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1.
Minerva Urol Nephrol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259193

RESUMEN

BACKGROUND: Overactive bladder (OAB) is a chronic condition. This study was prompted by the need to fill the gap between medical treatment and advanced therapies allowing improvement in Quality of Life. The aim of the current study was to evaluate the association between treatment type (Ialuril®; IBSA Farmaceutici, Lodi, Italy; in combination with antimuscarinic or alone after drop-out of antimuscarinic, relative to antimuscarinic alone treatment) and functional outcomes (number of micturitions, pelvic pain, urinary incontinence, nocturia, urgency). METHODS: Of all patients newly diagnosed (January 2016 - January 2022) with OAB syndrome, we retrospectively identified 150 patients. They harbored three groups of 50 patients each: group 1 (antimuscarinic drug), group 2 (antimuscarinic drug + hyaluronic acid-chondroitin sulphate [HA-CS]), group 3 (antimuscarinic dropout patients). Univariable linear and logistic regression models were fitted for number and rates of incontinence, urgency, pelvic pain, nocturia, respectively. RESULTS: A significant mean reduction of 1.5 micturition (P=0.02) was recorded in group 2 compared to group 1. Conversely, no statistically significant mean difference was recorded in group 3 compared to group 1. Regarding pelvic pain, both group 2 and group 3 were associated with lower rate of pelvic pain (P<0.001). Regarding urgency, a statistically significant protective OR was recorded for group 2 (OR=0.39; P=0.04), compared to group 1. CONCLUSIONS: The combination therapy was associated with symptom improvement in antimuscarinic naïve OAB patients. Conversely in antimuscarinic dropped-out patients only pelvic pain improved with the HS-CA. No statistically significant differences were recorded for other functional outcomes, such as incontinence and nocturia.

2.
Front Plant Sci ; 15: 1416539, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220011

RESUMEN

Introduction: The current investigation presents a two-fold approach to rediscovering the potential of Sonchus asper as a wild edible plant, both in its raw extract form and as a nanoformulated product. Furthermore, the study aimed to promote the valorization of traditional dishes and contribute to biodiversity conservation and sustainable use of S. asper, thus enhancing economic profits. Methods: Liquid chromatography-mass spectrometry analyses were conducted to characterize the metabolite profile of the raw and cooked leaf extracts, and the extract from discarded leaves. The antioxidant activity, the hypoglycaemic effect and the incorporation into liposomes were evaluated. Results: 38 compounds and 6 essential amino acids were identified. The incorporation into liposomes maximized the health-promoting properties for potential pharmaceutical or food applications. Discussion: The commercialization of S. asper could: (i) contribute to improving the well-being of rural and urban communities, being S. asper a wild edible plant available at low cost, environmentally friendly, resilient, and adaptable; (ii) generate landowner economic returns.

3.
J Nat Prod ; 87(8): 2021-2033, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39126694

RESUMEN

Bitter taste receptors, also known as taste 2 receptors (T2R), are expressed throughout the body and are involved in regulating different physiological processes. T2R expression in the intestinal tract regulates orexigenic and anorexigenic peptide secretion, thus becoming potential a potential target for controlling food intake and the prevalence of obesity and overweight. The present study aims to investigate the implication of hop bitter compounds such as α-acids, ß-acids, and xanthohumol in the secretion of anorexigenic hormones and T2R expression in intestinal STC-1 cells. The tested bitter compounds induced the secretion of the anorexigenic hormones glucagon-like peptide 1 and cholecystokinin concurrently with a selective increase of murine Tas2r expression. Xanthohumol and α-acids selectively increase Tas2r138 and Tas2r130-Tas2r138 expression, respectively, in STC-1 cells, while ß-acids increased the expression of all bitter receptors studied, including Tas2r119, Tas2r105, Tas2r138, Tas2r120, and Tas2r130. Increased intracellular calcium levels confirmed this activity. As all investigated bitter molecules increased Tas2r138 expression, computational studies were performed on Tas2r138 and its human orthologue T2R38 for the first time. Molecular docking experiments showed that all molecules might be able to bind both bitter receptors, providing an excellent basis for applying hop bitter molecules as lead compounds to further design gastrointestinal-permeable T2R agonists.


Asunto(s)
Humulus , Simulación del Acoplamiento Molecular , Receptores Acoplados a Proteínas G , Humulus/química , Receptores Acoplados a Proteínas G/metabolismo , Animales , Ratones , Humanos , Propiofenonas/farmacología , Propiofenonas/química , Flavonoides/farmacología , Flavonoides/química , Péptido 1 Similar al Glucagón/metabolismo , Colecistoquinina/metabolismo , Colecistoquinina/química , Línea Celular , Tracto Gastrointestinal/metabolismo , Estructura Molecular
4.
Plants (Basel) ; 13(16)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39204746

RESUMEN

Exhausted olive pomace (EOP) represents the principal residue of olive pomace. Several studies have optimized the extraction of specialized metabolites from the EOP of Olea europaea L., but a comparison between different extractive methods has not been made. For this reason, the present investigation aims to compare four different extractive methods by using water and 15% ethanol/water as extractive solvents. Specifically, based on extract antioxidant activity, the methods compared were maceration (MAC), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and Accelerated Solvent Extraction (ASE). Between these, the UAE and ASE hydroalcoholic EOP extracts were demonstrated to have the highest antioxidant activity. Subsequently, these extracts were investigated for their hypoglycemic and antiradical activity using in vitro cell-free and cell-based assays, respectively. ASE hydroalcoholic EOP extract demonstrated the greatest ability to inhibit the α-amylase enzyme and an in vitro antioxidant activity comparable to N-acetyl cysteine in HepG2 cells. UAE and ASE extracts' phytochemical characterization was also performed, identifying seven phenolic compounds, including 3-hydroxytyrosol, tyrosol, and, for the first time, salidroside. The ASE hydroalcoholic EOP extract was the richest from a phytochemical point of view, thus confirming its major biological activity. Therefore, ASE and 15% ethanol/water may represent the best extractive method for EOP nutraceutical valorization.

5.
J Clin Med ; 13(14)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39064128

RESUMEN

Background and Objectives: Fibromyalgia is a multifaceted and frequently misunderstood chronic pain disease marked by widespread musculoskeletal pain and cognitive/somatic dysfunction. This trial aims to contribute to the existing knowledge on treating fibromyalgia (FM) with medical cannabis (Cannabis sativa L.) and explore a safer and more effective cannabis administration method. The goal is to provide evidence-based findings that can guide alternative treatment options for FM patients by assessing a pilot study. Materials and Methods: The trial was performed at the pain therapy unit of the San Carlo Hospital (Potenza, Italy) by administrating to 30 FM patients 100 mg/day of Bedrocan® (Bedrocan International, Veendam, The Netherlands) as a decoction. The Numerical Rating Scale (NRS) and SF-12 short-form health questionnaire were used to evaluate pain intensity and the quality of life at the beginning of the study and the 6th-month follow-up. A systematic review of all clinical studies investigating the use of cannabis to reduce FM was also undertaken to place this study in the context of the existing evidence base. Results: Pain intensity evaluated with the NRS lowered from a median of 8 [95% CI 7.66-8.54] at a baseline to a median of 4 (95% CI 3.28-4.79) after 6 months of follow-up (p-value < 0.001; t-test). Similarly, significant physical and mental state improvement, evaluated with the SF-12 questionnaire, was found in 96.67% and 82.33% of patients, respectively (95% CI 44.11-51.13 for the physical state, and 53.48-58.69 for mental state assessed after the 6th-month follow-up; p-value < 0.001; t-test). The systematic analysis of the literature identified 10 clinical trials concerning the treatment of fibromyalgia with cannabis. Conclusions: Considering results from the present pilot study and systematic review, it is possible to assume that medical cannabis may be considered an alternative therapy for FM patients who do not respond to conventional pharmacological therapy.

7.
Comput Biol Med ; 179: 108907, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39033680

RESUMEN

Multidrug-resistant (MDR) Staphylococcus aureus infections significantly threaten global health. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat diverse MDR S. aureus strains. Hence, in this study, we introduce an in silico phytochemical-based approach for discovering novel antibacterial agents, underscoring the potential of computational approaches in therapeutic discovery. Glucomoringin Isothiocyanate (GMG-ITC) from Moringa oleifera Lam. is one of the phytochemical compounds with several biological activities, including antimicrobial, anti-inflammatory, and antioxidant activities, and is also effective against S. aureus. This study focuses on screening GMG-ITC as a potential drug candidate to combat MDR S. aureus infections through a molecular docking approach. Moreover, interaction amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis and molecular dynamics (MD) simulations were conducted for further investigation. Molecular docking and interaction analysis showed strong binding affinity towards S. aureus lipase, dihydrofolate reductase, and other MDR S. aureus proteins, including penicillin-binding protein 2a, MepR, D-Ala:D-Ala ligase, and RPP TetM, through hydrophilic and hydrophobic interactions. GMG-ITC also showed a strong binding affinity to cyclooxygenase-2 and FAD-dependent NAD(P)H oxidase, suggesting that it is a potential anti-inflammatory and antioxidant candidate that may eliminate inflammation and oxidative stress associated with S. aureus infections. MD simulations validated the stability of the GMG-ITC molecular interactions determined by molecular docking. In silico pharmacokinetic analysis highlights its potency as a drug candidate, showing strong absorption, distribution, and excretion properties in combination with low toxicity. It acts as an active protease and enzyme inhibitor with moderate activity against GPCR ligands, ion channels, nuclear receptor ligands, and kinases. Enrichment analysis further elucidated its involvement in important biological, molecular, and cellular functions with potential therapeutic applications in diseases like cancer, hepatitis B, and influenza. Results suggest that GMG-ITC is an effective antibacterial agent that could treat MDR S. aureus-associated infections.


Asunto(s)
Antibacterianos , Isotiocianatos , Simulación del Acoplamiento Molecular , Antibacterianos/química , Antibacterianos/farmacología , Isotiocianatos/química , Isotiocianatos/farmacología , Moringa oleifera/química , Simulación de Dinámica Molecular , Descubrimiento de Drogas , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Fitoquímicos/química , Fitoquímicos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Simulación por Computador , Humanos
8.
FEBS Open Bio ; 14(6): 955-967, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38711215

RESUMEN

Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased ß-catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth-related factors.


Asunto(s)
Alopecia , Malus , Estrés Oxidativo , Extractos Vegetales , Especies Reactivas de Oxígeno , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Humanos , Malus/química , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Proantocianidinas/farmacología , Catequina/farmacología , Superóxido Dismutasa/metabolismo , Células Cultivadas , Biflavonoides/farmacología , Catalasa/metabolismo
9.
Plants (Basel) ; 13(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38592845

RESUMEN

Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.

10.
Environ Sci Pollut Res Int ; 31(12): 18887-18899, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38353820

RESUMEN

The scarcity of freshwater for agriculture in many regions has led to the application of sewage and saline water for irrigation. Irrigation with non-conventional water sources could become a non-harmful process for plant cultivation, and the effects of their use on crops should be monitored in order to develop optimal management strategies. One possibility to overcome potential barriers is to use biostimulants such as Trichoderma spp. fungi. Tomato is a crop of great economic importance in the world. This study investigated the joint effects of Trichoderma afroharzianum T-22 on tomato plants irrigated with simulated unconventional waters. The experiment consisted of a control and three water treatments. In the control, the plants were watered with distilled water. The three water treatments were obtained by using an irrigation water added with nitrogen, a wastewater effluent, and a mixed groundwater-wastewater effluents. Potted tomato plants (variety Bobcat) were grown in a controlled growth chamber. Antioxidant activity, susceptibility to the aphids Macrosiphum euphorbiae, and tomato plant growth parameters were estimated. Trichoderma afroharzianum T-22 had a positive effect on plant growth and antioxidant defenses when plants were irrigated with distilled water. Instead, no significant morphological effects induced by T. afroharzianum T-22 on plants were observed when unconventional water was used for irrigation. However, inoculation with T. afroharzianum T-22 activated a stress response that made the colonized plants more susceptible to aphid development and increased their fecundity and longevity. Thanks to this study, it may be possible for the first time to open a new discussion on the practical possibility of using reclaimed wastewater for crop irrigation with the addition of a growth-promoting fungal symbiont.


Asunto(s)
Áfidos , Hypocreales , Solanum lycopersicum , Trichoderma , Animales , Aguas Residuales , Áfidos/fisiología , Antioxidantes , Trichoderma/fisiología , Riego Agrícola
11.
Microorganisms ; 12(1)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38258001

RESUMEN

Unsaturated diacylglycerols are a class of antioxidant compounds with the potential to positively impact human health. Their ability to combat oxidative stress through radical scavenger activity underscores their significance in the context of preventive and therapeutic strategies. In this paper we highlight the role of Anabaena flos-aquae as a producer of unsaturated mono and diacylglycerols, and then demonstrate the antioxidant activity of its methanolic extract, which has as its main components a variety of acylglycerol analogues. This finding was revealed using a sustainable strategy in which the One Strain Many Compounds (OSMAC) cultivation in microscale was coupled with a bioinformatic approach to analyze a large dataset of mass spectrometry data using the molecular networking analyses. This strategy reduces time and costs, avoiding long and expensive steps of purification and obtaining informative data on the metabolic composition of the extracts. This study highlights the role of Anabaena as a sustainable and green source of novel bioactive compounds.

12.
Front Pharmacol ; 14: 1306135, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38074123

RESUMEN

Introduction: Solanum aethiopicum L., commonly known as scarlet eggplant (Solanaceae family) is one of the most traditionally cultivated vegetables in Basilicata, a southern region of Italy. Although multiple uses have been given to this vegetable, data about its anti-obesogenic activity are still limited. Methods: This study focuses on testing two different extracts obtained either from the peel or from the whole fruit of the Lucanian Solanum aethiopicum. Their ability to inhibit certain enzymatic activities was tested in vitro and then, the one that showed the better outcomes was tested on an experimental model of High-Fat Diet (HFD) induced obesity. Results: Spectrophotometric assays demonstrated that the peel extract possessed the highest ability to inhibit the selected enzymatic activities and so, its phytochemical profile was obtained through LC-MS chromatography. The oral administration of this extract (25 mg/kg) to HFD-fed mice reduced body weight gain and improved glucose and lipid metabolism. Similarly, the extract ameliorated the obesity-induced inflammatory status by reducing the expression of pro-inflammatory cytokines in both adipose and hepatic tissues. Interestingly, these effects were associated with the improvement of vascular dysfunction. Discussion: Lucanian Solanum aethiopicum extract may represent a new strategic approach for managing obesity and its associated diseases.

13.
Mar Drugs ; 21(12)2023 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-38132964

RESUMEN

Decreased adult neurogenesis, or the gradual depletion of neural stem cells in adult neurogenic niches, is considered a hallmark of brain aging. This review provides a comprehensive overview of the intricate relationship between aging, adult neurogenesis, and the potential neuroregenerative properties of astaxanthin, a carotenoid principally extracted from the microalga Haematococcus pluvialis. The unique chemical structure of astaxanthin enables it to cross the blood-brain barrier and easily reach the brain, where it may positively influence adult neurogenesis. Astaxanthin can affect molecular pathways involved in the homeostasis, through the activation of FOXO3-related genetic pathways, growth, and regeneration of adult brain neurons, enhancing cell proliferation and the potency of stem cells in neural progenitor cells. Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation. By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging.


Asunto(s)
Antioxidantes , Células-Madre Neurales , Humanos , Antioxidantes/farmacología , Enfermedades Neuroinflamatorias , Neurogénesis , Encéfalo , Antiinflamatorios/farmacología
14.
Plants (Basel) ; 12(15)2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37571013

RESUMEN

Obesity is widely associated with intestine barrier impairment, nonalcoholic fatty liver disease (NAFLD) outbreaks, oxidative stress, and inflammation. In a previous investigation, the Solanum aethiopicum L. growing in Basilicata Region has demonstrated to have antioxidant activity; hence this investigation was aimed to evaluate for the first time the antilipidemic and anti-inflammatory activity of the Lucanian S. aethiopicum L. peel extract in vitro on OA-treated HepG2 and Caco-2 cell lines. It was shown that the extract could reduce lipogenesis by down-regulating SREBP-1c and HMGCR expression and fatty acid ß-oxidation by up-regulating PPARα, CPT1A, and UCP2 expression. In addition, the S. aethiopicum L. peel extract might also improve oxidative stress by reducing endoplasmic reticulum stress and regulating the Nrf2 and Nf-κB molecular pathways. Altogether, these results demonstrated for the first time the possible application of the Lucanian S. aethiopicum peel extract for preventing obesity and managing NAFLD.

15.
Phytochem Rev ; : 1-79, 2023 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-37359711

RESUMEN

Viral infections have always been the main global health challenge, as several potentially lethal viruses, including the hepatitis virus, herpes virus, and influenza virus, have affected human health for decades. Unfortunately, most licensed antiviral drugs are characterized by many adverse reactions and, in the long-term therapy, also develop viral resistance; for these reasons, researchers have focused their attention on investigating potential antiviral molecules from plants. Natural resources indeed offer a variety of specialized therapeutic metabolites that have been demonstrated to inhibit viral entry into the host cells and replication through the regulation of viral absorption, cell receptor binding, and competition for the activation of intracellular signaling pathways. Many active phytochemicals, including flavonoids, lignans, terpenoids, coumarins, saponins, alkaloids, etc., have been identified as potential candidates for preventing and treating viral infections. Using a systematic approach, this review summarises the knowledge obtained to date on the in vivo antiviral activity of specialized metabolites extracted from plant matrices by focusing on their mechanism of action.

16.
Plants (Basel) ; 12(12)2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37375892

RESUMEN

Plant species are a reservoir of natural compounds that can potentially be used to treat different diseases. Citrus medica Linn. belonging to the Rutaceae family, has been used for centuries in medicine for its antioxidant, anti-inflammatory, antimicrobial, antiviral, and antihyperglycemic properties. These activities are ascribable not only to the presence of health-promoting macronutrients and micronutrients, such as carbohydrates, minerals, amino acids, and vitamins, but also to specialized metabolites, such as flavonoids (apigenin, hesperetin, hesperidin, naringin, naringenin, rutin, quercetin, and diosmin), coumarins (citropten, scoparone, and bergapten), terpenes (limonene, γ-terpinene, limonin, and nomilin), and phenolic acids (p-coumaric acid, trans-ferulic acid, and chlorogenic acid). In recent years, particular attention has been focused on the antioxidant, anti-inflammatory, antimicrobial activity, antidiabetic, anticancer, and neuroprotective activity of C. medica. However, although many studies have reported this species' chemical and biological properties, the literature has never been analyzed via a systematic approach. For this reason, using PubMed and Scopus as databases, we performed a systematic review of C. medica's chemical composition and biological properties to inspire new research approaches and increase its curative application.

17.
Cancers (Basel) ; 15(11)2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37296944

RESUMEN

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.

18.
Eur J Med Chem ; 254: 115386, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37094450

RESUMEN

The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders.


Asunto(s)
Neurotensina , Enfermedad de Parkinson , Animales , Humanos , Ratones , Dopamina , Ligandos , Neurotensina/farmacología , Neurotensina/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Unión Proteica , Receptores de Neurotensina/metabolismo
19.
Plants (Basel) ; 12(3)2023 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-36771653

RESUMEN

This study evaluates the effect of a chemical fertilizer (ammonium nitrate), a compost (vermicompost from cattle manure) and two biochars (from vine prunings and wood chips, respectively), applied to the soil alone or in mixture, on the yield, phytochemical content and biological activity of Beta vulgaris L. var. cycla (Swiss chard). The respective treatments, each replicated four times, were arranged according to a completely randomized block design. Results showed that vermicompost, both alone and in mixture with vine pruning biochar, significantly increased yield parameters (plant height and leaf area) and yield over the untreated soil and the biochars alone, similar to ammonium nitrate. Moreover, vermicompost, both alone and in mixture, respectively, with the two biochars, determined lower total N and NO3- contents than ammonium nitrate, both alone and in mixture, respectively, with the two biochars. In particular, NO3- content was within the safe thresholds fixed for leafy vegetables by the European Commission to prevent any adverse implication on human health from dietary NO3- exposure. The biochars alone resulted in very low yield and leaf total N content, likely due to a limited release of N for plant uptake, also evidenced by the undetectable NO3- leaf content, similarly shown by plants grown in untreated soil. Vermicompost, alone or in mixture, respectively, with the two biochars, increased the content of specialized metabolites, with a positive effect on antioxidant activity. The organic amendments, particularly compost, could be an alternative to chemical fertilizers to reach a trade-off between yield, nutritional and health qualities in Swiss chard, meeting the needs of farmers and consumers as well as the targets for sustainable food production.

20.
Plants (Basel) ; 12(2)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36679017

RESUMEN

Several specialized plant metabolites are reported to be enzyme inhibitors. In this investigation, the phytochemical composition and the biological activity of Rhanterium suaveolens Desf. were studied. One new lignan (rhanteriol 1) and seven known secondary metabolites were isolated from the aerial parts of R. suaveolens by using different chromatographic procedures. The biological properties of the R. suaveolens extracts and the new compound were evaluated by measuring their ability to inhibit the cholinesterase and carbohydrate-hydrolyzing enzymes, using cell-free in vitro methods. The new lignan, rhanteriol, was shown to inhibit α-amylase and α-glucosidase (IC50 = 46.42 ± 3.25 µM and 26.76 ± 3.29 µM, respectively), as well as butyrylcholinesterase (IC50 = 10.41 ± 0.03 µM), with an effect comparable to that of the respective standards, acarbose and galantamine. Furthermore, docking studies were performed suggesting the interaction mode of rhanteriol with the active sites of the investigated enzymes. The obtained data demonstrated that the aerial part of R. suaveolens could represent a source of active molecules, such as rhanteriol, usable in the development of treatments for preventing or treating type 2 diabetes mellitus and neurodegeneration.

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