RESUMO
Growing demand for the tasty and healthy food has driven the development of low-calorie sweeteners, sweet taste modulators, and bitter masking compounds originated from natural sources. With the discovery of human taste receptors, increasing numbers of sweet taste modulators have been identified through human taste response and molecular docking techniques. However, the discovery of novel taste-active molecules in nature can be accelerated by using advanced spectrometry technologies based on structure-activity relationships (SARs). SARs explain why structurally similar compounds can elicit similar taste qualities. Given the characterization of structural information from reported data, strategies employing SAR techniques to find structurally similar compounds become an innovative approach to expand knowledge of sweeteners. This review aims to summarize the structural patterns of known natural non-nutritive sweeteners, sweet taste enhancers, and bitter masking compounds. Innovative SAR-based approaches to explore sweetener derivatives are also discussed. Most sweet-tasting flavonoids belong to either the flavanonols or the dihydrochalcones and known bitter masking molecules are flavanones. Based on SAR findings that structural similarities are related to the sensory properties, innovative methodologies described in this paper can be applied to screen and discover the derivatives of taste-active compounds or potential taste modulators.
RESUMO
During an effort to find insulin mimetic compounds, the leaves of Gymnema inodorum were shown to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation on a 70% ethanol extract of G. inodorum was applied to yield two new (1 and 2) and two known (8 and 9) oleanane triterpenoids with a methyl anthranilate moiety together with five further new oleanane triterpenoids (3-7). The chemical structures of all isolates were determined based on their spectroscopic data, including IR, UV, NMR, and mass spectrometric analysis. The isolated compounds (1-9) were determined for their stimulatory activities on glucose uptake in differentiated 3T3-L1 adipocyte cells using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent-tagged glucose probe. Three compounds (3, 5, and 9) showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Chemicals with a methyl anthranilate moiety have been considered as crucial contributors of flavor odor in foods, and quantitative analysis showed the content of compound 8 to be 0.90 ± 0.01 mg/g of the total extract. These results suggest that the leaves of G. inodorum have the potential to be used as an antidiabetic functional food or tea.
Assuntos
4-Cloro-7-nitrobenzofurazano/análogos & derivados , Desoxiglucose/análogos & derivados , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Ácido Oleanólico/análogos & derivados , Triterpenos/farmacologia , Células 3T3-L1 , 4-Cloro-7-nitrobenzofurazano/química , 4-Cloro-7-nitrobenzofurazano/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Desoxiglucose/química , Desoxiglucose/farmacologia , Glucose/análise , Gymnema , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Insulina/química , Insulina/metabolismo , Camundongos , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Folhas de Planta , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Alzheimer's disease (AD), a neurocognitive impairment affecting human mental capacity, is related to the accumulation of amyloid-ß peptide (Aß) and the hyperphosphorylation of tau protein. In addition to modern therapies approved for AD treatment, natural products with antioxidant and anti-inflammatory properties have been studied for their potential to prevent AD pathogenesis. Six new noroleanane triterpenoids from the fruit peels of Camellia japonica were isolated, and their structures were determined by diverse spectroscopic methods. The neuroprotective effects of the six new compounds were tested against Aß-induced neurotoxicity and neuroinflammation in mouse hippocampal and microglial cells. In the model of HT22-transfected cells, compounds 1-4 showed strongly neuroprotective effects via antioxidant response element gene activation and decreased the level of glutamate uptake. Compounds 1-4 also appeared to have strong inhibitory effects on NO production in Aß1-42-transfected BV2 microglial cells. A docking simulation study was used to explain the inhibitory effects of compounds 1-4 on ß-secretase 1 (BACE1). Noroleanane triterpenoids 1-4 had potential neuroprotective and anti-inflammatory effects against Aß-induced neuronal damage. The structure-activity relationships of the 30 oleanane triterpenoids from C. japonica were assessed in a model of Aß1-42-transfected HT22 cells.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Camellia/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Triterpenos/farmacologia , Animais , Linhagem Celular , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/química , Análise Espectral/métodos , Relação Estrutura-Atividade , Triterpenos/químicaRESUMO
Using molecular networking-guided isolation, three new galloyl ester triterpenoids (1-3), two new hexahydroxydiphenic acid-conjugated triterpenoids (6 and 7), and four known compounds (4, 5, 8, and 9) were isolated from the fruits and leaves of Castanopsis sieboldii. The chemical structures of 1-3, 6, and 7 were elucidated on the basis of interpreting their NMR, HRESIMS, and ECD spectra. All compounds (1-9) were evaluated for their glucose uptake-stimulating activities in differentiated adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose as a fluorescent-tagged glucose probe. Compounds 2 and 9 resulted in a 1.5-fold increase in glucose uptake. Among them, compound 2 from the fruits showed an upregulation of p-AMPK/AMPK ratio in differentiated C2C12 myoblasts to support the mechanism proposed of glucose uptake stimulation.
Assuntos
Fagaceae/química , Glucose/metabolismo , Triterpenos/farmacologia , Células 3T3 , Adipócitos/efeitos dos fármacos , Animais , Dicroísmo Circular , Frutas/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Extratos Vegetais , Folhas de Planta/química , Espectrometria de Massas por Ionização por Electrospray , Estimulação Química , Triterpenos/isolamento & purificaçãoRESUMO
Obesity is a medical condition in which excess body fat has accumulated to a serious extent. It is a chronic disease that can lead to dyslipidemia, insulin resistance, and type 2 diabetes. In the present study, we investigated the anti-obesity effects of Sicyos angulatus (SA) extract on a high-fat diet (HFD)-induced C57BL/6J obese mice. The mice were divided into vehicle and three SA groups (25, 50, and 100 mg/kg body weight). The mice were fed a HFD with or without SA for 12 weeks. The oral administration of SA reduced body and adipose tissue weight in HFD-fed mice compared to those in the vehicle group (p<0.05). Adipocyte size and inflammation significantly decreased in the SA-administered groups in a dose-dependent manner. In particular, adipocytes larger than 5000 µm2 were remarkably reduced by around 50% in the SA-treated groups (p<0.05). In addition, SA contributes towards reducing insulin resistance (measured as the HOMA-IR index) and glucose intolerance in HFD-induced obese mice (p<0.05; Vehicle 21.5±3.1 vs. SA100 4.7±0.4). These beneficial effects of SA on obesity may be linked to the suppression of lipogenesis and stimulating energy metabolism in white adipose tissue and muscle. In white adipose tissue and muscle, the administration of SA activated AMPK pathway, leading to the inhibition of the development of pathophysiological conditions associated with obesity, including lipogenesis and inflammation. These findings suggest that SA may prevent obesity through inhibiting fat accumulation in HFD-induced obese mice. Therefore, SA is able to exert metabolic benefits in the prevention of obesity and insulin resistance.
Assuntos
Cucurbitaceae/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Resistência à Insulina/genética , Lipogênese/efeitos dos fármacos , Camundongos , Camundongos Obesos , Obesidade/etiologia , Obesidade/patologia , Extratos Vegetais/químicaRESUMO
Porcine epidemic diarrhea virus (PEDV), a serious swine epidemic, has been rampant in Asia since the 1990s. Despite the widespread use of PEDV vaccines, the occurrence of PEDV variants requires the discovery of new substances that inhibit these viruses. During a search for PEDV inhibitory materials from natural sources, seven new sabphenosides (1-7) and a new flavonoid (8), as well as eight known phenolic compounds (9-16), were obtained from the leaves of Sabia limoniacea. The structural determination of the new phenolic derivatives (1-8) was accomplished using comprehensive spectroscopic methods. Their absolute configurations were assigned by a combination of the ECD exciton chirality method following selective reduction and calculation of their ECD spectra. The bioactivities of the isolated compounds were measured based on their abilities to inhibit viral replication of PEDV. Among the test compounds, 15 and 16 exhibited the most promising antiviral activities, with IC50 values of 7.5 ± 0.7 µM and 8.0 ± 2.5 µM against PEDV replication. This study suggests that compounds 15 and 16 could serve as new scaffolds for the treatment of PEDV infection through the inhibition of PEDV replication.
Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Magnoliopsida/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Folhas de Planta/química , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Animais , Antivirais/química , Chlorocebus aethiops , Efeito Citopatogênico Viral/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenóis/química , Vírus da Diarreia Epidêmica Suína/fisiologia , Prenilação , Suínos , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
Melicope pteleifolia has long been consumed as a popular vegetable and tea in Southeast Asian countries, including Malaysia and southern mainland China, and is effective in the treatment of colds and inflammation. In the search for active metabolites that can explain its traditional use as an antipyretic, six new phloroacetophenone derivatives (3-8) along with seven known compounds (1, 2, and 9-13) were isolated from the leaves of M. pteleifolia. Their chemical structures were confirmed by extensive spectroscopic analysis including NMR, IR, ECD, and HRMS. All compounds isolated from the leaves of M. pteleifolia (1-13) have a phloroacetophenone skeleton. Notably, the new compound 8 contains an additional cyclobutane moiety in its structure. The bioactivities of the isolated compounds were evaluated, and compounds 1, 6, and 7 inhibited tumor necrosis factor-α-induced prostaglandin E2. Moreover, the major constituent, 3,5-di-C-ß-d-glucopyranosyl phloroacetophenone (1), was found to be responsible for the antipyretic activity of M. pteleifolia based on in vivo experiments.
Assuntos
Analgésicos/farmacologia , Folhas de Planta/química , Rutaceae/química , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Plantas Comestíveis/química , Análise Espectral/métodosRESUMO
The major class of bioactive metabolites in Gymnema sylvestre, a popular Ayurvedic medicinal plant for the treatment of diabetes mellitus, is oleanane triterpenoids. In this study, a targeted, biosynthesis-inspired approach using UHPLC-qTOF/MS was implemented to elucidate the whole chemical profile of this plant for the standardization of the Vietnamese G. sylvestre variety. The known compounds were first determined to identify the building blocks of the biosynthetic intermediates and the construction rules for synthesizing oleanane triterpenoids in the plant. These blocks were recombined to build a virtual library of all reasonable compounds consistent with the deduced construction rules. Various techniques, including relative mass defect filtering, multiple key ion analysis, mass fragmentation analysis, and comparison with standard references, were applied to determine the presence of these predicted compounds. Conventional isolation and structure elucidation of six of the new compounds were carried out to identify the new building blocks and validate the assignments. Consequently, 119 peaks were quickly assigned to oleanane triterpenoids, and among them, 77 peaks were predicted to be new compounds based on their molecular formulas and mass fragmentation patterns. All the identified metabolites were then classified into different layers to analyze their logical relationships, and a multilayered chemical profile of the oleanane triterpenoids was constructed. This new approach is expected to be practical for characterizing structures of modular secondary metabolites, such as triterpenoid saponins, and for proposing biosynthetic relationships among compounds of the same class of metabolites in medicinal plants.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Gymnema sylvestre/metabolismo , Ácido Oleanólico/análogos & derivados , Análise Espectral/métodos , Triterpenos/metabolismo , Glicosídeos/metabolismo , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/metabolismo , Triterpenos/químicaRESUMO
In Alzheimer's disease, amyloid-ß (Aß) accumulation in the brain results in neuronal cell death and is one of the major causes of dementia. Because the current therapeutic agents are not yet sufficiently effective or safe, there have been attempts to find new neuroprotective chemicals against Aß-induced cytotoxicity. A 70% EtOH extract of whole plants of Ambrosia artemisiifolia (common ragweed) was selected after the screening of a natural extract library. Seven new eudesmane-type glycosides (1-7) and seven known compounds (8-14) were obtained through bioactivity-guided fractionation from the aerial parts of this plant. Their structures were determined on the basis of their nuclear magnetic resonance spectra, high-resolution electrospray ionization mass spectrometry analysis, and electronic circular dichroism calculations. Among them, compounds 1, 2, 4-6, 8, 9, 11, 13, and 14 showed protective effects against Aß-induced cytotoxicity in Aß42-transfected HT22 cells. The most active compounds, 5 and 6, exhibited moderate protective activity dose-dependently (10, 20, and 40 µM).
Assuntos
Ambrosia/química , Glicosídeos/isolamento & purificação , Fármacos Neuroprotetores/isolamento & purificação , Sesquiterpenos de Eudesmano/isolamento & purificação , Peptídeos beta-Amiloides/toxicidade , Animais , Células Cultivadas , Glicosídeos/química , Glicosídeos/farmacologia , Camundongos , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologiaRESUMO
Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson's disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson's disease mouse model.
Assuntos
Humulus/química , Atividade Motora/efeitos dos fármacos , Doença de Parkinson Secundária/tratamento farmacológico , Extratos Vegetais/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Flavonas/administração & dosagem , Flavonas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/administração & dosagem , Glucosídeos/química , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Monoaminoxidase/genética , Atividade Motora/genética , Oxidopamina/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/patologia , Extratos Vegetais/administração & dosagem , Espectrometria de Massas em TandemRESUMO
As part of ongoing research to find new antidiabetic agents from medicinal plants, the chemical composition of Gynostemma longipes, an ethnomedicinal plant used to treat type 2 diabetes mellitus by local communities in Vietnam, was investigated. Ten new dammarane triterpenes, including two 3,4- seco-dammarane analogues, secolongipegenins S1 and S2 (1 and 2), a 3,4- seco-hexanordammarane, secolongipegenin S3 (3), two hexanordammarane glycosides, longipenosides ND1 and ND2 (4 and 5), and five other dammarane glycosides, longipenosides GL1-GL5 (6-10), were isolated from a 70% EtOH extract of the whole G. longipes plant. The structures of the new compounds were elucidated using diverse spectroscopic methods. All of the isolates were evaluated for their stimulatory activities on glucose uptake in differentiated 3T3-L1 adipocyte cells using 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose as a fluorescent-tagged glucose probe. The stimulant activities on glucose uptake by the test compounds were mediated via the activation of the AMPK pathway using differentiated mouse C2C12 skeletal myoblasts. Consequently, compounds 1, 2, and 4 enhanced glucose uptake and GLUT4 translocation significantly by regulating the AMPK signaling pathway.
Assuntos
Biomimética , Gynostemma/química , Insulina/farmacologia , Triterpenos/farmacologia , Animais , Linhagem Celular , Camundongos , Triterpenos/isolamento & purificaçãoRESUMO
Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (Aß)42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aß42 in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1ß, prostaglandin (PG)E2, and nitric oxide (NO) because of artificial phagocytic Aß42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aß42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.
Assuntos
Hidrolases de Éster Carboxílico/metabolismo , Diterpenos/farmacologia , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Western Blotting , Hidrolases de Éster Carboxílico/genética , Linhagem Celular , Dinoprostona/metabolismo , Heme Oxigenase-1/genética , Imuno-Histoquímica , Inflamação/genética , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteínas de Membrana/genética , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estrutura Molecular , Fator 2 Relacionado a NF-E2/genética , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacosRESUMO
PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2-14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS. Compounds 2, 3, 6, 8 and 11 showed significant inhibitory effects on the PTP1B enzyme, with IC50 values ranging from 4.08 ± 1.09 to 21.80 ± 4.74 µM. PTP1B inhibitors also had concentration-dependent cytotoxic effects on breast cancer cell lines, such as MCF7, MDA-MB-231 and tamoxifen-resistant MCF7 (MCF7/TAMR) (IC50 values ranging from 0.84 ± 0.04 to 7.91 ± 0.39 µM). These results indicate that compounds 6 and 8 from Akebia quinata may be lead compounds acting as anti-breast cancer agents.
Assuntos
Neoplasias da Mama/metabolismo , Inibidores Enzimáticos/farmacologia , Magnoliopsida/química , Extratos Vegetais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Feminino , Humanos , Células MCF-7 , Estrutura Molecular , Extratos Vegetais/química , Caules de Planta/químicaRESUMO
Bitter substances in functional foods and beverages can act as nutraceuticals, offering potential health benefits. However, their unpleasant sensory impact reduces the consumption of these foods. Consequently, the discovery of bitter masking compounds is crucial for enhancing the intake of bioactive compounds in functional foods and beverages. Bitter taste is mediated by TAS2Rs, a sub-family of G-protein-coupled receptors. TAS2R14 is especially pivotal in the perception of bitterness, as it is one of the most broadly tuned bitter receptors. In this study, allspice was extracted and purified to yield five single compounds based on sensory guided fractionation. The structures of each compound were determined based on nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HR-MS). In a sensory evaluation, compound 1 exhibited bitter masking activity against quinine. Molecular docking analysis revealed that compound 1 could act as an antagonist of the TAS2R14 bitter receptor.
RESUMO
This study investigates the inhibitory effects of polymethoxyflavones (PMFs) on enzymes involved in the production of trimethylamine (TMA) and trimethylamine-N-oxide (TMAO). PMFs were isolated from Valencia orange peel and identified using column separation and NMR techniques. The findings reveal that nobiletin and 3,6,7,8,2',5'-hexamethoxyflavone significantly suppress cntA/B and cutC/D, respectively. Furthermore, 3,6,7,8,2',5'-hexamethoxyflavone decreases the level of TMAO formation by suppressing the FMO3 mRNA level. This study elucidates that specific structural features of PMFs can contribute to their interactions with enzymes. Our study represents the first demonstration of the ability of PMFs to mitigate the risk of cardiovascular disease (CVD) by inhibiting enzymes responsible for TMA production, which are generated by gut microbiomes. Furthermore, we introduce a novel model system utilizing TMA-induced HepG2 cells to assess and compare the inhibitory effects of PMFs on TMAO production. These findings could pave the way for the development of novel therapeutic approaches to manage CVD.
Assuntos
Doenças Cardiovasculares , Citrus sinensis , Simulação de Acoplamento Molecular , Metilaminas , ÓxidosRESUMO
As a type of contact dermatitis (CD), irritant CD (ICD) is an acute skin inflammation caused by external irritants, such as soap, water and chemicals. Humulus japonicus (HJ) is a herbal medicine widely distributed in Asian countries and has anti-inflammatory, antimicrobial and antioxidant effects. The current study aimed to investigate the anti-dermatitis effect of HJ on ICD and determine the molecular basis of this effect using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis mice models and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Mice were orally administered HJ and luteolin, the major compound in HJ, and topically administered TPA on the right ear to induce dermatitis. Topical application of TPA induced ear redness, oedema and increased infiltration of neutrophils and macrophages, which ameliorated following HJ and luteolin administration. The gene expression levels of inflammatory cell migrating chemokines, chemokine ligand 3 (CCL3) and chemokine (C-X-C motif) ligand 2 (CXCL2), and pro-inflammatory cytokine, IL-1ß, were reduced in the ears of HJ- and luteolin-treated mice. HJ and luteolin also inhibited the gene expression of chemokines, CCL3 and CXCL2, and pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, in LPS-stimulated RAW264.7 cells. Moreover, HJ and luteolin decreased the expression levels of two key inflammatory enzymes, cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), and total and active phosphorylation of NF-κB p65. These results suggest that HJ could have a protective effect against ICD by suppressing inflammatory responses; therefore, HJ is a promising therapeutic strategy for ICD treatment.
RESUMO
The plant Allium hookeri, a member of the Allium genus, has a rich history of culinary and medicinal use. Recent studies have unveiled its potent antioxidant and anti-inflammatory properties. While research on A. hookeri has demonstrated its neuroprotective and anti-neuroinflammatory effects, the specific bioactive compounds responsible for these effects remain unidentified in prior research. This study utilized an untargeted metabolomic approach, employing HRESI-qTOF MS/MS-based molecular networking, to comprehensively profile the chemical composition of metabolites in A. hookeri and identify new compounds within the plant. As a result, ten compounds, comprising one novel flavonoid (2) and nine known compounds (1 and 3-10), were isolated and identified through NMR analysis. The inhibitory effects of all isolated compounds on the senescent cell-associated secretory phenotype (SASP), which is pivotal in neuroprotective actions, were evaluated. Biological activity testing revealed N-trans-feruloyltyramine (7) to be the most potent compound, effectively inhibiting SASP markers and contributing to the senomorphic activities of A. hookeri. These findings underscore the potential of phenolamides from A. hookeri as a promising source of bioactive compounds for mitigating senescence-associated diseases.
Assuntos
Allium , Allium/química , Senoterapia , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , FlavonoidesRESUMO
BACKGROUND: Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer's disease and Parkinson's disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed. RESULTS: We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. CONCLUSIONS: These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.
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Ten phenolic constituents, including three new macrocyclic glycosides (1-3), a new phenolic glycoside (5), a new biphenyl glycoside (6), and five known compounds (4, 7-10), were isolated from a 70% MeOH extract of the leaves of Heliciopsis terminalis by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-guided molecular networking. The chemical structures of new compounds 1-3, 5 and 6 were established based on comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS techniques. All isolated compounds (1-10) were evaluated for their stimulation of glucose uptake in differentiated 3T3-L1 adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent glucose analog. Compounds 3, 6 and 8 showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Among them, compounds 3 and 6 activated the AMPK signaling pathway in differentiated C2C12 myoblasts.
RESUMO
Humulus japonicus (HJ) is a traditional herbal medicine that exhibits antiinflammatory, antimicrobial and antitumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T+ Itpr3tf/J mouse model of ASD was used to investigate the antiautistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novelobject recognition in BTBR mice. Antiinflammatory effects of HJ in the brain were analysed using immunohistochemistry and reversetranscription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and proinflammatory cytokines, including CC Motif Chemokine Ligand 2, interleukin (IL)1ß and IL6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: NmethylDaspartate receptor subtype 2B and calcium/calmodulindependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.