Morusin is a flavonoid compound isolated and extracted from the root bark of Morus alba L.Studies have reported that morusin exerts anti-tumor effects by inhibiting cancer cell invasion and proliferation,as well as in...Morusin is a flavonoid compound isolated and extracted from the root bark of Morus alba L.Studies have reported that morusin exerts anti-tumor effects by inhibiting cancer cell invasion and proliferation,as well as inducing tumor cell apoptosis.This article comprehensively reviews recent research on the anti-tumor effects of morusin and its related molecular mechanisms,aiming to provide theoretical support for further studies and new drug development of morusin.展开更多
Objective To investigate the protective effects of morusin on lipopolysaccharide(LPS)-induced acute liver injury in mice and its underlying mechanisms.Methods Thirty-two male specific pathogen-free(SPF)C57BL/6J mice w...Objective To investigate the protective effects of morusin on lipopolysaccharide(LPS)-induced acute liver injury in mice and its underlying mechanisms.Methods Thirty-two male specific pathogen-free(SPF)C57BL/6J mice were randomly divided into four groups(n=8 per group):control,LPS,low-dose morusin(morusin-L,10 mg/kg),and high-dose morusin(morusin-H,20 mg/kg)groups.The mice in each group were administered the corresponding drugs or normal saline via continuous gavage daily for 16 consecutive days.Except for control group,which received an equal volume of normal saline,other groups were intraperitoneally injected with LPS(5 mg/kg)2 h after the last gavage to establish the acute liver injury model.Serum and liver tissues were collected for subsequent analysis 6 h after LPS injection.The activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were detected with biochemical methods.The levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-1βin serum were measured by enzyme-linked immunosorbent assay(ELISA).Hepatic pathological changes were evaluated by hematoxylin-eosin(HE)staining.The 16S ribosomal RNA(16S rRNA)sequencing was performed to assess the composition of intestinal flora,linear discriminant analysis effect size(LEfSe)was applied for multi-level species discrimination,and Spearman’s correlation analysis was performed.The liver tissues of mice with acute liver injury were analyzed by RNA sequencing(RNA-seq)technology to identify differentially expressed genes(DEGs),and then enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway was conducted.The expression levels of selected genes was validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR),while immunohistochemistry(IHC)was performed to examine the expression levels of IL-6,myeloid differentiation primary response 88(MYD88),and toll-like receptor 2(TLR2).Results Morusin significantly reduced the serum levels of ALT,AST,and inflammatory factors(TNF-α,IL-6,and IL-1β)(P<0.05,P<0.01,or P<0.001),while alleviating the hepatic pathological damage in mice.Based on efficacy comparisons,morusin-H group was selected for subsequent microbiome and transcriptome analyses.Microbiome analysis revealed that morusin-H effectively mitigated LPS-induced gut dysbiosis and restored the Firmicutes/Bacteroidota balance(P<0.01).At the genus level,morusin-H significantly reduced the abundances of norank_f_Muribaculaceae,Desulfovibrio,Parabacteroides,and Muribaculum(P<0.05,P<0.01,or P<0.001).At the phylum,family,and genus levels,our findings indicated that morusin-H treatment caused a significant decrease in the abundance of Desulfobacterota,Desulfovibrionaceae,and Desulfovibrio(P<0.01).Importantly,the abundance of Desulfovibrio was positively correlated with the levels of ALT,AST,TNF-α,IL-1β,and IL-6.Transcriptomic and molecular analyses showed that the therapeutic mechanism of morusin-H involved suppression of the IL-17/TNF signaling pathways and downregulating the mRNA levels of Tlr2,Tlr3,Myd88,Il6,and Cxcl10(P<0.05 or P<0.001),as well as the protein levels of key inflammatory mediators(IL-6,MYD88,and TLR2)(P<0.001).Conclusion Morusin demonstrates protective effects against LPS-induced acute liver injury,likely through modulation of gut microbiota and suppression of pro-inflammatory factor expression.These findings indicate that morusin exerts its effects through the"microbiota-inflammation-liver"axis,providing a theoretical basis for its use as a multi-target plant-based drug in the treatment of metabolic inflammation-related liver diseases.展开更多
The root bark of Morus alba L. or white mulberry is widely used as traditional medicine in China, Japan and Korea. Major classes and types of phenolic compounds isolated from the root bark are flavonoids(kuwanons, mor...The root bark of Morus alba L. or white mulberry is widely used as traditional medicine in China, Japan and Korea. Major classes and types of phenolic compounds isolated from the root bark are flavonoids(kuwanons, morusin, cyclomorusin and sanggenons), benzofurans(moracins and mulberrofurans), and stilbenoids(mulberrosides). Some of the flavonoids and benzofurans are products of Diel-Alder type adducts. Other classes of compounds include triterpenes, phenolic acids and coumarins. Morusin, a prenylated flavonoid, was first isolated from the root bark of M. alba, and later from the leaf, stem bark and twig of the plant. The potent anti-cancer properties of morusin have attracted much attention with research on-going and new findings being published. The compound inhibits angiogenesis, tumour progression and tumour migration, and triggers apoptosis, cell cycle arrest and autophagy in colorectal, cervical, prostate, breast, hepatoma, pancreatic, glioblastoma, gastric, ovarian and lung cancer cell lines. The anti-cancer activities of morusin are executed via various molecular targets and signalling pathways. It is anticipated that on-going in vitro studies will progress gradually to in vivo studies using animal models before efforts towards drug development can be initiated for clinical trials.展开更多
The distribution and content differentiation of morusin in the cultivated species of mulberry by HPLC-DAD are described in this paper. The experimental results showed that morusin is present in all parts of the mulber...The distribution and content differentiation of morusin in the cultivated species of mulberry by HPLC-DAD are described in this paper. The experimental results showed that morusin is present in all parts of the mulberry bush. The content of morusin was highest in root bark and second highest in branch bark. The difference in morusin content of 20 different species of cultivated mulberry branch bark was significant. The level of morusin was highest in the branch bark of cultivated mulberry No. 404, a tetraploid cultivar, and third in the Husang 32 cultivar of Morus multicaulis. The method used in this study for determining morusin content exhibited good repeatability (RSD 6.02%) and recovery (100.62%). Therefore, the results from this study provide reliable data, for research and development in the future, on the level and distribution of morusin in mulberry in general and the differences found between various cultivated mulberries in particular. Furthermore, the HPLC-DAD method to determine morusin content is fast and reliable and is applicable not only to mulberry bushes but also to other plants.展开更多
桑(Morus alba L.)为桑科重要药用植物,其根皮(桑根皮)富含黄酮、酚类等活性成分,具有抗炎、抗氧化等多种药理效应。桑辛素(morusin)为其代表性黄酮类成分,尚未明确其在运动性肾损伤中的作用。本研究探讨桑辛素对力竭运动诱导小鼠肾损...桑(Morus alba L.)为桑科重要药用植物,其根皮(桑根皮)富含黄酮、酚类等活性成分,具有抗炎、抗氧化等多种药理效应。桑辛素(morusin)为其代表性黄酮类成分,尚未明确其在运动性肾损伤中的作用。本研究探讨桑辛素对力竭运动诱导小鼠肾损伤的保护作用及机制。采用负重游泳法建立模型,分别给予不同剂量桑辛素,并联合STAT3激动剂C-TFA干预。结果显示,桑辛素可剂量依赖性降低Cr、BUN、NGAL、KIM-1水平,改善肾组织损伤,抑制STAT3磷酸化,降低促炎因子和氧化应激水平,调节Bcl-2/Bax表达,减少细胞凋亡,STAT3激动剂干预显著削弱桑辛素效应。结果表明,桑辛素通过靶向STAT3通路显著减轻运动性肾损伤,具有作为天然运动防护剂的潜力。展开更多
基金Supported by Heilongjiang Provincial Key Research and Development Program(Guided Category)(GZ20220039)Central Government Funds for Local University Reform and Development(Talent Cultivation Program)(2020GSP16).
文摘Morusin is a flavonoid compound isolated and extracted from the root bark of Morus alba L.Studies have reported that morusin exerts anti-tumor effects by inhibiting cancer cell invasion and proliferation,as well as inducing tumor cell apoptosis.This article comprehensively reviews recent research on the anti-tumor effects of morusin and its related molecular mechanisms,aiming to provide theoretical support for further studies and new drug development of morusin.
基金Shenzhen Science and Technology Program(JCYJ2022-0530150408018,JCYJ20250604180541051)Shenzhen Basic Discipline Layout Project(JCYJ20220818101806014)。
文摘Objective To investigate the protective effects of morusin on lipopolysaccharide(LPS)-induced acute liver injury in mice and its underlying mechanisms.Methods Thirty-two male specific pathogen-free(SPF)C57BL/6J mice were randomly divided into four groups(n=8 per group):control,LPS,low-dose morusin(morusin-L,10 mg/kg),and high-dose morusin(morusin-H,20 mg/kg)groups.The mice in each group were administered the corresponding drugs or normal saline via continuous gavage daily for 16 consecutive days.Except for control group,which received an equal volume of normal saline,other groups were intraperitoneally injected with LPS(5 mg/kg)2 h after the last gavage to establish the acute liver injury model.Serum and liver tissues were collected for subsequent analysis 6 h after LPS injection.The activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were detected with biochemical methods.The levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-1βin serum were measured by enzyme-linked immunosorbent assay(ELISA).Hepatic pathological changes were evaluated by hematoxylin-eosin(HE)staining.The 16S ribosomal RNA(16S rRNA)sequencing was performed to assess the composition of intestinal flora,linear discriminant analysis effect size(LEfSe)was applied for multi-level species discrimination,and Spearman’s correlation analysis was performed.The liver tissues of mice with acute liver injury were analyzed by RNA sequencing(RNA-seq)technology to identify differentially expressed genes(DEGs),and then enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway was conducted.The expression levels of selected genes was validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR),while immunohistochemistry(IHC)was performed to examine the expression levels of IL-6,myeloid differentiation primary response 88(MYD88),and toll-like receptor 2(TLR2).Results Morusin significantly reduced the serum levels of ALT,AST,and inflammatory factors(TNF-α,IL-6,and IL-1β)(P<0.05,P<0.01,or P<0.001),while alleviating the hepatic pathological damage in mice.Based on efficacy comparisons,morusin-H group was selected for subsequent microbiome and transcriptome analyses.Microbiome analysis revealed that morusin-H effectively mitigated LPS-induced gut dysbiosis and restored the Firmicutes/Bacteroidota balance(P<0.01).At the genus level,morusin-H significantly reduced the abundances of norank_f_Muribaculaceae,Desulfovibrio,Parabacteroides,and Muribaculum(P<0.05,P<0.01,or P<0.001).At the phylum,family,and genus levels,our findings indicated that morusin-H treatment caused a significant decrease in the abundance of Desulfobacterota,Desulfovibrionaceae,and Desulfovibrio(P<0.01).Importantly,the abundance of Desulfovibrio was positively correlated with the levels of ALT,AST,TNF-α,IL-1β,and IL-6.Transcriptomic and molecular analyses showed that the therapeutic mechanism of morusin-H involved suppression of the IL-17/TNF signaling pathways and downregulating the mRNA levels of Tlr2,Tlr3,Myd88,Il6,and Cxcl10(P<0.05 or P<0.001),as well as the protein levels of key inflammatory mediators(IL-6,MYD88,and TLR2)(P<0.001).Conclusion Morusin demonstrates protective effects against LPS-induced acute liver injury,likely through modulation of gut microbiota and suppression of pro-inflammatory factor expression.These findings indicate that morusin exerts its effects through the"microbiota-inflammation-liver"axis,providing a theoretical basis for its use as a multi-target plant-based drug in the treatment of metabolic inflammation-related liver diseases.
文摘The root bark of Morus alba L. or white mulberry is widely used as traditional medicine in China, Japan and Korea. Major classes and types of phenolic compounds isolated from the root bark are flavonoids(kuwanons, morusin, cyclomorusin and sanggenons), benzofurans(moracins and mulberrofurans), and stilbenoids(mulberrosides). Some of the flavonoids and benzofurans are products of Diel-Alder type adducts. Other classes of compounds include triterpenes, phenolic acids and coumarins. Morusin, a prenylated flavonoid, was first isolated from the root bark of M. alba, and later from the leaf, stem bark and twig of the plant. The potent anti-cancer properties of morusin have attracted much attention with research on-going and new findings being published. The compound inhibits angiogenesis, tumour progression and tumour migration, and triggers apoptosis, cell cycle arrest and autophagy in colorectal, cervical, prostate, breast, hepatoma, pancreatic, glioblastoma, gastric, ovarian and lung cancer cell lines. The anti-cancer activities of morusin are executed via various molecular targets and signalling pathways. It is anticipated that on-going in vitro studies will progress gradually to in vivo studies using animal models before efforts towards drug development can be initiated for clinical trials.
文摘The distribution and content differentiation of morusin in the cultivated species of mulberry by HPLC-DAD are described in this paper. The experimental results showed that morusin is present in all parts of the mulberry bush. The content of morusin was highest in root bark and second highest in branch bark. The difference in morusin content of 20 different species of cultivated mulberry branch bark was significant. The level of morusin was highest in the branch bark of cultivated mulberry No. 404, a tetraploid cultivar, and third in the Husang 32 cultivar of Morus multicaulis. The method used in this study for determining morusin content exhibited good repeatability (RSD 6.02%) and recovery (100.62%). Therefore, the results from this study provide reliable data, for research and development in the future, on the level and distribution of morusin in mulberry in general and the differences found between various cultivated mulberries in particular. Furthermore, the HPLC-DAD method to determine morusin content is fast and reliable and is applicable not only to mulberry bushes but also to other plants.
文摘桑(Morus alba L.)为桑科重要药用植物,其根皮(桑根皮)富含黄酮、酚类等活性成分,具有抗炎、抗氧化等多种药理效应。桑辛素(morusin)为其代表性黄酮类成分,尚未明确其在运动性肾损伤中的作用。本研究探讨桑辛素对力竭运动诱导小鼠肾损伤的保护作用及机制。采用负重游泳法建立模型,分别给予不同剂量桑辛素,并联合STAT3激动剂C-TFA干预。结果显示,桑辛素可剂量依赖性降低Cr、BUN、NGAL、KIM-1水平,改善肾组织损伤,抑制STAT3磷酸化,降低促炎因子和氧化应激水平,调节Bcl-2/Bax表达,减少细胞凋亡,STAT3激动剂干预显著削弱桑辛素效应。结果表明,桑辛素通过靶向STAT3通路显著减轻运动性肾损伤,具有作为天然运动防护剂的潜力。
