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1.
Nat Prod Res ; : 1-7, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206887

RESUMO

N-Lanosyl guanidine (1), a new bromophenol containing a guanidine moiety was isolated from the red alga Vertebrata lanosa (L.) T.A. Christensen, which is frequently used for cosmetic purposes. Structure elucidation was performed by means of mass spectrometry as well as 1D and 2D NMR spectroscopy. Due to its structural features, 1 might share a common biosynthetic route with known bromophenolic ureido derivatives. Regarding potential bioactivities, 1 has shown clear anti-inflammatory properties, reducing cytokine release in lipopolysaccharide-stimulated phorbol 12-myristate 13-acetate-differentiated THP-1 macrophages. No signs of toxicity were observed, in either the cell line nor in the nematode Caenorhabditis elegans. However, 1 was inactive against the gram-negative bacterium Pseudomonas aeruginosa.

2.
Pharmaceuticals (Basel) ; 16(11)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38004399

RESUMO

Glioblastoma is the most common and aggressive form of primary brain cancer and the lack of viable treatment options has created an urgency to develop novel treatments. Personalized or predictive medicine is still in its infancy stage at present. This research aimed to discover biomarkers to inform disease progression and to develop personalized prophylactic and therapeutic strategies by combining state-of-the-art technologies such as single-cell RNA sequencing, systems pharmacology, and a polypharmacological approach. As predicted in the pyroptosis-related gene (PRG) transcription factor (TF) microRNA (miRNA) regulatory network, TP53 was the hub gene in the pyroptosis process in glioblastoma (GBM). A LASSO Cox regression model of pyroptosis-related genes was built to accurately and conveniently predict the one-, two-, and three-year overall survival rates of GBM patients. The top-scoring five natural compounds were parthenolide, rutin, baeomycesic acid, luteolin, and kaempferol, which have NFKB inhibition, antioxidant, lipoxygenase inhibition, glucosidase inhibition, and estrogen receptor agonism properties, respectively. In contrast, the analysis of the cell-type-specific differential expression-related targets of natural compounds showed that the top five subtype cells targeted by natural compounds were endothelial cells, microglia/macrophages, oligodendrocytes, dendritic cells, and neutrophil cells. The current approach-using the pharmacogenomic analysis of combined therapies-serves as a model for novel personalized therapeutic strategies for GBM treatment.

3.
Eur J Pharm Sci ; 188: 106529, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37459901

RESUMO

Over the past decades, designing of privileged structures has emerged as a useful approach to the discovery and optimisation of novel biologically active molecules, and many have been successfully exploited across and within different target families. Examples include indole, quinolone, isoquinoline, benzofuran and chromone, etc. In the current study, we focus on synthesising a novel hybrid scaffold constituting naturally occurring benzophenone (14) and indanone (22) ring systems, leading to a general structure of 2-(diphenylmethylene)-2,3-dihydro-1H-inden-1-one (23). It was hypothesised this new hybrid system would provide enhanced anti-cancer activity owing to the presence of the common features associated with the tubulin binding small molecule indanocine (10) and the estrogen receptor (ER) antagonist tamoxifen (24). Key hybrid molecules were successfully synthesised and characterised, and the in vitro cytotoxicity assays were performed against cancer cell lines: MCF7 (breast) and SKBR3 (breast), DU145 (prostate) and A549 (lung). The methyl-, chloro- and methoxy-, para-substituted benzophenone hybrids displayed the greatest degree of cytotoxicity and the E-configuration derivatives 45, 47 and 49 being significantly most potent. We further verified that the second benzyl moiety of this novel hybrid scaffold is fundamental to enhance the cytotoxicity, especially in the SKBR3 (HER2+) by the E-methyl lead molecule 47, MCF7 (ER+) by 45 and 49, and A549 (NSCLC) cell lines by 49. These hybrid molecules also showed a significant accumulation of SKBR3 cells at S-phase of the cell cycle after 72 hrs, which demonstrates besides of being cytotoxic in vitro against SKBR3 cells, 47 disturbs the replication and development of this type of cancer causing a dose-dependent cell cycle arrest at S-phase. Our results suggest that DNA damage might be involved in the induction of SKBR3 cell death caused by the hybrid molecules, and therefore, this novel system may be an effective suppressor of HER2+/Neu-driven cancer growth and progression. The present study points to potential structural optimisation of the series and encourages further focussed investigation of analogues of this scaffold series toward their applications in cancer chemoprevention or chemotherapy.

4.
Molecules ; 28(10)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37241886

RESUMO

Acetylcholinesterase inhibitors remain the mainstay of symptomatic treatment for Alzheimer's disease. The natural world is rich in acetylcholinesterase inhibitory molecules, and research efforts to identify novel leads is ongoing. Cladonia portentosa, commonly known as reindeer lichen, is an abundant lichen species found in Irish Boglands. The methanol extract of Irish C. portentosa was identified as an acetylcholinesterase inhibitory lead using qualitative TLC-bioautography in a screening program. To identify the active components, the extract was deconvoluted using a successive extraction process with hexane, ethyl acetate and methanol to isolate the active fraction. The hexane extract demonstrated the highest inhibitory activity and was selected for further phytochemical investigations. Olivetolic acid, 4-O-methylolivetolcarboxylic acid, perlatolic acid and usnic acid were isolated and characterized using ESI-MS and two-dimensional NMR techniques. LC-MS analysis also determined the presence of the additional usnic acid derivatives, placodiolic and pseudoplacodiolic acids. Assays of the isolated components confirmed that the observed anticholinesterase activity of C. portentosa can be attributed to usnic acid (25% inhibition at 125 µM) and perlatolic acid (20% inhibition at 250 µM), which were both reported inhibitors. This is the first report of isolation of olivetolic and 4-O-methylolivetolcarboxylic acids and the identification of placodiolic and pseudoplacodiolic acids from C. portentosa.


Assuntos
Acetilcolinesterase , Inibidores da Colinesterase , Inibidores da Colinesterase/química , Hexanos , Metanol , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Antioxidantes/química
5.
Food Sci Nutr ; 11(4): 1634-1656, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37051359

RESUMO

Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato- and neuro-protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical data are still inconsistent and conflicting, more in-depth investigations are warranted to elucidate its potential as a therapeutic strategy to prevent and treat a range of disease conditions.

6.
J Sci Food Agric ; 103(10): 4983-4992, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37058580

RESUMO

BACKGROUND: Beef from pasture-fed animals is viewed as a healthier and more welfare-friendly alternative to concentrate-fed beef. Botanically-diverse pastures consisting of numerous plant species may alter the fatty acid (FA) profile and the tocopherol content of beef, as well as the oxidative stability of the meat. In the present study, steers were assigned to one of three botanically-diverse diets: perennial ryegrass (PRG), perennial ryegrass + white clover (PRG + WC) or multi-species (MS), all with a finishing diet of the respective botanically-diverse silages plus a cereal-based concentrate, consistent with production systems in Ireland. The FA profile, tocopherol content, oxidative stability and colour of meat during storage were measured. RESULTS: Compared to the other diets, the MS diet resulted in higher proportions of linolenic acid (C18:3n-3c), linoleic acid (C18:2n-6c) and total polyunsaturated fatty acids (PUFA), with higher PUFA:saturated fatty acid and n-6:n-3 ratios in the meat. α-Tocopherol concentrations were lowest in the meat of animals from the MS diet. In uncooked meat, lipid oxidation and colour values were affected by storage time across all diets, whereas the MS diet led to higher hue values only on day 14 of storage. When cooked, meat from animals on PRG + WC and MS diets had higher lipid oxidation on days 1 and 2 of storage than meat from animals on the PRG diet. CONCLUSION: Feeding steers on a botanically-diverse diet consisting of six plant species can improve the n-3 FA and PUFA concentration of beef, affecting the susceptibility of cooked, but not uncooked, beef to oxidation. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Ácidos Graxos , Lolium , Animais , Bovinos , Tocoferóis , Ração Animal/análise , Dieta/veterinária , Ácidos Graxos Insaturados , Vitamina E , Carne/análise , Estresse Oxidativo
7.
Meat Sci ; 197: 109055, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36512854

RESUMO

A desire for more sustainable pasture-based ruminant feeding systems has led to growing interest in utilising botanically-diverse pastures (BDP) over monoculture pastures. Research suggests that, from a human consumption viewpoint, grass-based ruminant feeding leads to more nutritionally desirable fatty acid (FA) and antioxidant concentrations in meat compared with concentrate feeding, which can affect meat quality. The FA, antioxidant and secondary metabolite content of plants differ, depending on species, maturity and seasonality, offering the potential through targeted feeding of BDP to produce meat with superior nutritional and antioxidant profiles. This review explores the effect, if any, that grazing ruminants on BDP has on the FA profile, fat-soluble vitamin, and antioxidant content of meat. The input-output relationship between forage and red meat constituents is complex and is likely affected by species diversity, forage consumption patterns and modulation of rumen fermentation processes. Further investigation is required to fully understand the effect that BDP may have on the composition and quality of ruminant meat.


Assuntos
Antioxidantes , Ruminantes , Animais , Humanos , Antioxidantes/metabolismo , Ácidos Graxos/metabolismo , Rúmen/metabolismo , Carne/análise , Ração Animal/análise , Dieta/veterinária
8.
Aging (Albany NY) ; 14(21): 8595-8614, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326669

RESUMO

Alzheimer's disease (AD) accounts for approximately 60% of dementia cases worldwide. Advanced age is the most significant risk factor for AD and approximately two-thirds of cases relate to women. While the previous meta-analysis suggests that estrogen receptor (ESR) genetic polymorphisms are closely associated with dementia, the implications of this observation on a molecular level are not entirely understood. Our study explores this intricate molecular puzzle through the use of a variety of bioinformatics tools. Initially, we attempted to elucidate mechanisms underlying breast cancer development by identifying the high-throughput dataset of ESR1-knockdown breast cancer tissue samples. Surprisingly, KEGG pathway enrichment showed that the most frequently occurring proteins were related to axonal guidance and inflammation-related gene markers. These observations were supported by an external high throughput dataset of AD inflammatory samples in vivo. Our results suggest that ESR1 is modulated by apolipoprotein E (APOE) through CEBPB/ATF4, mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1ß, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalised treatment of AD.


Assuntos
Doença de Alzheimer , Neoplasias da Mama , Feminino , Humanos , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide , Ácido Aspártico Endopeptidases , Simulação de Acoplamento Molecular , Doenças Neuroinflamatórias , Receptor alfa de Estrogênio/metabolismo
9.
J Biol Chem ; 298(11): 102569, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36209824

RESUMO

The nuclear bile acid receptor, farnesoid X receptor (FXR), is an important regulator of intestinal and metabolic function. Previous studies suggest that pentacyclic triterpenes (PCTs), a class of plant-derived bioactive phytochemical, can modulate FXR activity and may therefore offer therapeutic benefits. Here, we investigated the effects of a prototypical PCT, hederagenin (HG), on FXR expression, activity, and antisecretory actions in colonic epithelial cells. T84 cells and murine enteroid-derived monolayers were employed to assess HG effects on FXR expression and activity in colonic epithelia. We measured mRNA levels by qRT-PCR and protein by ELISA and immunoblotting. Transepithelial Cl- secretion was assessed as changes in short circuit current in Ussing chambers. We determined HG treatment (5-10 µM) alone did not induce FXR activation but significantly increased expression of the receptor, both in T84 cells and murine enteroid-derived monolayers. This effect was accompanied by enhanced FXR activity, as assessed by FGF-15/19 induction in response to the synthetic, GW4064, or natural FXR agonist, chenodeoxycholic acid. Effects of HG on FXR expression and activity were mimicked by another PCT, oleanolic acid. Furthermore, we found FXR-induced downregulation of cystic fibrosis transmembrane conductance regulator Cl- channels and inhibition of transepithelial Cl- secretion were enhanced in HG-treated cells. These data demonstrate that dietary PCTs have the capacity to modulate FXR expression, activity, and antisecretory actions in colonic epithelial cells. Based on these data, we propose that plants rich in PCTs, or extracts thereof, have excellent potential for development as a new class of "FXR-targeted nutraceuticals".


Assuntos
Ácido Quenodesoxicólico , Colo , Camundongos , Animais , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/metabolismo , Colo/metabolismo , Ácido Quenodesoxicólico/farmacologia , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo
10.
Phytomedicine ; 105: 154353, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932606

RESUMO

BACKGROUND: A traditionally prepared aqueous extract (= decoction) of Houttuynia cordata Thunb (Yu xing cao) (HC) is widely used in Traditional Chinese Medicine (TCM) to treat inflammatory disease. Previous chemical and biological studies on HC have mainly focused on organic extracts rather than the aqueous decoction, which is the traditional formulation. PURPOSE: The study aimed to investigate whether the chemical composition of HC aqueous decoction (HCD) varies with geographical sourcing, to investigate the mechanism of action of HCD, and to determine if chemical variation impacts on HCDs anti-inflammatory activity. METHOD: Sixteen samples of HC were purchased from Sichuan, Hubei and Anhui provinces in the People's Republic of China (PRC) and were prepared by the traditional decoction method to yield their corresponding HCDs. A Quality Control (QC) sample was prepared by combining individual HCD extracts. HCDs were analysed by Nuclear Magnetic Resonance (NMR) and High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS). The anti-inflammatory activities associated with intestinal barrier function of HCD were studied by tumor necrosis factor-α (TNF-α) activated Caco-2 monolayers in vitro and in vivo using Dextran Sulfate Sodium (DSS)-induced murine colitis. Proteins involved in inflammation, mRNA levels, disease severity scores, and histology involved in intestinal inflammation were analysed. RESULTS: HCD samples exhibited different chemical fingerprints and three regional outliers were identified by Principal Component Analysis (PCA). Fifteen phytochemical metabolites were identified and quantified. HCD showed in vitro anti-inflammatory activity, enhancing zonula occludens-1 (ZO-1), occludin, interleukin (IL)-10 and decreasing IL-1ß, IL-6 and epidermal growth factor receptor (EGFR) via an EGFR-dependent mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathway. This beneficial effect on intestinal inflammation was also seen in the in vivo colitis model at a molecular level in colonic tissues. CONCLUSION: This study shows that the test HCDs were chemically different, resulting in different levels of activity on intestinal barrier function and inflammation. Moreover, a "Daodi" product showed the greatest biological activity in this study, thus validating the importance of the "Daodi" quality material in TCM and supporting the traditional used of HCD for the treatment of inflammation.


Assuntos
Colite , Houttuynia , Animais , Anti-Inflamatórios , Células CACO-2 , Sulfato de Dextrana , Modelos Animais de Doenças , Receptores ErbB , Humanos , Inflamação , Sistema de Sinalização das MAP Quinases , Medicina Tradicional Chinesa , Camundongos , Proteína Quinase 3 Ativada por Mitógeno , Mitógenos , Extratos Vegetais , Transdução de Sinais
11.
Viruses ; 14(7)2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35891565

RESUMO

Used in Asian countries, including China, Japan, and Thailand, Houttuynia cordata Thumb (H. cordata; Saururaceae, HC) is a traditional herbal medicine that possesses favorable antiviral properties. As a potent folk therapy used to treat pulmonary infections, further research is required to fully elucidate the mechanisms of its pharmacological activities and explore its therapeutic potential for treating pneumonia caused by SARS-CoV-2. This study explores the pharmacological mechanism of HC on pneumonia using a network pharmacological approach combined with reprocessing expression profiling by high-throughput sequencing to demonstrate the therapeutic mechanisms of HC for treating pneumonia at a systemic level. The integration of these analyses suggested that target factors are involved in four signaling pathways, including PI3K-Akt, Jak-STAT, MAPK, and NF-kB. Molecular docking and molecular dynamics simulation were applied to verify these results, indicating a stable combination between four metabolites (Afzelin, Apigenin, Kaempferol, Quercetin) and six targets (DPP4, ELANE, HSP90AA1, IL6, MAPK1, SERPINE1). These natural metabolites have also been reported to bind with ACE2 and 3CLpro of SARS-CoV-2, respectively. The data suggest that HC exerts collective therapeutic effects against pneumonia caused by SARS-CoV-2 and provides a theoretical basis for further study of the active drug-like ingredients and mechanism of HC in treating pneumonia.


Assuntos
Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas , Houttuynia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Houttuynia/química , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , SARS-CoV-2 , Tailândia
12.
Nat Prod Res ; 36(4): 1129-1133, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33291984

RESUMO

Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.


Assuntos
Analgésicos , Fabaceae , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
13.
Crit Rev Food Sci Nutr ; 62(16): 4449-4464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33491467

RESUMO

Flavonoids are common in the plant kingdom and many of them have shown a wide spectrum of bioactive properties. Hesperetin (Hst), the aglycone form of hesperidin, is a great example, and is the most abundant flavonoid found in Citrus plants. This review aims to provide an overview on the in vitro, in vivo and clinical studies reporting the Hst pharmacological effects and to discuss the bioavailability-related issues. Preclinical studies have shown promising effects on cancer, cardiovascular diseases, carbohydrate dysregulation, bone health, and other pathologies. Clinical studies have supported the Hst promissory effects as cardioprotective and neuroprotective agent. However, further well-designed clinical trials are needed to address the other Hst effects observed in preclinical trials, as well as to a more in-depth understanding of its safety profile.


Assuntos
Citrus , Hesperidina , Antioxidantes/farmacologia , Disponibilidade Biológica , Flavonoides , Hesperidina/farmacologia , Hesperidina/uso terapêutico
15.
Front Mol Biosci ; 8: 649395, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540888

RESUMO

Resveratrol is a polyphenolic stilbene derivative widely present in grapes and red wine. Broadly known for its antioxidant effects, numerous studies have also indicated that it exerts anti-inflammatory and antiaging abilities and a great potential in cancer therapy. Regrettably, the oral administration of resveratrol has pharmacokinetic and physicochemical limitations such as hampering its effects so that effective administration methods are demanding to ensure its efficiency. Thus, the present review explores the published data on the application of resveratrol nanoformulations in cancer therapy, with the use of different types of nanodelivery systems. Mechanisms of action with a potential use in cancer therapy, negative effects, and the influence of resveratrol nanoformulations in different types of cancer are also highlighted. Finally, the toxicological features of nanoresveratrol are also discussed.

16.
Sci Total Environ ; 781: 146515, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33812119

RESUMO

Nitrous oxide (N2O) is a potent greenhouse gas (GHG) emitted from agricultural soils and is influenced by nitrogen (N) fertiliser management and weather and soil conditions. Source partitioning N2O emissions related to management practices and soil conditions could suggest effective mitigation strategies. Multispecies swards can maintain herbage yields at reduced N fertiliser rates compared to grass monocultures and may reduce N losses to the wider environment. A restricted-simplex centroid experiment was used to measure daily N2O fluxes and associated isotopomers from eight experimental plots (7.8 m2) post a urea-N fertiliser application (40 kg N ha-1). Experimental pastures consisted of differing proportions of grass, legume and forage herb represented by perennial ryegrass (Lolium perenne), white clover (Trifolium repens) and ribwort plantain (Plantago lanceolata), respectively. N2O isotopomers were measured using a cavity ring down spectroscopy (CRDS) instrument adapted with a small sample isotope module (SSIM) for the analysis of gas samples ≤20 mL. Site preference (SP = δ15Nα - δ15Nß) and δ15Nbulk ((δ15Nα + δ15Nß) / 2) values were used to attribute N2O production to nitrification, denitrification or a mixture of both nitrification and denitrification over a range of soil WFPS (%). Daily N2O fluxes ranged from 8.26 to 86.86 g N2O-N ha-1 d-1. Overall, 34.2% of daily N2O fluxes were attributed to nitrification, 29.0% to denitrification and 36.8% to a mixture of both. A significant diversity effect of white clover and ribwort plantain on predicted SP and δ15Nbulk indicated that the inclusion of ribwort plantain may decrease N2O emission through biological nitrification inhibition under drier soil conditions (31%-75% WFPS). Likewise, a sharp decline in predicted SP indicates that increased white clover content could increase N2O emissions associated with denitrification under elevated soil moisture conditions (43%-77% WFPS). Biological nitrification inhibition from ribwort plantain inclusion in grassland swards and management of N fertiliser source and application timing to match soil moisture conditions could be useful N2O mitigation strategies.

17.
J Ethnopharmacol ; 271: 113883, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33508366

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Copaifera species folkloric names are "copaíbas, copaibeiras, copaívas or oil stick", which are widely used in Brazilian folk medicine. Among all ethnopharmacological applications described for Copaifera spp oleoresins, their anti-inflammatory effect stands out. However, the knowledge of anti-inflammatory and antinociceptive properties of Copaifera pubiflora Benth is scarce. AIM OF THE STUDY: To investigate the cytotoxic, anti-inflammatory, and antinociceptive activities of C. pubiflora oleoresin (CPO), and its major compound ent-hardwickiic acid (HA). MATERIAL AND METHODS: The phosphatase assay was used to evaluate the cytotoxicity of CPO and HA in three different cell lines. CPO and HA doses of 1, 3, and 10 mg/kg were employed in the biological assays. The assessment of motor activity was performed using open-field and rotarod tests. Anti-inflammatory activity of CPO and HA was assessed through luciferase assay, measurement of INF-γ, IL-1ß, IL-6, IL-10, and TNF-α in a multi-spot system with the immortalized cell line THP-1, zymosan-induced arthritis, and carrageenan-induced paw edema. Acetic acid-induced abdominal writhing and formalin tests were undertaken to evaluate the antinociceptive potential of CPO and HA. In addition, the evaluation using carrageenan was performed to investigate the effect of CPO in pain intensity to a mechanical stimulus (mechanical hyperalgesia), using the von Frey filaments. A tail-flick test was used to evaluate possible central CPO and HA actions. RESULTS: In the cytotoxicity evaluation, CPO and HA were not cytotoxic to the cell lines tested. CPO and HA (10 mg/kg) did not affect animals' locomotor capacity in both open-field and rotarod tests. In the luciferase assay, CPO and HA significantly reduced luciferase activity (p < 0.05). This reduction indicates a decrease in NF-κB activity. HA and CPO decreased INF-γ, IL-1ß, IL-6, IL-10, and TNF-α at 24 and 72 h in the multi-spot system. In zymosan-induced arthritis, CPO and HA decreased the number of neutrophils in the joint of arthritic mice and the number of total leukocytes (p < 0.05). In experimental arthritis HA significantly decreased joint swelling (p < 0.05). CPO and HA also increased the mechanical threshold during experimental arthritis. HA and CPO significantly inhibited the carrageenan-induced paw edema, being the doses of 10 mg/kg the most effective, registering maximum inhibitions of 58 ± 8% and 76 ± 6% respectively, p < 0.05. CPO and HA reduced the nociceptive behavior in both phases of formalin at all tested doses. The highest doses tested displayed inhibitions of 87 ± 1% and 72 ± 4%, respectively, p < 0.001, in the first phase, and 87 ± 1% and 81 ± 2%, respectively, p < 0.001, in the second phase. Oral treatment of CPO and HA (1, 3, 10 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhings, and the 10 mg/kg dose was the most effective with maximum inhibitions of 86 ± 2% and 82 ± 1%, respectively, p < 0.001. Both HA and CPO significantly decreased the intensity of mechanical inflammatory hyper-nociception on carrageenan-induced hyperalgesia at all tested doses, and 10 mg/kg was the most effective dose with maximum inhibitions of 73 ± 5% and 74 ± 7%, respectively, p < 0.05.CPO increased the tail-flick latencies in mice, and concomitant administration of naloxone partially reduced its effect. CONCLUSIONS: CPO and HA may inhibit the production of inflammatory cytokines by suppressing the NF-κB signaling pathway, resulting in anti-inflammatory and antinociceptive activities.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Diterpenos/uso terapêutico , Edema/tratamento farmacológico , Fabaceae/química , Extratos Vegetais/uso terapêutico , Ácido Acético/toxicidade , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Experimental/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Brasil , Carragenina/toxicidade , Linhagem Celular , Citocinas/metabolismo , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Edema/induzido quimicamente , Formaldeído/toxicidade , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Locomoção/efeitos dos fármacos , Medicina Tradicional , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Zimosan/toxicidade
18.
Reprod Fertil Dev ; 33(2): 1-19, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38769670

RESUMO

Ruminant livestock are raised under diverse cultural and environmental production systems around the globe. Ruminant livestock can play a critical role in food security by supplying high-quality, nutrient-dense food with little or no competition for arable land while simultaneously improving soil health through vital returns of organic matter. However, in the context of climate change and limited land resources, the role of ruminant-based systems is uncertain because of their reputed low efficiency of feed conversion (kilogram of feed required per kilogram of product) and the production of methane as a by-product of enteric fermentation. A growing human population will demand more animal protein, which will put greater pressure on the Earth's planetary boundaries and contribute further to climate change. Therefore, livestock production globally faces the dual challenges of mitigating emissions and adapting to a changing climate. This requires research-led animal and plant breeding and feeding strategies to optimise ruminant systems. This study collated information from a global network of research farms reflecting a variety of ruminant production systems in diverse regions of the globe. Using this information, key changes in the genetic and nutritional approaches relevant to each system were drawn that, if implemented, would help shape more sustainable future ruminant livestock systems.

19.
Front Pharmacol ; 11: 584595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324215

RESUMO

A rich archive of oral and ethnological literature is housed in the National Folklore Collection, in University College Dublin, Ireland. The Schools' Manuscript Collection is one body of information that contains a wealth of ethnographic material, including that of an ethnomedicinal nature, collected by schoolchildren across Ireland in the 1930s, in an early example of Citizen Science. The collection has been digitized and is available online at Dúchas.ie. Furthermore, there is an on-going and related project, the Meitheal Dúchas.ie Community Transcription project that enables the database to be easily searched, and thus used for research purposes. This study analyses the user interface and functionality of the Dúchas database for ethnomedical research by utilizing probes in the form of plants, within the collection, that have been previously identified as used for medicinal purposes. Limitations and biases associated with both the original collection of the material and the Dúchas database, that impact on the quality and utility of extractable data have been identified, and where possible specific procedures adopted to counteract such limitations. This study provides an insight into; the use of Dúchas.ie for ethnographic research, the use of plants for medicinal purposes in post-famine Ireland and is the first tangible example of Citizen Science in ethnomedical research in Ireland.

20.
J Pharm Biomed Anal ; 189: 113430, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32615341

RESUMO

1H-NMR-based metabolomics have been applied to identify potential NMR-markers and biomarkers capable of distinguishing, qualifying and classifying three Mentha species:- Mentha pulegium L., Mentha × rotundifolia (L.) Huds., Mentha spicata L., and their ecotypes. Samples of the 3 species were collected in seven different locations in Algeria, with the aim to establish a quality control protocol based on the use of NMR fingerprint profiles of polar extracts. NMR data indicate that the identification of the Mentha genus can be confirmed by the presence of the doublet proton signals with identical coupling constants at δ 7.49 (d, 15.9 Hz) and δ 6.29 (d, 15.9 Hz); these correspond to the protons of the double-bond conjugated to the ester group of rosmarinic acid, a bioactive compound found in all three species. Differences in NMR proton chemical shifts and/or signal intensities were clearly demonstrated on the orthogonal projections to latent structures discriminating analysis (OPLS-DA). Several potential biomarkers discriminating the three Mentha species were originated using S-plots, loading score plots, NMR data analysis and literature search. These discriminating signals point to glycosylated flavonols, oxygenated terpenoids and hydrocarbon terpenoids to distinguish M. pulegium, M. × rotundifolia and M. spicata, respectively. Within the same species, Principal Component Analysis (PCA) scores clearly discriminated the metabolite content according to regions in which the plants were grown. The 6 zones in which Mentha pulegium samples were harvested were clearly separated along either or both PC1 and PC2; by contrast, the harvesting locations were divided into two groups along PC1 for both M. × rotundifolia and M. spicata. The total antioxidant activity of the Mentha species was impacted by the abiotic factors of the different regions.


Assuntos
Mentha , Argélia , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Prótons
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