RESUMEN
Iridoids are secondary plant metabolites that are multitarget compounds active against various diseases. Iridoids are structurally classified into iridoid glycosides and non-glycosidic iridoids according to the presence or absence of intramolecular glycosidic bonds; additionally, iridoid glycosides can be further subdivided into carbocyclic iridoids and secoiridoids. These monoterpenoids belong to the cyclopentan[c]-pyran system, which has a wide range of biological activities, including antiviral, anticancer, antiplasmodial, neuroprotective, anti-thrombolytic, antitrypanosomal, antidiabetic, hepatoprotective, anti-oxidant, antihyperlipidemic and anti-inflammatory properties. The basic chemical structure of iridoids in plants (the iridoid ring scaffold) is biosynthesized in plants by the enzyme iridoid synthase using 8-oxogeranial as a substrate. With advances in phytochemical research, many iridoid compounds with novel structure and outstanding activity have been identified in recent years. Biologically active iridoid derivatives have been found in a variety of plant families, including Plantaginaceae, Rubiaceae, Verbenaceae, and Scrophulariaceae. Iridoids have the potential of modulating many biological events in various diseases. This review highlights the multitarget potential of iridoids and includes a compilation of recent publications on the pharmacology of iridoids. Several in vitro and in vivo models used, along with the results, are also included in the paper. This paper's systematic summary was created by searching for relevant iridoid material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. The compilation will provide the researchers with a thorough understanding of iridoid and its congeners, which will further help in designing a large number of potential compounds with a strong impact on curing various diseases.
Asunto(s)
Glicósidos Iridoides , Iridoides , Iridoides/farmacología , Iridoides/química , Iridoides/metabolismo , Plantas , Extractos Vegetales/química , Monoterpenos , AntioxidantesRESUMEN
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.
Asunto(s)
Rehmannia , Saponinas , Carotenoides/metabolismo , Iridoides/metabolismo , Rehmannia/genética , Rehmannia/metabolismo , Saponinas/metabolismo , Esteroles/metabolismo , Terpenos/metabolismoRESUMEN
BACKGROUND: Picrorhiza kurroa has been reported as an age-old ayurvedic hepato-protection to treat hepatic disorders due to the presence of iridoids such as picroside-II (P-II), picroside-I, and kutkoside. The acylation of catalpol and vanilloyl coenzyme A by acyltransferases (ATs) is critical step in P-II biosynthesis. Since accumulation of P-II occurs only in roots, rhizomes and stolons in comparison to leaves uprooting of this critically endangered herb has been the only source of this compound. Recently, we reported that P-II acylation likely happen in roots, while stolons serve as the vital P-II storage compartment. Therefore, developing an alternate engineered platform for P-II biosynthesis require identification of P-II specific AT/s. METHODS AND RESULTS: In that direction, egg-NOG function annotated 815 ATs from de novo RNA sequencing of tissue culture based 'shoots-only' system and nursery grown shoots, roots, and stolons varying in P-II content, were cross-compared in silico to arrive at ATs sequences unique and/or common to stolons and roots. Verification for organ and accession-wise upregulation in gene expression of these ATs by qRT-PCR has shortlisted six putative 'P-II-forming' ATs. Further, six-frame translation, ab initio protein structure modelling and protein-ligand molecular docking of these ATs signified one MBOAT domain containing AT with preferential binding to the vanillic acid CoA thiol ester as well as with P-II, implying that this could be potential AT decorating final structure of P-II. CONCLUSIONS: Organ-wise comparative transcriptome mining coupled with reverse transcription real time qRT-PCR and protein-ligand docking led to the identification of an acyltransferases, contributing to the final structure of P-II.
Asunto(s)
Picrorhiza , Plantas Medicinales , Aciltransferasas/genética , Aciltransferasas/metabolismo , Cinamatos/metabolismo , Glicósidos , Glucósidos Iridoides/metabolismo , Iridoides/metabolismo , Ligandos , Simulación del Acoplamiento Molecular , Picrorhiza/genética , Picrorhiza/metabolismo , Plantas Medicinales/genética , Plantas Medicinales/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Current mainstream antidepressants have limited efficacy with a delayed onset of action. Yueju, a herbal medicine, has a rapid antidepressant action. Identification of the active ingredients in Yueju and the mechanism/s involved was carried out. EXPERIMENTAL APPROACH: Key molecule/s and compounds involved in this antidepressant action was identified by transcriptomic and HPLC analysis, respectively. Antidepressant effects were evaluated using various behavioural experiments. The signalling involved was assessed using site-directed pharmacological intervention or optogenetic manipulation. KEY RESULTS: Transcriptomic analysis showed that Yueju up-regulated pituitary adenylate cyclase activating polypeptide (PACAP) expression in the hippocampus. Two iridoids, geniposide and shanzhiside methyl ester, were identified and quantified from Yueju. Only co-treatment with both, at an equivalent concentrations found in Yueju, increased PACAP expression and elicited a rapid antidepressant action, which were blocked by intra-dentate gyrus infusion of a PACAP antagonist or optogenetic inactivation of PACAP expressing neurons. Geniposide and shanzhiside methyl ester co-treatment rapidly inhibited CaMKII phosphorylation and enhanced mTOR/4EBP1/P70S6k/BDNF ignalling, while intra-dentate gyrus infusions of a CaMKII activator blunted the rapid antidepressant action and BDNF expression up-regulation induced by the co-treatment. A single co-treatment of them rapidly improved depression-like behaviours and up-regulated hippocampal PACAP signalling in the repeated corticosterone-induced depression model, further confirming the involvement of PACAP. CONCLUSION AND IMPLICATIONS: Geniposide and shanzhiside methyl ester co-treatment had a synergistic rapid onset antidepressant action by triggering hippocampal PACAP activity and associated CaMKII-BDNF signalling. This mechanism could be targeted for development of fast onset antidepressants.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/farmacología , Ésteres/metabolismo , Ésteres/farmacología , Hipocampo , Iridoides/metabolismo , Iridoides/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacologíaRESUMEN
Inchinkoto (ICKT) is a popular choleretic and hepatoprotective herbal medicine that is widely used in Japan. Geniposide, a major ingredient of ICKT, is metabolized to genipin by gut microbiota, which exerts a choleretic effect. This study investigates the relationship between stool genipin-producing activity and diversity of the clinical effect of ICKT in patients with malignant obstructive jaundice. Fifty-two patients with malignant obstructive jaundice who underwent external biliary drainage were included. ICKT was administered as three packets per day (7.5 g/day) for three days and 2.5 g on the morning of the fourth day. Stool samples were collected before ICKT administration and bile flow was monitored on a daily basis. The microbiome, genipin-producing activity, and organic acids in stools were analyzed. The Shannon-Wiener (SW) index was calculated to evaluate gut microbiome diversity. The stool genipin-producing activity showed a significant positive correlation with the SW index. Stool genipin-producing activity positively correlated with the order Clostridia (obligate anaerobes), but negatively correlated with the order Lactobacillales (facultative anaerobes). Moreover, stool genipin-producing activity was positively correlated to the concentration valeric acid, but negatively correlated to the concentration of lactic acid and succinic acid. The change of bile flow at 2 and 3 days after ICKT administration showed significant positive correlation with genipin-producing activity (correlation coefficient, 0.40 and 0.29, respectively, P < 0.05). An analysis of stool profile, including stool genipin-producing activity, may predict the efficacy of ICKT. Modification of the microbiome may be a target to enhance the therapeutic effect of ICKT.
Asunto(s)
Colagogos y Coleréticos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Heces/química , Microbioma Gastrointestinal/efectos de los fármacos , Iridoides/metabolismo , Ictericia Obstructiva/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bilis/química , Ácidos Carboxílicos/metabolismo , Clostridium/genética , Clostridium/metabolismo , Femenino , Microbioma Gastrointestinal/genética , Humanos , Ictericia Obstructiva/microbiología , Lactobacillales/genética , Lactobacillales/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/microbiología , Resultado del TratamientoRESUMEN
The antidepressant activity of Spathodea campanulata flowers was evaluated in mice and in silico. When tested at doses of 200 and 400 mg/kg, the methanol extract of S. campanulata (MESC) showed dose-dependent antidepressant activity in the force swim test (FST), tail suspension test (TST), lithium chloride-induced twitches test and the open field test. In FST and TST, animals treated with MESC demonstrated a significant decrease in the immobility period compared to the control group. The lithium chloride-induced head twitches were significantly reduced following administration of MESC. The latter, at the dose of 400 mg/kg, also significantly reduced locomotor activity. Following administration of MESC, changes in the levels of serum corticosterone, and of norepinephrine, dopamine, serotonin, 4-hydroxy-3-methoxyphenylglycol (MHPG), 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in different brain regions using HPLC. The presence of spatheoside A (m/z 541) and spatheoside B (m/z 559) in MESC was detected using HPLC/ESI-MS. These two iridoids demonstrated a high predictive binding affinity for the active site of the type A monoamine oxidase (MAO-A) enzyme with scores of 99.40 and 93.54, respectively. These data suggest that S. campanulata flowers warrants further investigation as a source of novel templates for antidepressive drugs.
Asunto(s)
Antidepresivos/metabolismo , Bignoniaceae/química , Flores/química , Iridoides/metabolismo , Monoaminooxidasa/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Antidepresivos/química , Antidepresivos/farmacología , Unión Competitiva , Monoaminas Biogénicas/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/prevención & control , Ácido Hidroxiindolacético/metabolismo , Iridoides/farmacología , Masculino , Metanol/química , Ratones , Actividad Motora/efectos de los fármacos , Fitoterapia/métodos , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Zhi-zi-Hou-po decoction (ZZHPD) has been used to treat depression in the clinic for thousand years in China. However, the pharmacodynamic substance of ZZHPD is still not totally clear due to its complex components. The objective of this study was to identify the effectual combination ingredients (ECIs) of ZZHPD, which could represent the antidepressant effect of the original formula. Firstly, differential plasma absorbed components with different variable importance in projection (VIP) value in chronic unpredictable mild stress (CUMS)-induced depression and control rat were revealed by untargeted metabolomics-driven strategy based on HPLC-ESI-TOF/MS, XCMS online and SIMCA-p software. Secondly, network topology scores (NTS) of plasma absorbed components were exposed by protein-protein interaction (PPI) network analysis based on components-related genes and depression-related genes, which were performed by network pharmacology tools. Finally, the ECIs were screened by considered of VIP value and NTS. Then the bioactivity was evaluated by cell viability and expression of glial fibrillary acid protein (GFAP), tumor necrosis factor α (TNFα) and interleukin 1ß (IL-1ß) of a lipopolysaccharide-induced astrocyte depression model. An effective combination composed with 12 components was filtrated as ECIs of ZZHPD, exposed to which the cell viability effect, the expression of GFAP and IL-1ß in astrocytes were essentially equivalent with original ZZHPD (p > 0.05), and that both characteristic constituents and trace compounds of ZZHPD might exert synergistic actions through multi-targets. The result of this study provided useful information for the clinical application and modern development of ZZHPD, and the proposed strategy could be regard as an alternative solution for effective combination screening of herbal medicines.
Asunto(s)
Antidepresivos , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos , Iridoides , Espectrometría de Masas/métodos , Animales , Antidepresivos/análisis , Antidepresivos/química , Antidepresivos/metabolismo , Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Iridoides/análisis , Iridoides/química , Iridoides/metabolismo , Iridoides/farmacología , Masculino , Ratas , Ratas Sprague-Dawley , Estrés PsicológicoRESUMEN
Gardenia jasminoides Ellis (G. jasminoides) fruits are used as a resource for obtaining natural colorants and in traditional Chinese herbal medicine. However, G. jasminoides presents a relatively long flowering period and different ripening periods, so there are significant differences in the accumulation of metabolites in fruits of different colors. In addition, the complete metabolic pathways of iridoidsand crocins, which are used as medicinal composition of G. jasminoides, are poorly understood at present. In this research, we comprehensively compared the transcriptome and metabolites profiles of the developmental stages and locations of iridoid and crocin biosynthesis. A large number of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were detected in four groups of samples, and clear variation in the pattern of metabolite abundance and gene expression were observed among different fruit colors and parts. Geniposide and gardenoside mainly accumulated in the sarcocarp of green fruit (GFS) and the sarcocarp of red fruit (FS), respectively. Crocin mainly accumulated in the peel and sarcocarp of red fruits. In the iridoid pathway, we hypothesized that there was a transport mechanism from the sarcocarp to the peel of G. jasminoides because of the inconsistent expression of G8O, 10-HGO and IS associated with differences in fruit ripening. UGTs play an important role in the biosynthesis of the active components of G. jasminoides. Combined transcriptome and metabonomics analysis showed a negative correlation between the biosynthesis of geniposide and crocin. The redirection of the metabolic flux and the regulation of key enzymes may be the main reasons for the changes in the biosynthesis of iridoid and crocin in G. jasminoides fruit. Our study expended valuable information for functional genomic library and provided new insights for metabolic engineering of secondary metabolite in G. Jasminoides.
Asunto(s)
Carotenoides/metabolismo , Frutas , Gardenia , Iridoides/metabolismo , Frutas/genética , Frutas/metabolismo , Gardenia/genética , Gardenia/metabolismo , Metaboloma , TranscriptomaRESUMEN
BACKGROUND: Olive-derived antioxidants have been shown to affect the oxidative status of meat and have also been associated with greater consumption of glucose, which might affect glycogen stores and muscle characteristics. This study evaluated the effect of oleuropein extract supplementation (OLE) versus vitamin E + Se (VE), and their combination (VEOLE), in pig diets, on pH, drip loss, the proportion of free fatty acids, and meat stability, and their prediction by blood oxidative status markers. RESULTS: The drip loss of muscle was lower in antioxidant-supplemented groups when compared with controls. α-Tocopherol concentration and total fatty acids profile were not affected by dietary oleuropein supplementation. However, OLE and VEOLE had lower free n-3 polyunsaturated fatty acid (PUFA) levels when compared with VE and tended to have higher free monounsaturated fatty acid (MUFA) levels. Furthermore, the VEOLE group had lower free n-6 PUFA levels when compared with controls or VE, whereas the OLE group had intermediated values. Muscle samples from pigs subjected to the antioxidant-mixed supplementation (VEOLE) had lower malondialdehyde concentration when compared with the others. The VE and OLE groups showed intermediate malondialdehyde values. Chilled meat stability was highly correlated with antioxidant status in vivo. CONCLUSION: The administration of 96 mg oleuropein kg-1 feed produced similar meat quality characteristics as the use of 100 mg kg-1 α-tocopheryl acetate +0.26 mg kg-1 sodium selenite and it would be an interesting alternative in Mediterranean countries. The VEOLE group was the most effective for reducing lipid oxidation and for the production of polyunsaturated free fatty acids in meat, which would result in lower rancidity formation and better aroma development in products. © 2020 Society of Chemical Industry.
Asunto(s)
Ácidos Grasos no Esterificados/metabolismo , Iridoides/metabolismo , Carne/análisis , Selenio/metabolismo , Porcinos/metabolismo , alfa-Tocoferol/metabolismo , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Suplementos Dietéticos/análisis , Ácidos Grasos no Esterificados/química , Glucósidos Iridoides , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Oxidación-Reducción , Porcinos/crecimiento & desarrolloRESUMEN
Salt stress affects the metabolic homeostasis of medicinal plants. However, medicinal plants are sessile organisms that cannot escape from salt stress. They acclimatize themselves to the stress by reprogramming their metabolic pathways. Lonicerae Japonicae Flos (LJF) with strong antioxidant activity is commonly used in traditional Chinese medicine, tea, and beverage. Nevertheless, the variation of integrated metabolites in LJF under different salt stresses remains unclear. In this study, High Performance Liquid Chromatography tandem triple time-of-flight mass spectrometry (HPLC- triple TOF-MS/MS) coupled with multivariate statistical analysis was applied to comparatively investigate the metabolites changes in LJF under different salt stress (0, 100, 200, 300 mM NaCl). Total 47 differential metabolites were screened from 79 metabolites identified in LJF under different salt stress. Low salt-treated group (100 mM NaCl) appeared to be the best group in terms of relative contents (peak areas) of the wide variety in bioactive components. Additionally, the phenylpropanoid pathway, monoterpenoid biosynthesis, glycolysis, TCA cycle, and alkaloid biosynthesis were disturbed in all salt-stress LJF. The results showed that LJF metabolisms were dramatically induced under salt stress and the quality of LJF was better under low salt stress. The study provides novel insights into the quality assessment of LJF under salt stress and a beneficial framework of knowledge applied to improvement the medicinal value of LJF.
Asunto(s)
Lonicera/metabolismo , Extractos Vegetales/metabolismo , Plantas Medicinales/metabolismo , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/normas , Flavonoides/biosíntesis , Humanos , Hidroxibenzoatos/metabolismo , Iridoides/metabolismo , Medicina Tradicional China , Redes y Vías Metabólicas , Metaboloma , Metabolómica , Análisis Multivariante , Extractos Vegetales/normas , Control de Calidad , Estrés Salino/fisiología , Espectrometría de Masas en TándemRESUMEN
Lonicera japonica is used in Chinese herbal medicines with a wide spectrum of pharmacological properties associated with chlorogenic acid, flavonoid and iridoid. The biosynthesis of these compounds could be affected by genetic inheritance and epigenetic modification. However, the mechanisms that regulate the expression of genes involved in the biosynthesis of these compounds are rarely known. The results of qRT-PCR showed that the biosynthesis gene expression of these compounds was related to histone H3K4 and H3K9 methylation levels. These active compounds content of L. japonica were measured by UPLC-MS/MS. H3K4me3 showed a positive correlation with chlorogenic acid and loganic acid content, and H3K9me positively correlated with luteolin content. The correlation between histone methylation levels and the levels of luteolin and loganic acid in L. japonica from different producing areas validate the regulatory role of histone methylation in biosynthesis of bioactive compounds. Our study demonstrated a potential regulatory network of H3K9/H3K4 methylation to gene expression and content of secondary metabolites, and provided a basis for understanding the mechanism underlying the variation of major bioactive compounds in L. japonica.
Asunto(s)
Ácido Clorogénico/metabolismo , Flavonoides/biosíntesis , Histonas/metabolismo , Iridoides/metabolismo , Lonicera/genética , Lonicera/metabolismo , Proteínas de Plantas/metabolismo , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Metilación , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Espectrometría de Masas en TándemRESUMEN
Iridoids are a large family of monoterpenoids found in traditional medicinal plants and show significant effects for the human species. In addition to their wide range of biological activities, such as neuroprotective and antitumor activities, the cis-fused bicyclic ring systems of iridoids are still attractive as synthetic targets to apply novel synthetic methodologies. Accordingly, recent progress regarding the biosynthesis and chemical synthesis of iridoids is covered in this minireview. Identification of new enzymes for the iridoid biosynthesis in Catharanthus roseus and ingenious synthetic strategies for the construction of the iridoid skeleton are described.
Asunto(s)
Iridoides/síntesis química , Iridoides/metabolismo , Animales , Humanos , Iridoides/química , Estructura MolecularRESUMEN
Jasminum is an important genus in the olive family (Oleaceae), comprising about 200 species distributed all over the world. In the current study, the methanolic extract of Jasminum grandiflorum subsp. floribundum aerial parts and its respective fractions; dichloromethane and n-butanol fractions were analyzed using ultra-performance liquid chromatography coupled to high resolution mass (UPLC-HRMS) for profiling and characterization of the plant metabolites. More than seventy metabolites were identified belonging to different classes including phenolic acids, flavonoids, secoiridoids, iridoids, lignans, fatty acids, and triterpenes. The samples were also assessed for their angiotensin-I-converting enzyme (ACE) and renin inhibitory activity along with their antioxidant potential using five complementary assays: TAC (total antioxidant capacity), DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid), FRAP (ferric reducing antioxidant power) and iron reducing power. The results revealed that the n-butanol fraction showed a potent ACE and renin inhibition as compared to Lisinopril and Aliskiren standard drugs (24.66 ± 2.41 ng/mL vs. 18.37 ± 1.21 ng/mL and 141.14 ± 5.28 ng/mL vs. 447.87 ± 3.2 ng/mL, respectively) and also a strong antioxidant activity. Interestingly, the secoiridoids, dominated metabolites detected in the n-butanol fraction, revealed the potential of them for management of the hypertension diseases. The total extract and fractions were also standardized using HPLC analysis of the major secoiridoid glycoside; oleuropein. Finally, J. grandiflorum standardized extract could be considered as a target for further studies to discover a new therapeutic anti-hypertensive drug.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/análisis , Cromatografía Líquida de Alta Presión/métodos , Jasminum/química , Espectrometría de Masas/métodos , Extractos Vegetales/análisis , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Antihipertensivos/análisis , Antihipertensivos/metabolismo , Antioxidantes/análisis , Antioxidantes/metabolismo , Iridoides/análisis , Iridoides/metabolismo , Jasminum/metabolismo , Metaboloma , Extractos Vegetales/química , Renina/antagonistas & inhibidoresRESUMEN
Naozhenning (NZN) granule, a Chinese herbal formula, is widely used to treat craniocerebral trauma and promote functional recovery. In our previous study, the chemical components, as well as the serum metabolites in the male Sprague-Dawley rats of the NZN granule after oral administration were characterized. In this study, the urine metabolites in the male Sprague-Dawley rats were further investigated by ultrahigh-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry. In order to identify the urine metabolites comprehensively, three sample preparation methods were used, including solid-phase extraction, protein precipitation method and solvent partition. Based on the accurate molecular weight and the fragmentation information from the MS spectra, a total of 76 urine metabolites were identified, which including 17 prototypes and 59 metabolites. The results showed that the detected urine metabolites were different for the different pretreatment methods, as some metabolites could only be detected in the particular pretreatment method. In addition, the metabolic processes of the components from NZN granule to the serum and urine were also elucidated and discussed. The results will provide useful information for further studying the relationship between the chemical components and pharmacological activity of NZN granule.
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Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos , Administración Oral , Animales , Precipitación Química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/metabolismo , Flavonoides/metabolismo , Flavonoides/orina , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/orina , Iridoides/metabolismo , Iridoides/orina , Masculino , Espectrometría de Masas/métodos , Ratas , Ratas Sprague-Dawley , Extracción en Fase Sólida , Terpenos/metabolismo , Terpenos/orinaRESUMEN
OBJECTIVE: To study the compatibility regularity of Simiao Yong'an decoction by determining the plasma protein binding rate with the constituents in Simiao Yong'an decoction and to preliminarily clarify the effects of the compatibility on the plasma protein binding rate of different components. METHODS: Based on the equilibrium dialysis method, high-performance liquid chromatography was used to determine the contents of six constituents, which were divided into a single group and combination groups, in Simiao Yong'an decoction in the internal and external dialysis solutions. The obtained plasma protein binding rate through calculations was an index to evaluate the binding of the above components to plasma protein in different conditions. RESULTS: Harpagide, harpagoside, sweroside and loganin showed low plasma protein binding rates, ferulic acid exhibited a moderate plasma protein binding rate, and glycyrrhizic acid showed a high plasma protein binding rate. The compatibility study showed that glycyrrhizic acid promoted the binding of ferulic acid to plasma protein. Glycyrrhizic acid and ferulic acid were the key compounds to promote the binding of harpagide to plasma protein. Glycyrrhizic acid, harpagide, harpagoside and loganin had a significant inhibitory effects on the binding of sweroside to plasma protein. The plasma protein binding capacities of harpagoside and loganin were reduced by the other five constituents. Glycyrrhizic acid had the strongest plasma protein binding effect, and the binding effect was not affected by other components. CONCLUSION: This study explores the effects of compound compatibility on effective components from the perspective of plasma protein binding by high-performance liquid chromatography combined with the equilibrium dialysis method, and lays a foundation for clarifying the compatibility rule of Simiao Yong'an decoction and also provides a new idea for the study of the compatibility of traditional Chinese medicine formulas.
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Ácidos Cumáricos/metabolismo , Glicósidos/metabolismo , Ácido Glicirrínico/metabolismo , Iridoides/metabolismo , Piranos/metabolismo , Albúmina Sérica Bovina/metabolismo , Cromatografía Líquida de Alta Presión , Fitoquímicos/metabolismo , Unión ProteicaRESUMEN
Cornus officinalis, an important traditional medicinal plant, is used as major constituents of tonics, analgesics, and diuretics. While several studies have focused on its characteristic bioactive compounds, little is known on their biosynthesis. In this study, we performed LC-QTOF-MS-based metabolome and RNA-seq-based transcriptome profiling for seven tissues of C. officinalis. Untargeted metabolome analysis assigned chemical identities to 1,215 metabolites and showed tissue-specific accumulation for specialized metabolites with medicinal properties. De novo transcriptome assembly established for C. officinalis showed 96% of transcriptome completeness. Co-expression analysis identified candidate genes involved in the biosynthesis of iridoids, triterpenoids, and gallotannins, the major group of bioactive metabolites identified in C. officinalis. Integrative omics analysis identified 45 cytochrome P450s genes correlated with iridoids accumulation in C. officinalis. Network-based integration of genes assigned to iridoids biosynthesis pathways with these candidate CYPs further identified seven promising CYPs associated with iridoids' metabolism. This study provides a valuable resource for further investigation of specialized metabolites' biosynthesis in C. officinalis.
Asunto(s)
Cornus/genética , Metaboloma , Transcriptoma , Cornus/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Genómica/métodos , Taninos Hidrolizables/metabolismo , Iridoides/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Triterpenos/metabolismoRESUMEN
Iridoid synthase( IS),the key enzyme in the natural biosynthesis of vegetal iridoids,catalyzes the irreversible cyclization of 10-oxogeranial to epi-iridodial. In this study,we screened the Rehmannia glutinosa transcriptome data by BLASTn with Catharanthus roseus CrIS cDNA,and found four c DNA fragments with length of 1 527,1 743,1 425,1 718 bp,named RgIS1,RgIS2,RgIS3 and RgIS4,respectively. Bioinformatics analysis revealed that the four iridoid synthase genes encoding proteins with 389-392 amino acid residues,protein molecular weights were between 44. 30-44. 74 k Da,and theoretical isoelectric points were between 5. 30 and 5. 87. Subcellular localization predictions showed that the four iridoid synthase were distributed in the cytoplasm. Structure analysis revealed that R. glutinosa iridoid synthases contain six conserved short-chain dehydrogenase/reductase( SDR) motifs,and their 3 D models were composed typical dinucleotide-binding " Rossmann" folds covered by helical C-terminal extensions. Using the amino acid sequences of four R. glutinosa iridoid synthases,phylogenetic analysis was performed,the result indicated that RgIS3,CrIS and Olea europaea OeIS were grouped together,the other R. glutinosa iridoid synthases and fifteen proteins in other plants had close relationship. Real-time fluorescent quantitative PCR revealed that RgIS1 and RgIS3 highly expressed in unfold leaves,however,RgIS2 and RgIS4 highly expressed in stems and tuberous roots,respectively. RgIS3 showed higher expression levels in non-radial striations( nRS) of the two cultivars,and RgIS1 and RgIS2 had higher expression levels in nRS of QH,while RgIS4 had less expression levels in nRS of QH1. RgIS1,RgIS2 and RgIS3 were up-regulated by Me JA treatment,although the time and degree of response differed. Our findings are helpful to reveal molecular function of R. glutinosa iridoid synthases and provide a clue for studing the molecular mechanism of iridoid biosynthesis.
Asunto(s)
Iridoides/metabolismo , Ligasas/genética , Rehmannia/enzimología , Rehmannia/genética , Clonación Molecular , Genes de Plantas , FilogeniaRESUMEN
Cornus officinalis-Rehmannia glutinosa herb couple is widely used herb medicine in clinical practice to treat chronic kidney disease (CKD). However, the in vivo integrated metabolism of its main bioactive components in CKD rats remains unknown. In this study, UPLC-Q-TOF/MS technique combined with Metabolynx™ software, was developed and successfully applied for analysis of metabolic profiles of the bioactive components of the herb couple in normal and CKD rat biological samples. Main parent components of the herb couple extract such as loganin, morroniside and catalpol were absorbed into the blood circulation of the normal and CKD rats. Another parent component acteoside was almost completely degraded. Seventeen metabolites involved in the in vivo metabolism processes were tentatively identified. These metabolites indicated that loganin was mainly metabolized to the demethylated product, and morroniside was firstly deglycosylated to the aglycone and the latter was subsequently demethylated and acetylated. Additionally, hydrogenation and deglycosylation were the principal metabolic reactions of catalpol; while O-glucuronide and O-sulphate conjugates were observed as major metabolites for methylated caffeic acid and hydroxytyrosol released from acteoside. Compared with the normal group, the CKD rat showed lower conversion capability. Few kinds and minor amounts of the metabolites appeared in the CKD rat samples. While considerable amounts of the parent compounds were detected in the CKD plasma. This will help maintain a high blood drug concentration which might be beneficial for the treatment of CKD. The proposed method could develop an integrated template approach to analyze screening and identification of the bioactive components in plasma, urine and feces after oral administration of herb medicines. Additionally, this investigation might provide helpful chemical information for further pharmacology and active mechanism research on herb medicines.
Asunto(s)
Heces/química , Glucósidos/análisis , Glicósidos/análisis , Glucósidos Iridoides/análisis , Iridoides/análisis , Fenoles/análisis , Extractos Vegetales/análisis , Extractos Vegetales/metabolismo , Administración Oral , Animales , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/métodos , Cornus/química , Glucósidos/sangre , Glucósidos/metabolismo , Glucósidos/orina , Glicósidos/sangre , Glicósidos/metabolismo , Glicósidos/orina , Glucósidos Iridoides/sangre , Glucósidos Iridoides/metabolismo , Glucósidos Iridoides/orina , Iridoides/sangre , Iridoides/metabolismo , Iridoides/orina , Masculino , Fenoles/sangre , Fenoles/metabolismo , Fenoles/orina , Extractos Vegetales/sangre , Extractos Vegetales/orina , Ratas , Rehmannia/química , Insuficiencia Renal Crónica/sangre , Espectrometría de Masas en Tándem/métodosRESUMEN
BACKGROUND: Swertia nervosa (Wall. ex G. Don) C. B. Clarke, a promising traditional herbal medicine for the treatment of liver disorders, is endangered due to its extensive collection and unsustainable harvesting practices. OBJECTIVE: The aim of this study is to discuss the diversity of metabolites (loganic acid, sweroside, swertiamarin, and gentiopicroside) at different growth stages and organs of Swertia nervosa using the ultra-high-performance LC (UPLC)/UV coupled with chemometric method. METHODS: UPLC data, UV data, and data fusion were treated separately to find more useful information by partial least-squares discriminant analysis (PLS-DA). Hierarchical cluster analysis (HCA), an unsupervised method, was then employed for validating the results from PLS-DA. RESULTS: Three strategies displayed different chemical information associated with the sample discrimination. UV information mainly contributed to the classification of different organs; UPLC information was prominently responsible for both organs and growth periods; the data fusion did not perform with apparent superiority compared with single data analysis, although it provided useful information to differentiate leaves that could not be recognized by UPLC. The quantification result showed that the content of swertiamarin was the highest compared with the other three metabolites, especially in leaves at the rooted stage (19.57 ± 5.34 mg/g). Therefore, we speculated that interactive transformations occurred among these four metabolites, facilitated by root formation. CONCLUSIONS: This work will contribute to exploitation of bioactive compounds of S. nervosa, as well as its large-scale propagation. HIGHLIGHTS: The roots formation may influence the distribution and accumulation of metabolites.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Glucósidos Iridoides/análisis , Iridoides/análisis , Pironas/análisis , Swertia/crecimiento & desarrollo , Glucósidos Iridoides/metabolismo , Iridoides/metabolismo , Pironas/metabolismo , Swertia/química , Swertia/metabolismoRESUMEN
This study reports novel food-grade granules for co-delivery of L. plantarum 299v and a standardized extract of Olea europaea leaves (Phenolea®) as oral carrier of probiotics and hydroxytyrosol. Different granule formulations containing either L. plantarum 299v (Lac), or the olive leave extract (Phe) or their combination (Lac-Phe) have been successfully produced through wet granulation employing excipients generally regarded as safe as granulating/binding agents. L. plantarum cells withstood the manufacturing process and were stable upon storage at 4⯰C for more than 6â¯months. In vitro dissolution studies in simulated gastro-intestinal fluids showed the capability of the granules to rapidly dissolve and deliver both olive leave phenols and living L. plantarum cells. In simulated digestion conditions, Lac and Lac-Phe granules protected L. plantarum against the harsh environment of the gastro-intestinal tract. Co-administration of Lac and Phe oral granules to healthy mice provided for higher amounts of hydroxytyrosol in urines as compared to Phe granules alone, suggesting that L. plantarum 299v boosted in vivo conversion of oleuropein to hydroxytyrosol. On the other hand, PCR-assisted profiling of the Lactobacillus population in faeces obtained from mice treated with Lac or Lac plus Phe confirmed that the probiotic arrived alive to colon and was there able to exert a sort of perturbing effect on the climax colonic microflora. Overall, these results pave the way towards the development of a nutraceutical useful for combined delivery of bioactive hydroxytyrosol and probiotics to colon site.