BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the i...BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the impact of MV on acute liver injury(ALI)is unknown.AIM To investigate the hepatoprotective potential of MV against liver damage caused by APAP and to examine the underlying mechanisms.METHODS Mice were divided into three groups:Saline,APAP and APAP+MV.MV(10 mg/kg)was given intraperitoneally one hour before APAP(300 mg/kg)administration.Twenty-four hours after APAP exposure,serum transaminase levels,liver necrotic area,inflammatory responses,nitrotyrosine accumulation,and c-jun-N-terminal kinase(JNK)activation were assessed.Additionally,we analyzed reactive oxygen species(ROS)levels,JNK activation,and cell death in alpha mouse liver 12(AML12)cells.RESULTS MV pre-treatment in vivo led to a reduction in the rise of aspartate transaminase and alanine transaminase levels,mitigated liver damage,decreased nitrotyrosine accumulation,and blocked JNK phosphorylation resulting from APAP exposure,without affecting glutathione production.Similarly,MV diminished the APAP-induced increase in ROS,JNK phosphorylation,and cell death in vitro.CONCLUSION Our study suggests that MV treatment alleviates APAP-induced ALI by reducing ROS and JNK activation.展开更多
In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussiv...In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.展开更多
Fungal endophytes,as an untapped resource of glycoside hydrolase biocatalysts,need to be further developed.Mogroside V,the primary active compound in Siraitia grosvenorii fruit,can be converted into other various bioa...Fungal endophytes,as an untapped resource of glycoside hydrolase biocatalysts,need to be further developed.Mogroside V,the primary active compound in Siraitia grosvenorii fruit,can be converted into other various bioactive mogrosides by selective hydrolysis of glucose residues at C3 and C24 positions.In present study,20 fungal strains were randomly selected from our endophytic fungal strain library to assess their capability for mogroside V transformation.The results revealed that relatively high rate(30%)endophytic fungal strains exhibited transformative potential.Further analysis indicated that endophytic fungi could produce abundant mogrosides,and the pathways for biotransforming mogroside V showed diverse.Among the given fungal endophytes,Aspergillus sp.S125 almost completely converted mogroside V into the end-products mogroside II A and aglycone within just 2 days of fermentation;Muyocopron sp.A5 produced rich intermediate products,including siamenoside I,and the end-product mogroside II E.Subsequently,we optimized the fermentation conditions for Aspergillus sp.S125 and Muyocopron sp.A5 to evaluate the feasibility of large-scale mogroside V conversion.After optimization,Aspergillus sp.S125 converted 10 g/L of mogroside V into 4.5 g/L of mogroside II A and 3.6 g/L of aglycone after 3 days of fermentation,whereas Muyocopron sp.A5 selectively produced 4.88 g/L of siamenoside I from 7.5 g/L of mogroside V after 36 h of fermentation.This study not only identifies highly effective biocatalytic candidates for mogrosides transformation,but also strongly suggests the potential of plant endophytic fungi as valuable resources for the biocatalysis of natural compounds.展开更多
Aim To investigate the structure of mogroside Ⅳa isolated from traditionalChinese medicine fructus mo-mordicae [fruits of Siraitia grosvenori (Swingle) C. Jeffery] andsummarize the NMR characteristics of the structur...Aim To investigate the structure of mogroside Ⅳa isolated from traditionalChinese medicine fructus mo-mordicae [fruits of Siraitia grosvenori (Swingle) C. Jeffery] andsummarize the NMR characteristics of the structure. Methods Common extraction, separation andpurification methods were used. Various NMR techniques including ~1H NMR, ^(13)C NMR, DEPT, ~1H-~1HCOSY, HSQC, HMBC, NOESY and molecular model simulated by computer were used to elucidate thestructure. Results ~1H and ^(13)C NMR signals of mogroside Ⅳa were assigned, and spectroscopicbasis was obtained for identification of such type of compounds. Conclusion 1D and 2D NMR techniquesincluding ~1H-~1H COSY, HSQC, HMBC, NOESY spectra are powerful tools for structure analysis. Thestructure determined by NMR methods is identical with energy minimized conformation simulated bycomputer.展开更多
[Objectives]To explore the effects and mechanism of mogroside V(MV)on glucose and lipid metabolism in high-fat diet(HFD)mice.[Methods]The experiment fed mice with high-fat diet for 8 weeks,and 40 mice with successful ...[Objectives]To explore the effects and mechanism of mogroside V(MV)on glucose and lipid metabolism in high-fat diet(HFD)mice.[Methods]The experiment fed mice with high-fat diet for 8 weeks,and 40 mice with successful modeling were randomly divided into normal group,model group,and MV dose group(100,200 mg/kg),with 10 mice in each group.From the ninth week,the MV dose group was given intragastric administration,and the normal group and the model group were given an equal volume of distilled water by intragastric administration for 6 weeks,then killed and blood samples and livers were collected.Serum triglycerides(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),Advanced glycation end products(AGE-P)-peptides(AGE-P)and glycosylated hemoglobin(HbA1c)content,and TG and hepatic glycogen content in liver were detected by biochemical method.Fasting blood glucose(FBG)was measured by glucose oxidase method.The fasting serum insulin(FINS)content was detected by enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index(HOMA-IR)was calculated.Oil red O staining was used to observe the fat deposition in liver tissue.[Results]MV(100,200 mg/kg)dose groups could significantly down-regulate the contents of TC,TG,LDL-C,FBG,FINS,AGE-P and HbA1c and HOMA-IR,and up-regulate HDL-C and hepatic glycogen content and reduce the fat deposits.[Conclusions]The mechanism of MV regulating glucose and lipid metabolism in mice may be related to the regulation of insulin resistance.展开更多
Siraitia grosvenorii(SG),a traditional edible medicine in China,has shown potential application in health foods due to multiple bioactivities.However,few comparative studies have investigated the effect of daily intak...Siraitia grosvenorii(SG),a traditional edible medicine in China,has shown potential application in health foods due to multiple bioactivities.However,few comparative studies have investigated the effect of daily intake of SG products by traditional drinking way on alleviating metabolic disorders caused by long-term high fat and high sugar diet(HF-HSD).This study investigated the effects of 2 commercial SG products(SG juice containing comprehensive compositions and mogrosides extract containing high content of mogroside V)supplement on fat content,lipid accumulation,colon barrier and gut microbiota in a 38-week HF-HSD mice trial.Results showed that the SG intervention could decrease the weight gain and body fat content,alleviated lipid accumulation,low-grade inflammation and colon barrier injury.SG juice intake was found to increase the antioxidant enzyme activities of serum glutathione peroxidase and liver superoxide dismutase.16S r RNA analysis found that SG could restore the gut microbiota with downregulation of harmful bacteria increased by HF-HSD and enhancement of the abundances of beneficial genus.In particular,SG juice significantly enriched taxonomic family Prevotellaceae and genus Alloprevotella.These results indicated that SG might be a functional additive to prevent disease risk caused by excess fat and sugar diet,and active ingredients resulting to the discrepancy of performance especially on gut microbiota are worthy of in-depth investigation.展开更多
Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we inv...Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto<sup>ò</sup> (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G<sub>1</sub> cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.展开更多
Functional manipulation of biosynthetic enzymes such as cytochrome P450 s(or P450 s) has attracted great interest in metabolic engineering of plant natural products.Cucurbitacins and mogrosides are plant triterpenoids...Functional manipulation of biosynthetic enzymes such as cytochrome P450 s(or P450 s) has attracted great interest in metabolic engineering of plant natural products.Cucurbitacins and mogrosides are plant triterpenoids that share the same backbone but display contrasting bioactivities.This structural and functional diversity of the two metabolites can be manipulated by engineering P450 s.However,the functional redesign of P450 s through directed evolution(DE) or structure-guided protein engineering is time consuming and challenging,often because of a lack of high-throughput screening methods and crystal structures of P450 s.In this study,we used an integrated approach combining computational protein design,evolutionary information,and experimental data-driven optimization to alter the substrate specificity of a multifunctional P450(CYP87 D20)from cucumber.After three rounds of iterative design and evaluation of 96 protein variants,CYP87 D20,which is involved in the cucurbitacin C biosynthetic pathway,was successfully transformed into a P450 mono-oxygenase that performs a single specific hydroxylation at C11 of cucurbitadienol.This integrated P450-engineering approach can be further applied to create a de novo pathway to produce mogrol,the precursor of the natural sweetener mogroside,or to alter the structural diversity of plant triterpenoids by functionally manipulating other P450 s.展开更多
基金Supported by Guangxi Natural Science Foundation of China,No.2024GXNSFAA010040Special Fund of the Central Government Guiding Local Scientific and Technological Development by Guangxi Science and Technology Department,No.GuikeZY21195024National Natural Science Foundation of China,No.82260499 and No.82460463.
文摘BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the impact of MV on acute liver injury(ALI)is unknown.AIM To investigate the hepatoprotective potential of MV against liver damage caused by APAP and to examine the underlying mechanisms.METHODS Mice were divided into three groups:Saline,APAP and APAP+MV.MV(10 mg/kg)was given intraperitoneally one hour before APAP(300 mg/kg)administration.Twenty-four hours after APAP exposure,serum transaminase levels,liver necrotic area,inflammatory responses,nitrotyrosine accumulation,and c-jun-N-terminal kinase(JNK)activation were assessed.Additionally,we analyzed reactive oxygen species(ROS)levels,JNK activation,and cell death in alpha mouse liver 12(AML12)cells.RESULTS MV pre-treatment in vivo led to a reduction in the rise of aspartate transaminase and alanine transaminase levels,mitigated liver damage,decreased nitrotyrosine accumulation,and blocked JNK phosphorylation resulting from APAP exposure,without affecting glutathione production.Similarly,MV diminished the APAP-induced increase in ROS,JNK phosphorylation,and cell death in vitro.CONCLUSION Our study suggests that MV treatment alleviates APAP-induced ALI by reducing ROS and JNK activation.
基金the National Natural Science Foundation(81773982,82003937)Youth Academic leaders of the Qinglan Project in Jiangsu province for financial support。
文摘In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.
基金supported by the National Key R&D Program of China(2021YFC2101303)by the Natural Science Foundation of Jiangxi Province of China(20212BAB215006,20224BAB215023,20232BAB205008)by the Foundation of Jiangxi Educational Committee(GJJ2201346,GJJ2201319).
文摘Fungal endophytes,as an untapped resource of glycoside hydrolase biocatalysts,need to be further developed.Mogroside V,the primary active compound in Siraitia grosvenorii fruit,can be converted into other various bioactive mogrosides by selective hydrolysis of glucose residues at C3 and C24 positions.In present study,20 fungal strains were randomly selected from our endophytic fungal strain library to assess their capability for mogroside V transformation.The results revealed that relatively high rate(30%)endophytic fungal strains exhibited transformative potential.Further analysis indicated that endophytic fungi could produce abundant mogrosides,and the pathways for biotransforming mogroside V showed diverse.Among the given fungal endophytes,Aspergillus sp.S125 almost completely converted mogroside V into the end-products mogroside II A and aglycone within just 2 days of fermentation;Muyocopron sp.A5 produced rich intermediate products,including siamenoside I,and the end-product mogroside II E.Subsequently,we optimized the fermentation conditions for Aspergillus sp.S125 and Muyocopron sp.A5 to evaluate the feasibility of large-scale mogroside V conversion.After optimization,Aspergillus sp.S125 converted 10 g/L of mogroside V into 4.5 g/L of mogroside II A and 3.6 g/L of aglycone after 3 days of fermentation,whereas Muyocopron sp.A5 selectively produced 4.88 g/L of siamenoside I from 7.5 g/L of mogroside V after 36 h of fermentation.This study not only identifies highly effective biocatalytic candidates for mogrosides transformation,but also strongly suggests the potential of plant endophytic fungi as valuable resources for the biocatalysis of natural compounds.
文摘Aim To investigate the structure of mogroside Ⅳa isolated from traditionalChinese medicine fructus mo-mordicae [fruits of Siraitia grosvenori (Swingle) C. Jeffery] andsummarize the NMR characteristics of the structure. Methods Common extraction, separation andpurification methods were used. Various NMR techniques including ~1H NMR, ^(13)C NMR, DEPT, ~1H-~1HCOSY, HSQC, HMBC, NOESY and molecular model simulated by computer were used to elucidate thestructure. Results ~1H and ^(13)C NMR signals of mogroside Ⅳa were assigned, and spectroscopicbasis was obtained for identification of such type of compounds. Conclusion 1D and 2D NMR techniquesincluding ~1H-~1H COSY, HSQC, HMBC, NOESY spectra are powerful tools for structure analysis. Thestructure determined by NMR methods is identical with energy minimized conformation simulated bycomputer.
基金Supported by Science and Technology Planning Project of Guangxi,China (Gui Ke AA19254025)
文摘[Objectives]To explore the effects and mechanism of mogroside V(MV)on glucose and lipid metabolism in high-fat diet(HFD)mice.[Methods]The experiment fed mice with high-fat diet for 8 weeks,and 40 mice with successful modeling were randomly divided into normal group,model group,and MV dose group(100,200 mg/kg),with 10 mice in each group.From the ninth week,the MV dose group was given intragastric administration,and the normal group and the model group were given an equal volume of distilled water by intragastric administration for 6 weeks,then killed and blood samples and livers were collected.Serum triglycerides(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),Advanced glycation end products(AGE-P)-peptides(AGE-P)and glycosylated hemoglobin(HbA1c)content,and TG and hepatic glycogen content in liver were detected by biochemical method.Fasting blood glucose(FBG)was measured by glucose oxidase method.The fasting serum insulin(FINS)content was detected by enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index(HOMA-IR)was calculated.Oil red O staining was used to observe the fat deposition in liver tissue.[Results]MV(100,200 mg/kg)dose groups could significantly down-regulate the contents of TC,TG,LDL-C,FBG,FINS,AGE-P and HbA1c and HOMA-IR,and up-regulate HDL-C and hepatic glycogen content and reduce the fat deposits.[Conclusions]The mechanism of MV regulating glucose and lipid metabolism in mice may be related to the regulation of insulin resistance.
基金funded by Guangxi Science and Technology Major Project(Guike AA23023035,Guike AA22096020)the Joint Funds of the National Natural Science Foundation of China(U20A2004)+1 种基金Guilin Innovation Platform and Talent Plan(20210102-3)Guangxi Science and Technology Base and Talent Project(Guike AA21196009)。
文摘Siraitia grosvenorii(SG),a traditional edible medicine in China,has shown potential application in health foods due to multiple bioactivities.However,few comparative studies have investigated the effect of daily intake of SG products by traditional drinking way on alleviating metabolic disorders caused by long-term high fat and high sugar diet(HF-HSD).This study investigated the effects of 2 commercial SG products(SG juice containing comprehensive compositions and mogrosides extract containing high content of mogroside V)supplement on fat content,lipid accumulation,colon barrier and gut microbiota in a 38-week HF-HSD mice trial.Results showed that the SG intervention could decrease the weight gain and body fat content,alleviated lipid accumulation,low-grade inflammation and colon barrier injury.SG juice intake was found to increase the antioxidant enzyme activities of serum glutathione peroxidase and liver superoxide dismutase.16S r RNA analysis found that SG could restore the gut microbiota with downregulation of harmful bacteria increased by HF-HSD and enhancement of the abundances of beneficial genus.In particular,SG juice significantly enriched taxonomic family Prevotellaceae and genus Alloprevotella.These results indicated that SG might be a functional additive to prevent disease risk caused by excess fat and sugar diet,and active ingredients resulting to the discrepancy of performance especially on gut microbiota are worthy of in-depth investigation.
文摘Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto<sup>ò</sup> (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G<sub>1</sub> cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.
基金supported by the National Natural Science Foundation of China(31672171,81773597)Shenzhen municipal(JCYJ20160530191729620 to Y.S.)Dapeng district governments
文摘Functional manipulation of biosynthetic enzymes such as cytochrome P450 s(or P450 s) has attracted great interest in metabolic engineering of plant natural products.Cucurbitacins and mogrosides are plant triterpenoids that share the same backbone but display contrasting bioactivities.This structural and functional diversity of the two metabolites can be manipulated by engineering P450 s.However,the functional redesign of P450 s through directed evolution(DE) or structure-guided protein engineering is time consuming and challenging,often because of a lack of high-throughput screening methods and crystal structures of P450 s.In this study,we used an integrated approach combining computational protein design,evolutionary information,and experimental data-driven optimization to alter the substrate specificity of a multifunctional P450(CYP87 D20)from cucumber.After three rounds of iterative design and evaluation of 96 protein variants,CYP87 D20,which is involved in the cucurbitacin C biosynthetic pathway,was successfully transformed into a P450 mono-oxygenase that performs a single specific hydroxylation at C11 of cucurbitadienol.This integrated P450-engineering approach can be further applied to create a de novo pathway to produce mogrol,the precursor of the natural sweetener mogroside,or to alter the structural diversity of plant triterpenoids by functionally manipulating other P450 s.
