progress of SMSS under HM stress, examining factors affecting its safe utilization and remediation potential for HM-contaminated soils. HM tolerance of mulberry and silkworms relates to their growth stages. Based on the standards for HM contaminants in various mulberry and silkworm products and the bioconcentration factor of HMs at different parts of SMSS, we calculated maximum safe Cd and Pb levels for SMSS application on contaminated lands. Several remediation practices demonstrated mulberry's ability to grow on barren lands, absorb various HMs, while silkworm excreta can adsorb HMs and improve soil fertility. Considering multiple factors influencing HM tolerance and accumulation, we propose a decision model to guide SMSS application in polluted areas. Finally, we discussed the potential of using molecular breeding techniques to screen or develop varieties better suited for HM-contaminated regions. However, actual pollution scenarios are often complex, requiring consideration of multiple factors. More large-scale applications are crucial to enhance the theoretical foundation for applying SMSS in HM pollution risk areas.

Environmentally related microcystin-LR-induced ovarian dysfunction via the CCL2-CCR10 axis in mice ameliorated by dietary mulberry.

Microcystin-LR (MC-LR) is a reproductive toxin produced by cyanobacteria in the aquatic environment and can be ingested by humans through drinking water and the food chain, posing a threat to human reproductive health. However, the toxic mechanisms and prospective interventions for MC-LR-induced ovarian dysfunction at environmental doses are unknown. The mulberry fruit is a traditional natural product of plant origin, with various pharmacological effects, such as antioxidant and anti-inflammatory effects. Here, mice were exposed to MC-LR (10, 100 µg/L) in drinking water for 90 days, during which mice were gavage 600 mg/kg/week of mulberry fruit extract (MFE). It was found that MC-LR can accumulate in mouse ovaries, causing sexual hormone disturbance, inflammatory infiltration, and ovarian pathological damage. Results from RNA-seq were shown that CCL2, a chemokine associated with inflammatory response, was significantly increased in mouse ovary after MC-LR exposure. Further investigation revealed that MC-LR exposure aggravates apoptosis of granulosa cells via the CCL2-CCR10 axis-mediated Jak/Stat pathway. Importantly, MFE can significantly ameliorate these ovarian dysfunction phenotypes by inhibiting the activation of the CCL2-CCR10 axis. This study broadened new insights into the ovarian toxicity of MC-LR and clarified the pharmacological effects of mulberry fruit on ovarian function protection.

The biocontrol potentials of rhizospheric bacterium Bacillus velezensis K0T24 against mulberry bacterial wilt disease.

Mulberry bacterial wilt disease, caused by Ralstonia pseudosolanacearum, is a devastating soil-borne disease in the silk-mulberry-related industry. In this study, through high-throughput sequencing, we compared the rhizosphere bacterial composition of the mulberry-resistant cultivar (K10) and susceptible cultivar (G12), confirming Bacillus as a genus-level biomarker for K10. Next, twelve Bacillus spp. isolates, derived from the rhizosphere of K10, were screened for their antagonistic activity against R. pseudosolanacearum. The isolate showing strong antagonism was identified as B. velezensis K0T24 and selected for further analysis. The fermentation supernatant of B. velezensis K0T24 significantly inhibited the growth of R. pseudosolanacearum (82.47%) and the expression of its pathogenic genes. Using B. velezensis K0T24 in mulberry seedlings also increased defense enzyme activities and achieved a control efficacy of up to 55.17% against mulberry bacterial wilt disease. Collectively, our findings demonstrate the potential of B. velezensis K0T24 in suppressing mulberry bacterial wilt disease.

Transcriptomic and metabolomic analyses reveal the importance of ethylene networks in mulberry fruit ripening.

Mulberry (Morus alba L.) is a climacteric and highly perishable fruit. Ethylene has been considered to be an important trigger of fruit ripening process. However, the role of ethylene in the mulberry fruit ripening process remains unclear. In this study, we performed a comprehensive analysis of metabolomic and transcriptomic data of mulberry fruit and the physiological changes accompanying the fruit ripening process. Our study revealed that changes in the accumulation of specific metabolites at different stages of fruit development and ripening were closely correlated to transcriptional changes as well as underlying physiological changes and the development of taste biomolecules. The ripening of mulberry fruits was highly associated with the production of endogenous ethylene, and further application of exogenous ethylene assisted the ripening process. Transcriptomic analysis revealed that differential expression of diverse ripening-related genes was involved in sugar metabolism, anthocyanin biosynthesis, and cell wall modification pathways. Network analysis of transcriptomics and metabolomics data revealed that many transcription factors and ripening-related genes were involved, among which ethylene-responsive transcription factor 3 (MaERF3) plays a crucial role in the ripening process. The role of MaERF3 in ripening was experimentally proven in a transient overexpression assay in apples. Our study indicates that ethylene plays a vital role in modulating mulberry fruit ripening. The results provide a basis for guiding the genetic manipulation of mulberry fruits towards sustainable agricultural practices and improve post-harvest management, potentially enhancing the quality and shelf life of mulberry fruits for sustainable agriculture and forestry.

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling.

Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.

Ultrasound pretreatment enhances moisture migration and drying quality of mulberry via microstructure and cell-wall polysaccharides nanostructure modification.

The effects of ultrasound pretreatment (20 kHz, 30 W/L) on mulberries' texture, microstructure, characteristics of cell-wall polysaccharides, moisture migration, and drying quality were investigated over exposure times ranging from 15 to 45 min. Ultrasound induced softening of mulberry tissue, accompanied by an increase in water-soluble pectin and a decrease in chelate-soluble pectin and Na2CO3-soluble pectin concentrations. Noticeable depolymerization of the pectin nanostructure was observed in the pretreated mulberries, along with a decrease in molecular weight, attributed to side-chain structure cleavage. Ultrasound loosened the cell wall structure, increased free water content and freedom, thereby reducing water diffusion resistance. Ultrasound pretreatment reduced drying time by 11.2 % to 23.3 % at various processing times compared to controls. Due to significantly enhanced drying efficiency, the optimal pretreatment time (30 min) yielded dried mulberries with higher levels of total phenolics and total anthocyanins, along with an increased antioxidant capacity. The results of this study provide insights into the mechanisms by which ultrasound pretreatment can effectively enhance the mulberry drying process.

Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb).

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.

1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.

Mno-miR164a and MnNAC100 regulate the resistance of mulberry to Botrytis cinerea.

Although microRNAs (miRNAs) regulate the defense response of a variety of plant species against a variety of pathogenic fungi, the involvement of miRNAs in mulberry's defense against Botrytis cinerea has not yet been documented. In this study, we identified responsive B. cinerea miRNA mno-miR164a in mulberry trees. After infection with B. cinerea, the expression of mno-miR164a was reduced, which was fully correlated with the upregulation of its target gene, MnNAC100, responsible for encoding a transcription factor. By using transient infiltration/VIGS mulberry that overexpressed mno-miR164a or knocked-down MnNAC100, our study revealed a substantial enhancement in mulberry's resistance to B. cinerea when mno-miR164a was overexpressed or MnNAC100 expression was suppressed. This enhancement was accompanied by increased catalase (CAT) activity and reduced malondialdehyde (MDA) content. In addition, mno-miR164a-mediated inhibition of MnNAC100 enhanced the expression of a cluster of defense-related genes in transgenic plants upon exposure to B. cinerea. Meanwhile, MnNAC100 acts as a transcriptional repressor, directly suppressing the expression of MnPDF1.2. Our study indicated that the mno-miR164a-MnNAC100 regulatory module manipulates the defense response of mulberry to B. cinerea infection. This discovery has great potential in breeding of resistant varieties and disease control.

Mulberry Leaf Compounds and Gut Microbiota in Alzheimer's Disease and Diabetes: A Study Using Network Pharmacology, Molecular Dynamics Simulation, and Cellular Assays.

Recently, studies have reported a correlation that individuals with diabetes show an increased risk of developing Alzheimer's disease (AD). Mulberry leaves, serving as both a traditional medicinal herb and a food source, exhibit significant hypoglycemic and antioxidative properties. The flavonoid compounds in mulberry leaf offer therapeutic effects for relieving diabetic symptoms and providing neuroprotection. However, the mechanisms of this effect have not been fully elucidated. This investigation aimed to investigate the combined effects of specific mulberry leaf flavonoids (kaempferol, quercetin, rhamnocitrin, tetramethoxyluteolin, and norartocarpetin) on both type 2 diabetes mellitus (T2DM) and AD. Additionally, the role of the gut microbiota in these two diseases' treatment was studied. Using network pharmacology, we investigated the potential mechanisms of flavonoids in mulberry leaves, combined with gut microbiota, in combating AD and T2DM. In addition, we identified protein tyrosine phosphatase 1B (PTP1B) as a key target for kaempferol in these two diseases. Molecular docking and molecular dynamics simulations showed that kaempferol has the potential to inhibit PTP1B for indirect treatment of AD, which was proven by measuring the IC50 of kaempferol (279.23 µM). The cell experiment also confirmed the dose-dependent effect of kaempferol on the phosphorylation of total cellular protein in HepG2 cells. This research supports the concept of food-medicine homology and broadens the range of medical treatments for diabetes and AD, highlighting the prospect of integrating traditional herbal remedies with modern medical research.

Mulberry branch fiber improved lipid metabolism and egg yolk fatty acid composition of laying hens via the enterohepatic axis.

BACKGROUND: The utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens. RESULTS: Dietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition. CONCLUSIONS: The results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis. Video Abstract.