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Medicinas Complementárias
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1.
J Lipid Res ; 65(6): 100548, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38649096

RESUMEN

DHA is abundant in the brain where it regulates cell survival, neurogenesis, and neuroinflammation. DHA can be obtained from the diet or synthesized from alpha-linolenic acid (ALA; 18:3n-3) via a series of desaturation and elongation reactions occurring in the liver. Tracer studies suggest that dietary DHA can downregulate its own synthesis, but the mechanism remains undetermined and is the primary objective of this manuscript. First, we show by tracing 13C content (δ13C) of DHA via compound-specific isotope analysis, that following low dietary DHA, the brain receives DHA synthesized from ALA. We then show that dietary DHA increases mouse liver and serum EPA, which is dependant on ALA. Furthermore, by compound-specific isotope analysis we demonstrate that the source of increased EPA is slowed EPA metabolism, not increased DHA retroconversion as previously assumed. DHA feeding alone or with ALA lowered liver elongation of very long chain (ELOVL2, EPA elongation) enzyme activity despite no change in protein content. To further evaluate the role of ELOVL2, a liver-specific Elovl2 KO was generated showing that DHA feeding in the presence or absence of a functional liver ELOVL2 yields similar results. An enzyme competition assay for EPA elongation suggests both uncompetitive and noncompetitive inhibition by DHA depending on DHA levels. To translate our findings, we show that DHA supplementation in men and women increases EPA levels in a manner dependent on a SNP (rs953413) in the ELOVL2 gene. In conclusion, we identify a novel feedback inhibition pathway where dietary DHA downregulates its liver synthesis by inhibiting EPA elongation.


Asunto(s)
Ácidos Docosahexaenoicos , Regulación hacia Abajo , Ácido Eicosapentaenoico , Hígado , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/administración & dosificación , Animales , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones , Regulación hacia Abajo/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Ácido alfa-Linolénico/farmacología , Ácido alfa-Linolénico/metabolismo , Ácido alfa-Linolénico/administración & dosificación
2.
J Ethnopharmacol ; 330: 118239, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38657877

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus, a widespread chronic illness, affects millions worldwide, and its incidence is increasing alarmingly, especially in developing nations. Current pharmacological treatments can be costly and have undesirable side effects. To address this, medicinal plants with antidiabetic effects, particularly targeting α-glucosidase for controlling hyperglycaemia in type-2 diabetes mellitus (T2DM), hold promise for drug development with reduced toxicity and adverse reactions. AIM OF THIS REVIEW: This review aims to succinctly collect information about medicinal plant extracts that exhibit antidiabetic potential through α-glucosidase inhibition using acarbose as a standard reference in Southeast Asia. The characteristics of this inhibition are based on in vitro studies. MATERIALS AND METHODS: Relevant information on medicinal plants in Southeast Asia, along with α-glucosidase inhibition studies using acarbose as a positive control, was gathered from various scientific databases, including Scopus, PubMed, Web of Science, and Google Scholar. RESULTS: About 49 papers were found from specific counties in Southeast Asia demonstrated notable α-glucosidase inhibitory potential of their medicinal plants, with several plant extracts showcasing activity comparable to or surpassing that of acarbose. Notably, 19 active constituents were identified for their α-glucosidase inhibitory effects. CONCLUSIONS: The findings underscore the antidiabetic potential of the tested medicinal plant extracts, indicating their promise as alternative treatments for T2DM. This review can aid in the development of potent therapeutic medicines with increased effectiveness and safety for the treatment of T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de Glicósido Hidrolasas , Hipoglucemiantes , Extractos Vegetales , Plantas Medicinales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Plantas Medicinales/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Asia Sudoriental , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , alfa-Glucosidasas/metabolismo , Fitoterapia
3.
Plant Foods Hum Nutr ; 79(2): 468-473, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38668914

RESUMEN

The objective of our study was to analyse the extracts from six medicinal herb roots (marshmallow, dandelion, liquorice, angelica, burdock, and comfrey) in terms of antioxidant capacity (ABTS, DPPH) and inhibition of advanced glycation end product (AGEs) formation. The quantification of phenolic acids and flavonoids was analysed using the UHPLC-DAD-MS method. Fifteen polyphenolic compounds were detected in the studied herbs. The higher number of polyphenols were found in marshmallows (ten polyphenols), while the lowest was in comfrey (five compounds). Liquorice root revealed the highest individual phenolic concentration (382 µg/g dm) with the higher contribution of kaempferol-3-O-rutinoside. Comfrey root extract was characterised by the most abundant TPC (Total Phenolic Content) value (29.79 mg GAE/ g dm). Burdock and comfrey showed the strongest anti-AGE activity studies with the BDA-GLU model. Burdock root was also characterised by the highest anti-AGE activity in the BSA-MGO model. The highest antioxidant capacity was determined by ABTS (72.12 µmol TE/g dw) and DPPH (143.01 µmol TE/g dw) assays for comfrey extract. The p-coumaric acid content was significantly correlated with anti-AGE activity determined by the BSA-MGO model. This research sheds new light on the bioactivity of root herbs, explaining the role of p-coumaric acid in preventing diabetes.


Asunto(s)
Antioxidantes , Flavonoides , Productos Finales de Glicación Avanzada , Extractos Vegetales , Raíces de Plantas , Plantas Medicinales , Polifenoles , Antioxidantes/análisis , Antioxidantes/farmacología , Polifenoles/análisis , Polifenoles/farmacología , Raíces de Plantas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/análisis , Plantas Medicinales/química , Flavonoides/análisis , Flavonoides/farmacología , Angelica/química , Glycyrrhiza/química , Arctium/química , Propionatos , Ácidos Cumáricos/análisis , Ácidos Cumáricos/farmacología , Hidroxibenzoatos/análisis , Cromatografía Líquida de Alta Presión
4.
J Ethnopharmacol ; 330: 118195, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38641080

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated. AIM OF THE STUDY: This study aimed to investigate the anti-colorectal cancer effect and underlying mechanism of wighteone. MATERIALS AND METHODS: SW480 human colorectal cancer cells were used to evaluate the in vitro anti-colorectal cancer activity and Akt regulation effect of wighteone by flow cytometry, phosphoproteomic and Western blot analysis. Surface plasmon resonance (SPR) assay, molecular docking and dynamics simulation, and kinase activity assay were used to investigate the direct interaction between wighteone and Akt. A nude mouse xenograft model with SW480 cells was used to verify the in vivo anti-colorectal cancer activity of wighteone. RESULTS: Wighteone inhibited phosphorylation of Akt and its downstream kinases in SW480 cells, which led to a reduction in cell viability. Wighteone had direct interaction with both PH and kinase domains of Akt, which locked Akt in a "closed" conformation with allosteric inhibition, and Gln79, Tyr272, Arg273 and Lys297 played the most critical role due to their hydrogen bond and hydrophobic interactions with wighteone. Based on Akt overexpression or activation in SW480 cells, further mechanistic studies suggested that wighteone-induced Akt inhibition led to cycle arrest, apoptosis and autophagic death of SW480 cells. Moreover, wighteone exerted in vivo anti-colorectal cancer effect and Akt inhibition activity in the nude mouse xenograft model. CONCLUSION: Wighteone could inhibit growth of SW480 cells through allosteric inhibition of Akt, which led to cell cycle arrest, apoptosis and autophagic death. The results contributed to understanding of the anti-tumor mechanism of licorice, and also provided a rationale to design novel Akt allosteric inhibitors for the treatment of colorectal cancer.


Asunto(s)
Antineoplásicos Fitogénicos , Neoplasias Colorrectales , Flavonoides , Glycyrrhiza , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Masculino , Ratones , Regulación Alostérica/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Flavonoides/química , Glycyrrhiza/química , Ratones Endogámicos BALB C , Ratones Desnudos , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
5.
J Biosci Bioeng ; 138(1): 63-72, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38614831

RESUMEN

Among different microbial-induced calcium carbonate precipitation (MICCP) mechanisms utilized for biomineralization, ureolysis leads to the greatest yields of calcium carbonate. Unfortunately, it is reported that urea-induced growth inhibition can delay urea hydrolysis but it is not clear how this affects MICCP kinetics. This study investigated the impact of urea addition on the MICCP performance of Lysinibacillus sphaericus MB284 not previously grown on urea (thereafter named bio-agents), compared with those previously cultured in urea-rich media (20 g/L) (hereafter named bio-agents+ or bio-agents-plus). While it was discovered that initial urea concentrations exceeding 3 g/L temporarily hindered cell growth and MICCP reactions for bio-agents, employing bio-agents+ accelerated the initiation of bacterial growth by 33% and led to a 1.46-fold increase in the initial yield of calcium carbonate in media containing 20 g/L of urea. The improved tolerance of bio-agents+ to urea is attributed to the presence of pre-produced endogenous urease, which serves to reduce the initial urea concentration, alleviate growth inhibition, and expedite biomineralization. Notably, elevating the initial concentration of bio-agents+ from OD600 of 0.01 to 1, housing a higher content of endogenous urease, accelerated the initiation of MICCP reactions and boosted the ultimate yield of biomineralization by 2.6 times while the media was supplemented with 20 g/L of urea. These results elucidate the advantages of employing bio-agents+ with higher initial cell concentrations to successfully mitigate the temporary inhibitory effects of urea on biomineralization kinetics, offering a promising strategy for accelerating the production of calcium carbonate for applications like bio self-healing of concrete.


Asunto(s)
Bacillaceae , Carbonato de Calcio , Precipitación Química , Urea , Ureasa , Carbonato de Calcio/metabolismo , Carbonato de Calcio/farmacología , Carbonato de Calcio/química , Urea/metabolismo , Urea/farmacología , Bacillaceae/metabolismo , Cinética , Ureasa/metabolismo , Biomineralización , Medios de Cultivo/química
6.
Front Pharmacol ; 15: 1352045, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645558

RESUMEN

The bioactive extracts of traditional medicinal plants are rich in polyphenols and help to rejuvenate skin. The study was designed to assess the skin rejuvenating effects of a stable cream enriched with 4% I. argentea (IaMe) extract. The quantity of polyphenols by spectrophotometric methods was TPC, 101.55 ± 0.03 mg GAE/g and total flavonoid content; 77.14 ± 0.13 mg QE/g, while HPLC-PDA revealed gallic acid; 4.91, chlorogenic acid 48.12, p-coumaric acid 0.43, and rutin 14.23 µg/g. The significant results of biological activities were observed as DPPH; 81.81% ± 0.05%, tyrosinase; 72% ± 0.23% compared to ascorbic acid (92.43% ± 0.03%), and kojic acid (78.80% ± 0.19%) respectively. Moreover, the promising sun protection effects Sun protection factor of extract (20.53) and formulation (10.59) were observed. The active cream formulation (w/o emulsion) was developed with liquid paraffin, beeswax, IaMe extract, and ABIL EM 90, which was stable for 90 days as shown by various stability parameters. The rheological results demonstrated the active formulation's non-Newtonian and pseudo-plastic characteristics and nearly spherical globules by SEM. The IaMe loaded cream was further investigated on human trial subjects for skin rejuvenating effects and visualized in 3D skin images. Herein, the results were significant compared to placebo. IaMe formulation causes a substantial drop in skin melanin from -1.70% (2 weeks) to -10.8% (12 weeks). Furthermore, it showed a significant increase in skin moisture and elasticity index from 7.7% to 39.15% and 2%-30%, respectively. According to the findings, Indigofera argentea extract has promising bioactivities and skin rejuvenating properties, rationalizing the traditional use and encouraging its exploitation for effective and economical cosmeceuticals.

7.
Nat Prod Res ; : 1-7, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38590294

RESUMEN

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH· activity, superoxide anion (O2-) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

8.
Nat Prod Res ; : 1-10, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38577968

RESUMEN

Two heterodimers including a clovane-phenylpropanoid hybrid (1) and a clovane-menthane hybrid (2), five linear sesquiterpenoids incorporating a tetrahydrofuran ring (3-6 & 8), and four steroids (7 & 9-11), were separated from the ethanolic extract of a well-known aromatic and medicinal herb Eupatorium fortunei. Their structures were characterised by detailed analyses of spectroscopic data and comparison with known analogues, with seven (1-7) of them being described for the first time. The hybrids 1 and 2 represent the first examples of clovane type sesquiterpenoids hybridising with other class of natural products, and compounds 3-6 and 8 are first linear sesquiterpenyl constituents reported from the title species. All the isolates were evaluated for their inhibitory effect on the NO production induced by LPS in murine RAW264.7 macrophage cells, and 1, 7, 10 and 11 exhibited moderate activity with IC50 values in the range of 24.4-43.5 µM.

9.
Antibiotics (Basel) ; 13(4)2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38667034

RESUMEN

Teucrium montanum has widespread use in folk medicine on the Balkan peninsula. In order to scientifically justify this use, the composition and biological activity of aqueous, ethanol, and acetone extract were investigated in this study. Moreover, acetone and ethanol extracts were obtained from the plant material previously exhausted by water extraction. A total of 27 compounds were detected in extracts by UHPLC-DAD-MS/MS analysis, with all of them present in acetone and ethanol extracts. Consequentially, the acetone and ethanol extracts showed higher contents of total phenols of 23% and 18%, respectively, compared to the water extract. The results indicated high biological potential in the investigated extracts. Among all extracts, the aqueous extract showed slightly higher antimicrobial potential, especially against Gram-positive strains, probably due to the release of components soluble in water from the dry unexhausted plant material. On the other hand, the acetone and ethanol extracts had significantly higher antioxidative (by 20%), anti-inflammatory activity (up to 3 and 4 times higher, respectively), and α-glucosidase inhibitory potential (3 times higher) than the aqueous extract. The results of this investigation reveal the great potential of the use of T. montanum in various branches of food, cosmetics, and the pharmaceutical industry. An important part of this research is a confirmation that, once exhausted by water extraction, for example by hydrodistillation, T. montanum plant material can be reused for obtaining valuable products with a wide range of biological activities.

10.
Dev Psychobiol ; 66(2)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38646069

RESUMEN

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses. Paired stimuli, S1, S2, were presented 500 msec apart. Higher P50 amplitude in response to S1 (P50S1microV) assesses excitation, and lower P50S2microV assesses inhibition in this paired-stimulus paradigm. Development of inhibition was related solely to maternal choline plasma concentration and folate supplementation at 16 weeks' gestation. Development of excitation was related only to maternal choline at 28 weeks. Higher maternal choline concentrations later in gestation did not compensate for earlier lower concentrations. At 4 years of age, increased behavior problems on the Child Behavior Checklist 1½-5yrs were related to both newborn inhibition and excitation. Incomplete development of inhibition and excitation associated with lower choline and folate during relatively brief periods of gestation thus has enduring effects on child development.


Asunto(s)
Colina , Potenciales Evocados Auditivos , Ácido Fólico , Humanos , Colina/farmacología , Colina/metabolismo , Femenino , Ácido Fólico/farmacología , Masculino , Recién Nacido , Embarazo , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Auditivos/efectos de los fármacos , Preescolar , Desarrollo Fetal/fisiología , Desarrollo Fetal/efectos de los fármacos , Transmisión Sináptica/fisiología , Transmisión Sináptica/efectos de los fármacos , Adulto , Edad Gestacional , Desarrollo Infantil/fisiología , Desarrollo Infantil/efectos de los fármacos
11.
Zhongguo Zhong Yao Za Zhi ; 49(3): 653-660, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621869

RESUMEN

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.


Asunto(s)
Infecciones Bacterianas , Percepción de Quorum , Humanos , Percepción de Quorum/genética , Medicina Tradicional China , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias/genética , Biopelículas , Infecciones Bacterianas/tratamiento farmacológico
12.
Mar Drugs ; 22(4)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38667757

RESUMEN

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.


Asunto(s)
Antihipertensivos , Organismos Acuáticos , Suplementos Dietéticos , Alimentos Funcionales , Invertebrados , Péptidos , Animales , Humanos , Antihipertensivos/farmacología , Organismos Acuáticos/química , Productos Biológicos/farmacología , Hipertensión/tratamiento farmacológico , Invertebrados/química , Péptidos/análisis , Péptidos/farmacología
13.
Nat Prod Res ; : 1-7, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38440881

RESUMEN

Hawthorn plant is used among people due to its cardiovascular, anti-inflammatory, and antihistamine properties. But no scientific study has been done about Crataegus orientalis (Mill.) M.Bieb. The presented study was planned to determine the effects of ethanol and n-hexane extracts of Crataegus orientalis leaves on human plasma ACE enzyme. In the study, the effect of plant extracts on ACE was studied by the spectrophotometric method. The chemical composition of the plant extracts was determined by HPLC-DAD analyses. In addition, molecular doking and ADME prediction studies were carried out. As a result, the obtained data showed that Crataegus orientalis could have an important place in the pharmaceutical industry and drug discovery studies, as it supports the traditional use of Crataegus orientalis as hypotensive. The results of the molecular docking studies revealed that the interactions of the selected compounds with the human ACE enzyme caused inhibition.

14.
Parasit Vectors ; 17(1): 118, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459572

RESUMEN

BACKGROUND: Neospora caninum is an apicomplexan parasite that is particularly responsible for abortions in cattle and neuromuscular disease in dogs. Due to the limited effectiveness of currently available drugs, there is an urgent need for new therapeutic approaches to control neosporosis. Luciferase-based assays are potentially powerful tools in the search for antiprotozoal compounds, permitting the development of faster and more automated assays. The aim of this study was to construct a luciferase-expressing N. caninum and evaluate anti-N. caninum drugs. METHODS: Luciferase-expressing N. caninum (Nc1-Luc) was constructed using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). After testing the luciferase expression and phenotype of the Nc1-Luc strains, the drug sensitivity of Nc1-Luc strains was determined by treating them with known positive or negative drugs and calculating the half-maximal inhibitory concentration (IC50). The selective pan-rapidly accelerated fibrosarcoma (pan-RAF) inhibitor TAK-632 was then evaluated for anti-N. caninum effects using Nc1-Luc by luciferase activity reduction assay and other in vitro and in vivo studies. RESULTS: The phenotypes and drug sensitivity of Nc1-Luc strains were consistent with those of the parental strains Nc1, and Nc1-Luc strains can be used to determine the IC50 for anti-N. caninum drugs. Using the Nc1-Luc strains, TAK-632 showed promising activity against N. caninum, with an IC50 of 0.6131 µM and a selectivity index (SI) of 62.53. In vitro studies demonstrated that TAK-632 inhibited the invasion, proliferation, and division of N. caninum tachyzoites. In vivo studies showed that TAK-632 attenuated the virulence of N. caninum in mice and significantly reduced the parasite burden in the brain. CONCLUSIONS: In conclusion, a luciferase-expressing N. caninum strain was successfully constructed, which provides an effective tool for drug screening and related research on N. caninum. In addition, TAK-632 was found to inhibit the growth of N. caninum, which could be considered as a candidate lead compound for new therapeutics for neosporosis.


Asunto(s)
Enfermedades de los Bovinos , Coccidiosis , Enfermedades de los Perros , Neospora , Nitrilos , Enfermedades de los Roedores , Embarazo , Femenino , Animales , Ratones , Bovinos , Perros , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiosis/parasitología , Neospora/genética , Evaluación Preclínica de Medicamentos , Benzotiazoles/metabolismo , Benzotiazoles/farmacología , Benzotiazoles/uso terapéutico
15.
Artículo en Inglés | MEDLINE | ID: mdl-38484676

RESUMEN

The peroxyl radicals generated by the activity of lipoxygenases (LOX) are mediators to trigger inflammatory diseases. Therefore, it is important to investigate potent LOX inhibitor for modulating the occurrence and resolving inflammatory processes. Artemisa vulgaris, is a herbal plant that is known for flavonoids, potentially inhibiting lipid peroxidation and scavenging radicals. The objectives of the present study were to obtain flavonoids rich extract from A. vulgaris, and determine the inhibitory mode of the extract against LOX. The flavonoids rich extract was optimized in an ultrasound assisted extraction using ionic liquids as extraction solvent. The results found that the optimum conditions; ratio of solid-to-liquid (1:10) and 30 min of extraction time could produce the high yield (10.14 %) and flavonoid content (5.30 mg QE/g). The LOX activity was demonstrated to follow a mixed mode of inhibition in the presence of the flavonoid rich extract as an inhibitor. The Michaelis-Menten constant (Km) was increased from 0.283 µM to 0.435 µM, whereas the maximum velocity was reduced from 0.22 µM/min to 0.058 µM/min in the inhibition. The flavonoids rich extract is likely to be a natural potent non-competitive inhibitor which may bind to free LOX or substrate-bound LOX.


Asunto(s)
Artemisia , Flavonoides , Flavonoides/farmacología , Lipooxigenasas , Antioxidantes/farmacología , Extractos Vegetales/farmacología
16.
J Nat Med ; 78(3): 655-663, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38429480

RESUMEN

The preliminary α-glucosidase inhibitory activity of the methanol extract of the leaves of Sandoricum koetjape Merr. exhibited promising results. The leaves was extracted with methanol to obtain the methanol extract that was continuedly partitioned with hexane and ethyl acetate. Those fractions were further purified by various chromatographic techniques. The isolation of the potent fractions furnished two new cycloartane-type triterpenoids (1 and 2) along with ten known compounds (3-12). Their chemical structures were unambiguously established by interpretation of NMR (1 D & 2 D) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Furthermore, the configurations of two new compounds were determined by using NOESY spectrum as well as comparing their NMR data to the reference. These compounds were evaluated against α-glucosidase. All tested compounds revealed potent activity with IC50 value in the range of 2.17-49.2 µM compared to that of acarbose (IC50 100.6 µM). Compound 10 showed the lowest IC50 value. This compound was reported as a mixed-type inhibitor. Compound 3 possessed the second strong activity with an IC50 value of 14.0 µM and was further investigated on kinetic analysis which revealed as a mixed-type inhibitor with Ki and Ki' values of 59.1 and 155.2 µM, respectively.


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Extractos Vegetales , Hojas de la Planta , Triterpenos , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Triterpenos/química , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Hojas de la Planta/química , alfa-Glucosidasas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura Molecular , Espectroscopía de Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray
17.
Molecules ; 29(5)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38474653

RESUMEN

Matteuccia struthiopteris is one of the most globally consumed edible ferns and widely used in folk medicine. Reports mainly focus on young fronds and the rhizome which are common edible medicinal parts. However, there are few detailed reports on other parts. Therefore, the volatile components of different parts based on HS-SPME-GC-MS were identified, and total flavonoid contents, antioxidant activities and acetylcholinesterase inhibitory activities were compared in order to reveal the difference of volatile components and potential medicinal value of different parts. The results showed that total flavonoid contents, antioxidant activities and volatile components of different parts were obviously different. The crozier exhibited the strongest antioxidant activities, but only underground parts exhibited a dose-dependent inhibition potential against AChE. Common volatile compounds were furfural and 2-furancarboxaldehyde, 5-methyl-. In addition, it was found that some volatile components from adventitious root, trophophyll, sporophyll and petiole were important ingredients in food, cosmetics, industrial manufacturing and pharmaceutical applications.


Asunto(s)
Acetilcolinesterasa , Antioxidantes , Cromatografía de Gases y Espectrometría de Masas/métodos , Flavonoides , Microextracción en Fase Sólida/métodos
18.
Molecules ; 29(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474692

RESUMEN

Terpenes and their derivatives comprise a diverse group of natural compounds with versatile medicinal properties. This article elucidates the general characteristics of fungal terpenes and terpenoids, encompassing their structure and biogenesis. The focal point of this work involves a comprehensive overview of these compounds, highlighting their therapeutic properties, mechanisms of action, and potential applications in treating specific skin conditions. Numerous isolated terpenes and terpenoids have demonstrated noteworthy anti-inflammatory and anti-microbial effects, rivalling or surpassing the efficacy of currently employed treatments for inflammation or skin infections. Due to their well-documented antioxidant and anti-cancer attributes, these compounds exhibit promise in both preventing and treating skin cancer. Terpenes and terpenoids sourced from fungi display the capability to inhibit tyrosinase, suggesting potential applications in addressing skin pigmentation disorders and cancers linked to melanogenesis dysfunctions. This paper further disseminates the findings of clinical and in vivo research on fungal terpenes and terpenoids conducted thus far.


Asunto(s)
Enfermedades de la Piel , Neoplasias Cutáneas , Humanos , Terpenos/química , Antiinflamatorios , Inflamación/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico
19.
Plants (Basel) ; 13(4)2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38498494

RESUMEN

This study aimed to assess the antimicrobial activities of plant extracts from Artemisia afra and Eucalyptus globulus when used as coatings for textiles. A pulsed ultrasound-assisted extraction method (PUAE) was employed to obtain methanolic and hexanoic extracts from both plants. Eucalyptus globulus methanol extraction exhibited the highest yield at 22.76% (±0.61%), while Artemisia afra demonstrated lower yields. Phytochemical screening identified various secondary metabolites in the extracts, including phenols, quinones, and steroids. Antimicrobial tests against Staphylococcus aureus and Escherichia coli revealed varying degrees of susceptibility, with Eucalyptus globulus hexanoic extracts showing the highest activity against Staphylococcus aureus at an average percentage growth of 18.74% (±0.26%). Minimum inhibitory concentration (MIC) values were determined for the extracts, but complete inhibition did not occur at concentrations below 500 µg/mL. The extracts exhibited varying effects on Staphylococcus aureus and Escherichia coli growth, with some extracts promoting bacterial growth. Coating textiles with Eucalyptus globulus methanolic extracts demonstrated antibacterial activity against Staphylococcus aureus with the highest zone of inhibition observed in cotton-coated samples (258.4 mm2). Polyester-coated samples exhibited smaller inhibition zones, with the lowest observed in Eucalyptus globulus methanolic extract coating (65.97 mm2). Scanning electron microscope (SEM) analysis revealed visible surface morphology changes in coated fabrics, depicting fine, cluster, lumpy, flaky, and fragment-like morphologies. Laundering effects on coated fabrics were investigated, showing a significant decrease in antimicrobial activity after washing. Fourier-transform infrared spectroscopy (FTIR) identified functional groups in the extracts associated with antimicrobial properties. The complexity of the bioactive compounds suggests potential antimicrobial efficacy, resting on factors such as geographical location, climate, and extraction methods. Notwithstanding the limitations, this study contributes valuable insights into the use of plant extracts as antimicrobial coatings for textiles.

20.
Food Chem ; 447: 138743, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38452535

RESUMEN

Nitraria roborowskii Kom (NRK), with high economic and ecological value, is mainly distributed in the Qaidam Basin, China. However, research on its chemical components and bioactivities is still rare. In this study, its chemical constituents (52) including 10 ß-carboline alkaloids, nine cyclic peptides, three indole alkaloids, five pyrrole alkaloids, eight phenolic acids and 17 flavonoids were identified tentatively using UPLC-triple-TOF-MS/MS. Notablely, one new ß-carboline alkaloid and five new cyclic peptides were confirmed using MS/MS fragmentation pathways. In addition, experiments in vitro indicated that NRK-C had strong maltase and sucrase inhibitory activities (IC50 of 0.202 and 0.103 mg/mL, respectively). Polysaccharide tolerance experiments confirmed NRK-C (400 mg/kg) was associated with decreased postprandial blood glucose (PBG) in diabetic mice. These results suggested that NRK fruit might be used as a functional ingredient in food products.


Asunto(s)
Alcaloides , Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Ratones , Animales , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales/química , alfa-Glucosidasas/análisis , Frutas/química , Sacarasa , Alcaloides/análisis , Fenoles/análisis , Carbolinas/análisis , Péptidos Cíclicos/análisis , Medicamentos Herbarios Chinos/análisis
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