Prenylated Flavanone Enantiomers with α-Glucosidase Inhibitory Activity from the Root Bark of Morus alba.

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target a-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

Structurally Diverse Stilbenoids as Potent α-Glucosidase Inhibitors with Antidiabetic Effect from Morus alba.

Fifteen stilbenoid derivatives, including five previously undescribed ones (albaphenols A-E, 1-5) with diverse scaffolds, were obtained from the well-known agricultural economic tree Morus alba. Their structures, including absolute stereochemistries, were fully characterized by detailed interpretation of spectroscopic data and quantum chemical computational analyses of nuclear magnetic resonance (NMR) and electric circular dichroism (ECD). Albaphenol A (1) features an unprecedented rearranged carbon skeleton incorporating a novel 2-oxaspiro[bicyclo[3.2.1]octane-6,3'-furan] motif; albaphenol C (3) is likely derived from a cometabolite through an interesting intramolecular transesterification reaction; and albaphenol E (5) bears a cleavage-reconnection scaffold via a dioxane ring. All of the compounds exhibited significant inhibition against the diabetic target α-glucosidase, with low to submicromole IC50 values (0.70-8.27 µM), and the binding modes of selected molecules with the enzyme were further investigated by fluorescence quenching, kinetics, and molecular docking experiments. The antidiabetic effect of the most active and abundant mulberrofuran G (6) was further assessed in vivo in diabetic mice, revealing potent antihyperglycemic activity and comparable antidiabetic efficacy to the clinical drug acarbose.

Functional assessments of Psidium guajava L. and Morus alba L. leaf extracts on postprandial glucose control.

Diabetes is a leading cause of death, according to statistics published by the Department of Health, Executive Yuan of Taiwan. In modern medicine, diabetes can be controlled using various medications; however, some drugs often have undesirable side effects. It therefore became a goal to find plant-based material that can reduce glucose concentration in the blood while reducing the incidence of complications and not causing side effects. Alpha-glucosidase inhibitors (AGIs) are effective glucose-lowering medicines and are enzymes essential to carbohydrate digestion. Inhibition of α-glucosidase leads to a delayed and reduced rise in postprandial blood glucose levels. This study evaluates the inhibitory effect of mixed extracts of Psidium guajava L. and Morus alba L. leaves on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. The inhibition of α-glucosidase activity was assayed in vitro. Half maximal inhibitory concentration (IC50) values of Psidium guajava L. and Morus alba L. were 2.25 and 0.1 mg/mL, respectively. The IC50 value of a commercial anti-hyperglycemic agent (Glucobay) is 6.41 mg/mL. The IC50 value of a mixture of extracts of Psidium guajava L. and Morus alba L. was 0.07 mg/mL. In cytotoxicity tests, survival percentages and shape did not significantly affect the murine embryonic liver cell line (BNL CL.2) when treated with varying concentrations of mixture extracts for varying periods of time. In summary, Psidium guajava L. and Morus alba L. showed positive anti-diabetes activity and suggested promising potential for alternative functional foods for diabetes mellitus (DM) patients.

Biosynthesis and Pharmacological Activities of the Bioactive Compounds of White Mulberry (Morus alba): Current Paradigms and Future Challenges.

Traditional natural products have been the focus of research to explore their medicinal properties. One such medicinally important plant is the white mulberry, Morus alba, widely distributed in the Asian subcontinent. It is one of the most cultivated species of mulberry tree and has attracted more focus from researchers because of its abundance in phytochemicals as well as multipurpose uses. The leaves, fruits and other parts of the white mulberry plant act as a source of valuable bioactive compounds like flavonoids, phenolic acids, terpenoids and alkaloids. These secondary metabolites have manifold healthy uses as they possess antioxidant, anti-inflammatory, antidiabetic, neutrotrophic, and anticancer properties. Despite the increasing scientific interest in this plant, there are very few reviews that highlight the phytochemistry and biological potential of white mulberry for biomedical research. To this end, this review elaborates the phytochemistry, biosynthetic pathways and pharmacological activities of the glycoside flavonoids of Morus alba. A comprehensive analysis of the available literature indicates that Morus alba could emerge as a promising natural agent to combat diverse conditions including diabetes, cancer, inflammation and infectious diseases. To achieve such important objectives, it is crucial to elucidate the biosynthesis and regulation mechanisms of the bioactive compounds in white mulberry as well as the multifaceted pharmacological effects attributed to this plant resource. The present review paper is intended to present a summary of existing scientific data and a guide for further research in the phytochemistry and pharmacology of white mulberry. Further, a biosynthetic pathway analysis of the glycoside flavonoid in mulberry is also given. Lastly, we discuss the pros and cons of the current research to ensure the prudent and effective therapeutic value of mulberry for promoting human and animal health.

Biological potential, chemical profiling, and molecular docking study of Morus alba L. extracts.

Morus alba L. is a plant with a long history of dietary and medicinal uses. We hypothesized that M. alba possesses a significant biological potential. In that sense, we aimed to generate the chemical, antimicrobial, toxicological, and molecular profile of M. alba leaf and fruit extracts. Our results showed that extracts were rich in vitamin C, phenols, and flavonoids, with quercetin and pterostilbene concentrated in the leaf, while fisetin, hesperidin, resveratrol, and luteolin were detected in fruit. Extracts exhibited antimicrobial activity against all tested bacteria, including multidrug-resistant strains. The widest inhibition zones were in Staphylococcus aureus ATCC 33591. The values of the minimum inhibitory concentration ranged from 15.62 µg/ml in Enterococcus faecalis to 500 µg/ml in several bacteria. Minimum bactericidal concentration ranged from 31.25 µg/ml to 1000 µg/ml. Extracts impacted the biofilm formation in a concentration-dependent and species-specific manner. A significant difference in the frequency of nucleoplasmic bridges between the methanolic extract of fruit (0.5 µg/ml, 1 µg/ml, 2 µg/ml), as well as for the frequency of micronuclei between ethanolic extract of leaf (2 µg/ml) and the control group was observed. Molecular docking suggested that hesperidin possesses the highest binding affinity for multidrug efflux transporter AcrB and acyl-PBP2a from MRSA, as well as for the SARS-CoV-2 Mpro. This study, by complementing previous research in this field, gives new insights that could be of great value in obtaining a more comprehensive picture of the Morus alba L. bioactive potential, chemical composition, antimicrobial and toxicological features, as well as molecular profile.

Contribution of Extracellular Particles Isolated from Morus sp. (Mulberry) Fruit to Their Reported Protective Health Benefits: An In Vitro Study.

Morus sp. (mulberry) has a long tradition of use as a medicinal treatment, including for cardiovascular disease and type 2 diabetes, being shown to have antioxidant properties and to promote wound healing. Extracellular vesicles (EVs) are sub-micron, membrane-enclosed particles that were first identified in mammalian bodily fluids. EV-like particles have been described in plants (PDVs) and shown to have similar characteristics to mammalian EVs. We hypothesised that some of the health benefits previously attributed to the fruit of Morus sp. could be due to the release of PDVs. We isolated PDVs from Morus nigra and Morus alba via ultracentrifugation and incubated THP-1 monocytes, differentiated THP-1 macrophages, or HMEC-1 endothelial cells with pro-oxidant compounds DMNQ (THP-1) and glucose oxidase (HMEC-1) or lipopolysaccharide (LPS) in the presence of different fractions of mulberry EVs. Mulberry EVs augmented ROS production with DMNQ in THP-1 and caused the downregulation of ROS in HMEC-1. Mulberry EVs increased LPS-induced IL-1ß secretion but reduced CCL2 and TGF-ß secretion in THP-1 macrophages. In scratch wound assays, mulberry EVs inhibited HMEC-1 migration but increased proliferation in both low and high serum conditions, suggesting that they have opposing effects in these two important aspects of wound healing. One of the limitations of plant-derived therapeutics has been overcoming the low bioavailability of isolated compounds. We propose that PDVs could provide the link between physiological dose and therapeutic benefit by protecting plant active compounds in the GIT as well as potentially delivering genetic material or proteins that contribute to previously observed health benefits.

A 90-day preclinical toxicological evaluation in rats of a highly purified and concentrated mulberry leaf extract.

Mulberry (genus Morus) leaves have long been used as a human food, especially in Asia, and animal feed. More recently, mulberry leaf extracts have been introduced as a convenient way to consume mulberry for non-nutritional functional effects. Reducose® 5% is an Morus alba leaf extract that has been highly purified and standardized to a content of 5 ± 0.5% 1-deoxynojirimycin, a naturally present polyhydroxylated piperidine alkaloid analog of D-glucose. This extract has previously been evaluated in acute and subacute (28-day) oral toxicity studies in which no adverse effects of the test item were observed in mice or rats, respectively. Due to continued and growing interest in the extract in multinational markets, we have now further investigated potential toxic effects in subchronic (90-day) oral toxicity study in male and female Han:WIST rats. The test item was administered at doses of 850, 1700, and 2550 mg/kg bw/day, and did not cause adverse effects in clinical signs, body weight development, clinical pathology, gross pathology, or histopathology in comparison to the vehicle-control group. The no-observed-adverse-effect-level was determined to be 2550 mg/kg bw/day. These results add to the existing body of both preclinical and clinical work relevant to the safety of the extract and of interest to regulators in various global markets.

Hair growth-promoting effects of Enz_MoriL on human dermal papilla cells through modulation of the Wnt/ß-Catenin and JAK-STAT signaling pathways.

Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for its potential to promote hair regrowth. However, the precise mechanism by which Enz_MoriL affects human hair follicle dermal papilla cells (hDPCs) remains unclear. The aim of this study was to investigate the molecular basis of Enz_MoriL's effect on hair growth in hDPCs. Interferon-gamma (IFN-γ) was used to examine the effects of Enz_MoriL on hDPCs during the anagen and catagen phases, as well as under conditions mimicking alopecia areata (AA). Enz_MoriL demonstrated the ability to promote cell proliferation in both anagen and catagen stages. It increased the levels of active ß-catenin in the catagen stage induced by IFN-γ, leading to its nuclear translocation. This effect was achieved by increasing the phosphorylation of GSK3ß and decreasing the expression of DKK-1. This stimulation induced proliferation in hDPCs and upregulated the expression of the Wnt family members 3a, 5a, and 7a at the transcript level. Additionally, Enz_MoriL suppressed JAK1 and STAT3 phosphorylation, contrasting with IFN-γ, which induced them in the catagen stage. In conclusion, Enz_MoriL directly induced signals for anagen re-entry into hDPCs by affecting the Wnt/ß-catenin pathway and enhancing the production of growth factors. Furthermore, Enz_MoriL attenuated and reversed the interferon-induced AA-like environment by blocking the JAK-STAT pathway in hDPCs.

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.

Pharmacological Properties of White Mulberry (Morus alba L.) Leaves: Suppressing Migratory and Invasive Activities Against A549 Lung Cancer Cells.

Morus alba known as a white mulberry is a medicinal plant that has been used in food ingredients and traditional medicine. M. alba leaves contain various bioactive phenolic compounds, in particular chlorogenic acid (CGA), which is a major bioactive ingredient. Their anticancer potency of M. alba leaf extracts derived from Soxhlet extraction was evaluated based on cytotoxicity and antimigratory and antiinvasive properties. The dichloromethane extract exhibited the highest nitric oxide radical scavenging activity with a half-maximal inhibitory concentration (IC50) value of 780 µg/mL, promising cytotoxicity against HuCCA-1, MCF-7, and A-549 cells with IC50 values of 59.18, 62.20, and 103.25 µg/mL, respectively. CGA selectively inhibited the growth of MCF-7 cells with an IC50 value of 26.75 µg/mL and showed potent radical scavenging activity against DPPH radicals (IC50 = 18.85 µg/mL). An ethanolic extract derived from the gradient Soxhlet extraction suppressed A549 lung cancer cell migration and invasion more effectively than CGA with no migratory inhibition effect on noncancerous HaCaT cells. Furthermore, the ethanolic extract and CGA accelerated HaCaT wound closure at 20 µg/mL, which was the same as allantoin. Bioactive ingredients including triterpenes, steroids, phenolics, and flavonoids were mainly detected in all extracts. The highest content of CGA (52.23 g/100 g dry weight) was found in the ethanolic extract derived from the gradient Soxhlet extraction. These findings show the potency of the dichloromethane extract as a cytotoxic agent against various cancer types and the ethanolic extract as an antimetastatic agent by their antimigratory and antiinvasive activities.

Comparative Physio-Biochemical and Transcriptome Analyses Reveal Contrasting Responses to Magnesium Imbalances in Leaves of Mulberry (Morus alba L.) Plants.

Magnesium (Mg) deficiency is a major factor limiting the growth and development of plants. Mulberry (Morus alba L.) is an important fruit tree crop that requires Mg for optimal growth and yield, especially in acid soils. However, the molecular mechanism of Mg stress tolerance in mulberry plants remains unknown. In this study, we used next-generation sequencing technology and biochemical analysis to profile the transcriptome and physiological changes of mulberry leaves under different Mg treatments (deficiency: 0 mM, low: 1 mM, moderate low: 2 mM, sufficiency: 3 mM, toxicity: 6 mM, higher toxicity: 9 mM) as T1, T2, T3, CK, T4, T5 treatments, respectively, for 20 days. The results showed that Mg imbalance altered the antioxidant enzymatic activities, such as catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), and non-enzymatic, including soluble protein, soluble sugar, malondialdehyde (MDA), and proline (PRO), contents of the plant. The Mg imbalances disrupted the ultrastructures of the vital components of chloroplast and mitochondria relative to the control. The transcriptome data reveal that 11,030 genes were differentially expressed (DEGs). Genes related to the photosynthetic processes (CAB40, CAB7, CAB6A, CAB-151, CAP10A) and chlorophyll degradation (PAO, CHLASE1, SGR) were altered. Antioxidant genes such as PER42, PER21, and PER47 were downregulated, but DFR was upregulated. The carbohydrate metabolism pathway was significantly altered, while those involved in energy metabolism processes were perturbed under high Mg treatment compared with control. We also identified several candidate genes associated with magnesium homeostasis via RT-qPCR validation analysis, which provided valuable information for further functional characterization studies such as promoter activity assay or gene overexpression experiments using transient expression systems.

Green synthesis and anthelmintic activity of silver nanoparticles using Morus Alba Fruit extract against different stages of equine strongyles.

The current study was designed to green synthesize silver nanoparticles (GRAgNPs) using Morus alba fruit extract and evaluate their nematicidal effects against strongyle nematodes compared to commercial silver nanoparticles (CAgNPs) in vitro. The nanoparticles were characterized by Ultraviolet-visual absorption spectrography, transmission electron microscopy, and X-ray diffraction. Next, uptake of AgNPs by the first stage larvae (L1), egg hatch inhibition (EHI) and the motility of infectious larvae (L3s), and the ultrastructural analysis of the eggs and worms were conducted. Moreover, some of oxidative/nitrosative stress indicators, including total antioxidant status content (TAC), protein carbonylation (PCO), lipid peroxidation (MDA), and DNA damage were assessed in the homogenized samples of strongyle L3s. We found that the GRAgNPs had spherical shape, 20-30 nm in diameter with rough surface. Following incubation with GRAgNPs at concentrations of 43.40, 21.70 and 10.85 ppm and CAgNPs at concentrations of 43.40 and 21.70, EHI was more than 90%. In addition, concentrations of 43.40 and 21.70 ppm of GRAgNPs led to inhibition of larval motility by more than 90%. The LC50 at 24 h of treatment for GRAgNPs and CAgNPs was determined to be 8.62 and 10.34 ppm, respectively. GRAgNPs and CAgNPs, in a concentration-dependent manner, resulted in the induction of oxidative/nitrosative stress evidenced by decreased TAC levels, and increased levels of MDA and PCO, together with increased DNA damage. The uptake of AgNPs by the L1 larvae revealed that FITC labeled GRAgNPs fluoresced with high intensity largely in the intestinal area. Scanning Electron Microscopy analysis of eggs and larvae revealed that GRAgNPs penetrated the cuticle of larvae, changed the tegmentum, and ultimately killed the worm. In conclusion, GRAgNPs had more robust anthelminthic effects than the standard antiparasitic and CAgNPs. They could be considered as a promising antiparasitic agent.

Hematological, biochemical, and histopathological evaluation of the Morus alba L. leaf extract from Brunei Darussalam: Acute toxicity study in ICR mice.

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.

Genome-Wide Analysis of the Xyloglucan Endotransglucosylase/Hydrolase (XTH) Gene Family: Expression Pattern during Magnesium Stress Treatment in the Mulberry Plant (Morus alba L.) Leaves.

Mulberry (Morus alba L.), a significant fruit tree crop, requires magnesium (Mg) for its optimal growth and productivity. Nonetheless, our understanding of the molecular basis underlying magnesium stress tolerance in mulberry plants remains unexplored. In our previous study, we identified several differential candidate genes associated with Mg homeostasis via transcriptome analysis, including the xyloglucan endotransglucosylase/hydrolase (XTH) gene family. The XTH gene family is crucial for plant cell wall reconstruction and stress responses. These genes have been identified and thoroughly investigated in various plant species. However, there is no research pertaining to XTH genes within the M. alba plant. This research systematically examined the M. alba XTH (MaXTH) gene family at the genomic level using a bioinformatic approach. In total, 22 MaXTH genes were discovered and contained the Glyco_hydro_16 and XET_C conserved domains. The MaXTHs were categorized into five distinct groups by their phylogenetic relationships. The gene structure possesses four exons and three introns. Furthermore, the MaXTH gene promoter analysis reveals a plethora of cis-regulatory elements, mainly stress responsiveness, phytohormone responsiveness, and growth and development. GO analysis indicated that MaXTHs encode proteins that exhibit xyloglucan xyloglucosyl transferase and hydrolase activities in addition to cell wall biogenesis as well as xyloglucan and carbohydrate metabolic processes. Moreover, a synteny analysis unveiled an evolutionary relationship between the XTH genes in M. alba and those in three other species: A. thaliana, P. trichocarpa, and Zea mays. Expression profiles from RNA-Seq data displayed distinct expression patterns of XTH genes in M. alba leaf tissue during Mg treatments. Real-time quantitative PCR analysis confirmed the expression of the MaXTH genes in Mg stress response. Overall, this research enhances our understanding of the characteristics of MaXTH gene family members and lays the foundation for future functional genomic study in M. alba.

Morusacerane: A new gammacerane triterpenoid from the trunk of Morus Alba linn. with α-glucosidase inhibitory activity.

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid - morusacerane (1); along with two known compounds of betulinic acid (2) and ursolic acid (3). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α-glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane (1), betulinic acid (2), and ursolic acid (3) demonstrate the strong inhibitory with the IC50 values of 106.1, 11.12, and 7.20 µM, respectively. All of these compounds interacted well with the allosteric site enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

Genome-wide analysis of the mulberry (Morus abla L.) GH9 gene family and the functional characterization of MaGH9B6 during the development of the abscission zone.

Plant glycoside hydrolase family 9 genes (GH9s) are widely distributed in plants and involved in a variety of cellular and physiological processes. In the current study, nine GH9 genes were identified in the mulberry and were divided into two subfamilies based on the phylogenetic analysis. Conserved motifs and gene structure analysis suggested that the evolution of the two subfamilies is relatively conserved and the glycoside hydrolase domain almost occupy the entire coding region of the GH9s gene. Only segmental duplication has played a role in the expansion of gene family. Collinearity analysis showed that mulberry GH9s had the closest relationship with poplar GH9s. MaGH9B1, MaGH9B6, MaGH9B5, and MaGH9B3 were detected to have transcript accumulation in the stalk of easy-to drop mature fruit drop, suggesting that these could play a role in mulberry fruit drop. Multiple cis-acting elements related to plant hormones and abiotic stress responses were found in the mulberry GH9 promoter regions and showed different activities under exogenous abscisic acid (ABA) and 2,4- dichlorophenoxyacetic acid (2,4-D) stresses. We found that the lignin content in the fruit stalk decreased with the formation of the abscission zone (AZ), which could indirectly reflect the formation process of the AZ. These results provide a theoretical basis for further research on the role of GH9s in mulberry abscission.

[Fire resistance of 15 main economic tree species in Liangshan Prefecture, Sichuan, China.] / 凉山州15ç§ä¸»è¦ç»æµŽæ ‘ç§çš„é˜²ç«æ€§èƒ½.

Liangshan Prefecture is one of the three major forest areas in Sichuan Province and one of the three major disaster areas of forest fire. We measured the physicochemical properties and combustion performances of different organs (leaves and branches) of 15 main economic tree species in Liangshan, and analyzed the bioecology characteristics, silviculture characteristics and value characteristics of different tree species. We investigated the fire resistance of different tree species to screen out fire-resistant species suitable for economic forest development in Liangshan Prefecture, and improve the biological fire prevention ability. The seven physicochemical properties and combustion performances indices of 15 tree species showed significant differences. Except for crude ash and lignin, the weights of moisture content, caloric value, ignition point, crude fat, and crude fibre of leaves were higher than those of branches. Crude fibre index of leaves (9.6%) and the crude ash index of branches (9.9%) were the highest weight indices of the two organs, respectively. Based on the fire resistance, we divided all the species into three classes, i.e., class Ⅰ (excellent fire-resistance trees) Juglans regia and Morus alba; class Ⅱ (better fire-resistant trees) Sapium sebiferum, Mangifera indica, Phyllanthus emblica, Eriobotrya japonica, Ligustrum lucidum, Castanea mollissima, and Punica granatum; class Ⅲ (poor fire-resistant trees) Pinus armandii, Illicium simonsii, Morella rubra, Sapindus mukorossi, Olea europaea and Camellia oleifera. J. regia and M. alba had fireproof solid performance and could be used as the preferred species for fireproof economic forest in Liangshan region. It was suggested that to use class Ⅰ to Ⅱ fire-resistant tree species built the main fireproof isolated forest belt, and pay attention to fire prevention after planting class Ⅲ tree species in a large area.

Phytotherapeutic potential of compounds identified from fractionated extracts of Morus alba L., as an inhibitor of interleukin-6 in the treatment of rheumatoid arthritis: computational approach.

The presence of HLA-DRB1 alleles that encode critical points associated with environmental interactions is associated with increased risk of rheumatoid arthritis caused by anti-citrullinated protein antibodies. Therefore, interleukin-6 (IL-6), a multifunctional cytokine that controls both local and systemic acute inflammatory responses through its ability to induce a phase response, plays a serious role. Its overexpression leads to pathological challenges such as rheumatoid arthritis and menopausal osteoporosis. However, targeting the IL-6 receptor and its region could be the major step in controlling the overexpression of this cytokine for therapeutic importance. Therefore, our research explored the computational insight needed to investigate the anti-RFA potential of phytochemicals from fractionated extracts of Morus alba L. against receptors, which have been implicated as druggable targets for the treatment of rheumatoid arthritis. In this study, fifty-nine (59) previously isolated and characterized phytochemicals from M. alba L. were identified from the literature and retrieved from the PubChem database. In silico screening was used to assess the mode of action of these phytochemicals from M. alba L. against receptors that may serve as therapeutic targets for rheumatoid arthritis. Molecular docking studies, toxicity prediction, drug visualization and molecular dynamics simulation (MD) of the ligands together with the receptor-identified target were carried out using the Schrodinger Molecular Drug Discovery Suite. The findings indicated that a selected group of ligands displayed significant binding strength to specific amino acid residues, revealing an important link between the building blocks of proteins (amino acids) and ligands at the inhibitor binding site through traditional chemical interactions, such as interactions between hydrophobic and hydrogen bonds. The binding affinities of the receptors were carefully checked via comparison with those of the approved ligands, and the results suggested structural and functional changes in the lead compounds. Therefore, the bioactive component from M. alba L. could be a lead foot interleukin-6 (IL-6) inhibitor and could be a promising lead compound for the treatment of rheumatoid arthritis and related challenges.Communicated by Ramaswamy H. Sarma.

Identified phytocompounds from the fractionated extract of Morus alba inhibit IL-6 production via molecular docking and molecular simulation analysisChanges in the structure and function of these hit compounds show promising potential in the treatment of rheumatoid arthritis and related challenges.

Morushalunin D, a tri-O-bridged Diels-Alder type adduct from Morus alba var. shalun root cultures and the related precursors.

Three Diels-Alder type adducts (1-3) along with their precursors, including one 2-arylbenzofuran (4) and one stilbene (5), were isolated from the MeOH extract of M. alba var. shalun root cultures. Among them, 1 is a new Diels-Alder type adduct named morushalunin D. The molecular structures of 1-5 were elucidated based on spectroscopic data and comparison with the literatures. Cytotoxic properties of compounds 1-5 were evaluated against murine leukemia P-388 cells. Morushalunin D (1), mulberrofuran T (2), sorocein A (3), moracin M (4), and oxyresveratrol (5) were active, significantly inhibiting the growth of P-388 cells with IC50 values of 0.5, 1.0, 0.6, 2.0, and 3.3 µg/ml, respectively.

Effect of hot-melt extruded Morus alba leaves on intestinal microflora and epithelial cells.

Although rutin and isoquercitrin have many effects, they are insoluble substances, making it difficult to obtain pure substances. This study was to investigate whether Morus alba leaves containing rutin and isoquercitrin could improve intestinal health by making a sustained-release formulation through a hot-melt extrusion (HME) process with improved stability and solubility and determine whether it could upregulate the balance of intestinal microorganisms and intestinal epithelial cells. A sustained-release formulation was prepared by the HME process using Morus alba leaves and a hydrophilic polymer matrix. Antibacterial activities of pathogenic microorganisms (Escherichia coli, Streptococcus aureus, Enterococcus faecalis) and proliferative effect of probiotics (Lactobacillus rhamnosus, Pediococcus pentosaceus) were tested against intestinal microorganisms. Regarding intestinal epithelial cells, a co-culture model of Caco-2 cells and RAW 264.7 cells was used. It was confirmed that the extrudate exhibited high antibacterial activities against pathogenic microorganisms and affected the proliferation of probiotics. Furthermore, after inducing inflammation through LPS, it recovered transepithelial electrical resistance-increased levels of tight junction proteins and decreased expression levels of pro-inflammatory cytokines. HME of Morus alba leaves containing rutin and isoquercitrin can upregulate intestinal microbial balance and intestinal epithelial cells.