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1.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474193

RESUMO

Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia-reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR.


Assuntos
Acetofenonas , Injúria Renal Aguda , Traumatismo por Reperfusão , Camundongos , Animais , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Camundongos Endogâmicos C57BL , Rim/metabolismo , Traumatismo por Reperfusão/genética , Xantina Desidrogenase/metabolismo , RNA Mensageiro
3.
Phytomedicine ; 126: 155447, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38394732

RESUMO

BACKGROUD: High comorbidity rates have been reported in patients with atherosclerosis and osteoporosis, posing a serious risk to the health and well-being of elderly patients. To improve and update clinical practice regarding the joint treatment of these two diseases, the common mechanisms of atherosclerosis and osteoporosis need to be clarified. MicroRNAs (miRNAs), are importance molecules in the pathogenesis of human diseases, including in cardiovascular and orthopedic fields. They have garnered interest as potential targets for novel therapeutic strategies. However, the key miRNAs involved in atherosclerosis and osteoporosis and their precise regulation mechanisms remain unknown. Paeonol (Pae), an active ingredient in Cortex Moutan, has shown promising results in improving both lipid and bone metabolic abnormalities. However, it is uncertain whether this agent can exert a cotherapeutic effect on atherosclerosis and osteoporosis. OBJECTIVE: This study aimed to screen important shared miRNAs in atherosclerotic and osteoporotic complications, and explore the mechanism of the protective effects of Pae against atherosclerosis and osteoporosis in high-fat diet (HFD)-fed ApoE-/- mice. METHODS: An experimental atherosclerosis and osteoporosis model was established in 40-week-old HFD ApoE-/- mice. Various techniques such as Oil Red O staining, HE staining and micro-CT were used to confirm the co-occurrence of these two diseases and efficacy of Pae in addition to the associated biochemical changes. Bioinformatics was used to screen key miRNAs in the atherosclerosis and osteoporosis model, and gene involvement was assessed through serum analyses, qRT-PCR, and western blot. To investigate the effect of Pae on the modulation of the miR let-7g/HMGA2/CEBPß pathway, Raw 264.7 cells were cocultured with bone marrow mesenchymal stem cells (BMSCs) and treated with an miR let-7g mimic/inhibitor. RESULTS: miR let-7g identified using bioinformatics was assessed to evaluate its participation in atherosclerosis-osteoporosis. Experimental analysis showed reduced miR let-7g levels in the atherosclerosis-osteoporosis mice model. Moreover, miR let-7g was required for BMSC - Raw 264.7 cell crosstalk, thereby promoting foam cell formation and adipocyte differentiation. Treatment with Pae significantly reduced plaque accumulation and foam cell number in the aorta while increasing bone density and improving trabecular bone microarchitecture in HFD ApoE-/- mice. Pae also increased the level of miR let-7g in the bloodstream of model mice. In vitro studies, Pae enhanced miR let-7g expression in BMSCs, thereby suppressing the HMGA2/CEBPß pathway to prevent the formation of foam cells and differentiation of adipocytes induced by oxidized low-density lipoprotein (ox-LDL). CONCLUSION: The study results suggested that miR let-7g participates in atherosclerosis -osteoporosis regulation and that Pae acts as a potential therapeutic agent for preventing atherosclerosis-osteoporosis through regulatory effects on the miR let-7g/HMGA2/CEBPß pathway to hinder foam cell formation and adipocyte differentiation.


Assuntos
Acetofenonas , Aterosclerose , MicroRNAs , Osteoporose , Humanos , Animais , Camundongos , Idoso , Células Espumosas , MicroRNAs/genética , MicroRNAs/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Diferenciação Celular , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Apolipoproteínas E/genética
4.
Molecules ; 29(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38338367

RESUMO

Moutan Cortex (MC) is a traditional Chinese medicine that contains abundant medicinal components, such as paeonol, paeoniflorin, etc. Paeonol is the main active component of MC. In this study, paeonol was extracted from MC through an ultrasound-assisted extraction process, which is based on single-factor experiments and response surface methodology (RSM). Subsequently, eight macroporous resins of different properties were used to purify paeonol from MC. The main components of the purified extract were identified by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS/MS). The results indicate the optimal parameters are as follows: liquid-to-material ratio 21:1 mL/g, ethanol concentration 62%, ultrasonic time 31 min, ultrasonic temperature 36 °C, ultrasonic power 420 W. Under these extraction conditions, the actual yield of paeonol was 14.01 mg/g. Among the eight tested macroporous resins, HPD-300 macroporous resin was verified to possess the highest adsorption and desorption qualities. The content of paeonol increased from 6.93% (crude extract) to 41.40% (purified extract) after the HPD-300 macroporous resin treatment. A total of five major phenolic compounds and two principal monoterpene glycosides were characterized by comparison with reference compounds. These findings will make a contribution to the isolation and utilization of the active components from MC.


Assuntos
Acetofenonas , Medicamentos de Ervas Chinesas , Paeonia , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química
5.
J Food Sci ; 89(2): 1280-1293, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38193205

RESUMO

The Fusarium verticillioides produces a mycotoxin, that is, fumonisin b1 (Fb1), which commonly infects corn and agricultural commodities. The Fb1 showed hepatotoxicity, neurotoxicity, and carcinogenicity in animals. Hence, the present investigation aimed to evaluate the effect of apocynin (AP) on Fb1-induced neurotoxic effects and its mechanism in the mice model and cell line. The male Balb/c mice, with the 6.75 mg/kg bwt of Fb1 were injected subcutaneously for 5 days to induce neurotoxicity. A significant elevation of serotonin (5-HT) was observed in mice treated with Fb1 in the whole brain showing biogenic amines may reflect Fb1 neurotoxicity, but the negatively regulated mechanisms were attenuated by the pretreatment of AP. In addition, AP pretreatment normalized apoptotic changes in histology and immunohistochemistry studies. In Western blotting studies, apoptotic genes were upregulated and oxidative stress genes were downregulated due to Fb1 treatment; while treating with AP, these gene expressions were rectified. Further cell cytotoxicity was investigated by MTT and lactate dehydrogenase (LDH) assays in SH-SY5Y cell line. MTT and LDH assays indicated the IC50 value to be 150 µM of Fb1, which was protected by 100 µg of AP. The electron microscopy evaluated the Fb1-induced apoptotic conditions and its cell morphology recovery by AP. These results suggest that nicotinamide adenine dinucleotide phosphate hydrogen oxidase-mediated reactive oxygen species is the primary upstream signal leading to increased Fb1-mediated neurotoxicity in mice. The use of the antioxidant AP reversed the toxin-induced oxidative stress and apoptosis by its antioxidant potency.


Assuntos
Acetofenonas , Fumonisinas , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Masculino , Camundongos , Animais , Fármacos Neuroprotetores/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fumonisinas/toxicidade , Fumonisinas/metabolismo , Apoptose , Estresse Oxidativo , Modelos Animais
6.
ACS Chem Neurosci ; 15(4): 724-734, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38290213

RESUMO

Herbs themselves and various herbal medicines are great resources for discovering therapeutic drugs for various diseases, including Alzheimer's disease (AD), one of the common neurodegenerative diseases. Utilizing mouse primary cortical neurons and DiBAC4(3), a voltage-sensitive indicator, we have set up a drug screening system and identified an herbal extraction compound, paeonol, obtained from Paeonia lactiflora; this compound is able to ameliorate the abnormal depolarization induced by Aß42 oligomers. Our aim was to further find effective paeonol derivatives since paeonol has been previously studied. 6'-Methyl paeonol, one of the six paeonol derivatives surveyed, is able to inhibit the abnormal depolarization induced by Aß oligomers. Furthermore, 6'-methyl paeonol is able to alleviate the NMDA- and AMPA-induced depolarization. When a molecular mechanism was investigated, 6'-methyl paeonol was found to reverse the Aß-induced increase in ERK phosphorylation. At the animal level, mice injected with 6'-methyl paeonol showed little change in their basic physical parameters compared to the control mice. 6'-Methyl paeonol was able to ameliorate the impairment of memory and learning behavior in J20 mice, an AD mouse model, as measured by the Morris water maze. Thus, paeonol derivatives could provide a structural foundation for developing and designing an effective compound with promising clinical benefits.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Neurônios , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Modelos Animais de Doenças , Peptídeos beta-Amiloides/toxicidade , Aprendizagem em Labirinto
7.
Phytochemistry ; 219: 113984, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266953

RESUMO

Thirty-nine thymol and acetophenone derivatives, including eight pairs of enantiomers, were isolated from the aerial parts of Eupatorium fortunei. Their structures were assigned by detailed analyses of spectroscopic data and NMR calculations based on density functional theory, with 18 ones (1a/1b-14) being previously undescribed compounds. While the absolute configurations of 1a/1b, 2a/2b, 4, 6a/6b, 7, 11a/11b and 15a/15b-18a/18b were established by calculations of electronic circular dichroism data, that of 14 was determined by modified Mosher's method. Compounds 1a/1b and 2a/2b represent a previously unreported type of monoterpenoid dimers via an amide linkage, and compound 3 is a monoterpene-phenylpropanoid hybrid connected through an ester bond. Among the known molecules, the formerly mis-assigned structures of 15a/15b and 22 were revised, and pure natural enantiomers of 16a/16b-18a/18b were reported for the first time. Selective compounds showed antiradical and NO production inhibitory activities in the preliminary biological screening. Compound 31 was further demonstrated to alleviate oxidative stress by activating Nrf2 signaling pathway.


Assuntos
Eupatorium , Eupatorium/química , Monoterpenos/farmacologia , Monoterpenos/análise , Estrutura Molecular , Componentes Aéreos da Planta/química , Acetofenonas/análise
8.
Molecules ; 29(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38202844

RESUMO

Atherosclerosis is a chronic inflammatory disease leading to various vascular diseases. Vascular smooth muscle cell (VSMC) senescence promotes atherosclerotic inflammation and the formation of plaque necrosis core, in part through telomere damage mediated by a high-fat diet. Our previous research found that paeonol, a potential anti-inflammatory agent extracted from Cortex Moutan, could significantly improve VSMCs dysfunction. However, the impact of paeonol on the senescence of VSMCs remains unexplored. This study presents the protective effects of paeonol on VSMCs senescence, and its potential activity in inhibiting the progression of atherosclerosis in vivo and in vitro. Sirtuin 1 (SIRT1) is a nuclear deacetylase involved in cell proliferation, senescence, telomere damage, and inflammation. Here, SIRT1 was identified as a potential target of paeonol having anti-senescence and anti-atherosclerosis activity. Mechanistic studies revealed that paeonol binds directly to SIRT1 and then activates the SIRT1/P53/TRF2 pathway to inhibit VSMCs senescence. Our results suggested that SIRT1-mediated VSMCs senescence is a promising druggable target for atherosclerosis, and that pharmacological modulation of the SIRT1/P53/TRF2 signaling pathway by paeonol is of potential benefit for patients with atherosclerosis.


Assuntos
Acetofenonas , Aterosclerose , Sirtuínas , Humanos , Sirtuína 1 , Músculo Liso Vascular , Proteína Supressora de Tumor p53 , Aterosclerose/tratamento farmacológico , Inflamação , Transdução de Sinais
9.
Elife ; 122024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206122

RESUMO

Phage satellites commonly remodel capsids they hijack from the phages they parasitize, but only a few mechanisms regulating the change in capsid size have been reported. Here, we investigated how a satellite from Vibrio cholerae, phage-inducible chromosomal island-like element (PLE), remodels the capsid it has been predicted to steal from the phage ICP1 (Netter et al., 2021). We identified that a PLE-encoded protein, TcaP, is both necessary and sufficient to form small capsids during ICP1 infection. Interestingly, we found that PLE is dependent on small capsids for efficient transduction of its genome, making it the first satellite to have this requirement. ICP1 isolates that escaped TcaP-mediated remodeling acquired substitutions in the coat protein, suggesting an interaction between these two proteins. With a procapsid-like particle (PLP) assembly platform in Escherichia coli, we demonstrated that TcaP is a bona fide scaffold that regulates the assembly of small capsids. Further, we studied the structure of PLE PLPs using cryogenic electron microscopy and found that TcaP is an external scaffold that is functionally and somewhat structurally similar to the external scaffold, Sid, encoded by the unrelated satellite P4 (Kizziah et al., 2020). Finally, we showed that TcaP is largely conserved across PLEs. Together, these data support a model in which TcaP directs the assembly of small capsids comprised of ICP1 coat proteins, which inhibits the complete packaging of the ICP1 genome and permits more efficient packaging of replicated PLE genomes.


Assuntos
Acetofenonas , Bacteriófagos , Vibrio cholerae , Capsídeo , Proteínas do Capsídeo , Bacteriófagos/genética , Escherichia coli
10.
J Adv Res ; 57: 135-147, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37061215

RESUMO

INTRODUCTION: Apocynin (Apo), an NADPH oxidase (NOX) inhibitor, has been widely used to treat various inflammatory diseases. However, the therapeutic effects of Apo on benign prostatic hyperplasia (BPH), a multifactorial disease associated with chronic inflammation and hormone imbalance, remain unknown. OBJECTIVES: The link between androgen signaling, reactive oxygen species (ROS), and prostate cell proliferation may contribute to the pathogenesis of BPH; therefore, the aim of this study was to identify the specific signaling pathway involved and to demonstrate whether the anti-oxidant Apo plays a role in the prevention and treatment of BPH. METHODS: Ingenuity pathway analysis and si-RNA transfection were conducted to demonstrate the androgen receptor (AR) and NOX4 linkage in BPH. Pathological markers of BPH were measured by H&E staining, immunoblotting, ELISA, qRT-PCR, and immunofluorescence to examine the effect of Apo. Rats stimulated with testosterone and BPH-1 cells were used as BPH models. RESULTS: AR and NOX4 network-mediated oxidative stress was upregulated in the BPH model. Next, we examined the effects of Apo on oxidative stress and chronic prostatic inflammation in BPH mouse models. In a testosterone-induced BPH rat model, Apo alleviated pathological prostate enlargement and suppressed androgen/AR signaling. Apo suppressed the upregulation of proinflammatory markers and promoted the expression of anti-oxidant factors. Furthermore, Apo regulated the TGF-ß/Glut9/activin pathway and macrophage programming. In BPH-1 cells, Apo suppressed AR-mediated proliferation and upregulation of TGFB and NOX4 expression by alleviating oxidative stress. Apo activated anti-oxidant and anti-inflammatory systems and regulated macrophage polarization in BPH-1 cells. AR knockdown partially abolished the beneficial effects of Apo in prostate cells, indicating AR-dependent effects of Apo. CONCLUSION: In contrast with existing BPH therapies, Apo may provide a new application for prostatic disease treatment, especially for BPH, by targeting the AR/TGF-ß/NOX4 signaling pathway.


Assuntos
Acetofenonas , Androgênios , Hiperplasia Prostática , Camundongos , Masculino , Humanos , Animais , Ratos , Receptores Androgênicos , Antioxidantes , Hiperplasia , Próstata , Hiperplasia Prostática/tratamento farmacológico , Inflamação/tratamento farmacológico , Testosterona , Proliferação de Células , NADPH Oxidase 4
11.
Phytother Res ; 38(2): 470-488, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37872838

RESUMO

Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.


Assuntos
Transtornos Cerebrovasculares , Paeonia , Humanos , Sistema Nervoso Central , Anti-Inflamatórios , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Transtornos Cerebrovasculares/tratamento farmacológico
12.
Inflammation ; 47(1): 438-453, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37880427

RESUMO

Ulcerative colitis is an inflammatory bowel disease with a complex aetiology characterised by abnormal immune responses and oxidative stress-induced tissue injury. Inflammatory cells play an important role in the progression of this pathology through the overproduction of reactive oxygen species (ROS) from various sources including the NADPH oxidases (NOXs). The aim of this study was to investigate the preventive effect of apocynin, a natural antioxidant molecule and a selective inhibitor of NOXs, on acetic acid (AA)-induced ulcerative colitis in rats. Our results first confirmed that apocynin has a high free radical scavenging capacity as well as a potent iron chelating ability. Oral pretreatment of rats with apocynin (200 mg/kg and 400 mg/kg) for 7 days prior to AA-induced colitis suppressed the increase in pro-oxidant markers in colonic homogenates and preserved colonic cytoarchitecture from acetic acid-induced damage. Oral administration of apocynin (200 mg/kg and 400 mg/kg) also reduced several systemic inflammatory markers such as alkaline phosphatase, iron, pro-inflammatory cytokines, C-reactive protein and myeloperoxidase. This study shows that apocynin protects rats from acetic acid-induced colonic inflammation and suggests that apocynin may have a promising beneficial effect in the prevention of ulcerative colitis.


Assuntos
Acetofenonas , Colite Ulcerativa , Colite , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Ácido Acético , Colite/induzido quimicamente , Espécies Reativas de Oxigênio , NADPH Oxidases , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
13.
Microcirculation ; 31(1): e12837, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37985248

RESUMO

OBJECTIVE: This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA). METHODS: Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography. RESULTS: High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619. CONCLUSION: These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.


Assuntos
Acetofenonas , Benzamidas , Células Endoteliais , Endotélio Vascular , NADPH Oxidase 1 , NADPH Oxidase 4 , Animais , Ratos , Acetilcolina/metabolismo , Benzamidas/administração & dosagem , Dilatação , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Artérias Mesentéricas/metabolismo , Músculo Esquelético/metabolismo , NADPH Oxidases , Espécies Reativas de Oxigênio/metabolismo , Vasodilatação , NADPH Oxidase 4/metabolismo , NADPH Oxidase 1/metabolismo
14.
J AOAC Int ; 107(2): 362-370, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070148

RESUMO

BACKGROUND: Tramadol (TRM) and celecoxib (CLX) form a novel mixture that helps relieve acute pain when other painkillers have no action. It is also reported that these drugs, TRM and CLX, are used to control COVID-19 symptoms. OBJECTIVE: The current work highlights three important pillars of modern pharmaceutical analysis, which are as follows; impurity profiling, greenness/whiteness studies and simplicity accompanied by sensitivity. Since 4-methyl acetophenone inhibits the human carbonyl reductase enzyme (type I) and since this compound may pose a health risk, it is crucial to regulate its concentration in all dosage forms of CLX. METHODS: Two simple and green spectrophotometric methods were developed, namely third derivative (D3) and Fourier self- deconvulation (FSD), for resolving severely overlapped spectra of TRM and CLX in the presence of 4-methyl acetophenone (4-MAP) as a process-related impurity in their novel tablet combination. RESULTS: The two approaches showed acceptable linearity with an excellent correlation coefficient. In both methods, TRM was measured when CLX and 4-methyl acetophenone were zero-crossing. The same procedure was applied for measuring CLX and its process-related impurity 4-MAP. CONCLUSION: The methodologies developed were thoroughly validated in compliance with ICH (International Council on Harmonisation) guidelines. Student t- and F-tests revealed no statistically significant variation among the current methods and the reported method. HIGHLIGHTS: No spectrophotometric methods have been published previously for the simultaneous analysis of TRM and CLX along with 4-MAP. As a result, the newly developed spectrophotometric approaches have great relevance and originality in the field of pharmaceutical analysis.


Assuntos
Tramadol , Humanos , Celecoxib , Espectrofotometria/métodos , Comprimidos , Acetofenonas
15.
Environ Sci Pollut Res Int ; 31(1): 1664-1673, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38097845

RESUMO

The subject of the research was the recovery of raw materials from waste generated in the production of cable insulation and the management of aluminum sludge. It was found that 49% (w/w) acetophenone, 6.8% (w/w) α-methylstyrene, and 17.2% (w/w) cumyl alcohol can be recovered from waste with a loss on ignition of 95% and used in various industries. A gas chromatograph equipped with a mass spectrometry detector was used to identify the recovered compounds. A waste distillation process was proposed to remove the water layer and obtain a concentrated acetophenone fraction. A method of neutralizing the water fraction and distillation residues is presented. The proposed waste management method is an alternative method to the currently used thermal transformation method. In turn, aluminum sludge was used to produce aluminum sulfate, which was used in the plant's sewage treatment plant as a coagulant. The effect of this action was a reduction of 67% in the content of total iron, 60% of trivalent iron, and 32% of chemical oxygen demand. The above-mentioned examples of waste management are part of a closed-loop waste management strategy.


Assuntos
Esgotos , Gerenciamento de Resíduos , Esgotos/química , Alumínio/química , Cromatografia Gasosa-Espectrometria de Massas , Água , Ferro , Acetofenonas , Eliminação de Resíduos Líquidos/métodos
16.
ACS Appl Mater Interfaces ; 15(51): 59145-59154, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38078429

RESUMO

Untethered mobile micromachines have considerable potential to realize more effective and minimally invasive medicine. Although diverse medical micromachines have been reported over the past few decades, these machines were developed for performing only specific tasks and the functions imparted to them were limited to a few. Hence, the methodologies for imparting a wide variety of functions to machines have not been fully explored. In this study, a novel construction strategy for the multifunctional micromachines is presented, where a specific function can be added to the machine in one step by directly combining the protein-based component, possessing the biological function of constituent proteins, to an arbitrary position of the machine by using an inkjet printing technique. As a proof-of-concept demonstration, various types of machines were constructed by combining multiple components with different functions. These constructed machines successfully performed functions as diverse as enzyme-powered self-propulsion, collection of target objects, including the bilirubin and living cells, enzyme-mediated conversion of substrate molecules to different ones, magnetic guidance, and release of anti-inflammatory drug diapocynin. The study's progressive approach as well as multifunctional and biocompatible machines composed of proteins will profoundly impact the development of intelligent machines equipped with multiplex sophisticated functionalities.


Assuntos
Magnetismo , Proteínas , Impressão , Acetofenonas
17.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5898-5907, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114186

RESUMO

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.


Assuntos
Glomerulonefrite , Puromicina Aminonucleosídeo , Humanos , Criança , Ratos , Animais , Metabolômica/métodos , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão/métodos , Acetofenonas , Fenilalanina , Aminoácidos
18.
Brain Res Bull ; 205: 110830, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38036272

RESUMO

Premenstrual dysphoric disorder (PMDD) is a periodic psychiatric disorder with high prevalence in women of childbearing age, seriously affecting patients' work and life. Currently, the international first-line drugs for PMDD have low efficiency and increased side effects. Paeonol, a major component of the traditional Chinese medicine Cortex Moutan, has been applied in treating PMDD in China with satisfactory results, but the therapeutic mechanism is not fully understood. This study aims to evaluate the therapeutic effects and pharmacological mechanisms of paeonol on the main psychiatric symptoms and hippocampal damage in PMDD. We established a premenstrual irritability rat model by the resident-intruder paradigm and performed elevated plus maze and social interactions. And we employed the HE and Nissl staining techniques to observe the therapeutic effect of paeonol on hippocampal damage in PMDD rats. Subsequently, Elisa, qRT-PCR Array, Western Blotting, and cell models were utilized to elucidate the underlying molecular mechanisms through which paeonol intervenes in treating PMDD. In this study, we demonstrated the therapeutic effects of paeonol on irritability, anxiety, and social withdrawal behaviors in rats. In addition, we found that paeonol significantly reduced the serum corticosterone (CORT) level, improved hippocampal morphological structure and neuron number, and reduced hippocampal neuron apoptosis in PMDD rats. Paeonol reduced GRM5, GABBR2, ß-arrestin2, and GRK3 expression levels in hippocampal brain regions of PMDD rats and activated the cAMP/PKA signaling pathway. Inhibitor cell experiments showed that paeonol specifically ameliorated hippocampal injury by modulating the ß-arrestin2/PDE4-cAMP/PKA signaling pathway. The present study demonstrates, for the first time, that paeonol exerts a therapeutic effect on periodic psychotic symptoms and hippocampal injury in PMDD through inhibiting GRM5/GABBR2/ß-arrestin2 and activating cAMP-PKA signaling pathway. These findings enhance our understanding of the pharmacological mechanism underlying paeonol and provide a solid scientific foundation for its future clinical application.


Assuntos
Transtorno Disfórico Pré-Menstrual , Animais , Feminino , Ratos , Acetofenonas , Ansiedade , Hipocampo/metabolismo , Transtorno Disfórico Pré-Menstrual/diagnóstico , Transtorno Disfórico Pré-Menstrual/epidemiologia , Transtorno Disfórico Pré-Menstrual/psicologia , Receptores de GABA-B/metabolismo
19.
Int J Biol Macromol ; 253(Pt 3): 126962, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37722636

RESUMO

Paeonol, as one effective tyrosinase inhibitor, had been used as food preservative and clinical medication for skin disorders. In this study, the inhibition mechanism and binding behavior of paeonol to tyrosinase and its anti-browning property were investigated using multi-spectroscopic and molecular docking methods. Activity assay and kinetic results confirmed paeonol as a reversible mixed-type tyrosinase inhibitor. Results of the mechanistic studies were clarified using fluorescence quenching, synchronous fluorescence, CD spectra and 3D fluorescence, and showed that the binding of paeonol to tyrosinase might change the chromophore microenvironment and conformation of tyrosinase to inhibit enzyme catalytic activity. Molecular docking results revealed the detailed binding between paeonol and tyrosinase. Moreover, paeonol could prevent the browning of fresh-cut apples, as well as inhibiting PPO and POD activities and increasing APX activity. All above findings established a reliable basis for the inhibitory mechanism of paeonol against tyrosinase and therefore contributed to its application in anti-browning.


Assuntos
Malus , Monofenol Mono-Oxigenase , Simulação de Acoplamento Molecular , Acetofenonas/farmacologia , Acetofenonas/química , Malus/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Cinética
20.
J Cell Mol Med ; 27(23): 3911-3927, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37749949

RESUMO

Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC-induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low-dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)-treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex-induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex-induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.


Assuntos
Dexametasona , Doenças Mitocondriais , Ratos , Animais , Dexametasona/farmacologia , Dexametasona/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Osteogênese , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Estresse Oxidativo , Acetofenonas/farmacologia , Apoptose , Osteoblastos/metabolismo , Doenças Mitocondriais/metabolismo
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