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1.
J Comp Eff Res ; 13(6): e230190, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38771012

ABSTRACT

Aim: To assesses the cost-effectiveness of sotagliflozin for the treatment of patients hospitalized with heart failure and comorbid diabetes. Materials & methods: A de novo cost-effectiveness model with a Markov structure was created for patients hospitalized for heart failure with comorbid diabetes. Outcomes of interest included hospital readmissions, emergency department visits and all-cause mortality measured over a 30-year time horizon. Baseline event frequencies were derived from published real-world data studies; sotagliflozin's efficacy was estimated from SOLOIST-WHF. Health benefits were calculated quality-adjusted life years (QALYs). Costs included pharmaceutical costs, rehospitalization, emergency room visits and adverse events. Economic value was measured using the incremental cost-effectiveness ratio (ICER). Results: Sotagliflozin use decreased annualized rehospitalization rates by 34.5% (0.228 vs 0.348, difference: -0.120), annualized emergency department visits by 40.0% (0.091 vs 0.153, difference: -0.061) and annualized mortality by 18.0% (0.298 vs 0.363, difference: -0.065) relative to standard of care, resulting in a net gain in QAYs of 0.425 for sotagliflozin versus standard of care. Incremental costs using sotagliflozin increased by $19,374 over a 30-year time horizon of the patient, driven largely by increased pharmaceutical cost. Estimated ICER for sotagliflozin relative to standard of care was $45,596 per QALY. Conclusion: Sotagliflozin is a cost-effective addition to standard of care for patients hospitalized with heart failure and comorbid diabetes.


Subject(s)
Cost-Benefit Analysis , Glycosides , Heart Failure , Markov Chains , Quality-Adjusted Life Years , Sodium-Glucose Transporter 2 Inhibitors , Humans , Heart Failure/drug therapy , Heart Failure/economics , Heart Failure/mortality , Glycosides/therapeutic use , Glycosides/economics , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/economics , Patient Readmission/statistics & numerical data , Patient Readmission/economics , Female , Male , Hospitalization/economics , Hospitalization/statistics & numerical data , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/economics , Diabetes Mellitus, Type 2/complications , Aged , Emergency Service, Hospital/economics , Emergency Service, Hospital/statistics & numerical data
2.
Phytomedicine ; 129: 155695, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728922

ABSTRACT

BACKGROUND: Exercise is an effective strategy to prevent sarcopenia, but high physical inactivity in the elderly requires alternative therapeutic approaches. Exercise mimetics are therapeutic compounds that simulate the beneficial effects of exercise on skeletal muscles. However, the toxicity and adverse effects of exercise mimetics raise serious concerns. PURPOSE: We aimed to search novel plant-based alternatives to activate exercise induced-signaling. METHODS: We used open databases and luciferase assays to identify plant-derived alternatives to activate exercise-induced signaling and compared its efficacy to mild intensity continuous training (MICT) in aged C57BL/6 mice. The nineteen-month-old mice were either fed an experimental diet supplemented with the isolated alternative or subjected to MICT for up to 21 mo of age. RESULTS: Our analysis revealed that Chrysanthemum zawadskii Herbich var latillobum (Maxim.) Kitamura (CZH), a medicinal plant rich in linarin, is a novel activator of peroxisome proliferator-activated receptor δ (PPARδ) and estrogen-related receptor γ (ERRγ), key regulators of exercise-induced positive effects on muscles. CZH supplementation ameliorated the loss of muscle function and mass, and increased PPARδ and ERRγ expression in mouse muscles. CZH also improved mitochondrial functions and proteostasis in aged mice, similar to MICT. Furthermore, CZH and linarin induced the activation of Sestrin 1, a key mediator of exercise benefits, in muscle. Silencing Sestrin 1 negated the increase in myogenesis and mitochondrial respiration by CZH and linarin in primary myoblasts from old mice. CONCLUSION: Our findings suggest the potential of CZH as a novel plant-derived alternative to activate exercise-induced signaling for preventing sarcopenia in sedentary older adults. This could offer a safer therapeutic option for sarcopenia treatment.


Subject(s)
Chrysanthemum , Mice, Inbred C57BL , Sarcopenia , Signal Transduction , Animals , Chrysanthemum/chemistry , Signal Transduction/drug effects , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Physical Conditioning, Animal , Male , PPAR delta/metabolism , Plant Extracts/pharmacology , Receptors, Estrogen/metabolism , Humans , Aging/drug effects , Glycosides
3.
Int J Biol Macromol ; 270(Pt 1): 132090, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705322

ABSTRACT

Calceorioside B, a multifunctional phenylethanol glycosides (PhGs) derivative, exhibits a variety of notable properties, such as antithrombotic, anti-tumorigenic, anti-neocoronavirus, anti-inflammatory, and neuroprotective effects. However, the large-scale production of calceorioside B is routinely restricted by its existence as an intermediary compound derived from plants, and still unachieved through excellent and activity chemical synthesis. Here, a total of 51 fungal endophytes were isolated from four PhGs-producing plants, and endophyte Simplicillium sinense EFF1 from Echinacea purpurea was identified with the ability to de-rhamnosing isoacteoside to generate calceorioside B. According to the RNA-transcription of EFF1 under the various substrates, a key gene CL1206.Contig2 that undertakes the hydrolysis function was screened out and charactered by heterologous expression. The sequence alignment, phylogenetic tree construction and substrate specificity analysis revealed that CL1206 was a novel α-L-rhamnosidase that belongs to the glycosyl hydrolase family 78 (GH78). The optimum catalytic conditions for CL1206 were at pH 6.5 and 55 °C. Finally, the enzyme-catalyzed approach to produce calceorioside B from 50 % crude isoacteoside extract was explored and optimized, with the maximum conversion rate reaching 69.42 % and the average producing rate reaching 0.37 g-1.L-1.h-1, which offered a great biocatalyst for potential industrial calceorioside B production. This is the first case for microorganism and rhamnosidase to show the hydrolysis ability to caffeic acid-modified PhGs.


Subject(s)
Endophytes , Glycoside Hydrolases , Phylogeny , Glycoside Hydrolases/metabolism , Glycoside Hydrolases/genetics , Endophytes/metabolism , Substrate Specificity , Hydrolysis , Hydrogen-Ion Concentration , Glycosides/chemistry , Glycosides/biosynthesis , Glycosides/metabolism , Kinetics
4.
Food Chem ; 453: 139622, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38761729

ABSTRACT

For health and safety reasons, the search for green, healthy, and low-calorie sweeteners with good taste has become the demand of many consumers. Furthermore, the need for sugar substitutes of natural origin has increased dramatically. In this review, we briefly discussed the safety and health benefits of stevia sweeteners and enumerated some examples of physiological functions of steviol glycosides (SGs), such as anti-inflammatory, anti-obesity, antihypertensive, anti-diabetes, and anticaries, citing various evidence related to their application in the food industry. The latest advances in emerging technologies for extracting and purifying SGs and the process variables and operational strategies were discussed. The impact of the extraction methods and their comparison against the conventional techniques have also been demonstrated. These technologies use minimal energy solvents and simplify subsequent purification stages, making viable alternatives suitable for a possible industrial application. Furthermore, we also elucidated the potential for advancing and applying the natural sweeteners SGs.


Subject(s)
Diterpenes, Kaurane , Plant Extracts , Stevia , Sweetening Agents , Stevia/chemistry , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/chemistry , Sweetening Agents/isolation & purification , Sweetening Agents/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Humans , Glucosides/isolation & purification , Glucosides/chemistry , Animals , Glycosides/isolation & purification , Glycosides/chemistry
5.
Nat Commun ; 15(1): 4588, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816433

ABSTRACT

Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry. Notably, LbUGT3 acts as a distinctive enzyme that catalyzes a tandem sugar transfer to the ortho-dihydroxy group on the caffeoyl moiety to form the unusual ortho-diglucosylated product, while LbUGT1 accurately discriminates caffeoyl and dihydrocaffeoyl groups to catalyze a site-selective sugar transfer. Crystal structure analysis of the complexes of LbUGT1 and LbUGT3 with UDP, combined with molecular dynamics simulations, revealed the structural basis of the difference in glycosylation selectivity between LbUGT1 and LbUGT3. Site-directed mutagenesis illuminates a conserved tyrosine residue (Y389 in LbUGT1 and Y390 in LbUGT3) in PSPG box that plays a crucial role in regulating the regioselectivity of LbUGT1 and LbUGT3. Our study thus sheds light on the enzymatic underpinnings of the chemical diversity of lycibarbarspermidines in wolfberry, and expands the repertoire of glycosyltransferases in nature.


Subject(s)
Glycosyltransferases , Lycium , Glycosyltransferases/metabolism , Glycosyltransferases/chemistry , Glycosyltransferases/genetics , Glycosylation , Lycium/enzymology , Lycium/metabolism , Lycium/chemistry , Molecular Dynamics Simulation , Mutagenesis, Site-Directed , Plant Proteins/metabolism , Plant Proteins/genetics , Plant Proteins/chemistry , Glycosides/metabolism , Glycosides/chemistry , Crystallography, X-Ray , Piperidines/metabolism , Piperidines/chemistry , Substrate Specificity
6.
Chem Biol Interact ; 396: 111044, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38729284

ABSTRACT

Mastitis is an inflammatory disease of the mammary gland with a high incidence in lactating animals, significantly impacting their health and breastfeeding. Moreover, mastitis adversely affects milk quality and yield, resulting in substantial economic losses for the dairy farming industry. Forsythiaside A (FTA), a phenylethanol glycoside analog extracted from Forsythia, exhibits notable anti-inflammatory and antioxidant properties. However, its protective effects and specific mechanisms against mastitis remain unclear. In this study, a lipopolysaccharide (LPS)-induced mouse mastitis model was used to investigate the protective effect of FTA on LPS-induced mastitis and its potential mechanism using histological assays, Western blot, qRT-PCR, FITC-albumin permeability test, 16s rRNA gene sequencing analysis and non-targeted metabolomics assays to investigate the protective effect of FTA on LPS-induced mastitis model and its potential mechanism. The results demonstrated that FTA significantly mitigated LPS-induced mouse mastitis by reducing inflammation and apoptosis levels, modulating the PI3K/AKT/mTOR signaling pathways, inducing autophagy, and enhancing antioxidant capacity and the expression of tight junction proteins. Furthermore, FTA increased the abundance of beneficial microbiota while decreasing the levels of harmful microbiota in mice, thus counteracting the gut microbiota disruption induced by LPS stimulation. Intestinal metabolomics analysis revealed that FTA primarily regulated LPS-induced metabolite alterations through key metabolic pathways, such as tryptophan metabolism. This study confirms the anti-inflammatory and antioxidant effects of FTA on mouse mastitis, which are associated with key metabolic pathways, including the restoration of gut microbiota balance and the regulation of tryptophan metabolism. These findings provide a novel foundation for the treatment and prevention of mammalian mastitis using FTA.


Subject(s)
Autophagy , Gastrointestinal Microbiome , Glycosides , Lipopolysaccharides , Mastitis , Animals , Female , Autophagy/drug effects , Mice , Mastitis/chemically induced , Mastitis/metabolism , Mastitis/drug therapy , Mastitis/microbiology , Gastrointestinal Microbiome/drug effects , Glycosides/pharmacology , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Apoptosis/drug effects , TOR Serine-Threonine Kinases/metabolism , Mice, Inbred BALB C
7.
mSphere ; 9(5): e0076423, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38722162

ABSTRACT

Cervimycins A-D are bis-glycosylated polyketide antibiotics produced by Streptomyces tendae HKI 0179 with bactericidal activity against Gram-positive bacteria. In this study, cervimycin C (CmC) treatment caused a spaghetti-like phenotype in Bacillus subtilis 168, with elongated curved cells, which stayed joined after cell division, and exhibited a chromosome segregation defect, resulting in ghost cells without DNA. Electron microscopy of CmC-treated Staphylococcus aureus (3 × MIC) revealed swollen cells, misshapen septa, cell wall thickening, and a rough cell wall surface. Incorporation tests in B. subtilis indicated an effect on DNA biosynthesis at high cervimycin concentrations. Indeed, artificial downregulation of the DNA gyrase subunit B gene (gyrB) increased the activity of cervimycin in agar diffusion tests, and, in high concentrations (starting at 62.5 × MIC), the antibiotic inhibited S. aureus DNA gyrase supercoiling activity in vitro. To obtain a more global view on the mode of action of CmC, transcriptomics and proteomics of cervimycin treated versus untreated S. aureus cells were performed. Interestingly, 3 × MIC of cervimycin did not induce characteristic responses, which would indicate disturbance of the DNA gyrase activity in vivo. Instead, cervimycin induced the expression of the CtsR/HrcA heat shock operon and the expression of autolysins, exhibiting similarity to the ribosome-targeting antibiotic gentamicin. In summary, we identified the DNA gyrase as a target, but at low concentrations, electron microscopy and omics data revealed a more complex mode of action of cervimycin, which comprised induction of the heat shock response, indicating protein stress in the cell.IMPORTANCEAntibiotic resistance of Gram-positive bacteria is an emerging problem in modern medicine, and new antibiotics with novel modes of action are urgently needed. Secondary metabolites from Streptomyces species are an important source of antibiotics, like the cervimycin complex produced by Streptomyces tendae HKI 0179. The phenotypic response of Bacillus subtilis and Staphylococcus aureus toward cervimycin C indicated a chromosome segregation and septum formation defect. This effect was at first attributed to an interaction between cervimycin C and the DNA gyrase. However, omics data of cervimycin treated versus untreated S. aureus cells indicated a different mode of action, because the stress response did not include the SOS response but resembled the response toward antibiotics that induce mistranslation or premature chain termination and cause protein stress. In summary, these results point toward a possibly novel mechanism that generates protein stress in the cells and subsequently leads to defects in cell and chromosome segregation.


Subject(s)
Anti-Bacterial Agents , Bacillus subtilis , Microbial Sensitivity Tests , Staphylococcus aureus , Streptomyces , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Streptomyces/genetics , Streptomyces/metabolism , Streptomyces/drug effects , Bacillus subtilis/drug effects , Bacillus subtilis/genetics , Bacillus subtilis/metabolism , Polyketides/pharmacology , Polyketides/metabolism , Glycosides/pharmacology , Cell Wall/drug effects , Cell Wall/metabolism , Proteomics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , DNA Gyrase/genetics , DNA Gyrase/metabolism
8.
Phytomedicine ; 129: 155703, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723527

ABSTRACT

BACKGROUND: Non-alcoholic steatohepatitis (NASH), the inflammatory subtype in the progression of non-alcoholic fatty liver disease, is becoming a serious burden threatening human health, but no approved medication is available to date. Mononoside is a natural active substance derived from Cornus officinalis and has been confirmed to have great potential in regulating lipid metabolism in our previous studies. However, its effect and mechanism to inhibit the progression of NASH remains unclear. PURPOSE: Our work aimed to explore the action of mononoside in delaying the progression of NASH and its regulatory mechanisms from the perspective of regulating lipophagy. METHODS AND RESULTS: Male C57BL/6 mice were fed with a high-fat and high-fructose diet for 16 weeks to establish a NASH mouse model. After 8 weeks of high-fat and high-fructose feeding, these mice were administrated with different doses of morroniside. H&E staining, ORO staining, Masson staining, RNA-seq, immunoblotting, and immunofluorescence were performed to determine the effects and molecular mechanisms of morroniside in delaying the progression of NASH. In this study, we found that morroniside is effective in attenuating hepatic lipid metabolism disorders and inflammatory response activation, thereby limiting the progression from simple fatty liver to NASH in high-fat and high-fructose diet-fed mice. Mechanistically, we identified AMPK signaling as the key molecular pathway for the positive efficacy of morroniside by transcriptome sequencing. Our results revealed that morroniside maintained hepatic lipid metabolism homeostasis and inhibited NLRP3 inflammasome activation by promoting AMPKα phosphorylation-mediated lipophagy and fatty acid oxidation. Consistent results were observed in palmitic acid-treated cell models. Of particular note, silencing AMPKα both in vivo and in vitro reversed morroniside-induced lipophagy flux enhancement and NLRP3 inflammasome inhibition, emphasizing the critical role of AMPKα activation in the effect of morroniside in inhibiting NASH progression. CONCLUSION: In summary, the present study provides strong evidence for the first time that morroniside inhibits NASH progression by promoting AMPK-dependent lipophagy and inhibiting NLRP3 inflammasome activation, suggesting that morroniside is expected to be a potential molecular entity for the development of therapeutic drugs for NASH.


Subject(s)
AMP-Activated Protein Kinases , Diet, High-Fat , Disease Models, Animal , Lipid Metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Male , Mice , Diet, High-Fat/adverse effects , AMP-Activated Protein Kinases/metabolism , Lipid Metabolism/drug effects , Disease Progression , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Glycosides/pharmacology , Liver/drug effects , Cornus/chemistry , Humans , Fructose , Inflammasomes/metabolism , Inflammasomes/drug effects
9.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1882-1887, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812200

ABSTRACT

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.


Subject(s)
Glycosides , Picrorhiza , Glycosides/chemistry , Glycosides/isolation & purification , Humans , Cell Line, Tumor , Picrorhiza/chemistry , Molecular Structure , Magnetic Resonance Spectroscopy , Drugs, Chinese Herbal/chemistry , Triterpenes
10.
J Phys Chem B ; 128(19): 4621-4630, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38697651

ABSTRACT

Thymine DNA glycosylase (TDG)-mediated excision of 5-formylcytosine and 5-carboxylcytosine (5-caC) is a critical step in active DNA demethylation. Herein, we employed a combined quantum mechanics/molecular mechanics approach to investigate the reaction mechanism of TDG-catalyzed N-glycosidic bond cleavage of 5-caC. The calculated results show that TDG-catalyzed 5-caC excision follows a concerted (SN2) mechanism in which glycosidic bond dissociation is coupled with nucleophile attack. Protonation of the 5-caC anion contributes to the cleavage of the N-glycoside bond, in which the N3-protonated zwitterion and imino tautomers are more favorable than carboxyl-protonated amino tautomers. This is consistent with the experimental data. Furthermore, our results reveal that the configuration rearrangement process of the protonated 5-caC would lower the stability of the N-glycoside bond and substantially reduce the barrier height for the subsequent C1'-N1 bond cleavage. This should be attributed to the smaller electrostatic repulsion between the leaving base and the negative phosphate group as a result of the structural rearrangement.


Subject(s)
Cytosine , Glycosides , Quantum Theory , Thymine DNA Glycosylase , Thymine DNA Glycosylase/metabolism , Thymine DNA Glycosylase/chemistry , Cytosine/chemistry , Cytosine/metabolism , Cytosine/analogs & derivatives , Glycosides/chemistry , Glycosides/metabolism , Molecular Dynamics Simulation
11.
Biochem Biophys Res Commun ; 716: 150038, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38704891

ABSTRACT

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.


Subject(s)
Glycosides , Hyperuricemia , NLR Family, Pyrin Domain-Containing 3 Protein , Pyrans , Uric Acid , Animals , Hyperuricemia/drug therapy , Hyperuricemia/metabolism , Uric Acid/blood , Male , Glycosides/pharmacology , Glycosides/therapeutic use , Pyrans/pharmacology , Pyrans/therapeutic use , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , NF-kappa B/metabolism , Mice, Inbred C57BL
12.
J Microbiol Methods ; 221: 106942, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38704038

ABSTRACT

Methylation analysis was performed on methylated alditol acetate standards and Streptococcus mutans extracellular polymeric substances (EPS) produced from wild-type and Gtf knockout strains (∆GtfB, ∆GtfB, and ∆GtfD). The methylated alditol acetate standards were representative of glycosidic linkages found in S. mutans EPS and were used to calibrate the GC-MS system for an FID detector and MS (TIC) and produce molar response factor, a necessary step in quantitative analysis. FID response factors were consistent with literature values (Sweet et al., 1975) and found to be the superior option for quantitative results, although the TIC response factors now give researchers without access to an FID detector a needed option for molar response factor correction. The GC-MS analysis is then used to deliver the ratio of the linkage types within a biofilm.


Subject(s)
Biofilms , Gas Chromatography-Mass Spectrometry , Polysaccharides, Bacterial , Streptococcus mutans , Biofilms/growth & development , Streptococcus mutans/genetics , Streptococcus mutans/metabolism , Gas Chromatography-Mass Spectrometry/methods , Polysaccharides, Bacterial/metabolism , Glycosides/metabolism , Methylation , Extracellular Polymeric Substance Matrix/metabolism , Extracellular Polymeric Substance Matrix/chemistry , Polysaccharides/metabolism
13.
J Biochem Mol Toxicol ; 38(6): e23735, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773908

ABSTRACT

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.


Subject(s)
Isoflavones , Neoplasms , Isoflavones/pharmacology , Isoflavones/chemistry , Isoflavones/therapeutic use , Humans , Animals , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Glucosides/pharmacology , Glucosides/therapeutic use , Glucosides/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/therapeutic use , Glycosides/pharmacology , Glycosides/therapeutic use , Glycosides/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry
14.
Phytomedicine ; 129: 155681, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38718638

ABSTRACT

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.


Subject(s)
Cistanche , Drugs, Chinese Herbal , Animals , Female , Humans , Male , Cistanche/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , Glucosides/pharmacology , Glucosides/therapeutic use , Glycosides , Infertility/drug therapy , Oxidative Stress/drug effects , Phenols/pharmacology , Phenols/therapeutic use , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Polyphenols , Reproduction/drug effects
15.
Reprod Toxicol ; 126: 108604, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703919

ABSTRACT

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.


Subject(s)
Autophagy , Glycosides , Pentacyclic Triterpenes , Spermatogonia , Testis , Tripterygium , Triterpenes , Animals , Male , Tripterygium/chemistry , Tripterygium/toxicity , Autophagy/drug effects , Testis/drug effects , Testis/pathology , Glycosides/toxicity , Glycosides/pharmacology , Spermatogonia/drug effects , Mice , Triterpenes/pharmacology , Triterpenes/toxicity , Cell Line , Cell Survival/drug effects
16.
J Agric Food Chem ; 72(20): 11617-11628, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38728580

ABSTRACT

When grapes are exposed to wildfire smoke, certain smoke-related volatile phenols (VPs) can be absorbed into the fruit, where they can be then converted into volatile-phenol (VP) glycosides through glycosylation. These volatile-phenol glycosides can be particularly problematic from a winemaking standpoint as they can be hydrolyzed, releasing volatile phenols, which can contribute to smoke-related off-flavors. Current methods for quantitating these volatile-phenol glycosides present several challenges, including the requirement of expensive capital equipment, limited accuracy due to the molecular complexity of the glycosides, and the utilization of harsh reagents. To address these challenges, we proposed an enzymatic hydrolysis method enabled by a tailored enzyme cocktail of novel glycosidases discovered through genome mining, and the generated VPs from VP glycosides can be quantitated by gas chromatography-mass spectrometry (GC-MS). The enzyme cocktails displayed high activities and a broad substrate scope when using commercially available VP glycosides as the substrates for testing. When evaluated in an industrially relevant matrix of Cabernet Sauvignon wine and grapes, this enzymatic cocktail consistently achieved a comparable efficacy of acid hydrolysis. The proposed method offers a simple, safe, and affordable option for smoke taint analysis.


Subject(s)
Fruit , Gas Chromatography-Mass Spectrometry , Glycoside Hydrolases , Glycosides , Phenols , Smoke , Vitis , Hydrolysis , Glycosides/chemistry , Glycosides/metabolism , Glycosides/analysis , Smoke/analysis , Glycoside Hydrolases/metabolism , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/genetics , Phenols/chemistry , Phenols/metabolism , Vitis/chemistry , Fruit/chemistry , Fruit/enzymology , Wine/analysis , Wildfires , Biocatalysis
17.
Carbohydr Res ; 540: 109142, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38718742

ABSTRACT

Resin glycosides act as laxatives in crude drugs derived from plants of the Convolvulaceae family. These compounds have exhibited antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug resistance-modulating properties, as well as cytotoxicity against cancer cells. This study investigated the organic acid, hydroxyl fatty acid, monosaccharide, and glycosidic acid components of the crude resin glycoside fraction obtained from the methanol extract of Ipomoea alba L. (Convolvulaceae) seeds, which was subjected to alkaline and acidic hydrolysis. The alkaline hydrolysis yielded acetic, isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids as organic acid components, along with a glycosidic acid fraction. The acidic hydrolysis of the glycosidic acid fraction resulted in the isolation of 11S-hydroxytetradecanoic and 11S-hydroxyhexadecanoic acids as hydroxyl fatty acid components, as well as d-glucose, d-quinovose, d-fucose, d-xylose, and l-rhamnose as monosaccharide components. In addition, 10 new glycosidic acid methyl esters were isolated from the glycosidic acid fraction treated with trimethylsilyldiazomethane-hexane, along with one known glycosidic acid methyl ester. Of these, eight compounds contained new glycans. Four of these compounds were unusual natural glycosides with four glycosidic linkages to one monosaccharide. Their structures were determined using MS and NMR spectral analyses, which provided valuable insights into the unique glycosidic composition of I. alba seeds.


Subject(s)
Glycosides , Ipomoea , Seeds , Ipomoea/chemistry , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Seeds/chemistry , Resins, Plant/chemistry , Hydrolysis , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification
18.
Mar Drugs ; 22(5)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38786583

ABSTRACT

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more responses in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.


Subject(s)
Gas Chromatography-Mass Spectrometry , Polysaccharides , Rhodophyta , Seaweed , Polysaccharides/chemistry , Seaweed/chemistry , Gas Chromatography-Mass Spectrometry/methods , Rhodophyta/chemistry , Methylation , Glycosides/chemistry
19.
Microb Genom ; 10(5)2024 May.
Article in English | MEDLINE | ID: mdl-38785231

ABSTRACT

The genus Catenibacillus (family Lachnospiraceae, phylum Bacillota) includes only one cultivated species so far, Catenibacillus scindens, isolated from human faeces and capable of deglycosylating dietary polyphenols and degrading flavonoid aglycones. Another human intestinal Catenibacillus strain not taxonomically resolved at that time was recently genome-sequenced. We analysed the genome of this novel isolate, designated Catenibacillus decagia, and showed its ability to deglycosylate C-coupled flavone and xanthone glucosides and O-coupled flavonoid glycosides. Most of the resulting aglycones were further degraded to the corresponding phenolic acids. Including the recently sequenced genome of C. scindens and ten faecal metagenome-assembled genomes assigned to the genus Catenibacillus, we performed a comparative genome analysis and searched for genes encoding potential C-glycosidases and other polyphenol-converting enzymes. According to genome data and physiological characterization, the core metabolism of Catenibacillus strains is based on a fermentative lifestyle with butyrate production and hydrogen evolution. Both C. scindens and C. decagia encode a flavonoid O-glycosidase, a flavone reductase, a flavanone/flavanonol-cleaving reductase and a phloretin hydrolase. Several gene clusters encode enzymes similar to those of the flavonoid C-deglycosylation system of Dorea strain PUE (DgpBC), while separately located genes encode putative polyphenol-glucoside oxidases (DgpA) required for C-deglycosylation. The diversity of dgpA and dgpBC gene clusters might explain the broad C-glycoside substrate spectrum of C. scindens and C. decagia. The other Catenibacillus genomes encode only a few potential flavonoid-converting enzymes. Our results indicate that several Catenibacillus species are well-equipped to deglycosylate and degrade dietary plant polyphenols and might inhabit a corresponding, specific niche in the gut.


Subject(s)
Flavonoids , Gastrointestinal Microbiome , Polyphenols , Humans , Polyphenols/metabolism , Flavonoids/metabolism , Genome, Bacterial , Genomics , Flavones/metabolism , Glycosides/metabolism , Phylogeny , Feces/microbiology , Glycosylation , Xanthones/metabolism
20.
PeerJ ; 12: e17112, 2024.
Article in English | MEDLINE | ID: mdl-38560474

ABSTRACT

Solanum rostratum Dunal, belongs to the Solanaceae family and has drawn attention for its intricate interplay of invasiveness, phytochemical composition, and potential bioactivities. Notably invasive, S. rostratum employs adaptive mechanisms during senescence, featuring thorn formation on leaves, fruits, and stems seed self-propulsion, and resistance to drought. This adaptability has led to its proliferation in countries such as China, Canada, and Australia, extending beyond its Mexican origin. Despite its invasive historical reputation, recent studies unveil a rich array of phytochemicals in S. rostratum, suggesting untapped economic potential due to under-exploration. This review delves into exploring the potential uses of S. rostratum while elucidating the bioactive compounds associated with diverse identified bioactivities. In terms of phytochemistry, S. rostratum reveals an abundance of various bioactive compounds, including alkaloids, flavonoids, phenols, saponins, and glycosides. These compounds confer a range of beneficial bioactivities, encompassing antioxidant, antifungal, anticarcinogenic, anti-inflammatory, phytotoxic, and pesticidal properties. This positions S. rostratum as a reservoir of valuable chemical constituents with potential applications, particularly in medicine and agriculture. The review provides comprehensive insights into the phytochemistry, bioactivities, and bioactivity-guided fractionation of S. rostratum. In this review, we focus on the potential utilization of S. rostratum by emphasizing its phytochemical profile, which holds promise for diverse applications. This review is the first that advocates for further exploration and research to unlock the plant's full potential for both economic and environmental benefit.


Subject(s)
Solanum , Animals , Solanum/chemistry , Buffaloes , Glycosides , Seeds , Phytochemicals/pharmacology
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