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Common wheat (Triticum aestivum L.) is one of the most valuable cereal crops worldwide. This study examined leaf extracts of 30 accessions of T. aestivum and its subspecies using 48 h maceration with methanol by GC-MS and GCxGC-MS. The plants were grown from seeds of the wheat genetics collection of the Wheat Genetics Sector of the Institute of Cytology and Genetics, SB RAS. The analysis revealed 263 components of epicuticular waxes, including linear and branched alkanes, aliphatic alcohols, aldehydes, ketones, ß-diketones, carboxylic acids and their derivatives, mono- and diterpenes, phytosterols, and tocopherols. Hierarchical cluster analysis and principal component analysis were used to identify and visualize the differences between the leaf extracts of different wheat cultivars. Three clusters were identified, with the leading components being (1) octacosan-1-ol, (2) esters of saturated and unsaturated alcohols, and (3) fatty acid alkylamides, which were found for the first time in plant extracts. The results highlight the importance of metabolic studies in understanding the adaptive mechanisms and increasing wheat resistance to stress factors. These are crucial for breeding new-generation cultivars with improved traits.
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The pericarps of Zanthoxylum schinifolium Sieb. et Zucc were called "green huajiao", which were used as traditional folk medicine and popular seasoning in China. In this study, twenty-seven alkylamides, including a rare alkylamide containing two amide groups (1), an alkylamide with a furan ring (5), six new alkylamide analogues (2-4, 6-8), together with nineteen known alkylamides (9-27) were isolated from green huajiao. Their structures were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and UV spectra. Furthermore, compounds 5, 18, 21, and 22 exhibited weak protective activity for corticosterone-induced PC12 cells damage.
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Zanthoxylum , Zanthoxylum/química , Animales , Estructura Molecular , Ratas , Células PC12 , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China , Amidas/química , Amidas/aislamiento & purificación , Amidas/farmacología , CorticosteronaRESUMEN
Zanthoxylum oleoresin, a concentrated extract derived from Zanthoxylum bungeanum, is rich in non-volatile, intensely flavorful substances and amide compounds, such as hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-ε-sanshool. The production process of Zanthoxylum oleoresin remains unstandardized, and there is still a lack of research on the precise classification and quantification of its key chemical constituents, as well as the stability of these compounds when produced using different extraction methods. This study utilized preparative liquid chromatography to extract and purify amide compounds from Zanthoxylum oleoresin, successfully isolating three sanshools: hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-ε-sanshool. The stability of three these sanshools under UVB irradiation in different solvents was explored in UVB-simulated sunlight conditions to investigate the degradation or transformation mechanism of Zanthoxylum alkylamides under UVB irradiation. The findings indicate a rapid decrease in the hydroxy-α-sanshool content under UVB ultraviolet light, aligning with the second-order kinetics. This study revealed alterations in the contents of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-ε-sanshool and the formation of a new compound following exposure to UVB light. This new compound, along with the three sanshools, possesses a uniform m/z 264 and shares similar chemical structures. Further analysis also uncovered that these compounds are capable of undergoing isomerization reactions under UVB irradiation. This demonstrates that UVB irradiation of certain intensities can modify the concentrations and chemical structures of these Zanthoxylum alkylamides. These insights offer crucial guidance for future studies on the processing and preservation of Zanthoxylum alkylamides and their derivatives.
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This study analysed the phytochemical profile of Acmella oleracea extract and the molecular interactions of its main compounds with TRPV1 and CB2, target receptors in the Burning Mouth Syndrome (BMS) pathogenesis. The phytochemical profile of A. oleracea's floral buds extract treated with activated charcoal (TCEE) was analysed by High-Performance Liquid Chromatography (HPLC) coupled to Mass Spectrometry (LC-MS). The quantification of spilanthol was analysed by HPLC coupled to a Diode-Array Detector (HPLC-DAD). The phytochemical analysis revealed the presence of nine alkylamides and phenolic compounds. The TCEE showed a significant increase in spilanthol content compared to the crude extract (CEE), going from 28.33 mg/g to 117.96 mg/g. The molecular docking indicated a behaviour of the alkylamides as partial TRPV1 agonists and CB2 agonists and, for the first time, indicates the action of these compounds in the symptomatic management of BMS.
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Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo2(OAc)4-induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum.
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Neuroblastoma , Zanthoxylum , Humanos , Zanthoxylum/química , Peróxido de Hidrógeno/farmacología , Espectrometría de Masas , Estructura MolecularRESUMEN
Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1/2, STAT 3, and/or NF-κB signaling pathways, and/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases.
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Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1ß, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.
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Productos Biológicos , Echinacea , Mediadores de Inflamación , Especies Reactivas de Oxígeno , Extractos Vegetales/farmacología , Adyuvantes Inmunológicos , Factor de Necrosis Tumoral alfa , Antiinflamatorios/farmacología , Ácido SalicílicoRESUMEN
The spicy taste and medicinal properties of Zanthoxylum bungeanum are imparted by several alkylamides. Although most studies have focused on their isolation and identification, few have reported their biosynthesis pathways. Among the differentially expressed genes (DEGs) reported in the numerous varieties of Z. bungeanum, some might contribute to alkylamide biosynthesis. However, they are not yet functionally validated. The present study explored the function of two genes, ZbFAD2 and ZbFAD3, in the alkylamide biosynthesis pathway, and their stable and transient expression in Arabidopsis thaliana and Nicotiana benthamiana were also analyzed. As compared with the wild-type (WT), the fatty acid content analysis indicated that ZbFAD2-A. thaliana transgenic seeds had lower oleic acid and higher linoleic acid contents, while the ZbFAD3-A. thaliana transgenic seeds showed lower linoleic acid and higher α-linolenic acid levels. Moreover, hydroxy-α-sanshool, a major alkylamide, was considerably higher in the ZbFAD2-N. benthamiana transgenic plants (0.2167 ± 0.0026 mg/g) than in the WT (0.0875 ± 0.0049 mg/g), while it was lower in the ZbFAD3-N. benthamiana transgenic plants (0.0535 ± 0.0037 mg/g). These results suggest that both ZbFAD2 and ZbFAD3 are vital alkylamide biosynthesis enzymes in Z. bungeanum. Our study not only helps to scale up the alkylamide production, but also establishes the role of the uncharacterized genes.
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Alkylamides are used as plastic additives in various materials and products, potentially posing risks to human health and the environment. Besides reported alkylamides in plastics, many unknown alkylamides may exist in various plastics, which are needing identification and characterization. This study performed nontarget analysis of alkylamides in electrical product plastics by gas chromatography-positive chemical ionization high-resolution mass spectrometry in full scan mode and an in-house developed data-processing algorithm. The algorithm was based on exact mass discrepancies and signal intensities of specific fragment and adduct ions of alkylamides, and was able to efficiently screen and anchor quasi-molecular ions. As a whole, 36 alkylamides were identified, of which 7 were found in all the plastics and 14 were observed in ≥ 2 plastics. The content distributions were elucidated with normalized abundances of quasi-molecular ions of alkylamides. Oleamide showed chromatographic peaks with the highest abundances in individual samples and was the most abundant alkylamide in all the plastics, of which the normalized abundances accounted for 57.42-70.06% of the total abundances of all alkylamides. Besides, (2E)-2-hexenamide, palmitamide and stearamide showed relatively high abundances, of which the relative abundances were 6.99-25.79%. The high abundances together with predicted environmental behaviors and toxicities indicate that alkylamides in plastics are worthy of further in-depth research. The nontarget analysis method including the instrumental analysis and data-processing algorithm can be applied to identification and characterization of alkylamides in more diverse matrices. In addition, the analysis results for the first time provide knowledge about the specific characteristics and relative content distributions of alkylamides in electrical product plastics from a comprehensive perspective.
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Amidas , Plásticos , Algoritmos , Amidas/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Iones , Plásticos/químicaRESUMEN
Neuropathic and postoperative pain are clinical conditions that impair the patient's quality of life. The current pharmacotherapy of both painful states is ineffective and accompanied by several side effects. In order to develop new therapeutics targets, the secondary metabolites of plants have been extensively studied. Acmella oleracea ("jambu") is a native plant from the Amazon region and rich in alkylamides, bioactive compounds responsible for inducing anesthetic and chemesthetic sensations. We previously demonstrated that the intraplantar administration of an hexanic fraction (HF) rich in alkylamides from jambu and the synthetic isobutylalkyl amide (IBA) at 0.1 µg/20 µL can promote antinociceptive and anti-inflammatory effects. Thus, this study aimed to evaluate the local effect of HF and IBA (0.1 µg/20 µL) on neuropathic (partial sciatic nerve ligation, PSNL) and postoperative pain (plantar incision surgery, PIS) models in mice. Seven days after the PSNL, the mechanical (von Frey test) and cold (acetone-evoked evaporative cooling) allodynia, and digital gait parameters were analyzed. The intraplantar HF and IBA treatments attenuated the mechanical and cold allodynia as well as the static (max. Contact and print area) and dynamic (stand duration) parameters of digital gait analyses. On the day after PIS, the mechanical allodynia, heat hyperalgesia (hot plate, 52 ± 0.1°C), and spontaneous nociception scores were evaluated. Topical treatment with HF reduced the mechanical allodynia, heat hyperalgesia, and spontaneous nociception scores. In contrast, IBA treatment only partially reduced the mechanical allodynia. In summary, the local treatment with HF was effective on both neuropathic and postoperative pain, as opposed to IBA, which only had an effect on neuropathic pain.
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Asteraceae , Neuralgia , Amidas/farmacología , Animales , Modelos Animales de Enfermedad , Hiperalgesia/tratamiento farmacológico , Ratones , Estructura Molecular , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Dolor Postoperatorio/tratamiento farmacológico , Calidad de VidaRESUMEN
Crinum biflorum Rottb. (syn. Crinum distichum) is an Amaryllidaceae plant used in African traditional medicine but very few studies have been performed on this species from a chemical and applicative point of view. Bulbs of C. biflorum, collected in Senegal, were extracted with ethanol by Soxhlet and the corresponding organic extract was purified using chromatographic methods. The pure compounds were chemically characterized by spectroscopic techniques (1D and 2D 1H and 13C NMR, HR MS and ECD) and X-ray analysis. Four homoisoflavonoids (1-4) and one alkylamide (5) were isolated and characterized as 5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (1), as 3-hydroxy-5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (2), as 3-hydroxy-5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (3) and as 5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (4), and the alkylamide as (E)-N-(4-hydroxyphenethyl)-3-(4-hydroxyphenyl)acrylamide (5), commonly named N-p-coumaroyltyramine. The relative configuration of compound 1 was verified thanks to the X-ray analysis which also allowed us to confirm its racemic nature. The absolute configurations of compounds 2 and 3 were assigned by comparing their ECD spectra with those previously reported for urgineanins A and B. Flavanoids 1, 3 and 4 showed promising anticancer properties being cytotoxic at low micromolar concentrations towards HeLa and A431 human cancer cell lines. The N-p-coumaroyltyramine (5) was selectively toxic to A431 and HeLa cancer cells while it protected immortalized HaCaT cells against oxidative stress induced by hydrogen peroxide. Compounds 1-4 also inhibited acetylcholinesterase activity with compound 3 being the most potent. The anti-amylase and the strong anti-glucosidase activity of compound 5 were confirmed. Our results show that C. biflorum produces compounds of therapeutic interest with anti-diabetic, anti-tumoral and anti-acetylcholinesterase properties.
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Amaryllidaceae/química , Ácidos Cumáricos/aislamiento & purificación , Crinum/química , Flavonoides/aislamiento & purificación , Acetilcolinesterasa/metabolismo , Antivirales/farmacología , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Ácidos Cumáricos/química , Flavonoides/química , Fluoresceínas/metabolismo , VIH-1/efectos de los fármacos , Células HaCaT , Células HeLa , Humanos , Hipoglucemiantes/farmacología , Metaboloma , Conformación Molecular , Senegal , alfa-Amilasas/metabolismoRESUMEN
Alkylamides, as the representative hemp flavor and active ingredients, can reflect the quality of Zanthoxylum bungeanum Maxim. However, conjugated triene structure exists in alkylamides, which is easy to be oxidized and decomposed in air, making it difficult to quantify. In this study, a method for the quantitative determination of alkylamides by 1 H-NMR technology was developed with 85% ethanol as the best extraction solvent, CDCl3 as the best deuterium dissolution reagent, pyrazine as the internal standard, and triple peaks of hydrogen protons on the amide bond at δ 6.33 ppm as the quantitative signal peak. Meanwhile, methodological verification was carried out to prove the reliability and effectiveness of the method. On this basis, the contents of alkylamides in nine germplasms of Zanthoxylum with monthly dynamics were obtained. The results showed that the alkylamides of Hancheng stingless Z. bungeanum (HC) exhibited the highest content in August (51.92 ± 0.96 mg/g), while the lowest was FG in June (1.23 ± 0.21 mg/g). The results of 1 H-NMR corresponded to those of HPLC, and the effectiveness of this method was verified. Accumulation dynamic results show that the best harvest period of Z. bungeanum is July and August. Moreover, the quality of nine varieties of Zanthoxylum bungeanum from a common garden was evaluated by the established 1 H-NMR fingerprint and chemometric analyses. The results showed that Hancheng stingless Z. bungeanum was the best germplasm. This study provides a new strategy for the quantitative determination of alkylamides in Z. bungeanum and improves the quality evaluation system of Z. bungeanum. PRACTICAL APPLICATION: The results provide a new research idea for the analysis of important chemical components of Z. bungeanum. Meanwhile, the study provides a scientific basis for the quality evaluation and high-quality germplasm resources of Z. bungeanum.
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Amidas , Análisis de los Alimentos , Espectroscopía de Resonancia Magnética , Zanthoxylum , Amidas/análisis , Cromatografía Líquida de Alta Presión , Análisis de los Alimentos/métodos , Protones , Reproducibilidad de los Resultados , Zanthoxylum/químicaRESUMEN
Historical ethnobotanies of indigenous peoples of the North American prairies reveal treatment of many painful conditions by Echinacea spp. Recent evidence suggests a pharmacological basis for such use as the bioactivity of E. angustifolia and E. purpurea is mediated, in part, through activation of the endocannabinoid system (ECS). Whereas the cannabimimetic effects of individual echinacea products and alkylamides have been described, the activity of crude extracts has not been compared between cannabinoid (CB) receptors or across species or genotypes. Moreover, few studies have explored echinacea's engagement of the ECS for historic treatments or new therapeutic applications in peripheral inflammatory pain. We hypothesized that 1) the in vitro effects of root extracts on CB receptor internalization would vary with species and phytochemistry, and that echinacea root extracts would reduce inflammatory pain in vivo through activation of the ECS. Root extracts of different E. angustifolia and E. purpurea accessions were prepared, analyzed by HPLC-DAD to quantify caffeic acid derivatives and alkylamides (AKA), and tested for agonist and antagonist activities using receptor redistribution assays. Linear regression of activity relative to phytochemistry identified predictive compounds that were assessed individually in redistribution assays. Extracts were evaluated in the Hargreaves model of chronic inflammatory pain in rats with co-administration of selective CB1/2 antagonists to gauge involvement of the ECS. CB receptor agonist activity varied among accessions of both species with linear regression revealing a significant relationship between CB1 activity and AKA2 for E angustifolia, and AKA 9 + 10 for E purpurea. CB2 activity was positively related with AKA 9 + 10 and total AKAs in E. angustifolia. Four isolated AKA demonstrated agonist activity in the CB2, but not CB1, assay. In the inflammatory pain model, oral administration of either E angustifolia or E. purpurea root extract produced dose-dependent analgesic effects that were partially reversed by co-administration of CB receptor antagonists. This study demonstrates that in vitro effects of crude echinacea root extracts on CB receptors is predicted by phytochemistry. In vivo, echinacea has potential applications for peripheral inflammatory pain such as arthritis and burns, reflecting the traditional uses of Indigenous North Americans.
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This research aimed at exploring the effect of Zanthoxylum alkylamides on lipid metabolism and its potential mechanisms using high-fat diet rat model. Treatment with Zanthoxylum alkylamides for 6 weeks, food efficiency and atherogenic index of the low, medium, and high doses of Zanthoxylum alkylamides-treated groups were significantly reduced. Meanwhile, the histopathological structure of the livers showed that hepatic steatosis in the groups treated with Zanthoxylum alkylamides was reduced, particularly the HD group. Moreover, the related genes were studied, such as, liver X receptor (LXR), cholesterol 7 alpha-hydroxylase (CYP7A1), hepatic 3-hydroxyl-2-methylglutaryl CoA (HMG-CoA) reductase, sterol regulatory element-binding protein 2 (SREBP-2), ileal bile acid-binding protein (IBABP), sodium-dependent bile acid transporter (ASBT), and transient receptor potential vanilloid subtype1 (TRPV1). These results demonstrated that Zanthoxylum alkylamides could ameliorate abnormal lipid metabolism in rats fed with a high-fat diet. The underlying mechanism may be the downregulation of the expression levels of cholesterol synthesis and bile acid reabsorption-related genes, reduction of endogenous cholesterol synthesis, and increase in bile acid and neutral sterol excretion. PRACTICAL APPLICATIONS: High-energy diet is a potential risk of lipid metabolic disorder. Many studies have shown that hyperlipidemia can lead to atherosclerosis and even hemangioma, cerebral thrombosis, coronary heart disease, and other diseases, which seriously threaten human health. Therefore, seeking an effective and safe way to prevent the obesity-related disease is necessary. This research found that Zanthoxylum alkylamide could ameliorate abnormal lipid metabolism in rats fed with a high-fat diet. The underlying mechanism may be the downregulation of the expression levels of cholesterol synthesis and ileal absorption of bile acid genes, reduction of endogenous cholesterol synthesis, and increase in bile acid and neutral sterol excretion. Therefore, Zanthoxylum alkylamide has the potential for preventing or alleviating high-energy intake-related obesity.
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Metabolismo de los Lípidos , Zanthoxylum , Animales , Dieta Alta en Grasa/efectos adversos , Lípidos , Hígado/metabolismo , RatasRESUMEN
Polysaccharides have been used widely in many industries, from food technology and mining to cosmetics and biomedical applications. Over recent years there has been growing interest in the development of responsive polysaccharides with unique and switchable properties, particularly systems that display lower-critical solution temperatures (LCSTs). Therefore, in this study we aimed to investigate a novel strategy that would allow the conversion of non-responsive polysaccharides into thermoresponsive polysaccharides with tuneable LCSTs. Through the functionalisation of dextran with alkylamide groups (isopropyl amide, diethyl amide, piperidinyl and diisobutyl amide) using a carbodiimide coupling approach in conjunction with amic acid derivatives, we prepared a library of novel dextrans with various degrees of substitution (DS), which were characterised via nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The alkylamide-functionalised dextrans were found to have good solubility in aqueous solutions, with the exception of those having a high DS of large hydrophobic substituents. Determination of the thermoresponsive characteristics of the polymer solutions via UV-vis spectroscopy revealed that the LCST of the alkylamide-functionalised dextrans was highly dependent on the type of alkylamide group and the DS and could be tuned over a large range (5-35 °C). Above the LCST, all of the thermoresponsive alkylamide-functionalised dextrans formed colloidal dispersions with particles sizes ranging from 400 -600 nm, as determined by dynamic light scattering (DLS). In addition, the polymers were found to exhibit a fast and reversible phase transition in solution with narrow hysteresis (â¼ 1-5 °C). Finally, the injectability and biocompatibility of the novel thermoresponsive dextrans was confirmed in vivo via subcutaneous and intracranial ventricle injections, with no local or systemic toxicity noted over a 14 d period. Overall, the alkylamide-functionalised dextrans display interesting thermoresponsive properties and trends that may make them useful in biomedical applications, such as drug-delivery.
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Polisacáridos/química , Alquilación , Amidas/química , Animales , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Materiales Biocompatibles/toxicidad , Cromatografía en Gel , Dextranos/administración & dosificación , Dextranos/química , Dextranos/toxicidad , Dispersión Dinámica de Luz , Ensayo de Materiales , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Peso Molecular , Resonancia Magnética Nuclear Biomolecular , Tamaño de la Partícula , Transición de Fase , Polisacáridos/administración & dosificación , Polisacáridos/toxicidad , Espectrofotometría , TemperaturaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Acmella oleracea (L.) R. K. Jansen (Asteraceae), known as jambú in Brazil, is used in traditional medicine as analgesic and for inflammatory conditions, characterized by the presence of N-alkylamides, mainly spilanthol. This bioactive compound is responsible for the above-described pharmacological properties, including sialagogue and anesthetic. AIM OF THE STUDY: This study aimed to characterize the anti-inflammatory effects of A. oleracea leaves (AOEE-L) and flowers (AOEE-F) extracts, including an isolated alkylamide (spilanthol), using in vitro and in vivo models. The mechanism underlying this effect was also investigated. MATERIALS AND METHODS: Extracts were analyzed by HPLC-ESI-MS/MS in order to characterize the N-alkylamides content. AOEE-L, AOEE-F (25-100 µg/mL) and spilanthol (50-200 µM) were tested in vitro on VSMC after stimulation with hyperglycemic medium (25 mM glucose). Their effects over nitric oxide (NO) generation, chymase inhibition and expression, catalase (CAT), superoxide anion (SOD) radical activity were evaluated. After an acute administration of extracts (10-100 mg/mL) and spilanthol (6.2 mg/mL), the anti-inflammatory effects were evaluated by applying the formalin test in rats. Blood was collected to measure serum aminotransferases activities, NO activity, creatinine and urea. RESULTS: A number of distinct N-alkylamides were detected and quantified in AOEE-L and AOEE-F. Spilanthol was identified in both extracts and selected for experimental tests. Hyperglycemic stimulation in VSMC promoted the expression of inflammatory parameters, including chymase, NO, CAT and SOD activity and chymase expression, all of them attenuated by the presence of the extracts and spilanthol. The administration of extracts or spilanthol significantly inhibited edema formation, NO production and cell tissue infiltration in the formalin test, without causing kidney and liver toxicity. CONCLUSION: Taken together, these results provide evidence for the anti-inflammatory activity of leaves and flowers extracts of jambú associated distinctly with their chemical profile. The effects appear to be associated with the inhibition of chymase activity, suppression of the proinflammatory cytokine NO and antioxidant activities.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Asteraceae/química , Quimasas/antagonistas & inhibidores , Extractos Vegetales/farmacología , Alcamidas Poliinsaturadas/farmacología , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/química , Antioxidantes/uso terapéutico , Brasil , Línea Celular , Quimasas/metabolismo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/patología , Etanol/química , Flores/química , Formaldehído/toxicidad , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Medicina Tradicional , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Alcamidas Poliinsaturadas/uso terapéutico , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of the existing herbicides in the field. Sanshools, which are well known as spices, are N-alkyl substituted compounds extracted from the Zanthoxylum species and have several essential physiological and pharmacological functions. Sanshools display excellent safener activity for the herbicide metolachlor in rice seedlings. However, the high cost of sanshools extraction and difficulties in the synthesis of their complicated chemical structures limit their utilization in agricultural fields. Thus, the present study designed and synthesized various N-alkyl amide derivatives via the scaffold-hopping strategy to solve the challenge of complicated structures and find novel potential safeners for the herbicide metolachlor. In total, 33 N-alkyl amide derivatives (2a-k, 3a-k, and 4a-k) were synthesized using amines and saturated and unsaturated fatty acids as starting materials through acylation and condensation. The identity of all the target compounds was well confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectrometry (HRMS). The primary evaluation of safener activities for the compounds by the agar method indicated that most of the target compounds could protect rice seedlings from injury caused by metolachlor. Notably, compounds 2k and 4k displayed excellent herbicide safener activities on plant height and demonstrated relatively similar activities to the commercialized compound dichlormid. Moreover, we showed that compounds 2k and 4k had higher glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO) activities in rice seedlings, compared to the metolachlor treatment. In particular, 2k and 4k are safer for aquatic organisms than dichlormid. Results from the current work exhibit that compounds 2k and 4k have excellent crop safener activities toward rice and can, thus, be promising candidates for further structural optimization in rice protection.
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Acetamidas/efectos adversos , Descubrimiento de Drogas/métodos , Herbicidas/efectos adversos , Animales , Relación Dosis-Respuesta a Droga , Oryza/efectos de los fármacos , Seguridad , Pez Cebra/embriologíaRESUMEN
Interest in alkylamide, as a class of compound, has grown tremendously in recent years. This interest is due to the many presumed benefits in food, cosmetics, and medicine. This review focuses on the different alkylamides naturally occurring in many plant species. Several methods have been employed for their identification as well as isolation and several in vitro and in vivo studies have revealed their therapeutic effects in various diseases. In general, alkylamides have been reported to have several biological activities and pharmacological effects which include immunomodulatory, antithrombotic, antimicrobial, antiviral, antioxidant, anti-inflammatory, analgesic, anticancer, antidiabetic, and antiprotozoal activities. Moreover, many studies have reported on their mechanisms of action, structure-activity relationship, pharmacokinetics, and toxicity. We herein present an updated report on the chemistry and pharmacology of alkylamides of natural origin.
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To investigate the effect of Zanthoxylum alkylamides (ZA) on amino acid metabolism of type 2 diabetes mellitus (T2DM), the present study was performed with T2DM rats model induced with high fat and sugar fodder combined with low-dose of streptozotocin. ZA were fed to rats at three different doses of 2, 4, and 8 mg/kg for 28 days and metformin was fed to rats at 135 mg/kg as positive control. The results showed that compared with the normal control, the amino acid levels and the expression of related carrier genes were disordered in T2DM rats. Compared with the model, different doses of ZA could significantly resist (p < .05) the decrease in body weight of T2DM rats and improve hyperglycemia, with the best result observed with the high dose (8 mg/kg). Different doses of ZA could ameliorate the levels of 19 kinds of amino acid in the plasma, jejunum, liver, and skeletal muscle of T2DM rats by regulating the expression of related amino acid transporters including LAT1, SNAT2, CAT1, et al. to thereby ameliorating amino acid metabolism disorder in T2DM rats. PRACTICAL APPLICATIONS: Previous studies showed that Zanthoxylum alkylamides (ZA) could promote the amino acid metabolism in the jejunum of healthy SD rats, improve protein metabolism disorder of type 1 diabetic rats, and also reduce the risk of metabolic syndrome in fat rats model. Herein, we investigated the effect of ZA on amino acid metabolism in type 2 diabetes mellitus (T2DM) rats. The results indicated that ZA could remarkably improve the abnormal expression of amino acid carriers in the jejunum, liver, and skeletal muscle, thereby ameliorating the disorder of amino acid metabolism in the plasma, jejunum, liver, and skeletal muscle of T2DM rats. Therefore, ZA are potential antidiabetic food/medicine product for the T2DM treatment.
RESUMEN
Piper longum L., known as long pepper, is an edible and medicinal plant used as spice and for the treatment of stomach disease and analgesia in traditional Chinese medicine. N-Alkylamides are the major secondary metabolites in this plant. Sixteen known N-alkylamides were isolated from P. longum. Their structures were established on the basis of spectroscopic data and comparison to reported literatures. Among them, five compounds were isolated from this plant for the first time. Ethanol extract, compounds 1, 2, 3, 7 and 11 exhibited potent ability to increase the melanin content and weak stimulative effect on the tyrosinase activity in a concentration-dependent manner. Moreover, compound 2 also presented strong capacity to increase the tyrosinase activity in a concentration-dependent manner. These results indicated that P. longum might be a good natural source of lead compound for skin disorder diseases.