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1.
J Agric Food Chem ; 70(26): 8010-8023, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35729681

RESUMO

Switchgrass (Panicum virgatum L.) is a bioenergy crop that grows productively on lands not suitable for food production and is an excellent target for low-pesticide input biomass production. We hypothesize that resistance to insect pests and microbial pathogens is influenced by low-molecular-weight compounds known as specialized metabolites. We employed untargeted liquid chromatography-mass spectrometry, quantitative gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy to identify differences in switchgrass ecotype metabolomes. This analysis revealed striking differences between upland and lowland switchgrass metabolomes as well as distinct developmental profiles. Terpenoid- and polyphenol-derived specialized metabolites were identified, including steroidal saponins, di- and sesqui-terpenoids, and flavonoids. The saponins are particularly abundant in switchgrass extracts and have diverse aglycone cores and sugar moieties. We report seven structurally distinct steroidal saponin classes with unique steroidal cores and glycosylated at one or two positions. Quantitative GC-MS revealed differences in total saponin concentrations in the leaf blade, leaf sheath, stem, rhizome, and root (2.3 ± 0.10, 0.5 ± 0.01, 2.5 ± 0.5, 3.0 ± 0.7, and 0.3 ± 0.01 µg/mg of dw, respectively). The quantitative data also demonstrated that saponin concentrations are higher in roots of lowland (ranging from 3.0 to 6.6 µg/mg of dw) than in upland (from 0.9 to 1.9 µg/mg of dw) ecotype plants, suggesting ecotypic-specific biosynthesis and/or biological functions. These results enable future testing of these specialized metabolites on biotic and abiotic stress tolerance and can provide information on the development of low-input bioenergy crops.


Assuntos
Panicum , Saponinas , Ecótipo , Genótipo , Metabolômica , Panicum/química , Saponinas/metabolismo
2.
Int J Mol Sci ; 23(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35742835

RESUMO

Camellia oleifera is an economically important oilseed tree. Seed meals of C. oleifera have a long history of use as biocontrol agents in shrimp farming and as cleaning agents in peoples' daily lives due to the presence of theasaponins, the triterpene saponins from the genus Camellia. To characterize the biosynthetic pathway of theasaponins in C. oleifera, members of gene families involved in triterpenoid biosynthetic pathways were identified and subjected to phylogenetic analysis with corresponding members in Arabidopsis thaliana, Camellia sinensis, Actinidia chinensis, Panax ginseng, and Medicago truncatula. In total, 143 triterpenoid backbone biosynthetic genes, 1169 CYP450s, and 1019 UGTs were identified in C. oleifera. The expression profiles of triterpenoid backbone biosynthetic genes were analyzed in different tissue and seed developmental stages of C. oleifera. The results suggested that MVA is the main pathway for triterpenoid backbone biosynthesis. Moreover, the candidate genes for theasaponin biosynthesis were identified by WGCNA and qRT-PCR analysis; these included 11 CYP450s, 14 UGTs, and eight transcription factors. Our results provide valuable information for further research investigating the biosynthetic and regulatory network of theasaponins.


Assuntos
Camellia , Saponinas , Triterpenos , Camellia/genética , Camellia/metabolismo , Filogenia , Saponinas/metabolismo , Sementes , Triterpenos/metabolismo
3.
Genes (Basel) ; 13(6)2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35741854

RESUMO

Terpenoids are naturally occurring compounds involved in respiration, photosynthesis, membrane fluidity, and pathogen interactions and are classified according to the structure of their carbon skeleton. Although most terpenoids possess pharmacological activity, knowledge about terpenoid metabolism in medicinal plants is insufficient. Rehmannia glutinosa (R. glutinosa) is a traditional herb that is widely used in East Asia and has been reported to contain various terpenoids. In this study, we performed a comprehensive transcriptome analysis of terpenoid metabolism in R. glutinosa using two RNA sequencing platforms: Illumina and PacBio. The results show that the sterol, saponin, iridoid, and carotenoid pathways are active in R. glutinosa. Sterol and saponin biosynthesis were mevalonate pathway dependent, whereas iridoid and carotenoid biosynthesis were methylerythritol 4-phosphate pathway dependent. In addition, we found that the homologous genes of key enzymes involved in terpenoid metabolism were expressed differentially and that the differential expression of these genes was associated with specific terpenoid biosynthesis. The different expression of homologous genes encoding acetyl-CoA acetyltransferase, 3-hydroxy-3-methylglutaryl-CoA reductase, mevalonate kinase, mevalonate diphosphate decarboxylase, farnesyl pyrophosphate synthase, squalene synthase, and squalene epoxidase was associated with sterol and saponin biosynthesis. Homologous genes encoding 1-deoxy-D-xylulose 5-phosphate synthase were also differentially expressed and were associated with carotenoid and iridoid biosynthesis. These results suggest that the biosynthesis of specific terpenoids can be regulated by the homologous of key enzymes involved in plant terpenoid metabolism.


Assuntos
Rehmannia , Saponinas , Carotenoides/metabolismo , Iridoides/metabolismo , Rehmannia/genética , Rehmannia/metabolismo , Saponinas/metabolismo , Esteróis/metabolismo , Terpenos/metabolismo
4.
Phytomedicine ; 102: 154190, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35636173

RESUMO

BACKGROUND: Islet transplantation is an effective treatment for the type 1 and severe type 2 diabetes, but it is restricted by the severe lack of pancreas donors. In vitro differentiation of pancreatic progenitors into insulin-secreting cells is one of the hopeful strategies in the cell transplantation therapy of diabetes. Isoastragaloside I is one of the saponin molecules found in Astragalus membranaceus, which has been demonstrated to alleviate insulin resistance and glucose intolerance in obese mice. STUDY DESIGN: We established mouse pancreatic ductal organoids (mPDOs) with progenitor characteristics and an insulin promoter-driven EGFP reporter system to screen astragalus saponin components for monomers that can promote insulin-producing cell differentiation. METHODS: mPDOs treated with or without astragalus saponin monomers were investigated by the insulin promoter-driven EGFP reporter, quantitative PCR, immunofluorescence and flow cytometry to evaluate the expression of endocrine progenitor and ß-cell markers. RESULTS: Isoastragaloside I significantly promoted the expression of ß-cell differentiation genes, which was demonstrated by the activation of the insulin promoter-driven EGFP reporter, as well as the significant increase of mRNA levels of the endocrine progenitor marker Ngn3 and the ß-cell markers insulin1 and insulin2. Immunostaining studies indicated that the ß-cell-specific C-peptide was upregulated in isoastragaloside I-treated mPDOs. FACS analysis revealed that the ratio of C-peptide-secreting cells in isoastragaloside I-treated mPDOs was over 40%. Glucose tolerance tests demonstrated that the differentiated mPDOs could secrete C-peptide in response to glucose stimulation. CONCLUSIONS: We discover a novel strategy of inducing pancreatic ductal progenitors to differentiate into insulin-producing cells using isoastragaloside I. This approach can be potentially applied to ß-cell transplantation in diabetes therapies.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Saponinas , Animais , Peptídeo C/metabolismo , Diferenciação Celular/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Camundongos , Organoides/metabolismo , Saponinas/metabolismo , Saponinas/farmacologia
5.
Microbiol Spectr ; 10(3): e0032922, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35583337

RESUMO

The gut microbiota is important in the occurrence and development of obesity. It can not only via its metabolites, but also through microbiota-gut-brain-liver interactions, directly or indirectly, influence obesity. Quinoa, known as one kind of pseudocereals and weight loss food supplements, has been high-profile for its high nutritional value and broad applications. In this context, we produced high-fat diet-induced (HFD) obese mouse models and assessed the efficacy of quinoa with saponin and quinoa without saponin on obesity. We explored the potential therapeutic mechanisms of quinoa using methods such as 16S rRNA, Western blotting, Immunohistochemical (IHC). Our results indicated that quinoa can improve the obese symptoms significantly on HFD mice, as well as aberrant glucose and lipid metabolism. Further analyses suggest that quinoa can regulate microbiota in the colon and have predominantly regulation on Bacteroidetes, Actinobacteria and Desulfovibrio, meanwhile can decrease the F/B ratio and the abundance of Blautia. Contemporaneously, quinoa can upregulate the expression of TGR5 in the colon and brain, as well as GLP-1 in the colon, liver and brain. while downregulate the expression of TLR4 in the colon and liver, as well as markers of ER stress and oxidative stress in livers and serums. Beyond this, tight junctional proteins in colons and brains are also increased in response to quinoa. Therefore, quinoa can effectively reduce obesity and may possibly exert through microbiota-gut-brain-liver interaction mechanisms. IMPORTANCE Gut microbiota has been investigated extensively, as a driver of obesity as well as a therapeutic target. Studies of its mechanisms are predominantly microbiota-gut-brain axis or microbiota-gut-liver axis. Recent studies have shown that there is an important correlation between the gut-brain-liver axis and the energy balance of the body. Our research focus on microbiota-gut-brain-liver axis, as well as influences of quinoa in intestinal microbiota. We extend this study to the interaction between microbiota and brains, and the result shows obvious differences in the composition of the microbiome between the HFD group and others. These observations infer that besides the neurotransmitter and related receptors, microbiota itself may be a mediator for regulating bidirectional communication, along the gut-brain-liver axis. Taken together, these results also provide strong evidence for widening the domain of applicability of quinoa.


Assuntos
Chenopodium quinoa , Microbioma Gastrointestinal , Saponinas , Animais , Encéfalo/metabolismo , Chenopodium quinoa/genética , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/microbiologia , RNA Ribossômico 16S , Saponinas/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico
6.
Biomed Pharmacother ; 149: 112823, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35334426

RESUMO

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease. Aiming at assessing the effect of total saponins from American ginseng on COPD, both the chemical composition and anti-COPD activity of total saponins from wild-simulated American ginseng (TSW) and field-grown American ginseng (TSF) were investigated in this study. Firstly, a HPLC-ELSD chromatographic method was established to simultaneously determine the contents of 22 saponins in TSW and TSF. Secondly, CS-induced COPD mouse model was established to evaluate the activity of TSW and TSF. The results indicated that both TSW and TSF had the protective effect against COPD by alleviating oxidative stress and inflammatory response. TSW showed a stronger effect than TSF. Thirdly, an integrated approach involving metabolomics and network pharmacology was used to construct the "biomarker-reaction-enzyme-target" correlation network aiming at further exploring the observed effects. As the results, 15 biomarkers, 9 targets and 5 pathways were identified to play vital roles in the treatment of TSW and TSF on COPD. Fourthly, based on network pharmacology and the CS-stimulated A549 cell model, ginsenoside Rgl, Rc, oleanolic acid, notoginsenoside R1, Fe, silphioside B were certified to be the material basis for the stronger effect of TSW than TSF. Finally, the molecular docking were performed to visualize the binding modes. Our findings suggested that both TSW and TSF could effectively ameliorate the progression of COPD and might be used for the treatment of COPD.


Assuntos
Fumar Cigarros , Panax , Doença Pulmonar Obstrutiva Crônica , Saponinas , Animais , Biomarcadores/metabolismo , Metabolômica/métodos , Camundongos , Simulação de Acoplamento Molecular , Panax/química , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Saponinas/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico
7.
Appl Microbiol Biotechnol ; 106(5-6): 1837-1854, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35218388

RESUMO

Bacopa monnieri (L.) Wettst. or water hyssop commonly known as "Brahmi" is a small, creeping, succulent herb from the Plantaginaceae family. It is popularly employed in Ayurvedic medicine as a nerve tonic to improve memory and cognition. Of late, this plant has been reported extensively for its pharmacologically active phyto-constituents. The main phytochemicals are brahmine, alkaloids, herpestine, and saponins. The saponins include bacoside A, bacoside B, and betulic acid. Investigation into the pharmacological effect of this plant has thrived lately, encouraging its neuroprotective and memory supporting capacity among others. Besides, it possesses many other therapeutic activities like antimicrobial, antioxidant, anti-inflammatory, gastroprotective properties, etc. Because of its multipurpose therapeutic potential, it is overexploited owing to the prioritization of natural remedies over conventional ones, which compels us to conserve them. B. monnieri is confronting the danger of extinction from its natural habitat as it is a major cultivated medico-botanical and seed propagation is restricted due to less seed availability and viability. The ever-increasing demand for the plant can be dealt with mass propagation through plant tissue culture strategy. Micropropagation utilizing axillary meristems as well as de novo organogenesis have been widely investigated in this plant which has also been explored for its conservation and production of different types of secondary metabolites. Diverse in vitro methods such as organogenesis, cell suspension, and callus cultures have been accounted for with the aim of production and/or enhancement of bacosides. Direct shoot-organogenesis was initiated in excised leaf and internodal explants without any exogenous plant growth regulator(s) (PGRs), and the induction rate was improved when exogenous cytokinins and other supplements were used. Moreover, biotechnological toolkits like Agrobacterium-mediated transformation and the use of mutagens have been reported. Besides, the molecular marker-based studies demonstrated the clonal fidelity among the natural and in vitro generated plantlets also elucidating the inherent diversity among the natural populations. Agrobacterium-mediated transformation system was mostly employed to optimize bacoside biosynthesis and heterologous expression of other genes. The present review aims at depicting the recent research outcomes of in vitro studies performed on B. monnieri which include root and shoot organogenesis, callus induction, somatic embryogenesis, production of secondary metabolites by in vitro propagation, acclimatization of the in vitro raised plantlets, genetic transformation, and molecular marker-based studies of clonal fidelity. KEY POINTS: • Critical and up to date records on in vitro propagation of Bacopa monnieri • In vitro propagation and elicitation of secondary metabolites from B. monnieri • Molecular markers and transgenic studies in B. monnieri.


Assuntos
Bacopa , Saponinas , Triterpenos , Agrobacterium/genética , Bacopa/química , Bacopa/metabolismo , Biotecnologia , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Saponinas/metabolismo , Triterpenos/metabolismo
8.
Curr Drug Metab ; 23(1): 21-29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35114917

RESUMO

Platycodonis Radix (Jiegeng), the dried root of Platycodon grandiflorum, is a traditional herb used as both medicine and food. Its clinical application for the treatment of cough, phlegm, sore throat, pulmonary and respiratory diseases has been thousands of years in China. Platycodin D is the main active ingredient in Platycodonis Radix, which belongs to the family of pentacyclic triterpenoid saponins because it contains an oleanolane type aglycone linked with double sugar chains. Modern pharmacology has demonstrated that Platycodin D displays various biological activities, such as analgesics, expectoration and cough suppression, promoting weight loss, anti-tumor and immune regulation, suggesting that Platycodin D has the potential to be a drug candidate and an interesting target as a natural product for clinical research. In this review, the distribution and biotransformation, pharmacological effects, metabolic mechanism and safety evaluation of Platycodin D are summarized to lay the foundation for further studies.


Assuntos
Saponinas , Triterpenos , Biotransformação , Tosse , Humanos , Saponinas/efeitos adversos , Saponinas/metabolismo , Triterpenos/efeitos adversos
9.
Am J Chin Med ; 50(1): 261-274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34983328

RESUMO

Peritoneal fibrosis (PF) is a disease caused by prolonged exposure of the peritoneum to high levels of dialysis fluid. Astragalus total saponins (ATS) is a phytochemical naturally occurring in Radix Astragali that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an in vivo model of PF using 4.25% glucose-containing administered intraperitoneally to rats and incubated peritoneal mesothelial cells (PMCs) with 4.25% glucose-containing peritoneal dialysis fluid to construct an in vitro model of PF. Furthermore, siRNA of PGC-1[Formula: see text] was used to inhibit the expression of PGC-1[Formula: see text] to further investigate the mechanism of the protective effect of ATS on PF. In both in vivo and in vitro models, ATS treatment showed a protective effect against PF, with ATS reducing the thickness of peritoneal tissues in PF rats, increasing the viability of PMCs, increasing the mitochondrial membrane potential and reducing apoptosis ratio. ATS treatment also reduced the expressions of peritoneal fibrosis markers (Smad2, p-Smad2 and [Formula: see text]-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1[Formula: see text], NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1[Formula: see text] inhibition, the protective effect of ATS on PF was blocked. In conclusion, ATS treatment may be an effective therapeutic agent to inhibit high glucose-induced in peritoneal fibrosis through PGC-1[Formula: see text]-mediated apoptosis.


Assuntos
Fibrose Peritoneal , Saponinas , Animais , Apoptose , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/tratamento farmacológico , Fibrose Peritoneal/prevenção & controle , Peritônio/metabolismo , Peritônio/patologia , Ratos , Saponinas/metabolismo , Saponinas/farmacologia , Transdução de Sinais
10.
Microbiol Spectr ; 10(1): e0232421, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019691

RESUMO

Plant secondary metabolites (PSMs) can affect the structures and functions of soil microbiomes. However, the core bacteria associated with PSMs, and their corresponding functions have not been explored extensively. In this study, soil physicochemical properties, tea saponin (TS) contents, microbial community compositions, and microbial community functions of different-age Camellia oleifera plantation soils from representative regions were analyzed. We evaluated the effects of plantation age increase on PSM accumulation, and the subsequent consequences on the structures and functions of soil microbiomes. Plantation ages increase positively correlated with accumulated TS contents, negative effects on soil physicochemical properties, and soil microbiome structures and functions. Clearly, the core functions of soil microbiomes transitioned to those associated with PSM metabolisms, while microbial pathways involved in cellulose degradation were inhibited. Our study systematically explored the influences of PSMs on soil microbiomes via the investigation of key bacterial populations and their functional pathways. With the increase in planting years, increased TS content simplified soil microbiome diversity, inhibited the degradation of organic matter, and enriched the genes related to the degradation of TS. These findings significantly advance our understanding on PSMs-microbiome interactions and could provide fundamental and important data for sustainable management of Camellia plantations. IMPORTANCE Plant secondary metabolites (PSMs) contained in plant litter will be released into soil with the decomposition process, which will affect the diversity and function of soil microbiomes. The response of soil microbiomes to PSMs in terms of diversity and function can provide an important theoretical basis for plantations to put forward rational soil ecological management measures. The effects of planting years on PSM content, soil physicochemical properties, microbial diversity, and function, as well as the interaction between each index in Camellia oleifera plantation soil are still unclear. We found that, with planting years increased, the accumulation of tea saponin (TS) led to drastic changes in the diversity and function of soil microbiomes, which hindered the decomposition of organic matter and enriched many genes related to PSM degradation. We first found that soil bacteria, represented by Acinetobacter, were significantly associated with TS degradation. Our results provide important data for proposing rational soil management measures for pure forest plantations.


Assuntos
Bactérias/isolamento & purificação , Camellia sinensis/química , Camellia sinensis/metabolismo , Microbiota , Saponinas/análise , Bactérias/classificação , Bactérias/genética , Camellia sinensis/crescimento & desenvolvimento , Saponinas/metabolismo , Metabolismo Secundário , Solo/química , Microbiologia do Solo
11.
Cells ; 11(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35011696

RESUMO

Platycodin D (PD) is a potent adjuvant with dual Th1 and Th2 potentiating activity, but its mechanisms of action remain unclear. Here, the C2C12 myoblast cell line and mice were used as in vitro and in vivo models to identify potential signaling pathways involved in the adjuvant activity of PD. PD induced a transient cytotoxicity and inflammatory response in the C2C12 cells and in mouse quadricep muscles. A comparative analysis of microarray data revealed that PD induced similar gene expression profiles in the C2C12 cells and in the quadricep muscles, and triggered rapid regulation of death, immune, and inflammation-related genes, both in vivo and in vitro. It was further demonstrated that caspase-1-dependent pyroptosis was involved in the PD-induced cytotoxicity and inflammatory response in the C2C12 cells via the Ca2+-c-jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)-NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. Consistently, the in vivo analysis revealed that a local blockage of NLRP3 and caspase-1 inhibited PD-induced cytokine production and immune cell recruitment at the injection site, and impaired the adjuvant activity of PD on antigen-specific immune responses to model antigen ovalbumin (OVA) in mice. These findings identified the caspase-1-dependent adjuvanticity of PD and expanded the current knowledge on the mechanisms of action of saponin-based adjuvants.


Assuntos
Caspase 1/metabolismo , Piroptose/fisiologia , Saponinas/metabolismo , Triterpenos/metabolismo , Vacinas/uso terapêutico , Animais , Feminino , Humanos , Injeções Intramusculares , Camundongos , Transdução de Sinais , Vacinas/farmacologia
12.
Chem Biodivers ; 19(1): e202100778, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34904789

RESUMO

Astragalus membranaceus is a well-known herb that is widely used in the food and pharmaceutical industries. However, its commercial development has been limited due to wild resource shortages. This study was conducted in 2018 and 2019 to assess the effect of planting density on the major chemical compounds and mineral elements and biomass yield of A. membranaceus. The biomass yield (7,700.956 kg) reached the maximum at M2 planting density in 2018. In 2019, astragaloside IV reached its maximum concentration (0.117 %) at M2 group, which was significantly different from the concentrations obtained at the other groups. Calycosin-7-O-ß-D-glucoside (0.062 %) reach its maximum concentration in 2019 at M5, but not significant with M2. The concentration of major chemical compounds among the five groups in 2018 and 2019 all conformed to the Chinese Pharmacopoeia standards. In 2018, the mineral elements (Al, Ba, Fe, Li and Mn) content was higher at M2 than other groups. However, a general decrease in the mineral elements content was observed at M2 group in 2019. Enrichment analysis demonstrated that the enrichment capacity was highest for phosphorus. In conclusion, according to the TOPSIS results, M2 planting density was recommended as the optimal application. For optimal economic benefits, A. membranaceus should be harvested when it is 2 years old.


Assuntos
Astragalus propinquus/química , Minerais/análise , Astragalus propinquus/metabolismo , Biomassa , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Análise de Componente Principal , Saponinas/metabolismo , Tibet , Triterpenos/metabolismo
13.
Food Funct ; 13(6): 3590-3602, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35262135

RESUMO

Panax notoginseng has been used both as a traditional medicine and as a functional food for hundreds of years in Asia. However, the active constituents from P. notoginseng and their pharmacologic properties still need to be further explored. In this study, one new dammarane-type triterpenoid saponin (1), along with fourteen known analogs (2-15) were isolated and identified from the roots of P. notoginseng. The anti-inflammatory, anti-angiogenetic and anti-dengue virus effects of these isolated compounds were further evaluated. Compounds 1, 3, 5-7 and 10-12 exerted anti-inflammatory effects in two different zebrafish inflammatory models. Among them, 11, with the most significant activities, alleviated the inflammatory response by blocking the MyD88/NF-κB and STAT3 pathways. Moreover, compound 15 showed anti-angiogenetic activities in Tg(fli1:EGFP) and Tg(flk1:GFP) zebrafish, while 3 and 5 only inhibited angiogenesis in Tg(fli1:EGFP) zebrafish. Additionally, compounds 1, 3, 6, 8, 9 and 12 suppressed the replication of dengue virus either at the viral adsorption and entry stages or at the intracellular replication step. In conclusion, these findings enrich knowledge of the diversity of saponins in P. notoginseng and suggest that the dammarane-type triterpenoid saponins from P. notoginseng may be developed as potential functional foods to treat inflammation, angiogenesis or dengue-related diseases.


Assuntos
Panax notoginseng , Panax , Saponinas , Triterpenos , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Raízes de Plantas/metabolismo , Saponinas/metabolismo , Saponinas/farmacologia , Peixe-Zebra
14.
Oxid Med Cell Longev ; 2021: 1020614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616501

RESUMO

Astragaloside IV (AS-IV) is an active component in Astragalus membranaceus with the potential to treat neurodegenerative diseases, especially Alzheimer's diseases (ADs). However, its mechanisms are still not known. Herein, we aimed to explore the systematic pharmacological mechanism of AS-IV for treating AD. Drug prediction, network pharmacology, and functional bioinformatics analyses were conducted. Molecular docking was applied to validate reliability of the interactions and binding affinities between AS-IV and related targets. Finally, experimental verification was carried out in AßO infusion produced AD-like phenotypes to investigate the molecular mechanisms. We found that AS-IV works through a multitarget synergistic mechanism, including inflammation, nervous system, cell proliferation, apoptosis, pyroptosis, calcium ion, and steroid. AS-IV highly interacted with PPARγ, caspase-1, GSK3Β, PSEN1, and TRPV1 after docking simulations. Meanwhile, PPARγ interacts with caspase-1, GSK3Β, PSEN1, and TRPV1. In vivo experiments showed that AßO infusion produced AD-like phenotypes in mice, including impairment of fear memory, neuronal loss, tau hyperphosphorylation, neuroinflammation, and synaptic deficits in the hippocampus. Especially, the expression of PPARγ, as well as BDNF, was also reduced in the hippocampus of AD-like mice. Conversely, AS-IV improved AßO infusion-induced memory impairment, inhibited neuronal loss and the phosphorylation of tau, and prevented the synaptic deficits. AS-IV prevented AßO infusion-induced reduction of PPARγ and BDNF. Moreover, the inhibition of PPARγ attenuated the effects of AS-IV on BDNF, neuroflammation, and pyroptosis in AD-like mice. Taken together, AS-IV could prevent AD-like phenotypes and reduce tau hyperphosphorylation, synaptic deficits, neuroinflammation, and pyroptosis, possibly via regulating PPARγ.


Assuntos
Doença de Alzheimer/prevenção & controle , Astragalus propinquus/química , Medicamentos de Ervas Chinesas/administração & dosagem , Fenótipo , Fitoterapia/métodos , Saponinas/administração & dosagem , Triterpenos/administração & dosagem , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/efeitos adversos , Animais , Biologia Computacional/métodos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular/métodos , /induzido quimicamente , PPAR gama/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/efeitos adversos , Fosforilação/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Máquina de Vetores de Suporte , Triterpenos/metabolismo , Proteínas tau/metabolismo
15.
Mol Biol Rep ; 48(12): 7853-7863, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34714484

RESUMO

BACKGROUND: Hepatic fibrosis is the final pathway of chronic liver disease characterized by excessive accumulation of extracellular matrix (ECM), which eventually develop into cirrhosis and liver cancer. Emerging studies demonstrated that Saikosaponin-d (SSd) exhibits a protective role in liver fibrosis. However, the mechanism underlying anti-liver fibrosis of SSd in vivo and in vitro remains unclear. METHODS AND RESULTS: Transforming growth factor (TGF)-ß and carbon tetrachloride (CCl4) were used for creating liver fibrosis model in vitro and in vivo, respectively. The role of SSd in regulating liver fibrosis was assessed through Sirius red and Masson staining, and IHC assay. We found that SSd attenuated remarkably CCl4-induced liver fibrosis as evidenced by decreased collagen level, and decreased expression of fibrotic markers Col 1 and α-SMA. Meanwhile, SSd repressed autophagy activation as suggested by decreased BECN1 expression and increased p62 expression. Compared with HSCs from CCl4-treated group, the primary HSCs from SSd-treated mice exhibited a marked inactivation of autophagy. Mechanistically, SSd treatment enhanced the expression of GPER1 in primary HSCs and in TGF-ß-treated LX-2 cells. GPER1 agonist G1 repressed autophagy activation, whereas GPER1 antagonist G15 activated autophagy and G15 also damaged the function of SSd on suppressing autophagy, leading to subsequent increased levels of fibrotic marker level in LX-2 cells. CONCLUSIONS: Our findings highlight that SSd alleviates hepatic fibrosis by regulating GPER1/autophagy pathway.


Assuntos
Cirrose Hepática/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Saponinas/farmacologia , Animais , Autofagia/fisiologia , Tetracloreto de Carbono/farmacologia , Células Cultivadas , China , Fibrose , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Saponinas/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
16.
Int J Mol Sci ; 22(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34681613

RESUMO

Dioscorea zingiberensis is a medicinal herb containing a large amount of steroidal saponins, which are the major bioactive compounds and the primary storage form of diosgenin. The CYP72A gene family, belonging to cytochromes P450, exerts indispensable effects on the biosynthesis of numerous bioactive compounds. In this work, a total of 25 CYP72A genes were identified in D. zingiberensis and categorized into two groups according to the homology of protein sequences. The characteristics of their phylogenetic relationship, intron-exon organization, conserved motifs and cis-regulatory elements were performed by bioinformatics methods. The transcriptome data demonstrated that expression patterns of DzCYP72As varied by tissues. Moreover, qRT-PCR results displayed diverse expression profiles of DzCYP72As under different concentrations of jasmonic acid (JA). Likewise, eight metabolites in the biosynthesis pathway of steroidal saponins (four phytosterols, diosgenin, parvifloside, protodeltonin and dioscin) exhibited different contents under different concentrations of JA, and the content of total steroidal saponin was largest at the dose of 100 µmol/L of JA. The redundant analysis showed that 12 DzCYP72As had a strong correlation with specialized metabolites. Those genes were negatively correlated with stigmasterol and cholesterol but positively correlated with six other specialized metabolites. Among all DzCYP72As evaluated, DzCYP72A6, DzCYP72A16 and DzCYP72A17 contributed the most to the variation of specialized metabolites in the biosynthesis pathway of steroidal saponins. This study provides valuable information for further research on the biological functions related to steroidal saponin biosynthesis.


Assuntos
Ciclopentanos/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Dioscorea/efeitos dos fármacos , Oxilipinas/farmacologia , Proteínas de Plantas/genética , Saponinas/metabolismo , Sequência de Aminoácidos , Sistema Enzimático do Citocromo P-450/classificação , Sistema Enzimático do Citocromo P-450/metabolismo , Dioscorea/química , Dioscorea/genética , Dioscorea/metabolismo , Diosgenina/metabolismo , Filogenia , Fitosteróis/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Alinhamento de Sequência
17.
Biomed Res Int ; 2021: 5845554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513994

RESUMO

OBJECTIVE: Neuroblastoma (NB) is a highly metastatic tumor in children that develops in the sympathetic nervous system and has a low curative rate. Saikosaponin A (SSA), an active ingredient isolated from the root of Radix Bupleuri, is a natural compound with various pharmacological activities and shows good application prospects in antitumors. This study investigated the antihuman NB activity of SSA and underlying mechanisms associated with its actions. MATERIALS AND METHODS: The MTT method was used to detect the activity of SSA in inhibiting human NB cell SK-N-AS proliferation. Cell morphology was observed. The flow cytometry technology was used in analyzing the cell apoptosis rate. The Transwell assay evaluated cell migration and invasion following SSA treatment, apoptosis-related protein expression, and angiogenesis-related protein expression, and EMT-related proteins were detected by western blot analysis. RESULTS: SSA showed an inhibitory effect on SK-N-AS cells with the IC50 values of 14.14 µM at 24 h and 12.41 µM at 48 h. Results indicated that SSA has proapoptotic activity, and its proapoptotic activity is positively correlated with the Bax/Bcl-2/caspase-9/caspase-7/PARP pathway. Furthermore, SSA inhibited the invasion and migration of SK-N-AS cells via regulating the angiogenesis-related VEGFR2/Src/Akt pathway and the epithelial-mesenchymal transition- (EMT-) related protein expression. CONCLUSION: SSA exerts an antihuman NB effect and thus provides foundations for NB treatment.


Assuntos
Neuroblastoma/metabolismo , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Apoptose/efeitos dos fármacos , Bupleurum/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Humanos , Concentração Inibidora 50 , Neuroblastoma/tratamento farmacológico , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Extratos Vegetais/farmacologia , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Chem Biodivers ; 18(11): e2100272, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34532975

RESUMO

The aim of the present work is to isolate a series of triterpene derivatives with rhamnosyl linking acetyl groups from Glechoma longituba according to the structural characteristics of previously described triterpene saponins. The extract ion chromatography spectrum of the crude extract of G. longituba was detected and analyzed by HPLC-HR-ESI-MS to determine possible components, and these metabolites were traced and separated by combining high-resolution mass spectrometry and predicted liquid chromatography retention time. Three 11α, 12α-epoxypentacyclic oleanolic acid triterpene saponins (glechomanosides H-J) and one ursane triterpene aldehyde saponin with a C-28 aldehyde group were isolated from G. longituba. The structure of these compounds was confirmed by NMR and compared with those of previously characterized compounds. The strategy described in this report enables a rapid, reliable, and complete analysis of glycoside compounds containing different numbers of acetyl groups at different positions on the sugar.


Assuntos
Lamiaceae/química , Extratos Vegetais/análise , Ramnose/análise , Saponinas/análise , Triterpenos/análise , Acetilação , Cromatografia Líquida de Alta Pressão , Conformação Molecular , Extratos Vegetais/metabolismo , Ramnose/metabolismo , Saponinas/metabolismo , Espectrometria de Massas em Tandem , Triterpenos/metabolismo
19.
Food Funct ; 12(21): 10571-10580, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34581363

RESUMO

Oil/water (O/W) emulsion droplets coated with soyasaponin (Ssa) were used as emulsifiers to prepare emulsions with hierarchical configurations (2.82 µm). Ssa is a natural triterpenoid with amphiphilic properties and an excellent emulsifying activity. Stable O/W emulsions were prepared and characterized using an ultrasonic method at a Ssa concentration of 2.5 wt%. The resultant hierarchical emulsions were further prepared using O/W droplets as emulsifiers. It was observed that the stability of the hierarchical emulsions changed with alterations to the ratio of O/W droplets to the oil phase. As the number of droplets increased, the more the surface area of the hierarchical emulsion was covered. Additional observations included a decreased particle size, increased negative charge and viscoelastic behavior, and enhanced emulsion stability. The emulsion was most stable when the O/W droplet addition was 29%. The addition of O/W droplets continued to increase, and there was an imbalance in the ratio of O/W droplets to the oil phase; the excess O/W droplets induced instability in the emulsion, resulting in a degradation of the emulsion quality. We monitored hierarchical emulsions with different concentrations of emulsifiers for 30 days, and the results indicated that hierarchical emulsions could meet the demand for long-term storage. This provides a new theoretical basis for the construction and application of complex emulsion systems.


Assuntos
Emulsificantes/química , Emulsificantes/metabolismo , Saponinas/química , Saponinas/metabolismo , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Emulsões , Tamanho da Partícula , Tensoativos , Viscosidade
20.
J Zhejiang Univ Sci B ; 22(8): 682-694, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34414702

RESUMO

Hemin can improve the stress resistance of plants through the heme oxygenase system. Additionally, substances contained in plants, such as secondary metabolites, can improve stress resistance. However, few studies have explored the effects of hemin on secondary metabolite content. Therefore, the effects of hemin on saponin synthesis and the mechanism of plant injury relief by hemin in Conyza blinii were investigated in this study. Hemin treatment promoted plant growth and increased the antioxidant enzyme activity and saponin content of C. blinii under osmotic stress and cold stress. Further study showed that hemin could provide sufficient precursors for saponin synthesis by improving the photosynthetic capacity of C. blinii and increasing the gene expression of key enzymes in the saponin synthesis pathway, thus increasing the saponin content. Moreover, the promotion effect of hemin on saponin synthesis is dependent on heme oxygenase-1 and can be reversed by the inhibitor Zn-protoporphyrin-IX (ZnPPIX). This study revealed that hemin can increase the saponin content of C. blinii and alleviate the damage caused by abiotic stress, and it also broadened the understanding of the relationship between hemin and secondary metabolites in plant abiotic stress relief.


Assuntos
Resposta ao Choque Frio , Conyza/fisiologia , Heme Oxigenase-1/fisiologia , Hemina/farmacologia , Pressão Osmótica , Saponinas/metabolismo , Antioxidantes/metabolismo , Conyza/efeitos dos fármacos , Metabolismo Secundário
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