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1.
Mol Cell ; 81(16): 3368-3385.e9, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34375583

RESUMO

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.


Assuntos
Adenosina/análogos & derivados , Proteínas de Ciclo Celular/genética , Proteínas do Tecido Nervoso/genética , Fatores de Processamento de RNA/genética , RNA/genética , Fatores de Transcrição/genética , Adenosina/genética , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica/genética , Humanos , Metilação , Elementos Reguladores de Transcrição/genética , Ativação Transcricional/genética
2.
J Biol Chem ; 300(1): 105541, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072052

RESUMO

Munc18-interacting proteins (Mints) are multidomain adaptors that regulate neuronal membrane trafficking, signaling, and neurotransmission. Mint1 and Mint2 are highly expressed in the brain with overlapping roles in the regulation of synaptic vesicle fusion required for neurotransmitter release by interacting with the essential synaptic protein Munc18-1. Here, we have used AlphaFold2 to identify and then validate the mechanisms that underpin both the specific interactions of neuronal Mint proteins with Munc18-1 as well as their wider interactome. We found that a short acidic α-helical motif within Mint1 and Mint2 is necessary and sufficient for specific binding to Munc18-1 and binds a conserved surface on Munc18-1 domain3b. In Munc18-1/2 double knockout neurosecretory cells, mutation of the Mint-binding site reduces the ability of Munc18-1 to rescue exocytosis, and although Munc18-1 can interact with Mint and Sx1a (Syntaxin1a) proteins simultaneously in vitro, we find that they have mutually reduced affinities, suggesting an allosteric coupling between the proteins. Using AlphaFold2 to then examine the entire cellular network of putative Mint interactors provides a structural model for their assembly with a variety of known and novel regulatory and cargo proteins including ADP-ribosylation factor (ARF3/ARF4) small GTPases and the AP3 clathrin adaptor complex. Validation of Mint1 interaction with a new predicted binder TJAP1 (tight junction-associated protein 1) provides experimental support that AlphaFold2 can correctly predict interactions across such large-scale datasets. Overall, our data provide insights into the diversity of interactions mediated by the Mint family and show that Mints may help facilitate a key trigger point in SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) complex assembly and vesicle fusion.


Assuntos
Mentha , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Membrana Celular/metabolismo , Mentha/metabolismo , Proteínas Munc18/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Ligação Proteica , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Sintaxina 1/metabolismo , Humanos , Animais , Ratos , Células PC12
3.
Plant J ; 118(5): 1589-1602, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489316

RESUMO

Iridoids are non-canonical monoterpenoids produced by both insects and plants. An example is the cat-attracting and insect-repelling volatile iridoid nepetalactone, produced by Nepeta sp. (catmint) and aphids. Recently, both nepetalactone biosynthetic pathways were elucidated, showing a remarkable convergent evolution. The iridoid, dolichodial, produced by Teucrium marum (cat thyme) and multiple insect species, has highly similar properties to nepetalactone but its biosynthetic origin remains unknown. We set out to determine the genomic, enzymatic, and evolutionary basis of iridoid biosynthesis in T. marum. First, we generated a de novo chromosome-scale genome assembly for T. marum using Oxford Nanopore Technologies long reads and proximity-by-ligation Hi-C reads. The 610.3 Mb assembly spans 15 pseudomolecules with a 32.9 Mb N50 scaffold size. This enabled identification of iridoid biosynthetic genes, whose roles were verified via activity assays. Phylogenomic analysis revealed that the evolutionary history of T. marum iridoid synthase, the iridoid scaffold-forming enzyme, is not orthologous to typical iridoid synthases but is derived from its conserved paralog. We discovered an enzymatic route from nepetalactol to diverse iridoids through the coupled activity of an iridoid oxidase cytochrome P450 and acetyltransferases, via an inferred acylated intermediate. This work provides a genomic resource for specialized metabolite research in mints and demonstration of the role of acetylation in T. marum iridoid diversity. This work will enable future biocatalytic or biosynthetic production of potent insect repellents, as well as comparative studies into iridoid biosynthesis in insects.


Assuntos
Iridoides , Iridoides/metabolismo , Vias Biossintéticas/genética , Filogenia , Genoma de Planta/genética , Genômica , Animais , Monoterpenos Ciclopentânicos/metabolismo , Pironas
4.
Proc Natl Acad Sci U S A ; 119(7)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35135884

RESUMO

Mitochondrial inner NEET (MiNT) and the outer mitochondrial membrane (OMM) mitoNEET (mNT) proteins belong to the NEET protein family. This family plays a key role in mitochondrial labile iron and reactive oxygen species (ROS) homeostasis. NEET proteins contain labile [2Fe-2S] clusters which can be transferred to apo-acceptor proteins. In eukaryotes, the biogenesis of [2Fe-2S] clusters occurs within the mitochondria by the iron-sulfur cluster (ISC) system; the clusters are then transferred to [2Fe-2S] proteins within the mitochondria or exported to cytosolic proteins and the cytosolic iron-sulfur cluster assembly (CIA) system. The last step of export of the [2Fe-2S] is not yet fully characterized. Here we show that MiNT interacts with voltage-dependent anion channel 1 (VDAC1), a major OMM protein that connects the intermembrane space with the cytosol and participates in regulating the levels of different ions including mitochondrial labile iron (mLI). We further show that VDAC1 is mediating the interaction between MiNT and mNT, in which MiNT transfers its [2Fe-2S] clusters from inside the mitochondria to mNT that is facing the cytosol. This MiNT-VDAC1-mNT interaction is shown both experimentally and by computational calculations. Additionally, we show that modifying MiNT expression in breast cancer cells affects the dynamics of mitochondrial structure and morphology, mitochondrial function, and breast cancer tumor growth. Our findings reveal a pathway for the transfer of [2Fe-2S] clusters, which are assembled inside the mitochondria, to the cytosol.


Assuntos
Citosol/metabolismo , Compostos Ferrosos/metabolismo , Mitocôndrias/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Simulação por Computador , Matriz Extracelular , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Glicólise , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Neoplasias Experimentais , Consumo de Oxigênio , Canal de Ânion 1 Dependente de Voltagem/genética
5.
Planta ; 260(1): 3, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767800

RESUMO

MAIN CONCLUSION: Transcription factors MhMYB1 and MhMYB2 correlate with monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq, which could affect the contents of ( -)-menthol and ( -)-menthone. Mentha haplocalyx Briq., a plant with traditional medicinal and edible uses, is renowned for its rich essential oil content. The distinct functional activities and aromatic flavors of mint essential oils arise from various chemotypes. While the biosynthetic pathways of the main monoterpenes in mint are well understood, the regulatory mechanisms governing different chemotypes remain inadequately explored. In this investigation, we identified and cloned two transcription factor genes from the M. haplocalyx MYB family, namely MhMYB1 (PP236792) and MhMYB2 (PP236793), previously identified by our research group. Bioinformatics analysis revealed that MhMYB1 possesses two conserved MYB domains, while MhMYB2 contains a conserved SANT domain. Yeast one-hybrid (Y1H) analysis results demonstrated that both MhMYB1 and MhMYB2 interacted with the promoter regions of MhMD and MhPR, critical enzymes in the monoterpenoid biosynthesis pathway of M. haplocalyx. Subsequent virus-induced gene silencing (VIGS) of MhMYB1 and MhMYB2 led to a significant reduction (P < 0.01) in the relative expression levels of MhMD and MhPR genes in the VIGS groups of M. haplocalyx. In addition, there was a noteworthy decrease (P < 0.05) in the contents of ( -)-menthol and ( -)-menthone in the essential oil of M. haplocalyx. These findings suggest that MhMYB1 and MhMYB2 transcription factors play a positive regulatory role in ( -)-menthol biosynthesis, consequently influencing the essential oil composition in the l-menthol chemotype of M. haplocalyx. This study serves as a pivotal foundation for unraveling the regulatory mechanisms governing monoterpenoid biosynthesis in different chemotypes of M. haplocalyx.


Assuntos
Regulação da Expressão Gênica de Plantas , Mentha , Mentol , Monoterpenos , Proteínas de Plantas , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Mentha/genética , Mentha/metabolismo , Monoterpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mentol/metabolismo , Óleos Voláteis/metabolismo , Vias Biossintéticas/genética , Regiões Promotoras Genéticas/genética
6.
Contact Dermatitis ; 90(1): 74-78, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37915267

RESUMO

BACKGROUND: Contact allergy to the mint-tasting flavour carvone has been observed in patients with oral lichenoid lesions (OLL). Mint-flavoured products such as toothpaste frequently contain carvone. Snuff is a smokeless tobacco product that is chewed or placed in the mouth rather than smoked. In Sweden, the use of snuff and its flavoured versions is extremely common. OBJECTIVES: To investigate whether the consumption of mint-flavoured snuff is associated with contact allergy to carvone and subsequently plays a role in the aetiology of OLL. METHODS: Regarding the two patients, patch testing with snuff pouches was performed. High-performance liquid chromatography and gas chromatography-mass spectrometry analysis were used for identification of carvone in different snuff samples. RESULTS: Two patients with OLL were contacted allergic to carvone when patch tested. Both were using mint-flavoured snuffs several hours a day for many years. One patient was contacted allergic to the snuff pouch tested as is. Carvone was detected in the snuff samples of both patients. CONCLUSIONS: The patients were recommended to avoid the use of mint-flavoured snuffs, toothpaste and foodstuffs. At follow-up 3 months later, the patients had a dramatic clinical improvement of the OLL and oral symptoms. Exposure to mint-flavoured snuffs can be overlooked as a possible aggravating/provoking factor in OLL.


Assuntos
Dermatite Alérgica de Contato , Tabaco sem Fumaça , Humanos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Tabaco sem Fumaça/efeitos adversos , Cremes Dentais , Monoterpenos Cicloexânicos
7.
Bioprocess Biosyst Eng ; 47(9): 1471-1482, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38874619

RESUMO

The present study optimized pre-treatment conditions for bioenzyme-mediated hydro-distillation (BMHD) for extraction of mint oil from mentha leaves and the results were compared with those of traditional hydro-distillation (HD) method using response surface methodology. The bio-enzymes produced from moringa leaves had maximum pectinase activity (287.04 µg of sugar/min/ml) followed by xylanase (87.78 µg of sugar/min/ml) while endoglucanase, exoglucanase and amylase activities were comparatively low. The optimized conditions for HD were 69.08 temperature for 173.70 min with water:sample of 10.0. The optimized conditions for enzyme pre-treatment of mentha leaves by BMHD were enzyme concentration of 8%, for a period of 120 min at an incubation period of 40 â„ƒ. The yield (%) and menthol content (%) of the oil at optimized conditions by HD were 1.55 ml/100 g of sample and 56.40% menthol content, respectively, and for BMHD the yield and menthol content (%) of the oil at optimized conditions were 3.69% and 72.80%, respectively. It was found that BMHD leads to a 130% increase in the yield of mint oil and a 10% increase in menthol content as compared to the HD method. No significant difference in physical parameters was observed in mint oil extracted via both methods. Therefore, BMHD is a cost-effective and sustainable approach having an edge over the HD method without compromising the quality and could be a viable approach for commercial purposes.


Assuntos
Destilação , Mentha , Mentol , Folhas de Planta , Mentha/química , Mentol/química , Folhas de Planta/química , Destilação/métodos , Óleos de Plantas/química
8.
Alzheimers Dement ; 20(1): 112-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37464962

RESUMO

INTRODUCTION: Evidence on the onset of naming deficits in Alzheimer's disease (AD) is mixed. Some studies showed an early decline, but others did not. The present study introduces evidence from a novel naming test. METHODS: Cognitively normal (n = 138), mild cognitive impairment (MCI; n = 21), and Alzheimer's disease (AD; n = 31) groups completed an expanded Multilingual Naming Test with a time-pressured administration procedure (MINT Sprint 2.0). Cerebrospinal fluid biomarkers classified participants as true controls (n = 61) or preclinical AD (n = 26). RESULTS: Total correct MINT Sprint 2.0 scores exhibited good sensitivity and specificity (>0.85) for discriminating true controls from cognitively impaired (MCI/AD) groups and showed significant differences between true controls and preclinical AD groups. Time measurement did not improve classification, but percent resolved scores exhibited promise as an independent AD marker. DISCUSSION: Naming deficits can be detected in the earliest stages of AD with tests and procedures designed for this purpose.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Multilinguismo , Humanos , Doença de Alzheimer/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/líquido cefalorraquidiano , Sensibilidade e Especificidade , Biomarcadores/líquido cefalorraquidiano , Testes Neuropsicológicos
9.
J Environ Manage ; 357: 120738, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574710

RESUMO

The pyrolysis of mint stalks and lemon peels was performed to synthesize mint-stalks (MBC) and lemon-peels (LBC) derived biochars for adsorbing methylene blue (MB). The preparation, characterization, and application of MBC in adsorption have not been reported in the literature. MBC showed higher surface area and carbon content than that of LBC. The removal ratios of MB were 87.5% and 60% within 90 min for MBC and LBC, respectively at pH 7, temperature of 30oC, adsorbent dose of 0.5 g/L, and MB concentration of 5 mg/L. The optimal MBC dose was 1 g/L achieving a removal efficiency of 93.6% at pH 7, temperature of 30oC, contact time of 90 min, and initial dye concentration of 5.0 mg/L. The adsorption efficiency decreased from 98.6% to 31.33% by raising the dye concentration from 3.0 mg/L to 30 mg/L. Further, the increase of adsorbent dose to 10 g/L could achieve 94.2%, 90.3%, 87.6%, and 84.1% removal efficiencies of MB in the case of initial concentrations of 200 mg/L, 300 mg/L, 400 mg/L, and 500 mg/L, respectively. MBC showed high stability in adsorbing MB under five cycles, and the performed analyses after adsorption reaffirmed the stability of MBC. The adsorption mechanism indicated that the adsorption of MB molecules on the biochar's surface was mainly because of the electrostatic interaction, hydrogen bonding, and π-π stacking. Pseudo-second-order and Langmuir models could efficiently describe the adsorption of MB on the prepared biochar. The adsorption process is endothermic and spontaneous based on the adsorption thermodynamics. The proposed adsorption system is promising and can be implemented on a bigger scale. Moreover, the prepared biochar can be implemented in other applications such as photocatalysis, periodate, and persulfate activation-based advanced oxidation processes.


Assuntos
Azul de Metileno , Poluentes Químicos da Água , Azul de Metileno/química , Adsorção , Concentração de Íons de Hidrogênio , Carvão Vegetal/química , Termodinâmica , Cinética
10.
Curr Issues Mol Biol ; 45(5): 4181-4199, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37232735

RESUMO

Chronic exposure to ultraviolet (UV) radiation is a major cause of photoaging. It involves extrinsic aging, wrinkle formation, and skin dehydration, and leads to excessive production of active oxygen that adversely affects the skin. Here, we investigated the antiphotoaging effect of AGEs BlockerTM (AB), which comprises Korean mint aerial part and fig and goji berry fruits. Compared to its individual components, AB was more potent at increasing the expression of collagen and hyaluronic acid and decreasing MMP-1 expression in UVB-irradiated Hs68 fibroblasts and HaCaT keratinocytes. In Skh:HR-1 hairless mice exposed to 60 mJ/cm2 UVB for 12 weeks, oral administration of 20 or 200 mg/kg/day AB restored skin moisture by improving UVB-induced erythema, skin moisture, and transepidermal water loss, and alleviated photoaging by improving UVB-induced elasticity and wrinkles. Moreover, AB upregulated the mRNA levels of hyaluronic acid synthase and collagen-related Col1a1, Col3a1, and Col4a1 genes, increasing hyaluronic acid and collagen expression, respectively. AB inhibited UVB-induced MAPK and AP-1 (c-fos) activation, resulting in significantly downregulated expression of MMP-1 and -9, which are responsible for collagen degradation. AB also stimulated the expression and activity of antioxidative enzymes and reduced lipid peroxidation. Thus, AB is a potential preventive and therapeutic agent for photoaging.

11.
BMC Plant Biol ; 23(1): 309, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37296388

RESUMO

Salinity, a severe worldwide issue, compromises the economic production of medicinal plants including mints and causes drug-yield decline. γ-Aminobutyric acid (GABA) is a tolerance-inducing signaling bio-molecule in various plant physiological processes. Pineapple mint (Mentha suaveolens Ehrh.) is a valuable medicinal herb with an exhilarating scent of citrus fruit. Piperitenone oxide is the major bioactive constituent of its essential oil, having significant demand by pharmaceutical industries. Nonetheless, modeling and optimizing the effective concentration of GABA remain within twin foci of interest. Therefore, a two factor-five level (NaCl 0-150 mM and GABA 0-2.4 mM) central composite design was conducted to model and optimize drug yield and physiological responses of M. suaveolens. Based on the design of experiments (DoE) approach, different linear, quadratic, cubic, and quartic models were assigned to the response variables. Change trends of shoot and root dry weights followed a simple linear model, whereas sophisticated models (i.e., multiple polynomial regression) were fitted to the other traits. NaCl stress inevitably reduced root and shoot dry weight, piperitenone oxide content, relative water content, pigments content, and maximum quantum yield of PSII. However, content of malondialdehyde (MDA) and total flavonoid, and DPPH radical scavenging activity were increased under salinity. Under severe NaCl stress (150 mM), the essential oil content (0.53%) was increased three times in comparison with control (0.18%). Optimization analysis demonstrated that the highest amount of essential oil (0.6%) and piperitenone oxide (81%) as a drug yield-determining component would be achievable by application of 0.1-0.2 mM GABA under 100 mM NaCl. The highest dry weight of root and shoot was predicted to be achieved at 2.4 mM GABA. Overall, extremely severe NaCl stress (i.e., more than 100 mM) in which a sharp drop in yield components value was observed seemed to be out of M. suaveolens salinity tolerance range. Hence, it is rationale to compensate the decrease of drug yield by foliar application of a dilute GABA solution (i.e., 0.1-0.2 mM) under 100 mM NaCl stress or lower levels.


Assuntos
Ananas , Mentha , Óleos Voláteis , Plantas Medicinais , Cloreto de Sódio/farmacologia , Cloreto de Sódio/metabolismo , Mentha/química , Mentha/metabolismo , Óleos Voláteis/metabolismo , Óxidos/metabolismo
12.
Eur J Nutr ; 62(8): 3411-3422, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37665425

RESUMO

PURPOSE: This study aimed to evaluate the capacity of peppermint essential oil to improve the physical performance of runners in running protocol until exhaustion. METHODS: In a clinical, randomized, double-blind, cross-over and controlled study, fourteen male recreational runners (37.1 ± 2.0 years; 24 ± 1.1 kg/m2; 53.1 ± 1.7 mL kg min) performed two runs to exhaustion at 70% of VO2max, after intake of 500 mL of water added with 0.05 mL of peppermint essential oil (PEO) or placebo (PLA), plus 400 mL of the drink during the initial part of the exercise. Records were made of body temperature (BT), thermal sensation (TS), thermal comfort (TC), subjective perception of effort (SPE), sweat rate (SR), and urine volume and density. RESULTS: Time to exhaustion was 109.9 ± 6.9 min in PEO and 98.5 ± 6.2 min in PLA (p = 0.009; effect size: 0.826). No significant changes were observed in the values of BT, TS, TC, SPE, SR, lost body mass, and urine volume and density (p > 0.05). CONCLUSION: Peppermint essential oil added to water before and during a race significantly increases the time to exhaustion of recreational runners but without altering BT, TS, TC, or hydration status, so the mechanisms involved were not clarified in this study. BRAZILIAN REGISTRY OF CLINICAL TRIALS (REBEC): RBR-75zt25z.


Assuntos
Mentha piperita , Óleos Voláteis , Resistência Física , Corrida , Exercício Físico , Mentha piperita/química , Óleos Voláteis/administração & dosagem , Água , Humanos , Masculino , Resistência Física/efeitos dos fármacos , Adulto
13.
Environ Res ; 236(Pt 1): 116718, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37481060

RESUMO

In ancient times, herbal plants were considered one of the greatest gifts from nature that human beings could receive, and about 80% of these plants have medicinal uses. In traditional medicine, Mentha arvensis, commonly known as mint, has many applications, and in the present study, the mint leaf extract has been used to synthesis nanoparticles using the mint leaf extract as a biosource for the extraction of nanoparticles. In addition to having a wide range of applications in various fields, calcium oxide (CaO) nanoparticles are also considered to be safe for human use. In order to assess the characteristics of the abstracted CaO nanoparticles, UV-visible absorption spectrophotometers, Fourier Transform Infrared spectrophotometers (FTIR), Scanning Electron Microscopes (SEMs), Dynamic Light Scattering (DLS), and X-ray Diffraction Spectrophotometers (XRDs) were used. By conducting a protein denaturation assay and nitric oxide scavenging assay, mint leaf mediated CaO nanoparticles were evaluated for their therapeutic applications. MTT assays were used to prove that the CaO nanoparticles mediated by mint leaf had anti-cancer properties. By examining the ability of mint leaf mediated CaO nanoparticles to degrade various dyes such as methyl red, methyl orange, and methylene blue, which are the most used azo dyes in textile industries resulting in water contamination, the ability of these nanoparticles to act as a photocatalytic agent was examined.


Assuntos
Mentha , Nanopartículas Metálicas , Nanopartículas , Humanos , Extratos Vegetais/farmacologia , Corantes , Difração de Raios X , Anti-Inflamatórios , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos
14.
BMC Biol ; 20(1): 264, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36447206

RESUMO

BACKGROUND: The SARS-CoV-2/COVID-19 pandemic has inflicted medical and socioeconomic havoc, and despite the current availability of vaccines and broad implementation of vaccination programs, more easily accessible and cost-effective acute treatment options preventing morbidity and mortality are urgently needed. Herbal teas have historically and recurrently been applied as self-medication for prophylaxis, therapy, and symptom alleviation in diverse diseases, including those caused by respiratory viruses, and have provided sources of natural products as basis for the development of therapeutic agents. To identify affordable, ubiquitously available, and effective treatments, we tested herbs consumed worldwide as herbal teas regarding their antiviral activity against SARS-CoV-2. RESULTS: Aqueous infusions prepared by boiling leaves of the Lamiaceae perilla and sage elicit potent and sustained antiviral activity against SARS-CoV-2 when applied after infection as well as prior to infection of cells. The herbal infusions exerted in vitro antiviral effects comparable to interferon-ß and remdesivir but outperformed convalescent sera and interferon-α2 upon short-term treatment early after infection. Based on protein fractionation analyses, we identified caffeic acid, perilla aldehyde, and perillyl alcohol as antiviral compounds. Global mass spectrometry (MS) analyses performed comparatively in two different cell culture infection models revealed changes of the proteome upon treatment with herbal infusions and provided insights into the mode of action. As inferred by the MS data, induction of heme oxygenase 1 (HMOX-1) was confirmed as effector mechanism by the antiviral activity of the HMOX-1-inducing compounds sulforaphane and fraxetin. CONCLUSIONS: In conclusion, herbal teas based on perilla and sage exhibit antiviral activity against SARS-CoV-2 including variants of concern such as Alpha, Beta, Delta, and Omicron, and we identified HMOX-1 as potential therapeutic target. Given that perilla and sage have been suggested as treatment options for various diseases, our dataset may constitute a valuable resource also for future research beyond virology.


Assuntos
Tratamento Farmacológico da COVID-19 , Chás de Ervas , Humanos , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/uso terapêutico , Pandemias , Soroterapia para COVID-19
15.
J Environ Manage ; 327: 116884, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36473361

RESUMO

This study focuses on uncovering the effect of country risks and renewable energy consumption on environmental quality. In this context, the study examines Mexico, Indonesia, Nigeria, and Turkey (MINT) nations; takes economic growth, trade openness, and urbanization into account; includes data from 1990 to 2018; applies cross-sectional autoregressive distributed lag (CS-ARDL) as the main model while common correlated effects mean group (CCEMG) and augmented mean group (AMG) for robustness checks. The empirical results show that (i) economic growth, political risk, urbanization, and trade openness contribute to an increase in ecological footprint; (ii) economic and financial risks as well as renewable energy use have a positive influence on environmental quality; (iii) a unidirectional causality exists from economic risk, financial risk, political risk, economic growth, urbanization, and trade openness to the ecological footprint: (iv) the validity of the EKC hypothesis for the MINT economies is verified; (v) the robustness of CS-ARDL results are validated by CCEMG and AMG approaches. Based on these results, policymakers should promote a sustainable environment to lessen the ecological footprint. Additionally, governments should firmly support investments in green technology as well as economic and financial stability to boost energy efficiency and promote the adoption and usage of energy-saving products.


Assuntos
Dióxido de Carbono , Dióxido de Carbono/análise , Estudos Transversais , Desenvolvimento Econômico , Indonésia , México , Nigéria , Energia Renovável , Turquia
16.
Molecules ; 28(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37570659

RESUMO

Helicobacter pylori infections are highly common amongst the global population. Such infections have been shown to be the cause of gastric ulcers and stomach carcinoma and, unfortunately, most cases are asymptomatic. Standard treatment requires antibiotics such as metronidazole or azithromycin to which many strains are now resistant. Mentha species have been used as a natural treatment for gastrointestinal diseases throughout history and essential oils (EOs) derived from these plants show promising results as potential antimicrobial agents. In this study, EOs obtained from the leaves and flowers of five cultivars of Mentha × piperita and M. spicata were examined by GC-MS. The investigated mints are representatives of four chemotypes: the menthol chemotype (M. × piperita 'Multimentha' and M. × piperita 'Swiss'), the piperitenone oxide chemotype (M. × piperita 'Almira'), the linalool chemotype (M. × piperita 'Granada'), and the carvone chemotype (M. spicata 'Moroccan'). The chemical composition of EOs from mint flowers and leaves was comparable with the exception of the Swiss cultivar. Menthol was the most abundant component in the leaves while menthone was highest in flowers. The H. pylori ATCC 43504 reference strain and 10 other H. pylori clinical strains were examined for their sensitivity to the EOs in addition to their major monoterpenoid components (menthol, menthone, carvone, dihydrocarvone, linalool, 1,8-cineole, and limonene). All tested mint EOs showed inhibitory activity against both the reference H. pylori ATCC 43504 strain (MIC 15.6-31.3 mg/L) and clinical H. pylori strains (MIC50/90 31.3-250 mg/L/62.5-500 mg/L). Among the reference monoterpenes, menthol (MIC50/90 7.8/31.3 mg/L) and carvone (MIC50/90 31.3/62.5 mg/L) had the highest anti-H. pylori activity, which also correlated with a higher activity of EOs containing these compounds (M. × piperita 'Swiss' and M. spicata 'Moroccan'). A synergistic and additive interaction between the most active EOs/compounds and antibiotics possibly points to a new plant-based anti-H. pylori treatment.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Mentha , Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Mentol/farmacologia , Mentol/química , Mentha/química , Mentha piperita/química , Antibacterianos/farmacologia
17.
Molecules ; 28(15)2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37570720

RESUMO

The incorporation of fermented camel milk with natural additives possesses numerous benefits for the treatment of various pathological and metabolic conditions. The present study investigated the impact of fortification of fermented camel milk with sage or mint leaves powder (1 and 1.5%, respectively) on glucose and insulin levels, lipid profile, and liver and kidney functions in alloxan-induced diabetic rats. The gross chemical composition of sage and peppermint leaves powder was studied. The chemical composition of sage and mint extracts was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS) of sage and mint extracts. Furthermore, a total of forty-two adult normal male albino rats were included in this study, whereas one group was kept as the healthy control group (n = 6 rats) and diabetes was induced in the remaining animals (n = 36 rats) using alloxan injection (150 mg/kg of body weight). Among diabetic rats groups, a control group (n = 6 rats) was kept as the diabetic control group whereas the other 5 groups (6 rats per group) of diabetic rats were fed fermented camel milk (FCM) or fermented camel milk fortified with 1 and 1.5% of sage or mint leaves powder. Interestingly, the oral administration of fermented camel milk fortified with sage or mint leaves powder, at both concentrations, caused a significant decrease in blood glucose level and lipid profile, and an increase in insulin level compared to the diabetic control and FCM groups. Among others, the best results were observed in the group of animals that received fermented camel milk fortified with 1.5% sage powder. In addition, the results revealed that the fermented camel milk fortified with sage or mint leaves powder improved the liver and kidney functions of diabetic rats. Our study concluded that the use of sage and mint leaves powder (at a ratio of 1.5%) with fermented camel milk produces functional food products with anti-diabetic activity.


Assuntos
Diabetes Mellitus Experimental , Insulinas , Mentha , Salvia officinalis , Ratos , Masculino , Animais , Leite/química , Mentha piperita , Salvia officinalis/química , Camelus , Pós/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Aloxano , Mentha/química , Lipídeos/análise , Folhas de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/análise
18.
J Biol Chem ; 297(5): 101304, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34655613

RESUMO

Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted thermodynamic and structural studies in solution to clarify the structural and thermodynamical changes of Mint3 binding to FIH-1. First, using a combination of circular dichroism, nuclear magnetic resonance, and hydrogen/deuterium exchange-mass spectrometry (HDX-MS), we confirmed that the N-terminal half, which is the interacting part of Mint3, is mostly disordered. Next, we revealed a large enthalpy and entropy change in the interaction of Mint3 using isothermal titration calorimetry (ITC). The profile is consistent with the model that the flexibility of disordered Mint3 is drastically reduced upon binding to FIH-1. Moreover, we performed a series of ITC experiments with several types of truncated Mint3s, an effective approach since the interacting part of Mint3 is disordered, and identified amino acids 78 to 88 as a novel core site for binding to FIH-1. The truncation study of Mint3 also revealed the thermodynamic contribution of each part of Mint3 to the interaction with FIH-1, where the core sites contribute to the affinity (ΔG), while other sites only affect enthalpy (ΔH), by forming noncovalent bonds. This insight can serve as a foothold for further investigation of intrinsically disordered regions (IDRs) and drug development for cancer therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Intrinsicamente Desordenadas/química , Oxigenases de Função Mista/química , Proteínas Repressoras/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular , Humanos , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Ligação Proteica , Domínios Proteicos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Termodinâmica
19.
Breed Sci ; 72(2): 181-187, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36275937

RESUMO

Mentha is a complex genus encompassing many species as a consequence of their interspecific hybridization and polyploidy. Southeast Asian mints have been poorly distinguished though they are widely used for culinary and medical purposes. In this study, we have analyzed Southeast Asian mints and known varieties as well as a related Lamiaceae species (Nepeta sp.) using simple sequence repeat (SSR) markers and leaf morphology. Two types of mints were clearly distinguished based on their venation pattern and leaf shape index. We developed 12 SSR markers that allowed good amplification in the Mentha and another Lamiaceae species. In the SSR-based phylogram, the Mentha lines could be delimited into groups I-VI. The Southeast Asian mints divided into groups I and II, and the phylogram separated most of the available species, with groups I and II containing the known species M. × cordifolia and M. arvensis, respectively. The separation of the two groups was supported by a population structure analysis. The SSR markers developed in this study enabled the simultaneous classification of mints and will help improve our understanding of the genetic composition of known mint varieties and as yet unclassified Southeast Asian mints.

20.
J Environ Manage ; 317: 115500, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751290

RESUMO

Pursuing ecological sustainability while mitigating the effects of environmental pollution has become a global pursuit. Moreover, the issue of how emerging economies like Mexico, Indonesia, Turkey, and Nigeria (MINT) economies can significantly reduce environmental pollution (EVP) remains elusive. This study sought to investigate the interplay between economic growth, green finance, renewable energy use, natural resource rent, energy innovation, urbanization and environmental pollution by analyzing panel data from 1990 to 2020. This research employed the novel econometrics approach CS-ARDL to examine the short and long-term relationships among the series. The research outcome disclosed that economic growth, natural resource rent and urbanization increase environmental pollution. In contrast, the empirical findings of this study revealed that environmental pollution could be neutralized through effective mechanisms such as green finance, renewable energy consumption, and the promotion of energy innovation. This research provides a fresh insight from the MINT economies and contributes to the existing literature by examining factors contributing to environmental pollution. This research also provides a benchmark for policy-makers and governments to invest in environmentally-friendly technologies to exploit the natural resources in these countries to mitigate the effect of environmental pollution.


Assuntos
Dióxido de Carbono , Dióxido de Carbono/análise , Desenvolvimento Econômico , Poluição Ambiental , Indonésia , México , Nigéria , Energia Renovável , Turquia
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