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1.
Med Oncol ; 41(6): 156, 2024 May 15.
Article En | MEDLINE | ID: mdl-38750377

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.


Colorectal Neoplasms , Molecular Docking Simulation , Molecular Dynamics Simulation , Morus , Phytochemicals , Morus/chemistry , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/pharmacokinetics , Humans , Proto-Oncogene Proteins c-akt/metabolism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , STAT3 Transcription Factor/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/chemistry , src-Family Kinases/metabolism
2.
Molecules ; 29(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38731405

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.


Bombyx , Chitin , Bombyx/chemistry , Animals , Chitin/chemistry , Chitin/isolation & purification , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction , Magnetic Resonance Spectroscopy , Morus/chemistry
3.
Nutrients ; 16(9)2024 Apr 27.
Article En | MEDLINE | ID: mdl-38732560

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.


Cardiovascular Diseases , Crataegus , Garlic , Hippophae , Morus , Plant Extracts , Crataegus/chemistry , Morus/chemistry , Animals , Hippophae/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Leonurus/chemistry , Elaeagnaceae/chemistry , Humans , Phytotherapy
4.
Nutrients ; 16(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38732606

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.


Antioxidants , Cell Proliferation , Fruit , Morus , Oxidative Stress , Phenols , Plant Extracts , Rubus , Humans , Caco-2 Cells , Plant Extracts/pharmacology , Rubus/chemistry , Morus/chemistry , Phenols/pharmacology , Phenols/analysis , Oxidative Stress/drug effects , Antioxidants/pharmacology , Cell Proliferation/drug effects , Fruit/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Chromatography, High Pressure Liquid
5.
Int J Mol Sci ; 25(10)2024 May 14.
Article En | MEDLINE | ID: mdl-38791372

Mulberry is a rapidly growing plant that thrives in diverse climatic, topographical, and soil types, spanning temperature and temperate countries. Mulberry plants are valued as functional foods for their abundant chemical composition, serving as a significant reservoir of bioactive compounds like proteins, polysaccharides, phenolics, and flavonoids. Moreover, these compounds displayed potent antioxidant activity by scavenging free radicals, inhibiting reactive oxygen species generation, and restoring elevated nitric oxide production induced by LPS stimulation through the downregulation of inducible NO synthase expression. Active components like oxyresveratrol found in Morus demonstrated anti-inflammatory effects by inhibiting leukocyte migration through the MEK/ERK signaling pathway. Gallic and chlorogenic acids in mulberry leaves (ML) powder-modulated TNF, IL-6, and IRS1 proteins, improving various inflammatory conditions by immune system modulation. As we delve deeper into understanding its anti-inflammatory potential and how it works therapeutically, it is crucial to refine the extraction process to enhance the effectiveness of its bioactive elements. Recent advancements in extraction techniques, such as solid-liquid extraction, pressurized liquid extraction, superficial fluid extraction, microwave-assisted extraction, and ultrasonic-assisted extraction, are being explored. Among the extraction methods tested, including Soxhlet extraction, maceration, and ultrasound-assisted extraction (UAE), UAE demonstrated superior efficiency in extracting bioactive compounds from mulberry leaves. Overall, this comprehensive review sheds light on the potential of mulberry as a natural immunomodulatory agent and provides insights into its mechanisms of action for future research and therapeutic applications.


Morus , Plant Extracts , Morus/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Humans , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Plant Leaves/chemistry
6.
Food Chem ; 451: 139439, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38692239

This study investigated the techno-functional conditions for producing fermented beverages using the kombucha artisanal consortium (kAC) while implementing sustainable strategies. According to the circular economy principles, the study focused on mulberry coproducts (MC) generated as agro-industrial waste during mulberry fruit production. The presence of target microorganisms in the beverage and biofilm was recorded to determine the MC content necessary for establishing kAC. Additionally, the physicochemical characteristics, carbohydrate and polyphenol profiles were analyzed to understand their impact on antioxidant activity and sensory responses in the soft drink. Notably, a concentration of 0.25% MC was found to yield fermented soft drinks rich in probiotic populations and displaying nutraceutical qualities that enhance antioxidant activity and sensory acceptability. This study offers valuable technical guidance for repurposing mulberry pruning coproducts in the creation of novel products.


Fermentation , Fruit , Morus , Morus/chemistry , Fruit/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Humans , Taste , Bacteria/drug effects
7.
Food Chem ; 450: 139318, 2024 Aug 30.
Article En | MEDLINE | ID: mdl-38613965

For texture control in plant-meat alternatives, the interrelationship between apparent characteristics and chemical bonds in high-fiber formulations remains unclear. The influence of mulberry leaf powder on apparent characteristics and chemical bonds of raw materials, block and strip products at addition amounts of 0.5-25% was analyzed. The results showed that 8% addition significantly increased the chewiness of the block by 98.12%. The strips' texture shows a downward trend, and the processing produced more redness and color difference. Additives promoted the formation of voids, lamellar and filamentous structures, and the strip produced more striped structures. Disulfide bonds significantly increased in the block, and the ß-turn in the secondary structure enhanced by 12.20%. The ß-turn transformed into a ß-sheet in strips. Principal component analysis revealed that the texture improvement was associated with producing disulfide bonds and ß-turn, providing a basis for high-fiber components to improve products' apparent characteristics by chemical bonds.


Morus , Plant Leaves , Powders , Principal Component Analysis , Morus/chemistry , Plant Leaves/chemistry , Powders/chemistry , Food Handling , Meat Products/analysis , Plant Extracts/chemistry , Color , Animals , Meat Substitutes
8.
Open Vet J ; 14(3): 750-758, 2024 Mar.
Article En | MEDLINE | ID: mdl-38682142

Background: Studies have reported that the phytochemical content of Mulberry (Morus alba Linn.) is influenced by the area where it grows. On the other hand, the study of the bioactivity and toxicity of mulberry leaves from Brunei Darussalam still needs to be completed. In particular, the investigation regarding the safe dose for Mulberry's application from Brunei Darussalam has yet to be studied. Hence, toxicity information must be considered even though the community has used it for generations. Aim: This study investigated Morus alba ethanolic leaf extract (MAE) to observe the acute toxicity in mice. Methods: In particular, this study utilized 12 female Institute of Cancer Research mice, 8 weeks old, divided into 2 groups: the control group and the MAE group (2,000 mg/kg single dose). Physiology, hematology, biochemistry, and histology were analyzed during the study. Results: The examination result indicated no mortality and behavioral changes throughout the testing period. However, the mice developed mild anemia and leukopenia, followed by decreased numbers of neutrophils, lymphocytes, and monocytes. In addition, the mice developed a mild hepatocellular injury, indicated by significant (p < 0.05) elevations of both alanine aminotransferase (ALT) and aspartate transaminase (AST). The histopathological findings of the liver were also consistent with the increment of ALT and AST, indicating mild hepatocellular necrosis through the eosinophilic cytoplasm and pyknosis (p > 0.05). Conclusion: It was evident that a single oral administration of MAE was not lethal for mice (LD50, which was higher than 2,000 mg/kg). However, the administration of high doses of MAE must be carefully considered.


Mice, Inbred ICR , Morus , Plant Extracts , Plant Leaves , Animals , Morus/chemistry , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Leaves/chemistry , Mice , Female , Brunei , Toxicity Tests, Acute , Liver/drug effects , Liver/pathology
9.
Molecules ; 29(8)2024 Apr 10.
Article En | MEDLINE | ID: mdl-38675536

Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.


Constipation , Morus , Plant Leaves , Sesamum , Morus/chemistry , Constipation/drug therapy , Plant Leaves/chemistry , Sesamum/chemistry , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Gastrointestinal Microbiome/drug effects , Metabolomics/methods , Male , Gastrointestinal Motility/drug effects , Gastrointestinal Transit/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Gene Expression Profiling , Disease Models, Animal , Multiomics
10.
J Agric Food Chem ; 72(18): 10366-10375, 2024 May 08.
Article En | MEDLINE | ID: mdl-38651967

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.


Enterotoxins , Flavonoids , Frizzled Receptors , Morus , Plant Leaves , Stem Cells , beta Catenin , Animals , Morus/chemistry , Flavonoids/pharmacology , Frizzled Receptors/metabolism , Frizzled Receptors/genetics , beta Catenin/metabolism , beta Catenin/genetics , Mice , Plant Leaves/chemistry , Plant Leaves/metabolism , Stem Cells/drug effects , Stem Cells/metabolism , Stem Cells/cytology , Humans , Enterotoxins/metabolism , Cell Proliferation/drug effects , Wnt Signaling Pathway/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestines/drug effects , Intestines/cytology , Flavones
11.
J Food Sci ; 89(5): 2645-2658, 2024 May.
Article En | MEDLINE | ID: mdl-38563094

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.


Diet, Gluten-Free , Flour , Morus , Oryza , Rheology , Flour/analysis , Oryza/chemistry , Morus/chemistry , Ascomycota/enzymology , Food Handling/methods , Endo-1,4-beta Xylanases/metabolism , Hardness , Cooking/methods , Dietary Fiber/analysis , Triticum/chemistry , Glutens/analysis
12.
Int J Biol Macromol ; 268(Pt 1): 131701, 2024 May.
Article En | MEDLINE | ID: mdl-38643920

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.


Morus , Plant Leaves , Polysaccharides , Morus/chemistry , Plant Leaves/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Structure-Activity Relationship , Antioxidants/pharmacology , Antioxidants/chemistry , Humans , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology
13.
Environ Pollut ; 349: 123929, 2024 May 15.
Article En | MEDLINE | ID: mdl-38582190

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.


Marine Toxins , Microcystins , Morus , Animals , Female , Microcystins/toxicity , Mice , Morus/chemistry , Ovary/drug effects , Chemokine CCL2/metabolism , Chemokine CCL2/genetics , Plant Extracts/pharmacology , Granulosa Cells/drug effects
14.
Phytomedicine ; 128: 155526, 2024 Jun.
Article En | MEDLINE | ID: mdl-38564921

BACKGROUND: Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear. PURPOSE: To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development. METHODS: Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro. RESULTS: SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis. CONCLUSION: SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.


Alkaloids , Atherosclerosis , Macrophages , Morus , Animals , Atherosclerosis/drug therapy , Macrophages/drug effects , Mice , Alkaloids/pharmacology , Morus/chemistry , Male , Mice, Inbred C57BL , Anti-Inflammatory Agents/pharmacology , Diet, High-Fat , Humans , RAW 264.7 Cells , Mice, Knockout, ApoE , Endothelial Cells/drug effects , Apolipoproteins E
15.
Phytomedicine ; 128: 155528, 2024 Jun.
Article En | MEDLINE | ID: mdl-38555774

BACKGROUND: Obesity and hyperlipidemia can induce a variety of diseases, and have become major health problems worldwide. How to effectively prevent and control obesity has become one of the hot-spots of contemporary research. Mulberry leaf is the dried leaf of Morus alba L., which is approved by the Ministry of Health as a "homology of medicine and food", rich in diverse active constituents and with a variety of health effects including anti-obesity and anti-hyperlipidemia activities. PURPOSE: The review attempts to summarize and provide the molecular basis, mechanism, safety and products for further exploration and application of mulberry leaf on the treatment on the control of weight gain and obesity. METHODS: This review is conducted by using ScienceDirect, PubMed, CNKI and Web of Science databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Based on the research progress of domestic and foreign scholars, the effective phytochemicals, molecular mechanisms and product applications of mulberry leaf in the prevention and treatment of obesity and related metabolic diseases were summarized. CONCLUSION: Mulberry leaf has excellent medicinal and health care value in obesity treatment. However, its pharmacodynamic substance basis and molecular mechanisms need to be further studied.


Anti-Obesity Agents , Morus , Obesity , Phytochemicals , Plant Leaves , Morus/chemistry , Plant Leaves/chemistry , Obesity/drug therapy , Humans , Phytochemicals/pharmacology , Phytochemicals/chemistry , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/chemistry , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phytotherapy
16.
Phytomedicine ; 128: 155527, 2024 Jun.
Article En | MEDLINE | ID: mdl-38489888

BACKGROUND: Pancreatic cancer, a tumor with a high metastasis rate and poor prognosis, is among the deadliest human malignancies. Investigating effective drugs for their treatment is imperative. Moracin D, a natural benzofuran compound isolated from Morus alba L., shows anti-inflammation and anti-breast cancer properties and is effective against Alzheimer's disease. However, the effect and mechanism of Moracin D action in pancreatic cancer remain obscure. PURPOSE: To investigate the function and molecular mechanism of Moracin D action in repressing the malignant progression of pancreatic cancer. METHODS: Pancreatic cancer cells were treated with Moracin D, and cell proliferation was evaluated by cell counting kit-8 (CCK-8) and immunofluorescence assays. The clonogenicity of pancreatic cancer cells was assessed based on plate colony formation and soft agar assay. Flow cytometry was used to detect cell apoptosis. The expression of proteins related to the apoptosis pathway was determined by Western blot analysis. Moracin D and XIAP were subjected to docking by auto-dock molecular docking analysis. Ubiquitination levels of XIAP and the interaction of XIAP and PARP1 were assessed by co-immunoprecipitation analysis. Moracin D's effects on tumorigenicity were assessed by a tumor xenograft assay. RESULTS: Moracin D inhibited cell proliferation, induced cell apoptosis, and regulated the protein expression of molecules involved in caspase-dependent apoptosis pathways. Moracin D suppressed clonogenicity and tumorigenesis of pancreatic cancer cells. Mechanistically, XIAP could interact with PARP1 and stabilize PARP1 by controlling its ubiquitination levels. Moracin D diminished the stability of XIAP and decreased the expression of XIAP by promoting proteasome-dependent XIAP degradation, further blocking the XIAP/PARP1 axis and repressing the progression of pancreatic cancer. Moracin D could dramatically improve the chemosensitivity of gemcitabine in pancreatic cancer cells. CONCLUSION: Moracin D repressed cell growth and tumorigenesis, induced cell apoptosis, and enhanced the chemosensitivity of gemcitabine through the XIAP/PARP1 axis in pancreatic cancer. Moracin D is a potential therapeutic agent or adjuvant for pancreatic cancer.


Apoptosis , Benzofurans , Benzopyrans , Cell Proliferation , Pancreatic Neoplasms , Poly (ADP-Ribose) Polymerase-1 , X-Linked Inhibitor of Apoptosis Protein , Pancreatic Neoplasms/drug therapy , X-Linked Inhibitor of Apoptosis Protein/metabolism , Humans , Apoptosis/drug effects , Poly (ADP-Ribose) Polymerase-1/metabolism , Cell Proliferation/drug effects , Cell Line, Tumor , Animals , Benzofurans/pharmacology , Mice, Nude , Morus/chemistry , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Molecular Docking Simulation , Mice, Inbred BALB C , Gemcitabine , Xenograft Model Antitumor Assays
17.
J Pharm Biomed Anal ; 244: 116125, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38554553

As a pivotal enzyme that regulates dephosphorylation in cell activities and participates in the insulin signaling pathway, protein tyrosine phosphatase 1B (PTP1B) is considered to be an important target for the therapy of diabetes. In this work, a rapid and efficient inhibitor screening method of PTP1B was established based on capillary electrophoresis (CE), and used for screening and evaluating the inhibition effect of Traditional Chinese Medicine on PTP1B. Response Surface Methodology was used for optimizing the conditions of analysis. After method validation, the enzyme kinetic study and inhibition test were performed. As a result, the IC50 of PTP1B inhibitors Ⅳ and ⅩⅧ were consistent with reported values measured by a conventional method. It was found that the extracts of Astragalus membranaceus (Fisch) Bunge and Morus alba L. showed prominent inhibition on the activity of PTP1B, which were stronger than the positive controls. Meanwhile, on top of the excellent advantages of CE, the whole analysis time is less than 2 min. Thus, the results demonstrated that a fast and efficient screening method was successfully developed. This method could be a powerful tool for screening inhibitors from complex systems. It can also provide an effective basis for lead compound development in drug discovery.


Drugs, Chinese Herbal , Electrophoresis, Capillary , Hypoglycemic Agents , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Humans , Astragalus propinquus/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Electrophoresis, Capillary/methods , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/analysis , Hypoglycemic Agents/pharmacology , Kinetics , Medicine, Chinese Traditional/methods , Morus/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism
18.
Food Funct ; 15(8): 4354-4364, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38533683

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.


Alzheimer Disease , Metabolome , Morus , Neuroprotective Agents , Plant Extracts , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Neuroprotective Agents/pharmacology , Mice , Plant Extracts/pharmacology , Male , Morus/chemistry , Metabolome/drug effects , Tandem Mass Spectrometry , Disease Models, Animal , Chromatography, High Pressure Liquid , Humans , Brain/metabolism , Brain/drug effects
19.
Food Funct ; 15(8): 3939-3958, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38536669

The mulberry plant is a member of the Moraceae family and belongs to the Morus genus. Its entire body is a treasure, with mulberries, mulberry leaves, and mulberry branches all suitable for medicinal use. The main active ingredient in mulberries is mulberry polysaccharide. Studies have shown that polysaccharides from different parts of mulberry exhibit antioxidant, antidiabetic, antibacterial, anti-inflammatory, and blood pressure-lowering properties. There are more studies on the biological activities, extraction methods, and structural characterization of polysaccharides from different parts of mulberry. However, the structural characterization of mulberry polysaccharides is mostly confined to the types and proportions of monosaccharides and the molecular weights of polysaccharides, and there are fewer systematic studies on polysaccharides from different parts of mulberry. In order to better understand the bioactive structure of mulberry polysaccharides, this article discusses the recent research progress in the extraction, separation, purification, bioactivity, structural modification, and application of polysaccharides from different parts of mulberry (mulberry leaves, mulberry fruits, and mulberry branches). It also delves into the pharmacological mechanisms of action of mulberry polysaccharides to provide a theoretical basis for further research on mulberry polysaccharides with a view to their deeper application in the fields of feed and nutraceuticals.


Fruit , Morus , Plant Extracts , Plant Leaves , Polysaccharides , Morus/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Fruit/chemistry , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Animals , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification
20.
Nat Commun ; 15(1): 2492, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38509059

Biosynthetic enzymes evolutionarily gain novel functions, thereby expanding the structural diversity of natural products to the benefit of host organisms. Diels-Alderases (DAs), functionally unique enzymes catalysing [4 + 2] cycloaddition reactions, have received considerable research interest. However, their evolutionary mechanisms remain obscure. Here, we investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites. Our findings suggest that these DAs have evolved from an ancestor functioning as a flavin adenine dinucleotide (FAD)-dependent oxidocyclase (OC), which catalyses the oxidative cyclisation reactions of isoprenoid-substituted phenolic compounds. Through crystal structure determination, computational calculations, and site-directed mutagenesis experiments, we identified several critical substitutions, including S348L, A357L, D389E and H418R that alter the substrate-binding mode and enable the OCs to gain intermolecular DA activity during evolution. This work provides mechanistic insights into the evolutionary rationale of DAs and paves the way for mining and engineering new DAs from other protein families.


Morus , Morus/genetics , Morus/chemistry , Terpenes , Catalysis , Cycloaddition Reaction
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