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Introduction: Artemisinin (ART) is very common as a diet additive due to its immunoregulatory activities. Nonetheless, the immunoregulatory mechanism of ART in marine fish remains unknown. This study comprehensively examined the effects and explored the potential mechanism of ART ameliorating intestinal immune disease (IID) in fat greenlings (Hexagrammos otakii). Methods and results: The targets of ART were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Here, eight putative targets of ART were collected and identified with the Uniprot database, and 1419 IID-associated target proteins were filtered through the Drugbank, Genecards, OMIM, and PHARMGKB Databases. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways point out that ART may have immunoprotective effects by regulating cellular responses to stress, hypoxia, inflammation, and vascular endothelial growth factor stimulus through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The findings of molecular docking indicated that ART contains one active ingredient and three cross-targets, which showed a kind combination with hypoxia-inducible factor 1-alpha (HIF1-a), transcription factor p65 (RELA), and vascular endothelial growth factor A (VEGF-A), respectively. Furthermore, an ART feeding model was established to assess the ART's immunoprotect effect on the intestine of H.otakii in vivo. The D48 group showed smaller intestinal structural changes after being challenged by Edwardsiella tarda. The supplementation of ART to the diet improved total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the malondialdehyde (MDA) in intestine of H. otakii. The expression of transcription factor p65, HIF1-α, VEGF-A, cyclin D1, matrix metalloprotease 9 (MMP9), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) was decreased after dietary ART in the intestinal of H. otakii. Discussion: The present results demonstrated that dietary ART improved antioxidants and immunity, optimized the intestinal structure, and increased resistance to E. tarda through the SOD2/nuclear-factor-kappa- B (NFkB)/HIF1-a/VEGF-A pathway in the intestinal tract of H.otakii. This study integrated pharmacological analysis and experimental validation and revealed the mechanism of ART on IID, which provides insight into the improvement of IID in H. otakii.
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Artemisininas , Perciformes , Animales , Factor A de Crecimiento Endotelial Vascular , Factor de Transcripción ReIA , Simulación del Acoplamiento Molecular , Suplementos Dietéticos , Dieta , Intestinos , Artemisininas/farmacologíaRESUMEN
Suberin in roots acts as a physical barrier preventing water/mineral losses. In Arabidopsis, root suberization is regulated by abscisic acid (ABA) and ethylene in response to nutrient stresses. ABA also mediates coordination between microbiota and root endodermis in mineral nutrient homeostasis. However, it is not known whether this regulatory system is common to plants in general, and whether there are other key molecule(s) involved. We show that serotonin acts downstream of ABA in regulating suberization in rice and Arabidopsis and negatively regulates suberization in rice roots in response to salinity. We show that ABA represses transcription of the key gene (OsT5H) in serotonin biosynthesis, thus promoting root suberization in rice. Conversely, overexpression of OsT5H or supplementation with exogenous serotonin represses suberization and reduces tolerance to salt stress. These results identify an ABA-serotonin regulatory module controlling root suberization in rice and Arabidopsis, which is likely to represent a general mechanism as ABA and serotonin are ubiquitous in plants. These findings are of significant importance to breeding novel crop varieties that are resilient to abiotic stresses and developing strategies for production of suberin-rich roots to sequestrate more CO2 , helping to mitigate the effects of climate change.
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Arabidopsis , Oryza , Ácido Abscísico/farmacología , Arabidopsis/fisiología , Dióxido de Carbono/farmacología , Etilenos/farmacología , Regulación de la Expresión Génica de las Plantas , Oryza/fisiología , Fitomejoramiento , Raíces de Plantas/fisiología , Plantas Modificadas Genéticamente , Salinidad , Tolerancia a la Sal , Serotonina/farmacología , Estrés Fisiológico , Agua/farmacologíaRESUMEN
Although fossil evidence suggests that various animal groups were able to move actively through their environment in the early stages of their evolution, virtually no direct information is available on the nature of their muscle systems. The origin of jellyfish swimming, for example, is of great interest to biologists. Exceptionally preserved muscles are described here in benthic peridermal olivooid medusozoans from the basal Cambrian of China (Kuanchuanpu Formation, ca. 535 Ma) that have direct equivalent in modern medusozoans. They consist of circular fibers distributed over the bell surface (subumbrella) and most probably have a myoepithelial origin. This is the oldest record of a muscle system in cnidarians and more generally in animals. This basic system was probably co-opted by early Cambrian jellyfish to develop capacities for jet-propelled swimming within the water column. Additional lines of fossil evidence obtained from ecdysozoans (worms and panarthropods) show that the muscle systems of early animals underwent a rapid diversification through the early Cambrian and increased their capacity to colonize a wide range of habitats both within the water column and sediment at a critical time of their evolutionary radiation.
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Evolución Biológica , Cnidarios/anatomía & histología , Cnidarios/fisiología , Músculos/fisiología , Animales , Ecosistema , Fósiles , Geografía , Filogenia , EscifozoosRESUMEN
Nutraceuticals containing modified starch with increased content of slowly-digestible starch (SDS) may reduce the prevalence of obesity, diabetes and cardiovascular diseases due to its slow digestion rate. Enzymatic methods for the preparation of modified starch have attracted increasing attention because of their low environmental impact, safety and specificity. In this study, the efficient glucan branching enzyme McGBE from Microvirga sp. MC18 was identified, and its relevant properties as well as its potential for industrial starch modification were evaluated. The purified McGBE exhibited the highest specificity for potato starch, with a maximal specific activity of 791.21 U/mg. A time-dependent increase in the content of α-1,6 linkages from 3.0 to 6.0% was observed in McGBE-modified potato starch. The proportion of shorter chains (degree of polymerization, DP < 13) increased from 29.2 to 63.29% after McGBE treatment, accompanied by a reduction of the medium length chains (DP 13-24) from 52.30 to 35.99% and longer chains (DP > 25) from 18.51 to 0.72%. The reduction of the storage modulus (G') and retrogradation enthalpy (ΔHr) of potato starch with increasing treatment time demonstrated that McGBE could inhibit the short- and long-term retrogradation of starch. Under the optimal conditions, the SDS content of McGBE-modified potato starch increased by 65.8% compared to native potato starch. These results suggest that McGBE has great application potential for the preparation of modified starch with higher SDS content that is resistant to retrogradation.
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Enzima Ramificadora de 1,4-alfa-Glucano/química , Proteínas Bacterianas/química , Suplementos Dietéticos/análisis , Methylobacteriaceae/enzimología , Almidón/química , Enzima Ramificadora de 1,4-alfa-Glucano/genética , Enzima Ramificadora de 1,4-alfa-Glucano/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Hidrólisis , Cinética , Methylobacteriaceae/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidad por SustratoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease for which there are currently no effective therapies. Although mesenchymal stem cells (MSCs) can prevent arthritis through immunomodulatory mechanisms, there are several associated risks. Alternatively, MSC-derived small extracellular vesicles (sEVs) can mimic the effects of MSCs, while reducing the risk of adverse events. However, few studies have examined sEVs in the context of RA. Here, we evaluate the immunomodulatory effects of human umbilical cord MSC (hUCMSC)-derived sEVs on T lymphocytes in a collagen-induced arthritis (CIA) rat model to elucidate the possible mechanism of sEVs in RA treatment. We then compare these mechanisms to those of MSCs and methotrexate (MTX). METHODS: The arthritis index and synovial pathology were assessed. T lymphocyte proliferation and apoptosis, Th17 and Treg proportions, and interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-ß expression were detected using flow cytometry. Retinoic acid receptor-related orphan receptor gamma t (RORγt) and forkhead box P3 (FOXP3), which are master transcriptional regulators of Th17 and Treg differentiation, were also assessed using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: sEV treatment ameliorated arthritis and inhibited synovial hyperplasia in a dose-dependent manner. These effects were mediated by inhibiting T lymphocyte proliferation and promoting their apoptosis, while decreasing Th17 cell proportion and increasing that of Treg cells in the spleen, resulting in decreased serum IL-17, and enhanced IL-10 and TGF-ß expression. Transcriptionally, sEVs decreased RORγt and increased FOXP3 expression in the spleen, and decreased RORγt and FOXP3 expression in the joints. In some aspects sEVs were more effective than MSCs and MTX in treating CIA. CONCLUSIONS: hUCMSC-derived sEVs ameliorate CIA via immunomodulatory T lymphocytes, and might serve as a new therapy for RA.
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Artritis Experimental/terapia , Vesículas Extracelulares/metabolismo , Inmunomodulación/inmunología , Células Madre Mesenquimatosas/metabolismo , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Animales , Artritis Experimental/inducido químicamente , Células Cultivadas , Colágeno/toxicidad , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inmunosupresores/farmacología , Interleucina-10/inmunología , Interleucina-17/inmunología , Metotrexato/farmacología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Ratas , Ratas Wistar , Membrana Sinovial/patología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
OBJECTIVE: To observe the clinical efficacy of silver needle heat conduction therapy combined with loxoprofen sodium patch in the treatment of knee osteoarthritis (KOA). METHODS: A total of ninety-two patients with KOA were randomly and equally divided into loxoprofen sodium group and silver needle heat conduction therapy + loxoprofen sodium (combination) group, with 46 cases in each group. Patients of the combination group were treated with silver needle heat conduction therapy combined with loxoprofen sodium patch, while those of the loxoprofen sodium group were treated with loxoprofen sodium patch. The treatment was conducted for 4 weeks. The Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), bone metabolism index ï¼»including bone gla protein (BGP), bone-specific alkaline phosphatase (BALP), tartrate resistant acid phosphatase isomer (TRACP)-5bï¼½, and inflammation factors ï¼»including the tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), interleukin-1ß (IL-1ß)ï¼½ were observed before and after treatment. The therapeutic effect was assessed after the treatment. RESULTS: After the treatment, the total scores of WOMAC, the levels of serum TRACP-5b, TNF-α and IL-1ß were significantly decreased (P<0.01), while the levels of serum BGP, BALP, and TGF-ß were significantly increased (P<0.01) in the two groups compared with their own pre-treatment. Silver needle plus loxoprofen sodium was more effective in reducing WOMAC score, TRACP-5b, TNF-α, IL-1ß level (P<0.01), and up-regulating BGP, BALP, and TGF-ß level (P<0.01) than loxoprofen. Of the 46 cases in the loxoprofen sodium and combination groups, 33 and 41 were effective, with the effective rate being 71.7% and 89.1%, respectively. The comprehensive therapeutic effect of the combination group was significantly superior to that of the loxoprofen group (P<0.05). CONCLUSION: Silver needle heat conduction therapy combined with loxoprofen sodium can effectively treat KOA, its mechanism may be related to alleviating inflammation and improving bone metabolism.
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Osteoartritis de la Rodilla , Plata , Calor , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Fenilpropionatos , Sodio , Resultado del TratamientoRESUMEN
Chinese herbal medicines (CHMs) are one of the important bioresources of medicine, which works by unlocking nature's ability to prevent diseases and recover from illnesses. Recently, it has ascended to the world stage and become a global icon. Nowadays, a considerable of researches have focused on the quality evaluation of CHMs. However, it is difficult to meet the reasonable needs of human beings for safe drug use to evaluate the quality of a huge number of inferior goods for the CHMs contaminated by pesticides and heavy metals. Hence to explore an eligible medicinal plant cultivation pattern, which can provide high quality CHMs sustainably, is most promising. This review analyzed the situation and characteristics of medicinal plant resources in different periods, including wild-harvested and cultivated resources during different stages, putting forward that ecological cultivation must be the way to develop medicinal plant cultivation and to obtain high quality CHMs.
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The Traditional Chinese Medicine formula Fufang Kushen Injection (FKI) has demonstrated potential to enhance the efficacy and reduce the toxicity of the chemotherapeutic drug cisplatin. However, there is insufficient evidence to determine whether the combination of matrine and cisplatin were linked to the angiogenesis pathway. In this study, we selected two zebrafish lines, AB and Tg (vegfr2: GFP), as in vivo models to rapidly assess the anti-angiogenesis effects. KFI and cisplatin had no obvious effects when used individually, but combined KFI (5 and 10 µL/mL) and cisplatin (50µg/mL) significantly inhibited the zebrafish intersegmental vessel (ISV) formation and growth. Matrine at 50 µg/mL also showed synergetic anti-angiogenesis activity with cisplatin (50µg/mL) in 48hpf zebrafish larvae. This study has shown the potential of FKI to enhance cisplatin efficacy and reduce its toxicity by inhibiting angiogenesis. These results contribute to the scientific evidence supporting the use of KFI in combination with cisplatin to treat cancer in the clinic.
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Inhibidores de la Angiogénesis/farmacología , Cisplatino/farmacología , Medicamentos Herbarios Chinos/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Animales , Animales Modificados Genéticamente , Cisplatino/toxicidad , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Otolith consisting largely of calcium carbonate, ï¬brous and proteins, is vital for maintaining body balance and/or hearing of fish. The formation of otolith involves Ca2+ transport and deposition. In the present study, we investigated the effects of Cd2+ on otoliths development by using zebrafish embryos as model. The results showed that exposure to Cd2+ inhibited the utricular and saccular otoliths growth, indicated by reduced lateral areas. Swimming speeds were reduced and a losing balance control was observed in Cd2+ exposed larvae. The genes related to Ca2+ transport (e.g. plasma membrane Ca2+-ATPase isoform 2, pmca2; Ca2+-ATPase isoform 2, atp2b1a) and regulation (e.g. parathyroid hormone ligand type-1, pth1; stanniocalcin isoform 1, stc1) were significantly downregulated. However, the adverse effects of Cd2+ on otoliths growth and swimming activity can be protected by supplementation of Ca2+ in exposure medium. Body burden of Cd2+ in larvae was reduced upon the supplement with Ca2+. The overall results suggest that exposure to Cd2+ can inhibit influx of Ca2+, leading to less deposition of CaCO3 for otolith growth, and finally result in impaired balance control and swimming activity in zebrafish larvae.
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Conducta Animal , Cadmio/toxicidad , Exposición a Riesgos Ambientales , Membrana Otolítica/crecimiento & desarrollo , Pez Cebra/fisiología , Animales , Conducta Animal/efectos de los fármacos , Calcio/análisis , Larva/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Membrana Otolítica/efectos de los fármacos , Factores de Tiempo , Pruebas de Toxicidad , Transcripción Genética/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
OBJECTIVE: To observe the effect of collecting and retransfusing autologous platelet rich plasma (aPRP) on the amount of allogeneic blood usage in total arch replacement (Sun's surgery) and the outcomes 30 days after surgery. DESIGN: A prospective, randomized trial. SETTING: A tertiary university hospital specialized in cardiovascular diseases. PARTICIPANTS: The study comprised 120 patients undergoing Sun's surgery for Stanford type A acute aortic dissection. INTERVENTIONS: aPRP was harvested before incision and was re-transfused after heparin neutralization for patients in the treatment group. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in preoperative demographic data between the 2 study groups. Intraoperative transfusions of erythrocyte (pâ¯=â¯0.009), plasma (pâ¯=â¯0.017), cryoprecipitate (pâ¯=â¯0.002), and platelets (p < 0.001) in the treatment group were reduced significantly. In addition, less blood loss was observed in the treatment group (pâ¯=â¯0.002). The durations of postoperative mechanical ventilation (pâ¯=â¯0.029) and hospitalization (pâ¯=â¯0.002) of the treatment group were significantly shorter. There were no statistically significant differences in the length of intensive care unit stay, the incidence of complications, and mortality 30 days after surgery. CONCLUSION: In total arch replacement (Sun's surgery), collecting and retransfusing aPRP reduced intraoperative transfusions of erythrocyte, plasma, and cryoprecipitate and decreased the duration of postoperative mechanical ventilation and hospitalization. This technique had no significant effect on the incidence of complications and mortality 30 days postoperatively.
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Disección Aórtica/sangre , Disección Aórtica/terapia , Transfusión de Sangre Autóloga/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Cuidados Intraoperatorios/métodos , Plasma Rico en Plaquetas , Adulto , Anciano , Disección Aórtica/diagnóstico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Plasma Rico en Plaquetas/fisiología , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Acute biliary pancreatitis (ABP) is a potentially life-threatening disease that is induced by the common bile duct (CBD) sludge or stones. This study aimed to investigate protective effects of Qingyi Decoction (QYT) on deoxycholic-acid-sodium salt (DCA) induced ABP in rats. Gpbar1 is a G-protein coupled receptor that can be activated by DCA. Both Gpbar1 overexpression vector and Gpbar1 RNAi were constructed and transfected into ABP cell models. Functional assays reveal that DCA significantly induced AR42J apoptosis and triggered Gpbar1 expression. Gpbar1 significantly activated caspase 8 and caspase 9 as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly triggered apoptosis associated inflammatory factors as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly induced calcium flux as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 up-regulated caspases and inflammatory factors in DCA treated pancreatic acinar cells. QYT reversed DCA induced apoptosis and inflammatory response. QYT significantly reduced Gpbar1 levels compared to no-QTY treated cells (p<0.05). In conclusion, QYT protects against DCA induced pancreatic acinar cell damage in ABP by inhibiting Gpbar1/NF-kB/p-RIP signaling pathway.
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Medicamentos Herbarios Chinos/farmacología , FN-kappa B/metabolismo , Pancreatitis/tratamiento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Enfermedad Aguda , Animales , Apoptosis , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular , Regulación Enzimológica de la Expresión Génica , Inflamación , Pancreatitis/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
RBOHF from Arabidopsis thaliana represents a multifunctional NADPH oxidase regulating biotic and abiotic stress tolerance, developmental processes and guard cell aperture. The molecular components and mechanisms determining RBOHF activity remain to be elucidated. Here we combined protein interaction studies, biochemical and genetic approaches, and pathway reconstitution analyses to identify and characterize proteins that confer RBOHF regulation and elucidated mechanisms that adjust RBOHF activity. While the Ca2+ sensor-activated kinases CIPK11 and CIPK26 constitute alternative paths for RBOHF activation, the combined activity of CIPKs and the kinase open stomata 1 (OST1) triggers complementary activation of this NADPH oxidase, which is efficiently counteracted through dephosphorylation by the phosphatase ABI1. Within RBOHF, several distinct phosphorylation sites (p-sites) in the N-terminus of RBOHF appear to contribute individually to activity regulation. These findings identify RBOHF as a convergence point targeted by a complex regulatory network of kinases and phosphatases. We propose that this allows for fine-tuning of plant reactive oxygen species (ROS) production by RBOHF in response to different stimuli and in diverse physiological processes.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Calcio/metabolismo , NADPH Oxidasas/metabolismo , Arabidopsis/genética , Activación Enzimática , Regulación de la Expresión Génica de las Plantas , Células HEK293 , Humanos , Modelos Biológicos , Mutación/genética , Fenotipo , Fosforilación , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cistanches Herba is a medicinal plant that has tonification properties and is commonly used in Asia. Owing to the imbalance between supply and demand, adulterants are frequently added for profit. However, there is no regulatory oversight because quality control tools are not sufficient for identifying heavily processed products. Thus, a novel molecular tool based on nucleotide signatures and species-specific primers was developed. The ITS2 regions from 251 Cistanches Herba and adulterant samples were sequenced. On the basis of SNP sites, four nucleotide signatures within 30~37 bp and six species-specific primers were developed, and they were validated by artificial experimental mixtures consisting of six different species and different ratios. This method was also applied to detect 66 Cistanches Herba products on the market, including extracts and Chinese patent medicines. The results demonstrated the utility of nucleotide signatures in identifying adulterants in mixtures. The market study revealed 36.4% adulteration: 19.7% involved adulteration with Cynomorium songaricum or Cistanche sinensis, and 16.7% involved substitution with Cy. songaricum, Ci. sinensis, or Boschniakia rossica. The results also revealed that Cy. songaricum was the most common adulterant in the market. Thus, we recommend the use of species-specific nucleotide signatures for regulating adulteration and verifying the quality assurance of medicinal product supply chains, especially for processed products whose DNA is degraded.
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The aim of the study was to determine the developmental toxicity of the traditional Chinese medicine Xiaoaiping (XAP) and to investigate its underlying mechanism of action. Zebrafish embryos were incubated with 0.4, 0.8, 1.2, and 1.6 mg/mL XAP. Endpoints such as mortality, hatching rate, malformation, body length, morphology score, swimming behavior, histological changes, reactive oxygen species (ROS) production, total superoxide dismutase (T-SOD) activity, and the mRNA expression of genes related to oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and the Wnt pathway were evaluated. Our results demonstrated that XAP exposure increased mortality and malformation and reduced the hatching rate. XAP resulted in severe malformation, including swim bladder deficiency, yolk retention, pericardial edema, and tail curvature. Histopathological analysis showed that XAP induced liver, heart and muscle injury. High doses (≥1.2 mg/mL) of XAP notably decreased the locomotor capacity of zebrafish. ROS generation was remarkably increased and T-SOD activity was decreased, confirming that oxidative stress was induced by XAP. The mRNA expression levels of ER stress-related genes (chop, hspa5, hsp90b1, and perk), apoptosis-related genes (caspase-3, bax, and p53) and wnt11 were significantly upregulated by XAP exposure. The expression levels of the oxidative stress-related genes (cat, sod1, and gstp2), Wnt pathway-related genes (ß-catenin, wnt3a, and wnt8a) and bcl-2 initially increased and then decreased as the XAP exposure dose increased. In conclusion, we provide evidence for the first time that XAP can induce dose-related developmental toxicity, and ER stress, apoptosis and the Wnt pathway participate in the toxicity regulation.
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Depression is a highly prevalent disorder that affects more than 300 million adults worldwide in 2015. Depression also frequently coexists with many other conditions such as osteoporosis and one-third of the Intensive Care Unit (ICU) survivors had depressive symptoms. Antidepressants have become the most commonly prescribed drugs in the United States. In addition to the regular process, drug discovery and development (R&D) for depression presents extra challenges because of the heterogeneity of the symptoms and various co-occurring disorders. Botanical medicine with multi-functional nature has been proposed to be more effective, providing rapid control of core and comorbid conditions of depression. With the technical advances in analytical instruments, metabolomics is entering into a "new generation". Next-generation metabolomics (NGM) has the capability to comprehensively characterize drug-induced metabolic changes in the biological systems. NGM has demonstrated great potential in all the stages of pharmaceutical R&D in the last 10 years. Albiflorin isolated from Peony roots is a promising drug candidate with multi-target for depression and is currently under development by Beijing Wonner Biotech. In this work, we summarized the common analytical platforms for NGM and its main applications in drug R&D. We used albiflorin as an example to illustrate how NGM improves our understanding of drug candidate actions and facilitates drug safety evaluation. Future directions on how to expand the use of NGM for new antidepressant development in pharmaceutical industry were also discussed.
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Antidepresivos/farmacología , Hidrocarburos Aromáticos con Puentes/farmacología , Depresión/tratamiento farmacológico , Metabolómica , Antidepresivos/química , Hidrocarburos Aromáticos con Puentes/química , Humanos , Estructura Molecular , Plantas Medicinales/químicaRESUMEN
Seven aromatic glycosides (1-7), including four phenylethanol glycosides, one phenylmethanol glycoside, one phenylpropane glycoside and one benzoside, were isolated from the methanolic extract of Uighur Medicine Elaeagnus angustifolia flowers. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HR-MS). Compound 1 is a new compound, named as angustifol A. Six known compounds were identified as 2-phenylethyl-O-ß-D-glucopyranoside(2), salidroside (3), vanillic acid 4-O-ß-D-glucopyranoside(4), vanilloloside (5), (Z)-isoconiferin (6), 2-phenylethyl-6-O-α-L-arabinofuranosyl-ß-D-glucopyranoside (7). Compounds 2-7 were isolated from the genus Elaeagnus for the first time. In vitro anti-inflammatory assays revealed that none of these compounds showed good COX inhibitory activities.
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Elaeagnaceae , Plantas Medicinales , Flores , Glicósidos , Medicina de Hierbas , Estructura MolecularRESUMEN
PREMISE OF THE STUDY: Microsatellite markers were developed for a medicinal herb, Gentiana lawrencei var. farreri (Gentianaceae), for the future assessment of population genetic structure and potential hybridization events with related taxa. METHODS AND RESULTS: Using the 454 FLX+ sequencing platform, we obtained 81,717 clean reads with an average length of 291 bp. A total of 3031 primer pairs were designed, and 96 were selected for validation. A set of 20 fluorescently labeled primer pairs was further selected and screened for polymorphisms in three G. lawrencei var. farreri populations and one G. veitchiorum population. Among the four populations, the average number of alleles per locus was 15.2. Finally, a set of 17 unlinked loci were determined to be in Hardy-Weinberg equilibrium after two linked loci were removed. CONCLUSIONS: The identified simple sequence repeat markers will be useful for genetic diversity and evolution studies in G. lawrencei var. farreri and related taxa.
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Species adulteration in herbal products (HPs) exposes consumers to health risks. Chemical and morphological methods have their own deficiencies when dealing with the detection of species containing the same active compounds in HPs. In this study, we developed a rapid identification method using the recombinase polymerase amplification (RPA) assay to detect two species, Ginkgo biloba and Sophora japonica (as adulteration), in Ginkgo biloba HPs. Among 36 Ginkgo biloba HP samples, 34 were found to have Ginkgo biloba sequences, and 9 were found to have Sophora japonica sequences. During the authentication process, the RPA-LFS assay showed a higher specificity, sensitivity and efficiency than PCR-based methods. We initially applied the RPA-LSF technique to detect plant species in HPs, demonstrating that this assay can be developed into an efficient tool for the rapid on-site authentication of plant species in Ginkgo biloba HPs.
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ADN de Plantas/análisis , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Ginkgo biloba/genética , Reacción en Cadena de la Polimerasa/métodos , Recombinasas/metabolismo , Suplementos Dietéticos/análisis , Contaminación de Medicamentos/prevención & control , Calidad de los Alimentos , Ginkgo biloba/química , Ginkgo biloba/clasificación , Humanos , Extractos Vegetales/análisis , Extractos Vegetales/genética , Sensibilidad y Especificidad , Sophora/genética , Factores de TiempoRESUMEN
Two new daphnane diterpenes named tianchaterpenes A and B were isolated from the roots of Stelleropsis tianschanica. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS. Compounds 1 and 2 were evaluated for their cytotoxic activities against HeLa and HCT-8 cell lines. The results showed that all compounds displayed weak cytotoxicities to the HeLa cells and were inactive to the HCT-8 cells.
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Antineoplásicos Fitogénicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Raíces de Plantas/química , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura MolecularRESUMEN
Two new lanostane triterpenoid acids, 12ß, 15α-dihydroxy-24-methyl-3,23-dioxo-lanosta-7,9(11)-dien-26-oic acid (1), and 3α, 12ß-dihydroxy-24-methyl-7,23-dioxo-lanosta-8-en-26-oic acid (2), were isolated from the methanolic extract of Uighur medicine Fomes officinalis. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HR-MS). Anti-inflammatory and cytotoxicity assays revealed that both compound 1 and 2 show no inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW264.7 cells, and no cytotoxicity activities against HepG2 cells.