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1.
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
2.
J Nat Med ; 78(3): 576-589, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38662301

RESUMEN

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.


Asunto(s)
Envejecimiento , Dieta Alta en Grasa , Medicamentos Herbarios Chinos , Obesidad , Animales , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Dieta Alta en Grasa/efectos adversos , Envejecimiento/efectos de los fármacos , Humanos , Células Hep G2 , Ratones Endogámicos C57BL , Proteína Desacopladora 1/metabolismo , Triglicéridos/sangre , Triglicéridos/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Aspartato Aminotransferasas/sangre
3.
J Nat Med ; 78(3): 599-607, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38662302

RESUMEN

In this study, the effects of 3,5,7,3',4'-pentamethoxyflavone (KP1), a major bioactive ingredient isolated from the Kaempferia parviflora rhizomes, on a neurite outgrowth in Neuro2a cells and its mechanism have been investigated. KP1 increased concentration-dependently the percentage of neurite-bearing cells. KP1 showed a remarkable capability to elicit neurite outgrowth in Neuro2a cells, as evidenced by morphological alterations and immunostaining using anti-class III ß-tubulin and anti-NeuN antibodies. KP1 also displayed a higher neurogenic activity than retinoic acid (RA), a promoter of neurite outgrowth in Neuro2a cells. KP1 treatment caused significant elevation in phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and glycogen synthase kinase-3ß (GSK-3ß). However, KP1-triggered neurite outgrowth was markedly inhibited by treatment with the ERK inhibitor U0126, whereas p38 MAPK inhibitor SB203580 and GSK-3ß inhibitor SB216763 did not influence KP1-induced neurite outgrowth. These results demonstrate that KP1 elicits neurite outgrowth and triggers cell differentiation of Neuro2a cells through ERK signal pathway.


Asunto(s)
Sistema de Señalización de MAP Quinasas , Proyección Neuronal , Animales , Proyección Neuronal/efectos de los fármacos , Ratones , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Neuritas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Fosforilación/efectos de los fármacos , Flavonoides/farmacología , Flavonas/farmacología , Flavonas/química , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Línea Celular
4.
J Ethnopharmacol ; 330: 118244, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38663781

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.


Asunto(s)
Bupleurum , Medicamentos Herbarios Chinos , Hepatopatías , Animales , Humanos , Bupleurum/química , Enfermedad Crónica , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Medicina Tradicional China/métodos , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/química
5.
J Nat Med ; 78(3): 618-632, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38668832

RESUMEN

Acute myeloid leukemia (AML) is a malignant disease that is difficult to completely cure. Polyphyllin I (PPI), a steroidal saponin isolated from Paris polyphylla, has exhibited multiple biological activities. Here, we discovered the superior cytotoxicity of PPI on AML cells MOLM-13 with an IC50 values of 0.44 ± 0.09 µM. Mechanically, PPI could cause ferroptosis via the accumulation of intracellular iron concentration and triggering lipid peroxidation. Interestingly, PPI could induced stronger ferroptosis in a short time of about 6 h compared to erastin. Furthermore, we demonstrate that PPI-induced rapid ferroptosis is due to the simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering lipid peroxidation, and PI3K inhibitor Alpelisib can enhance the activity of erastin-induced ferroptosis. Molecular docking simulations and kinase inhibition assays demonstrated that PPI is a PI3K inhibitor. In addition, PPI significantly inhibited tumor progression and prolonged mouse survival at 4 mg/kg with well tolerance. In summary, our study highlights the therapeutic potential of PPI for AML and shows its unique dual mechanism.


Asunto(s)
Diosgenina , Ferroptosis , Leucemia Mieloide Aguda , Peroxidación de Lípido , Fosfatidilinositol 3-Quinasas , Ferroptosis/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Animales , Humanos , Peroxidación de Lípido/efectos de los fármacos , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Diosgenina/farmacología , Diosgenina/análogos & derivados , Diosgenina/uso terapéutico , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Saponinas/farmacología , Saponinas/química
6.
J Nat Med ; 78(3): 753-767, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38668831

RESUMEN

Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 µM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.


Asunto(s)
Analgésicos , Flores , Extractos Vegetales , Rhododendron , Analgésicos/farmacología , Analgésicos/química , Analgésicos/aislamiento & purificación , Animales , Flores/química , Rhododendron/química , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Masculino , Dolor/tratamiento farmacológico , Cromatografía Líquida de Alta Presión
7.
Environ Sci Pollut Res Int ; 31(20): 28847-28855, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38561538

RESUMEN

The increasing demands for resources driven by the global population necessitate exploring sustainable alternatives for affordable animal protein over the use of traditional protein sources. Insects, with their high protein content, offer a promising solution, especially when reared on agricultural post-distillation residues for enhanced sustainability and cost-effectiveness. We assessed the development of Zophobas morio (F.) (Coleoptera: Tenebrionidae) larvae on diets enriched with essential oils and post-distillation residues from Greek aromatic and medicinal plants. Two aromatic plant mixtures (A and B) were examined. Mixture A consisted of post-distillation residues, while Mixture B incorporated these residues along with essential oils. Insect rearing diets were enriched with different proportions (10, 20, and 30 %) of these mixtures, with wheat bran serving as the control. Enrichment positively influenced larval development without compromising survival. Larval weight remained unchanged with Mixture A, but improved with Mixture B. No adverse effects were detected in the case of the enriched diets, although higher concentrations of Mixture B prolonged development time.


Asunto(s)
Escarabajos , Larva , Aceites Volátiles , Plantas Medicinales , Animales , Plantas Medicinales/química , Dieta , Alimentación Animal/análisis
8.
J Nutr Biochem ; 129: 109638, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38583499

RESUMEN

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.


Asunto(s)
Trastorno del Espectro Autista , Efectos Tardíos de la Exposición Prenatal , Resveratrol , Resveratrol/farmacología , Animales , Femenino , Embarazo , Ratones , Masculino , Lipopolisacáridos/toxicidad , Conducta Animal/efectos de los fármacos , Ratones Endogámicos C57BL , Trastorno Autístico/inducido químicamente , Modelos Animales de Enfermedad
9.
Ageing Res Rev ; 97: 102309, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615895

RESUMEN

Alzheimer's disease (AD), a multi-factorial neurodegenerative disorder has affected over 30 million individuals globally and these numbers are expected to increase in the coming decades. Current therapeutic interventions are largely ineffective as they focus on a single target. Development of an effective drug therapy requires a deep understanding of the various factors influencing the onset and progression of the disease. Aging and genetic factors exert a major influence on the development of AD. Other factors like post-viral infections, iron overload, gut dysbiosis, and vascular dysfunction also exacerbate the onset and progression of AD. Further, post-translational modifications in tau, DRP1, CREB, and p65 proteins increase the disease severity through triggering mitochondrial dysfunction, synaptic loss, and differential interaction of amyloid beta with different receptors leading to impaired intracellular signalling. With advancements in neuroscience tools, new inter-relations that aggravate AD are being discovered including pre-existing diseases and exposure to other pathogens. Simultaneously, new therapeutic strategies involving modulation of gene expression through targeted delivery or modulation with light, harnessing the immune response to promote clearance of amyloid deposits, introduction of stem cells and extracellular vesicles to replace the destroyed neurons, exploring new therapeutic molecules from plant, marine and biological sources delivered in the free state or through nanoparticles and use of non-pharmacological interventions like music, transcranial stimulation and yoga. Polypharmacology approaches involving combination of therapeutic agents are also under active investigation for superior therapeutic outcomes. This review elaborates on various disease-causing factors, their underlying mechanisms, the inter-play between different disease-causing players, and emerging therapeutic options including those under clinical trials, for treatment of AD. The challenges involved in AD therapy and the way forward have also been discussed.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Animales , Envejecimiento/fisiología
10.
Biomed Pharmacother ; 174: 116586, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626516

RESUMEN

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.


Asunto(s)
Liposomas , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Fototerapia/métodos , Terapia Fototérmica/métodos
11.
Microb Genom ; 10(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38630610

RESUMEN

Erwinia (Enterobacterales: Erwiniaceae) are a group of cosmopolitan bacteria best known as the causative agents of various plant diseases. However, other species in this genus have been found to play important roles as insect endosymbionts supplementing the diet of their hosts. Here, I describe Candidatus Erwinia impunctatus (Erwimp) associated with the Highland midge Culicoides impunctatus (Diptera: Ceratopogonidae), an abundant biting pest in the Scottish Highlands. The genome of this new Erwinia species was assembled using hybrid long and short read techniques, and a comparative analysis was undertaken with other members of the genus to understand its potential ecological niche and impact. Genome composition analysis revealed that Erwimp is similar to other endophytic and ectophytic species in the genus and is unlikely to be restricted to its insect host. Evidence for an additional plant host includes the presence of a carotenoid synthesis operon implicated as a virulence factor in plant-associated members in the sister genus Pantoea. Unique features of Erwimp include several copies of intimin-like proteins which, along with signs of genome pseudogenization and a loss of certain metabolic pathways, suggests an element of host restriction seen elsewhere in the genus. Furthermore, a screening of individuals over two field seasons revealed the absence of the bacteria in Culicoides impunctatus during the second year indicating this microbe-insect interaction is likely to be transient. These data suggest that Culicoides impunctatus may have an important role to play beyond a biting nuisance, as an insect vector transmitting Erwimp alongside any conferred impacts to surrounding biota.


Asunto(s)
Ceratopogonidae , Erwinia , Humanos , Animales , Genómica , Insectos Vectores , Ecosistema
12.
J Mater Chem B ; 12(19): 4629-4641, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38666407

RESUMEN

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.


Asunto(s)
Adenosina Trifosfato , Antineoplásicos , Rayos Infrarrojos , Animales , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/química , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Inmunoterapia , Reposicionamiento de Medicamentos , Humanos , Rayos Láser , Terapia Fototérmica , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Alginatos/química , Femenino , Hidrogeles/química , Hidrogeles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Tamaño de la Partícula , Artemisininas/química , Artemisininas/farmacología
13.
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
14.
ACS Nano ; 18(17): 11025-11041, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38626916

RESUMEN

ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics. However, they can also be programmed toward a pro-inflammatory tumor suppressive phenotype, which represents a highly active area of therapy development. Iron loading of TAMs can achieve such reprogramming correlating with an improved prognosis in lung cancer patients. We previously showed that superparamagnetic iron oxide nanoparticles containing core-cross-linked polymer micelles (SPION-CCPMs) target macrophages and stimulate pro-inflammatory activation. Here, we show that SPION-CCPMs stimulate TAMs to secrete reactive nitrogen species and cytokines that exert tumoricidal activity. We further show that SPION-CCPMs reshape the immunosuppressive Eml4-Alk lung tumor microenvironment (TME) toward a cytotoxic profile hallmarked by the recruitment of CD8+ T cells, suggesting a multifactorial benefit of SPION-CCPM application. When intratracheally instilled into lung cancer-bearing mice, SPION-CCPMs delay tumor growth and, after first line therapy with a TKI, halt the regrowth of relapsing tumors. These findings identify SPIONs-CCPMs as an adjuvant therapy, which remodels the TME, resulting in a delay in the appearance of resistant tumors.


Asunto(s)
Crizotinib , Neoplasias Pulmonares , Nanopartículas Magnéticas de Óxido de Hierro , Microambiente Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Microambiente Tumoral/efectos de los fármacos , Animales , Nanopartículas Magnéticas de Óxido de Hierro/química , Humanos , Ratones , Crizotinib/farmacología , Crizotinib/química , Antineoplásicos/farmacología , Antineoplásicos/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Línea Celular Tumoral , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Proliferación Celular/efectos de los fármacos , Femenino
15.
Zhen Ci Yan Jiu ; 49(4): 349-357, 2024 Apr 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38649202

RESUMEN

OBJECTIVES: To observe the effect of electroacupuncture (EA) on activation of silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway in type 2 diabetes (T2DM) rats with peripheral neuropathy (DPN) , so as to explore its possible mechanisms underlying improvement of DPN. METHODS: Thirty male SD rats were randomly divided into blank control group (n=8) and DPN model group (n=22) which were further divided into model group (n=8) and EA group (n=8) after successful modeling. The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin (35 mg/kg). For rats of the EA group (anesthetized with isoflurane), EA stimulation (2 Hz/15 Hz, 2 mA) was applied to "Tianshu"(ST25) for 20 min, once daily, 6 times a week for 6 weeks. The blood glucose level, body weight, area under curve (AUC) of glucose tolerance test, and hind-paw mechanical pain threshold and thermal pain threshold were observed. The intra-epidermal nerve fiber density (IENFD) of the hind-foot pad was observed by immunofluorescence staining. The motor nerve conduction velocity (MNCV) of the sciatic nerve was measured by using electrophysiological method. H.E. staining was used to observe the histopathological changes of the sciatic nerve after modeling. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the sciatic nerve. The protein expressions of energy-related Sirt1, PGC-1α and TFAM in the sciatic nerve was detected by Western blot. RESULTS: Compared with the blank control group, the model group had a higher blood glucose contents and AUC (P<0.001), a slower MNCV (P<0.01), and a decrease in the body weight and in the mechanical and thermal pain thresholds (P<0.001) and IENFD (P<0.001), and in the expression levels of Sirt1, PGC-1α and TFAM (P<0.05, P<0.01). In contrast to the model group, the EA group had a decrease in the blood glucose contents and AUC (P<0.05, P<0.01), and an increase in mechanical and thermal pain thresholds, MNCV, IENFD, and expression levels of Sirt1, PGC-1α and TFAM proteins (P<0.01, P<0.05). In addition, results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section, and extensive separation of myelin and axons, uneven myelin thickness, axonal degeneration and irregular shape in the model group, whereas in the EA group, the axons on the transverse section were relatively more dense and more complete, the myelin sheath of the sciatic nerve was relatively uniform, and the axonal shape was relatively regular with relatively milder lesions. CONCLUSIONS: EA up-regulates the expressions of Sirt1, PGC-1α, TFAM in T2DM rats with DPN, which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.


Asunto(s)
Puntos de Acupuntura , Diabetes Mellitus Tipo 2 , Electroacupuntura , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Sirtuina 1 , Animales , Humanos , Masculino , Ratas , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Enfermedades del Sistema Nervioso Periférico/terapia , Enfermedades del Sistema Nervioso Periférico/metabolismo , Enfermedades del Sistema Nervioso Periférico/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Ratas Sprague-Dawley , Nervio Ciático/metabolismo , Sirtuina 1/metabolismo , Sirtuina 1/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
16.
Zhen Ci Yan Jiu ; 49(4): 331-340, 2024 Apr 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38649200

RESUMEN

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.


Asunto(s)
Terapia por Acupuntura , Artritis Experimental , Quimiocina CXCL1 , Receptores de Interleucina-8B , Corteza Somatosensorial , Animales , Humanos , Masculino , Ratones , Ratas , Puntos de Acupuntura , Artritis Experimental/terapia , Artritis Experimental/metabolismo , Artritis Experimental/genética , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Inflamación/terapia , Inflamación/metabolismo , Inflamación/genética , Ratones Endogámicos BALB C , Dolor/metabolismo , Dolor/genética , Manejo del Dolor , Ratas Wistar , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Transducción de Señal , Corteza Somatosensorial/metabolismo
17.
Zhen Ci Yan Jiu ; 49(4): 376-383, 2024 Apr 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38649205

RESUMEN

OBJECTIVES: To observe the effects of moxibustion on blood lipid metabolism, pathological morphology of thoracic aorta, and the expression of silent information regulator 1 (SIRT1) and forkhead box transcription factor O3a (FOXO3a) in ApoE-/- atherosclerosis (AS) mice, so as to explore the potential mechanism of moxibustion in preventing and treating AS. METHODS: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, simvastatin group, and moxibustion group, with 10 mice in each group. From the first day of modeling, mice in the moxibustion group received mild moxibustion treatment at "Shenque"(CV8), "Yinlingquan"(SP9), bilateral "Neiguan"(PC6) and "Xuehai"(SP10) for 30 min per time;the mice in the simvastatin group were given simvastatin orally (2.5 mg·kg-1·d-1), with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. The body weight and general condition of the mice were observed and recorded during the intervention period. After the intervention, the contents of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemistry analyzer. Hematoxylin eosin (HE) staining was used to observe the pathological morphology of the thoracic aorta. ELISA was used to measure the contents of serum oxidized low-density lipoprotein (ox-LDL) and superoxide dismutase (SOD) activity. Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta. RESULTS: Compared with the control group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of the model group mice were significantly increased(P<0.05, P<0.01), while the HDL-C contents, SOD activity, and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05, P<0.01). HE staining showed thickening of the aortic intima, endothelial cell degeneration, swelling, and shedding. Compared with the model group, body weight at the 8th and 12th week, serum TC, TG, LDL-C, and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01), while the serum SOD activity, expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01). The HDL-C contents were significantly increased in the simvastatin group(P<0.05). The thoracic aortic structure was more intact in both groups, with a more regular lumen and orderly arrangement of the elastic membrane in the media, and a slight amount of endothelial cell degeneration and swelling in the intima. There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups. CONCLUSIONS: Moxibustion can reduce the body weight of AS model mice, regulate lipid levels, repair vascular intima, and alleviate endothelial damage. Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.


Asunto(s)
Apolipoproteínas E , Aterosclerosis , Proteína Forkhead Box O3 , Moxibustión , Sirtuina 1 , Animales , Humanos , Masculino , Ratones , Puntos de Acupuntura , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/terapia , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal , Sirtuina 1/metabolismo , Sirtuina 1/genética , Triglicéridos/sangre , Triglicéridos/metabolismo
18.
Zhen Ci Yan Jiu ; 49(4): 391-397, 2024 Apr 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38649207

RESUMEN

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased (P<0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased (P<0.01, P<0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased (P<0.05, P<0.01) in the EA group. CONCLUSIONS: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.


Asunto(s)
Isquemia Encefálica , Factor Neurotrófico Derivado del Encéfalo , Electroacupuntura , Trastornos de la Memoria , Plasticidad Neuronal , Precursores de Proteínas , Daño por Reperfusión , Animales , Humanos , Masculino , Ratas , Puntos de Acupuntura , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Isquemia Encefálica/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Hipocampo/metabolismo , Aprendizaje , Memoria , Trastornos de la Memoria/terapia , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/etiología , Ratas Sprague-Dawley , Receptor trkB/metabolismo , Receptor trkB/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/terapia , Daño por Reperfusión/genética
19.
J Ethnopharmacol ; 330: 118067, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38636574

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Baidu Powder (JFBDP) is a classic traditional Chinese medicine prescription. Although Jingfang Baidu powder obtained a general consensus on clinical efficacy in treating pneumonia, there were many Chinese herbal drugs in formula, complex components, and large oral dosage, which brings certain obstacles to clinical application. AIM OF THE STUDY: Therefore, screening of the active fraction that exerts anti-pneumonia helps improve the pharmaceutical preparation, improve the treatment compliance of patients, and further contribute to the clinical application, and the screening of the new active ingredients with anti-pneumonia. The histopathological observation, real-time quantitative PCR, western blotting, and immunofluorescence were applied to evaluate the anti-pneumonia efficacy of active fractions from JFBDP. RESULTS: Three fractions from JFBDP inhibit the gene expression of IL-1ß, IL-10, CCL3, CCL5, and CCL22 in lung tissue infected by Klebsiella at various degrees, and presented a good dose-response relationship. JF50 showed stronger anti-inflammatory effects among three fractions including JF30, JF50, and JF75. Besides, JF50 significantly reduced the protein expression of TLR4 and Myd88 in lung tissue infected with Klebsiella, and it also significantly inhibited p-ERK and p-NF-κB p65. JF50 significantly inhibits the protein expression of Caspase 3, Caspase 8, and Caspase 9 in lung tissue infected with Klebsiella at the dose of 25 mg/kg and 50 mg/kg. CONCLUSION: JF50 improves lung pathological damage in Klebsiella pneumonia mice by inhibiting the TLR4/Myd88/NF-κB-ERK signaling pathway, and inhibiting apoptosis of lung tissue cells. These findings provide a reference for further exploring the active substance basis of Jingfang Baidu Powder in treating bacterial pneumonia.


Asunto(s)
Medicamentos Herbarios Chinos , Infecciones por Klebsiella , Factor 88 de Diferenciación Mieloide , Polvos , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Factor 88 de Diferenciación Mieloide/metabolismo , Ratones , Masculino , Infecciones por Klebsiella/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Klebsiella pneumoniae/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL
20.
J Ethnopharmacol ; 330: 118206, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38636572

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Croton argyrophyllus Kunth., commonly known as "marmeleiro" or "cassetinga," is widely distributed in the Brazilian Northeast region. Its leaves and flowers are used in traditional medicine as tranquilizers to treat flu and headaches. AIM OF THE STUDY: This study was conducted to determine the chemical composition and toxicological safety of essential oil from C. argyrophyllus leaves using in vitro and in vivo models. MATERIALS AND METHODS: The chemical composition of the essential oil was determined using a gas chromatograph coupled to a mass spectrometer. Cytotoxicity was tested in the HeLa, HT-29, and MCF-7 cell lines derived from human cells (Homo sapiens) and Vero cell lines derived from monkeys (Cercopithecus aethiops) using the MTT method. Acute toxicity, genotoxicity. Mutagenicity tests were performed in Swiss mice (Mus musculus), which were administered essential oil orally in a single dose of 2000 mg/kg by gavage. RESULTS: The main components of the essential oil were p-mentha-2-en-1-ol, α-terpineol, ß-caryophyllene, and ß-elemene. The essential oil exhibited more than 90% cytotoxicity in all cell lines tested. No deaths or behavioral, hematological, or biochemical changes were observed in mice, revealing no acute toxicity. In genotoxic and mutagenic analyses, there was no increase in micronuclei in polychromatic erythrocytes or in the damage and index in the comet assay. CONCLUSIONS: The essential oil was cytotoxic towards the tested cell lines but did not exert toxic effects or promote DNA damage when administered orally at a single dose of 2000 mg/kg in mice.


Asunto(s)
Croton , Aceites Volátiles , Hojas de la Planta , Animales , Croton/química , Aceites Volátiles/toxicidad , Aceites Volátiles/farmacología , Aceites Volátiles/química , Humanos , Chlorocebus aethiops , Ratones , Células Vero , Pruebas de Mutagenicidad , Administración Oral , Células HeLa , Células HT29 , Células MCF-7 , Masculino , Femenino , Supervivencia Celular/efectos de los fármacos , Pruebas de Toxicidad Aguda , Daño del ADN/efectos de los fármacos
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