AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs) o...AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. RESULTS: A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001). Constipation (r 2 = 39%, P = 0.01), higher mean age (r 2 = 27%, P = 0.03), and higher percentage of female subjects (r 2 = 23%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79) vs 0.17 (95%CI: -0.08-0.42), P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis ) HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01) and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01) while other single strains and combination products yielded small treatment effects. CONCLUSION: Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains.展开更多
AIM: To determine the efficacy of probiotic supplementation on intestinal transit time(ITT) in adults and to identify factors that influence these outcomes. METHODS: We conducted a systematic review of randomized cont...AIM: To determine the efficacy of probiotic supplementation on intestinal transit time(ITT) in adults and to identify factors that influence these outcomes. METHODS: We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference(SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT.RESULTS: A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38(95%CI: 0.23-0.53, P < 0.001). Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation(SMD: 0.57 vs 0.22, P < 0.01) and in studies with high vs low study quality(SMD: 0.45 vs 0.00, P = 0.01). Constipation(R^2 = 38%, P < 0.01), higher study quality(R^2 = 31%, P = 0.01), older age(R^2 = 27%, P = 0.02), higher percentage of female subjects(R^2 = 26%, P = 0.02), and fewer probiotic strains(R^2 = 20%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019(SMD: 0.67, P < 0.001) and B. lactis DN-173 010(SMD: 0.54, P < 0.01) while other probiotic strains yielded negligible reductions in ITT relative to control.CONCLUSION: Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.展开更多
Objectives:to verify the feasibility and reliability of the electronic version of Chinese SF-36 based on the Quality-of-Life-Recorder. Design: A crossover randomized controlled trial, comparing a paper-based and an el...Objectives:to verify the feasibility and reliability of the electronic version of Chinese SF-36 based on the Quality-of-Life-Recorder. Design: A crossover randomized controlled trial, comparing a paper-based and an electronic version of the Chinese SF-36, was conducted. According to generated random numbers, interviewees were asked to fill out either the electronic version or the paper version first. The second version was filled in after a pause of at least 10 min. Settings and participants: One group of 100 medical students at the School of Medicine of Zhejiang University and the other group of 50 outpatients at a clinic for general practice in Hangzhou City (China) were eventually recruited in this study. Results: The acceptance of the electronic version was good (60% of medical students and 84% of outpatients preferred the electronic version). At the level of eight-scale scores, the mean-difference for each scale (except for general health) between the two versions was less than 5%. At the level of 36 questions, the percentage of "exact agreement" ranged within 64%～99%; the percentage of "global agreement" ranged within 72%～99%; 77% of the kappa coefficients demonstrated "good/excellent agreement" and 23% of the kappa coefficients demonstrated "medium agreement". Conclusion: This study, for the first time, can provide empirical basis for the confirmation of the feasibility and reliability of the electronic version of the Chinese SF-36 and may provide an impulse towards widespread deployment of the Quality-of-Life-Recorder in Chinese populations.展开更多
Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(no...Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.展开更多
Phytolacca(Shanglu)is a well-known traditional herbal medi-cine that has been used for thousands of years in China.Phytolacca is also used worldwide in different traditional phyto-medicines and homeopathic preparation...Phytolacca(Shanglu)is a well-known traditional herbal medi-cine that has been used for thousands of years in China.Phytolacca is also used worldwide in different traditional phyto-medicines and homeopathic preparations.The present work re-viewed advances in the traditional uses,plant origin,chemical constituents,pharmacology,and medicinal properties of Phytolacca.Phytolacca is usually made from the roots of Phytolacca acinosa and P.esculenta,but the invasive plant P.americana(American pokeweed)is also widely used.Different types of medicinal products made with Phytolacca are available,as well as various types of Phytolacca extracts,showing a range of pharmacological activities including antioxidant,anti-inflammat-ory,anti-parasitic,antifungal,anticancer,and insecticidal effects.The marked anti-inflammatory activity of Phytolacca extracts supports its use in treating diseases such as arthritis,nephritis,and rheumatism,as well as in combatting cancer.Several bioact-ive natural products have been identified from Phytolacca,in-cluding glycosylated saponins such as esculentosides and phytolaccosides,as well as a few flavones(cochliophilin A)and phytosterols(α-spinasterol),which contribute to Phytolacca’s anti-inflammatory and/or anticancer effects.A quality evaluation of Phytolacca-based extracts and products is highly recommen-ded;nevertheless,the use of Phytolacca can be encouraged to help regulate cytokine production and combat inflammatory dis-eases.展开更多
Objective Bouchardatine(1)is a β-indoloquinazoline alkaloid isolated from the plant Bouchardatia neurococca,acting as a modulator of adipogenesis and lipogenesis,and as an anticancer agent.The natural product functio...Objective Bouchardatine(1)is a β-indoloquinazoline alkaloid isolated from the plant Bouchardatia neurococca,acting as a modulator of adipogenesis and lipogenesis,and as an anticancer agent.The natural product functions as an activator of proteins adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)and sirtuin 1(SIRT1).We used molecular modeling to investigate the SIRT1-binding capacity of compound 1 and various structural analogues,such as orirenierine A(2)and orirenierine B(3)isolated from the medicinal plant Oricia renieri.Methods We investigated the binding to human SIRT1(hSIRT1)of 25 natural products including theβ-indoloquinazoline alkaloids 1−3 and analogues,in comparison with the reference product sirtinol(R and S isomers).A sirtinol binding model was elaborated starting from the closed and open state conformations of the catalytic domain of hSIRT1(PDB structures 4KXQ and 4IG9).For each compound bound to SIRT1,the empirical energy of interaction(ΔE)was calculated and compared to that of sirtinol.Results In our model,compound 1 was found to bind modestly to the sirtinol site of SIRT1.In contrast,the presence of a phenolic OH group at position 7 on the quinazolinone moiety conferred a much higher binding capacity.Compound 2 provided SIRT1 protein complexes as stable as those observed with sirtinol.The replacement of the hydroxy substituent(2)with a methoxy group(3)reduced the SIRT1 binding capacity.Other SIRT1-binding natural products were identified,such as the alkaloids orisuaveolines A and B.Structure-binding relationships were discussed.Conclusion The study underlines the capacity of β-indoloquinazoline alkaloids to interact with SIRT1.This deacetylase enzyme could represent a molecular target for the alkaloid 2.This compound merits further attention for the design of drugs active against SIRT1-dependent pathologies.展开更多
Objective The mangrove tree Xylocarpus granatum J.Koenig(X.granatum)is a medicinal plant used to treat various diseases in several Asian countries.Many bioactive natural products have been isolated from the plants,par...Objective The mangrove tree Xylocarpus granatum J.Koenig(X.granatum)is a medicinal plant used to treat various diseases in several Asian countries.Many bioactive natural products have been isolated from the plants,particularly several groups of limonoids,including 18 xylogranatins(Xyl-A to R),all of which bear a furyl-δ-lactone core commonly found in limonoids.Based on a structural analogy with the limonoids obacunone and gedunin,we hypothesized that xylogranatins could target the enzyme glycogen synthase kinase-3β(GSK-3β),a major target for the treatment of neurodegenerative pathologies,viral infections,and cancers.Methods We investigated the binding of the 18 xylogranatins to GSK-3βusing molecular docking in comparison with two known reference GSK-3βATP-competitive inhibitors,LY2090314 and AR-A014418.For each compound bound to GSK-3β,the empirical energy of interaction(ΔE)was calculated and compared to that obtained with known GSK-3βinhibitors and limonoid triterpenes that target this enzyme.Results Five compounds were identified as potential GSK-3βbinders,Xyl-A,-C,-J,-N,and-O,for which the calculated empiricalΔE was equivalent to that calculated using the best reference molecule AR-A014418.The best ligand is Xyl-C,which is known to have marked anticancer properties.Binding of Xyl-C to the ATP-binding pocket of GSK-3βpositions the furyl-δ-lactone unit deep into the binding-site cavity.Other xylogranatin derivatives bearing a central pyridine ring or a compact polycyclic structure are much less adapted for GSK-3βbinding.Structure-binding relationships are discussed.Conclusion GSK-3βmay contribute to the anticancer effects of X.granatum extract.This study paves the way for the identification of other furyl-δ-lactone-containing limonoids as GSK-3βmodulators.展开更多
It is important that scientific advice is taken into account in making decisions directed at meeting the needs of the rapidly increasing global population and the aspirations of developing nations,while sustaining Ear...It is important that scientific advice is taken into account in making decisions directed at meeting the needs of the rapidly increasing global population and the aspirations of developing nations,while sustaining Earth systems.However,this has not commonly been the case–it is an all too frequent complaint of scientists,that their advice has not been sought,or has been ignored.展开更多
The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenyletha...The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides(Ph Gs) such as the forsythosides(Fst A-to-P). The leading products, Fst-A,-B and-F(arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1(Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2(Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal(TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. Ph Gs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.展开更多
The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China...The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China). The multiple properties and applications of this herbal medicine have been analyzed. C. otophyllum is a perennial herbal liana, nonedible, and generally wild harvested. A cultivation method has been proposed to increase the fruit set level. Qingyangshen is used essentially to treat epilepsy, rheumatism, or other inflammatory diseases. The plant can be found also in diverse polyherbal preparations used in cosmetic or as food supplement(detox products), and in phyto-preparations claimed to reduce hair loss. The plant is a rich reservoir of C-21 steroidal glycosides. Many bioactive compounds have been isolated from this plant and some of them have been pharmacologically characterized, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, all briefly evocated here. The plant presents also interesting features in other domains. In particular, leave extracts of C. otophyllum C. K. Schneid contain proteases which are exploited for the local preparation of a cheese-like milk cake. Qingyangshen herbal preparation can be useful to treat epilepsy and inflammation. It has applications beyond medicine in the cosmetic and food industry.展开更多
The utilization of natural preservatives and active packaging in extending the shelf life of food products during storage is vital to meet consumer demand for minimally processed food under sustainable systems.Fiber a...The utilization of natural preservatives and active packaging in extending the shelf life of food products during storage is vital to meet consumer demand for minimally processed food under sustainable systems.Fiber and nanofiber,isolated from cells of different biologically active plants,possess antimicrobial activity and can be used as packaging material with an active ingredient.Soluble or insoluble fibers incorporated into edible films or coatings are particularly popular as functional food additives because of their characteristics.Moreover,fiber serves as an excellent packaging material with mechanical strength,antimicrobial properties,water vapor and oxygen permeability,high phenolic content,and thermal stability and therefore can be enhanced by the incorporation of different ingredients,which is also discussed in this work.It has been found that fiber and nanofiber based edible packaging materials can inhibit the growth of pathogenic bacteria and lipid oxidation.Furthermore,substantial changes have been reported in the surface morphology and mechanical properties of films/coatings with the addition of fiber based active materials like beta-glucan,pectin,guar gum,inulin,psyllium,cellulose,hemicellulose,chitosan and lignin.Hence,the existing literature articulates recent developments and their applications.Therefore,fiber/nanofiber can be a promising substitute for synthetic preservatives.展开更多
文摘AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. RESULTS: A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001). Constipation (r 2 = 39%, P = 0.01), higher mean age (r 2 = 27%, P = 0.03), and higher percentage of female subjects (r 2 = 23%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79) vs 0.17 (95%CI: -0.08-0.42), P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis ) HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01) and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01) while other single strains and combination products yielded small treatment effects. CONCLUSION: Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains.
文摘AIM: To determine the efficacy of probiotic supplementation on intestinal transit time(ITT) in adults and to identify factors that influence these outcomes. METHODS: We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference(SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT.RESULTS: A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38(95%CI: 0.23-0.53, P < 0.001). Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation(SMD: 0.57 vs 0.22, P < 0.01) and in studies with high vs low study quality(SMD: 0.45 vs 0.00, P = 0.01). Constipation(R^2 = 38%, P < 0.01), higher study quality(R^2 = 31%, P = 0.01), older age(R^2 = 27%, P = 0.02), higher percentage of female subjects(R^2 = 26%, P = 0.02), and fewer probiotic strains(R^2 = 20%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019(SMD: 0.67, P < 0.001) and B. lactis DN-173 010(SMD: 0.54, P < 0.01) while other probiotic strains yielded negligible reductions in ITT relative to control.CONCLUSION: Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.
基金Project (No. WKJ2006-2-016) supported by the project of "Effect of Chronic Disease and Health-Related Quality of Life on Health Service Utilization" from the Ministry of Health, China
文摘Objectives:to verify the feasibility and reliability of the electronic version of Chinese SF-36 based on the Quality-of-Life-Recorder. Design: A crossover randomized controlled trial, comparing a paper-based and an electronic version of the Chinese SF-36, was conducted. According to generated random numbers, interviewees were asked to fill out either the electronic version or the paper version first. The second version was filled in after a pause of at least 10 min. Settings and participants: One group of 100 medical students at the School of Medicine of Zhejiang University and the other group of 50 outpatients at a clinic for general practice in Hangzhou City (China) were eventually recruited in this study. Results: The acceptance of the electronic version was good (60% of medical students and 84% of outpatients preferred the electronic version). At the level of eight-scale scores, the mean-difference for each scale (except for general health) between the two versions was less than 5%. At the level of 36 questions, the percentage of "exact agreement" ranged within 64%～99%; the percentage of "global agreement" ranged within 72%～99%; 77% of the kappa coefficients demonstrated "good/excellent agreement" and 23% of the kappa coefficients demonstrated "medium agreement". Conclusion: This study, for the first time, can provide empirical basis for the confirmation of the feasibility and reliability of the electronic version of the Chinese SF-36 and may provide an impulse towards widespread deployment of the Quality-of-Life-Recorder in Chinese populations.
文摘Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.
基金The in silico molecular model presented in Figure 4 was kindly provided by Prof.Gérard Vergoten(Uni-versity of Lille,Inserm U1286,Lille,France).
文摘Phytolacca(Shanglu)is a well-known traditional herbal medi-cine that has been used for thousands of years in China.Phytolacca is also used worldwide in different traditional phyto-medicines and homeopathic preparations.The present work re-viewed advances in the traditional uses,plant origin,chemical constituents,pharmacology,and medicinal properties of Phytolacca.Phytolacca is usually made from the roots of Phytolacca acinosa and P.esculenta,but the invasive plant P.americana(American pokeweed)is also widely used.Different types of medicinal products made with Phytolacca are available,as well as various types of Phytolacca extracts,showing a range of pharmacological activities including antioxidant,anti-inflammat-ory,anti-parasitic,antifungal,anticancer,and insecticidal effects.The marked anti-inflammatory activity of Phytolacca extracts supports its use in treating diseases such as arthritis,nephritis,and rheumatism,as well as in combatting cancer.Several bioact-ive natural products have been identified from Phytolacca,in-cluding glycosylated saponins such as esculentosides and phytolaccosides,as well as a few flavones(cochliophilin A)and phytosterols(α-spinasterol),which contribute to Phytolacca’s anti-inflammatory and/or anticancer effects.A quality evaluation of Phytolacca-based extracts and products is highly recommen-ded;nevertheless,the use of Phytolacca can be encouraged to help regulate cytokine production and combat inflammatory dis-eases.
文摘Objective Bouchardatine(1)is a β-indoloquinazoline alkaloid isolated from the plant Bouchardatia neurococca,acting as a modulator of adipogenesis and lipogenesis,and as an anticancer agent.The natural product functions as an activator of proteins adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)and sirtuin 1(SIRT1).We used molecular modeling to investigate the SIRT1-binding capacity of compound 1 and various structural analogues,such as orirenierine A(2)and orirenierine B(3)isolated from the medicinal plant Oricia renieri.Methods We investigated the binding to human SIRT1(hSIRT1)of 25 natural products including theβ-indoloquinazoline alkaloids 1−3 and analogues,in comparison with the reference product sirtinol(R and S isomers).A sirtinol binding model was elaborated starting from the closed and open state conformations of the catalytic domain of hSIRT1(PDB structures 4KXQ and 4IG9).For each compound bound to SIRT1,the empirical energy of interaction(ΔE)was calculated and compared to that of sirtinol.Results In our model,compound 1 was found to bind modestly to the sirtinol site of SIRT1.In contrast,the presence of a phenolic OH group at position 7 on the quinazolinone moiety conferred a much higher binding capacity.Compound 2 provided SIRT1 protein complexes as stable as those observed with sirtinol.The replacement of the hydroxy substituent(2)with a methoxy group(3)reduced the SIRT1 binding capacity.Other SIRT1-binding natural products were identified,such as the alkaloids orisuaveolines A and B.Structure-binding relationships were discussed.Conclusion The study underlines the capacity of β-indoloquinazoline alkaloids to interact with SIRT1.This deacetylase enzyme could represent a molecular target for the alkaloid 2.This compound merits further attention for the design of drugs active against SIRT1-dependent pathologies.
文摘Objective The mangrove tree Xylocarpus granatum J.Koenig(X.granatum)is a medicinal plant used to treat various diseases in several Asian countries.Many bioactive natural products have been isolated from the plants,particularly several groups of limonoids,including 18 xylogranatins(Xyl-A to R),all of which bear a furyl-δ-lactone core commonly found in limonoids.Based on a structural analogy with the limonoids obacunone and gedunin,we hypothesized that xylogranatins could target the enzyme glycogen synthase kinase-3β(GSK-3β),a major target for the treatment of neurodegenerative pathologies,viral infections,and cancers.Methods We investigated the binding of the 18 xylogranatins to GSK-3βusing molecular docking in comparison with two known reference GSK-3βATP-competitive inhibitors,LY2090314 and AR-A014418.For each compound bound to GSK-3β,the empirical energy of interaction(ΔE)was calculated and compared to that obtained with known GSK-3βinhibitors and limonoid triterpenes that target this enzyme.Results Five compounds were identified as potential GSK-3βbinders,Xyl-A,-C,-J,-N,and-O,for which the calculated empiricalΔE was equivalent to that calculated using the best reference molecule AR-A014418.The best ligand is Xyl-C,which is known to have marked anticancer properties.Binding of Xyl-C to the ATP-binding pocket of GSK-3βpositions the furyl-δ-lactone unit deep into the binding-site cavity.Other xylogranatin derivatives bearing a central pyridine ring or a compact polycyclic structure are much less adapted for GSK-3βbinding.Structure-binding relationships are discussed.Conclusion GSK-3βmay contribute to the anticancer effects of X.granatum extract.This study paves the way for the identification of other furyl-δ-lactone-containing limonoids as GSK-3βmodulators.
文摘It is important that scientific advice is taken into account in making decisions directed at meeting the needs of the rapidly increasing global population and the aspirations of developing nations,while sustaining Earth systems.However,this has not commonly been the case–it is an all too frequent complaint of scientists,that their advice has not been sought,or has been ignored.
文摘The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides(Ph Gs) such as the forsythosides(Fst A-to-P). The leading products, Fst-A,-B and-F(arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1(Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2(Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal(TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. Ph Gs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.
文摘The roots of the plant Cynanchum otophyllum C. K. Schneid(Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province(China). The multiple properties and applications of this herbal medicine have been analyzed. C. otophyllum is a perennial herbal liana, nonedible, and generally wild harvested. A cultivation method has been proposed to increase the fruit set level. Qingyangshen is used essentially to treat epilepsy, rheumatism, or other inflammatory diseases. The plant can be found also in diverse polyherbal preparations used in cosmetic or as food supplement(detox products), and in phyto-preparations claimed to reduce hair loss. The plant is a rich reservoir of C-21 steroidal glycosides. Many bioactive compounds have been isolated from this plant and some of them have been pharmacologically characterized, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, all briefly evocated here. The plant presents also interesting features in other domains. In particular, leave extracts of C. otophyllum C. K. Schneid contain proteases which are exploited for the local preparation of a cheese-like milk cake. Qingyangshen herbal preparation can be useful to treat epilepsy and inflammation. It has applications beyond medicine in the cosmetic and food industry.
文摘The utilization of natural preservatives and active packaging in extending the shelf life of food products during storage is vital to meet consumer demand for minimally processed food under sustainable systems.Fiber and nanofiber,isolated from cells of different biologically active plants,possess antimicrobial activity and can be used as packaging material with an active ingredient.Soluble or insoluble fibers incorporated into edible films or coatings are particularly popular as functional food additives because of their characteristics.Moreover,fiber serves as an excellent packaging material with mechanical strength,antimicrobial properties,water vapor and oxygen permeability,high phenolic content,and thermal stability and therefore can be enhanced by the incorporation of different ingredients,which is also discussed in this work.It has been found that fiber and nanofiber based edible packaging materials can inhibit the growth of pathogenic bacteria and lipid oxidation.Furthermore,substantial changes have been reported in the surface morphology and mechanical properties of films/coatings with the addition of fiber based active materials like beta-glucan,pectin,guar gum,inulin,psyllium,cellulose,hemicellulose,chitosan and lignin.Hence,the existing literature articulates recent developments and their applications.Therefore,fiber/nanofiber can be a promising substitute for synthetic preservatives.
