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1.
Comb Chem High Throughput Screen ; 27(11): 1592-1601, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305401

RESUMO

BACKGROUND: Currently, endoplasmic reticulum stress is studied utilizing a dephosphorylation inhibitor (Sal). The traditional Chinese patent medicine and simple formulation Shensong Yangxin Capsule is a commonly used medication for the treatment of arrhythmia. However, the efficacy and underlying mechanism of the capsule in treating post-ischemic heart failure in myocardial tissue have not yet been investigated. OBJECTIVE: The therapeutic effects and the underlying mechanism of the Shensong Yangxin Capsule (SSYX) and the dephosphorylation inhibitor Salubrinal (Sal) on heart failure (HF) induced by high-intensity exercise in rats with acute myocardial infarction (AMI) were investigated. METHODS: Male infants of 8 weeks Spragge-Dawley (SD) rats were randomly assigned to one of four groups: sham surgery group, AMI+placebo group, AMI+Shensong Yangxin Capsule group (AMI+SSYX), and AMI+Sal administration group. Rats' myocardial infarction was induced by left coronary artery ligation. Rats were subjected to a 3-week high-intensity exercise program to simulate heart failure after 7 days of postoperative rest. After the fourth postoperative week, echocardiography was applied to determine the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular systolic volume (LVESV) in each group. HE and TUNEL labeling were employed to examine the morphology of cardiac cells and measure the percentage of apoptosis in each group; Western blotting was applied to detect the cardiomyocyte apoptosis-related proteins p-JNK, p-P38, and NOX2, while ELISA was used to detect glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum. RESULTS: Following a 4-week drug intervention:(1)LVFS and LVEF in the AMI+placebo group were statistically significantly reduced, while LVESV were significantly higher, compared to those in the sham surgery group (P<0.05); The AMI+SSYX group performed statistically significantly better than the AMI+placebo group(P<0.05). (2) The myocardial cells in the AMI+placebo group exhibited significant swelling and inflammatory cell infiltration; the myocardial cells in the AMI+SSYX group and AMI+Sal group displayed mild swelling and minimal inflammatory cell infiltration; the AMI+SSYX group's myocardial cell morphology was superior to that of the AMI+Sal group; (3) The apoptosis rate of the AMI+placebo group was around 95%, greater than that of the sham surgery group (2.55%). The apoptosis rate of the AMI+SSYX group is approximately 21%, while the apoptosis rate of the AMI+Sal group is about 43%. (4) In the AMI+placebo group, p-JNK, p-P38, and NOX2 protein expression dramatically increased compared to the sham surgery group. The expression of p-P38, NOX2, and p-JNK/t-JNK was considerably reduced in the AMI+Shensong group and AMI+Sal group, compared to the AMI+placebo group. (P<0.01)The AMI+SSYX group's result is superior to that of the AMI+Sal group. (5) Compared to the sham surgery group, the serum levels of SOD and GSH were significantly lower, and MDA was significantly higher in the AMI+placebo group. Compared to the AMI+placebo group, the serum levels of SOD and GSH were significantly higher, and MDA was significantly lower in the AMI+SSYX group and the AMI+Sal group. (P<0.05) Conclusion: In rats with acute myocardial infarction in high-intensity exercise-induced heart failure, Shensong Yangxin Capsule dramatically reduces myocardial cell death and cardiac dysfunction. SSYX has a shorter course of treatment and a better therapeutic effect than Sal.


Assuntos
Cápsulas , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Infarto do Miocárdio , Ratos Sprague-Dawley , Animais , Infarto do Miocárdio/tratamento farmacológico , Masculino , Insuficiência Cardíaca/tratamento farmacológico , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Cinamatos/farmacologia , Cinamatos/química , Medicina Tradicional Chinesa , Apoptose/efeitos dos fármacos
2.
Fish Shellfish Immunol ; 145: 109363, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185392

RESUMO

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.


Assuntos
Amônia , Gastrópodes , Animais , Dieta , Antioxidantes/metabolismo , Gastrópodes/metabolismo , Imunidade Inata , Expressão Gênica , Músculos/metabolismo , Superóxido Dismutase/metabolismo , Ração Animal/análise , Suplementos Nutricionais , Xantofilas
3.
Mol Nutr Food Res ; 68(3): e2200816, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38018298

RESUMO

SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.


Assuntos
Doença de Alzheimer , Juglans , Ratos , Animais , Juglans/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Escopolamina/efeitos adversos , Simulação de Acoplamento Molecular , Extratos Vegetais/química
4.
Neuromolecular Med ; 25(4): 545-562, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37735290

RESUMO

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). Sinomenine (SIN), a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, has powerful anti-inflammatory and immunosuppressive therapeutic benefits. In our previous research, we found that SIN increased resistance to oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in PC12 neuronal cells. However, whether SIN can improve the symptoms and pathological features of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, via the Nrf2 signaling pathway remains unclear. EAE was immunized followed by SIN treatment. Then we evaluated the effects of SIN in EAE. Subsequently, primary microglia were cultured to explore the effect of SIN on microglia activation. Further, the levels of Nrf2 and its downstream molecules were detected to assess the molecular mechanisms of SIN. We demonstrated that SIN effectively ameliorated the severity of EAE, accompanied by a reduction in the demyelination, axonal damage and inhibition of inflammatory cell infiltration. Mechanistically, SIN decreased the inflammatory cytokines expression, and suppressed microglia and astrocytes activation in EAE mice. Furthermore, SIN suppressed lipopolysaccharide (LPS)-induced microglial activation and the production of pro-inflammatory factors in vitro. Moreover, SIN inhibited oxidative stress via the activation of the Nrf2 signaling pathway. Our work proves that SIN exerts its neuroprotective effects by the Nrf2-dependent anti-oxidative stress and diminishing neuroinflammation, suggesting that the "antioxiflammation" effect of SIN is expected to be an ideal treatment strategy for MS/EAE.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Fármacos Neuroprotetores , Camundongos , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Camundongos Endogâmicos C57BL
5.
Foods ; 12(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569111

RESUMO

With the increasing awareness of ecological and environmental protection, the research on eco-friendly materials has experienced a considerable increase. The objective of our study was to explore a novel soy protein isolate (SPI) film functionalized with antioxidants extracted from Xanthoceras sorbifolia husk (XSHE) as bio-based active packaging films. The films were evaluated in light of their structure, physical machinery, and antioxidant performance using advanced characterization techniques. The FTIR and microscopy results revealed the hydrogen-bond interaction between the SPI and XSHE and their good compatibility, which contributed to the improvement in various properties of the composite films, such as tensile strength (TS), UV blocking, and the water barrier property. As the XSHE content increased to 5%, the TS of the films dramatically increased up to 7.37 MPa with 47.7% and the water vapor permeability decreased to 1.13 × 10-10 g m m-2 s-1 Pa-1 with 22.1%. Meanwhile, the introduction of XSHE caused further improvement in the antioxidant capacity of films, and the release of active agents from films was faster and higher in 10% ethanol than it was in a 50% ethanol food simulant. Overall, SPI-based films functionalized with XSHE demonstrated promising potential applications in food packaging.

6.
Huan Jing Ke Xue ; 44(7): 4162-4169, 2023 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-37438313

RESUMO

Biochar is widely used in agricultural production practices as a soil conditioner that can be used both alone and jointly with chemical fertilizer. However, there are few studies on the effects of the combined application of biochar and phosphate fertilizer with different particle sizes on soil and plants. In this experiment, pot experiments were used to study the effects of biochar with different particle sizes on soil nutrients, enzyme activity, and Alfalfa nutrient absorption under two phosphorus levels (according to diameter, the biochar was divided into C1:>1 mm and C2:<0.01 mm). This study showed that the combined application of biochar and phosphorus significantly improved soil nutrients, enzyme activity, and Alfalfa nutrient absorption. Among them, the C2 treatment significantly increased the soil available phosphorus content and phosphatase activity (P<0.05), whereas the C1 treatment had a significant effect on ammonium nitrogen, nitrate nitrogen, urease, and catalase activities (P<0.05). Moreover, the differences in nutrients and enzymes among biochar treatments with different particle sizes were affected by soil phosphorus levels. At the P0 level, there was no significant difference in ammonium nitrogen and nitrate nitrogen contents between the C1 and C2 treatments. At the P1 level, the contents of NH4+-N and NO3--N in the C1 treatment were 24.19% and 18.68% higher than those in the C2 treatment (P<0.05), but there was no significant difference between the C1 and C2 treatments. Phosphorus addition significantly increased the N and P contents of Alfalfa above ground and in the ground (P<0.05), but there was no significant effect on the nutrient content of Alfalfa between different particle sizes of biochar. In conclusion, biochar and phosphate fertilizer can be used as an effective means of soil improvement. In addition, when using biochar for soil improvement, the impact of particle size on soil nutrients and soil enzymes should be considered.


Assuntos
Fósforo , Solo , Fertilizantes , Medicago sativa , Nitratos , Fosfatos , Nitrogênio , Nutrientes
7.
Planta Med ; 89(13): 1259-1268, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37459861

RESUMO

A large variety of natural plants are widely produced and utilised because of their remarkable pharmacological effects. In this study, two phenolic glycosides were isolated for the first time from Vanilla pompona Schiede (Orchidaceae) from Kyushu, Japan: bis [4-(ß-D - O-glucopyranosyloxy)-benzyl] (S)-2-isopropylmalate (1: ) and bis 4-[ß-D-O-glucopyranosyloxy)-benzyl]-(2R,3S)-2-isopropyl tartrate (2: ). We have discovered that the crude extract of V. pompona leaves and stems and its two phenolic glycosides (compounds 1:  - 2: ) are highly effective in reversing skin senescence. V. pompona and compounds 1:  - 2: were found to promote the synthesis of collagen, hyaluronic acid, and elastin in skin fibroblasts in a normal skin cell model; in a replicative senescence model, V. pompona and compounds 1:  - 2: significantly reduced the ageing phenotype in skin fibroblasts. These compounds also demonstrated a significant protective effect in a UV-induced photo-senescence model; the possible mechanisms of this effect were investigated in this study. To the best of our knowledge, this study is the first to develop V. pompona leaves and stems as new sources of bioactive compounds and to examine their therapeutic potential for skin senescence. The development potential of V. pompona leaves and stems for use in the cosmetics, cosmeceutical, and pharmaceutical industries remains to be investigated.

8.
Sci Rep ; 13(1): 12069, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495623

RESUMO

Metastasis is a leading cause of mortality in patients with lung adenocarcinoma. Histone deacetylases have emerged as promising targets for anti-tumor drugs, with histone deacetylase inhibitors (HDACi) being an active area of research. However, the precise mechanisms by which HDACi inhibits lung cancer metastasis remain incompletely understood. In this study, we employed a range of techniques, including qPCR, immunoblotting, co-immunoprecipitation, chromatin-immunoprecipitation, and cell migration assays, in conjunction with online database analysis, to investigate the role of HDACi and HDAC2/YY1 in the process of lung adenocarcinoma migration. The present study has demonstrated that both trichostatin A (TSA) and sodium butyrate (NaBu) significantly inhibit the invasion and migration of lung cancer cells via Histone deacetylase 2 (HDAC2). Overexpression of HDAC2 promotes lung cancer cell migration, whereas shHDAC2 effectively inhibits it. Further investigation revealed that HDAC2 interacts with YY1 and deacetylates Lysine 27 and Lysine9 of Histone 3, thereby inhibiting Cdh1 transcriptional activity and promoting cell migration. These findings have shed light on a novel functional mechanism of HDAC2/YY1 in lung adenocarcinoma cell migration.


Assuntos
Adenocarcinoma de Pulmão , Antígenos CD , Caderinas , Histona Desacetilase 2 , Inibidores de Histona Desacetilases , Metástase Neoplásica , Fator de Transcrição YY1 , Humanos , Animais , Camundongos , Feminino , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Movimento Celular/efeitos dos fármacos , Ácido Butírico/farmacologia , Ácido Butírico/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Histona Desacetilase 2/antagonistas & inibidores , Histona Desacetilase 2/metabolismo , Fator de Transcrição YY1/metabolismo , Caderinas/genética , Caderinas/metabolismo , Antígenos CD/metabolismo , Ligação Proteica , Transcrição Gênica , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle
9.
Eur J Psychotraumatol ; 14(2): 2205667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37134018

RESUMO

Background: Traumatic events can cause social tension, anxiety, panic and other psychological crises, and can even cause post-traumatic stress disorder (PTSD) and suicide. Physical activity has a good role in promoting mental health, and has a great application prospect in individual psychological intervention after traumatic events. However, no systematic review of the relationship between physical activity and individual mental health after traumatic events affecting many people has been published so far, which makes it impossible for people to understand the research status in this field from a holistic perspective.Objective: This review explores the relationship between physical activity and individual psychology, physiology, subjective quality of life and well-being after traumatic events, so as to provide some valuable clues or enlightenment for individual psychological intervention after traumatic events.Method: Relevant literature was searched in five databases, summarised, sorted and studied.Results: Thirty-three study papers were included in this review, the main study findings include: (1) Physical activity is positively correlated with individual mental resilience and subjective well-being after traumatic events, and negatively correlated with anxiety, depression, tension and PTSD. (2) Individuals with higher levels of physical activity have better mental health status after traumatic events than those who do not regularly engage in physical activity. (3) Physical activity can promote sleep quality, self-efficacy, subjective quality of life and various physiological functions of those experiencing traumatic events. (4) Physical activity (including exercise) is regarded as one of the preferred nursing measures to buffer against mental stress and maintain physical and mental health for those experiencing traumatic events.Conclusion: The level of physical activity is positively correlated with individual physical and mental health before and after traumatic events. Physical activity can be used as one of the effective measures to improve individual mental health after traumatic events.


Physical activity can be used as one of the important measures to improve mental health of those experiencing traumatic events.Regular physical activity can reduce the impact of traumatic events on mental health, both before and after the events.


Assuntos
Saúde Mental , Transtornos de Estresse Pós-Traumáticos , Humanos , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Ansiedade , Exercício Físico
10.
J Ethnopharmacol ; 308: 116307, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36842722

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine and food, Euodiae Fructus (EF) is widely used in clinics to relieve pain and prevent vomiting and for making tea for more than a thousand years. In recent years, hepatotoxic reactions to EF have been reported. The intermediates produced by evodiamine and rutaecarpine metabolism in vitro were captured by glutathione (GSH), suggesting that the toxicity of EF may be related to metabolic activation. Whether licorice can inhibit the metabolic activation of EF has not been reported, which needed an effective strategy to clarify the correlation between protein conjugates and hepatotoxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: This study aimed to explore the toxic components and mechanisms of EF based on metabolic activation and the detoxification of licorice. MATERIALS AND METHODS: The content and toxicity index of protein conjugates in the liver were determined by orally administering mice and rats with EF. The attenuation mechanism of licorice was examined in cell and enzymology experiments. RESULTS: The change in evodiamine-cysteinylglycine (EVO-Cys-Gly) and evodiamine-cysteine (EVO-Cys) levels was consistent with the change in hepatotoxicity. Licorice inhibited the formation of the protein conjugates of EF and increased the content of GSH in L02 cells. CONCLUSION: EF mediated by P450 enzymes produced toxic intermediates, which combined with cysteine residues in animal liver and inactivate them, leading to hepatotoxicity. Interestingly, licorice can alleviate the GSH depletion caused by EF and inhibit the production of protein conjugates by inhibiting P450 enzymes.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Glycyrrhiza , Ratos , Camundongos , Animais , Cisteína , Sistema Enzimático do Citocromo P-450 , Glutationa/metabolismo
11.
Luminescence ; 38(3): 302-307, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36702476

RESUMO

The rapid and accurate identification of complex samples still remains a great challenge, especially for those with similar compositions. In this work, we report an integration strategy consisting of surface-enhanced Raman scattering (SERS) and machine learning to discriminate complex and similar analytes, in this case green tea products with different storage times. Surface-functionalized Ag nanoparticles (NPs) were used as a SERS substrate to reveal the changes in the sensory components of green tea with variable storage time. Principal components analysis (PCA)-based support vector machine (SVM) classification was used to extract the key spectral features and identify green tea with different storage times. The results showed that such an integration strategy achieved high predictive accuracy on time tag discrimination for green tea. The multiclass SVM classifier successfully recognized green tea with different storage times at a prediction accuracy of 95.9%, sensitivity of 96.6%, and specificity of 98.8%. Therefore, this work illustrates that the SERS-based PCA-SVM platform might be a facile and reliable tool for the identification of complex matrices with subtle differentiations.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Análise Espectral Raman/métodos , Chá/química , Nanopartículas Metálicas/química , Prata/química , Máquina de Vetores de Suporte
12.
Microsc Res Tech ; 86(3): 359-367, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36578188

RESUMO

Bistortae Rhizoma (Quanshen), a dried rhizome of Polygonum bistorta L., is edited in Chinese Pharmacopiea as only one of species of Polygonum. There are many adulterants were used as Quanshen such as "Eryeliao," "Taipingyangliao" and "Daogenliao" because of its remarkable functions. Previous researches had shown that there were not significant differences among them. Therefore, it is necessary to conduct a comprehensive authentication of these herbs samples. Analyses of the microscopic features of the powders and transverse sections of herbs are the most significant measures of accreditation of the quality of traditional Chinese medicine. In this study, microscopic observation of powders of the herbs and cross-sectional tissues were performed by using common light microscopy, polarized light microscopy and combining PCA analysis to identify Quanshen and three adulterants. We found that calcium oxalate clusters can be a good microscopic marker index to distinguish Quabshen and Eryeliao. In addition, Quanshen and the other two can be further distinguished by the characteristics of cork layer cells and vascular bundles on transverse section of the rhizome. Our results showed that the approach, microscopic features and digital characterization, is efficient, convenient, and reliable.


Assuntos
Medicamentos de Ervas Chinesas , Rizoma , Rizoma/anatomia & histologia , Estudos Transversais , Medicina Tradicional Chinesa , Microscopia de Polarização
13.
J Ethnopharmacol ; 303: 116005, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516906

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Euodiae Fructus (EF) has been used to treat stomachache, belching, and emesis for more than a thousand years. Ancient records and modern research have shown that EF has mild toxicity, which needs to be processed with licorice juice to reduce its toxicity. Research suggested that the toxicity of EF can be caused by in vivo metabolism, but whether its metabolites are related to hepatotoxicity and whether licorice can affect the metabolism of EF have not been reported, which needed an effective strategy to clarify the correlation between metabolites and toxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: The poisonous substances and metabolic pathways were clarified by comparing the mechanism in vivo process of the main alkaloids of EF in normal rats and rats treated with dexamethasone (DXMS), ketoconazole (KTC), and EF processed with licorice (EFP). MATERIALS AND METHODS: Rats were given EF and EFP by oral administration, respectively. The EF + DXMS and EF + KTC groups were pretreated with DXMS and KTC, respectively, by i. p. for seven days, and their toxicity differences were compared. The comprehensive strategy based on UPLC-Q-Exactive-MS and Orthogonal Partial Least Squares Discriminant Analysis was developed to compare the types and contents of metabolites and clarify the metabolic pathways of alkaloids among EF, EFP, EF + KTC, and EF + DXMS groups. RESULTS: EF + DXMS group significantly increased the hepatotoxicity, whereas the EF + KTC and EFP groups reduced the hepatotoxicity compared with the EF group. One hundred and thirty-five metabolites were detected, and the metabolic pathways of the main alkaloid components related to toxicity were inferred in the plasma, urine, feces, and bile of rats. KTC and licorice similarly inhibited the production of toxic metabolites, changed metabolism in vivo, and produced many new II and a few phases I metabolites, while the contents of toxic metabolites increased in the DXMS group. CONCLUSION: Licorice and KTC could inhibit the production of metabolites of EF related to toxicity, increase the production of other metabolites and promote the excretion of alkaloids, which may be why licorice and KTC can minimize EF toxicity.


Assuntos
Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Glycyrrhiza , Ratos , Animais , Inibidores do Citocromo P-450 CYP3A , Indutores do Citocromo P-450 CYP3A , Alcaloides/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Cetoconazol , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cromatografia Líquida de Alta Pressão
14.
Planta Med ; 89(3): 316-323, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35714650

RESUMO

Although considered an abundant source of agricultural by-products, avocado (Persea americana Mill.) seed, with several biological activities and bioactive components, might become a promising resource for phytopharmaceutical development. In this study, through bioassay-guided isolation of the main α-glucosidase inhibitors in avocado seed, we discovered the major α-glucosidase inhibitor to be avocado seed oligomeric proanthocyanidin complex (ASOPC). Thiolysis and UPLC-DAD-HRESIMS showed the presence of A- and B-type procyanidins, and B-type propelargonidin with (epi)afzelechin as extension unit. Mean degree of polymerization (mDP) of ASOPC was calculated as 7.3 ± 1. Furthermore, ASOPC appeared to be a strong, reversible, competitive inhibitor of α-glucosidase, with IC50 value of 0.1 µg/mL, which was significantly lower than Acarbose (IC50 = 75.6 µg/mL), indicated that ASOPC is a potential natural α-glucosidase inhibitor. These findings would contribute to the direction of utilizing avocado seed bioactive components with the possibility to be used as natural anti-diabetic agents.


Assuntos
Persea , Proantocianidinas , Proantocianidinas/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Sementes , Antioxidantes
15.
Cell Death Dis ; 13(11): 992, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424383

RESUMO

Methyltransferase-like protein 3 (METTL3) plays critical roles in acute myeloid leukemia (AML) progression, however, the mechanism of abnormal overexpression of METTL3 in AML remain elusive. In the current study, we uncovered that Yin Yang 1 (YY1) binds to the promoter region of METTL3 as a transcription factor and promotes its expression, which in turn enhances the proliferation of AML cells. Mechanistically, YY1 binds to HDAC1/3 and regulates METTL3 expression in a moderate liquid-liquid phase separation (LLPS) manner. After mutation of the HDAC-binding site of YY1 or HDAC inhibitor (HDACi) treatment, YY1 was separated from HDAC1/3, which resulted in an excessive LLPS state, thereby inhibiting the expression of METTL3 and the proliferation of AML cells. In conclusion, our study clarified the regulatory mechanism of the abnormal expression of METTL3 in AML, revealed the precise "Yin-Yang" regulatory mechanism of YY1 from the perspective of LLPS degree, and provided new ideas for the precise diagnosis and treatment of AML.


Assuntos
Histona Desacetilase 1 , Leucemia Mieloide Aguda , Metiltransferases , Fator de Transcrição YY1 , Humanos , Sítios de Ligação , Proliferação de Células/genética , Histona Desacetilase 1/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Regiões Promotoras Genéticas/genética , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
16.
Molecules ; 27(18)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36144809

RESUMO

Hibiscus sabdariffa L. (HS) has a long history of edible and medicinal uses. In this study, the biological activities of the extracts, chromatographic fractions, and hibiscus acid obtained from HS were evaluated for their potential bioactivities. Their ability to promote extracellular matrix synthesis in skin fibroblasts was evaluated by enzyme-linked immunosorbent assays. Their anti-inflammatory activity was evaluated in a nitric oxide (NO)-Griess inflammatory experiment. Furthermore, hibiscus acid was found to have a strong anti-oxidative stress effect through the establishment of an oxidative stress model induced by hydrogen peroxide. Several assays indicated that hibiscus acid treatment can effectively reduce extracellular adenosine triphosphate (ATP) secretion and carbonyl protein production, as well as maintain a high level of reduced/oxidized glutathione (GSH/GSSG) in skin cells, thus providing a possible mechanism by which hibiscus acid can counter antioxidative stress. The present study is the first to explore the reversing skin aging potential and the contributory component of HS.


Assuntos
Hibiscus , Envelhecimento da Pele , Trifosfato de Adenosina , Anti-Inflamatórios , Citratos , Dissulfeto de Glutationa , Hibiscus/química , Peróxido de Hidrogênio , Óxido Nítrico , Extratos Vegetais/química , Extratos Vegetais/farmacologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-35942377

RESUMO

Objective: The aim of this study is to investigate the effect of paclitaxel combined with doxorubicin hydrochloride liposome injection (DHLI) in the treatment of osteosarcoma and the MRI changes before and after treatment. Methods: A total of 108 osteosarcoma patients treated in our hospital (January 2020-April 2022) were selected to carry out a single-center retrospective study. Among them, 54 patients receiving the combination chemotherapy (MDT) with high-dose methotrexate, ifosfamide, cisplatin, and ADM were selected as the control group (COG), while 54 patients receiving MDT with high-dose methotrexate, ifosfamide, cisplatin, paclitaxel, and DHLI were chosen as the study group (STG). The COG and STG had the same dose intensity and chemotherapy cycles, and clinical and MRI evaluations were performed after treatment. Results: The evaluation of postoperative clinical efficacy showed that the disease control rate (DCR) of the STG was markedly higher than that of the COG (P < 0.05). The incidence of cardiac toxicity was remarkably lower in the STG than that in the COG (P < 0.05), with no between-group differences in the incidence of fever, abnormal liver function, myelosuppression, stomatitis, and alopecia (P > 0.05). Obvious differences were found in the semiquantitative parameters of MRI in the STG before and after chemotherapy (P < 0.05) and were also found in the SImax, TTP, SEE, PPE, WOR, and R values in the COG before and after chemotherapy (P < 0.05). After chemotherapy, statistical differences were observed in the semiquantitative parameters of MRI between the two groups, with lower parameters such as Slope, SImax, SEE, and R values and higher parameters such as TTP, PPE, and WOR values in the STG than those in the COG (P < 0.05). Conclusion: Paclitaxel combined with DHLI has definite efficacy in osteosarcoma chemotherapy, which is conducive to narrowing the lesion, controlling the disease, and reducing the occurrence of cardiac-related risk events. In addition, the semiquantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) have a high predictive value for the efficacy of chemotherapy, which can reflect the degree of tumor necrosis and contribute to a timely and objective assessment of the efficacy of osteosarcoma chemotherapy.

18.
Metab Brain Dis ; 37(6): 2039-2052, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35731324

RESUMO

Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50 mg/kg per day, i.g.) for 28 days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aß) generation and the levels of amyloid precursor protein (APP) and ß-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases.


Assuntos
Arctium , Disfunção Cognitiva , Lignanas , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Arctium/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Furanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Lignanas/farmacologia , Lignanas/uso terapêutico , Lipopolissacarídeos/farmacologia , Transtornos da Memória/metabolismo , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Receptor 4 Toll-Like/metabolismo
19.
Food Chem ; 389: 133067, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35490520

RESUMO

Frankincense (FRA), the oily resin consisting of essential oils, boswellic acids (BAs) and polysaccharides, has been used to improve the blood circulation and relieve pain against carbuncles. According to the theory of traditional Chinese medicine, vinegar processed frankincense (VPF) can increase the effects of promoting blood circulation and relieving pain. Existing studies have carried out much on BAs and essential oils. However, the comparative analysis of polysaccharides from FRA and VPF has not been reported. In this paper, two polysaccharides were isolated and purified from FRA and the other two were from VPF, and their structures and physicochemical properties were analyzed. The immunological and anticoagulatant activities of the four polysaccharides were tested in RAW 264.7 cell and Sprague-Dawley rats, respectively. The polysaccharides purified from VPF showed better immunological and anticoagulatant activities than those in FRA. Therefore, polysaccharides may be one of the active substances for the synergistic effect of VPF.


Assuntos
Boswellia , Franquincenso , Óleos Voláteis , Ácido Acético , Animais , Boswellia/química , Franquincenso/química , Franquincenso/farmacologia , Óleos Voláteis/farmacologia , Dor , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley
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