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1.
Pharmacol Res ; 204: 107201, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704108

RESUMO

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like ß-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.


Assuntos
Estrogênios , Terapia por Exercício , Transtornos Mentais , Animais , Humanos , Estrogênios/metabolismo , Exercício Físico/fisiologia , Transtornos Mentais/metabolismo , Transtornos Mentais/terapia , Receptores de Estrogênio/metabolismo , Transdução de Sinais
2.
Pharmacol Res ; 204: 107215, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744399

RESUMO

The ubiquitinproteasome system (UPS) is the main mechanism responsible for the intracellular degradation of misfolded or damaged proteins. Under inflammatory conditions, the immunoproteasome, an isoform of the proteasome, can be induced, enhancing the antigen-presenting function of the UPS. Furthermore, the immunoproteasome also serves nonimmune functions, such as maintaining protein homeostasis and regulating signalling pathways, and is involved in the pathophysiological processes of various cardiovascular diseases (CVDs). This review aims to provide a comprehensive summary of the current research on the involvement of the immunoproteasome in cardiovascular diseases, with the ultimate goal of identifying novel strategies for the treatment of these conditions.


Assuntos
Doenças Cardiovasculares , Complexo de Endopeptidases do Proteassoma , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/imunologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/metabolismo , Animais , Ubiquitina/metabolismo , Ubiquitina/imunologia , Transdução de Sinais
3.
Food Chem X ; 22: 101396, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38699585

RESUMO

With the proliferation of the consumer's awareness of wine provenance, wines with unique origin characteristics are increasingly in demand. This study aimed to investigate the influence of geographical origins and climatological characteristics on grapes and wines. A total of 94 anthocyanins and 78 non-anthocyanin phenolic compounds in grapes and wines from five Chinese viticultural vineyards (CJ, WH, QTX, WW, and XY) were identified by UHPLC-QqQ-MS/MS. Chemometric methods PCA and OPLS-DA were established to select candidate differential metabolites, including flavonols, stilbenes, hydroxycinnamic acids, peonidin derivatives, and malvidin derivatives. CCA showed that malvidin-3-O-glucoside had a positive correlation with mean temperature, and quercetin-3-O-glucoside had a negative correlation with precipitation. In addition, enrichment analysis elucidated that the metabolic diversity in different origins mainly occurred in flavonoid biosynthesis. This study would provide some new insights to understand the effect of geographical origins and climatological characteristics on phenolic compounds in grapes and wines.

4.
Pharmacol Res ; 203: 107164, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569981

RESUMO

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.


Assuntos
Doenças Cardiovasculares , Proteínas Mitocondriais , Proteínas Musculares , Humanos , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Proteínas Mitocondriais/metabolismo , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos
5.
Pharmacol Res ; 202: 107141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490314

RESUMO

Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartments,alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.


Assuntos
Glucose , Osteoartrite , Sirtuína 1 , Animais , Humanos , Cartilagem Articular/patologia , Glucose/metabolismo , Osteoartrite/metabolismo , Sirtuína 1/metabolismo , Sirtuínas/metabolismo
6.
Pharmacol Res ; 199: 107037, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38070792

RESUMO

Sirtuins, also called silent information regulator 2, are enzymes that rely on nicotinamide adenine dinucleotide (NAD+) to function as histone deacetylases. Further investigation is warranted to explore the advantageous impacts of Sirtuin 1 (SIRT1), a constituent of the sirtuin group, on lipid metabolism, in addition to its well-researched involvement in extending lifespan. The regulation of gene expression has been extensively linked to SIRT1. Sterol regulatory element-binding protein (SREBP) is a substrate of SIRT1 that has attracted significant interest due to its role in multiple cellular processes including cell cycle regulation, DNA damage repair, and metabolic functions. Hence, the objective of this analysis was to investigate and elucidate the correlation between SIRT1 and SREBPs, as well as assess the contribution of SIRT1/SREBPs in mitigating lipid metabolism dysfunction. The objective of this research was to investigate whether SIRT1 and SREBPs could be utilized as viable targets for therapeutic intervention in managing complications associated with diabetes.


Assuntos
Sirtuína 1 , Sirtuínas , Sirtuína 1/metabolismo , Metabolismo dos Lipídeos , Sirtuínas/metabolismo , NAD/metabolismo
7.
Pharmacol Res ; 197: 106950, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37820854

RESUMO

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.


Assuntos
Nefropatias , Humanos , Acetilação , Nefropatias/tratamento farmacológico , Rim , Epigênese Genética , Epigenômica
8.
Biomed Pharmacother ; 168: 115634, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879211

RESUMO

Peripheral arterial disease (PAD) has been historically neglected, which has resulted in a lack of effective drugs in clinical practice. However, with the increasing prevalence of diseases like atherosclerosis and diabetes, the incidence of PAD is rising and cannot be ignored. Researchers are exploring the potential of promoting angiogenesis through exogenous compounds to improve PAD. This paper focuses on the therapeutic effect of natural products (Salidroside, Astragaloside IV, etc.) and synthetic compounds (Cilostazol, Dapagliflozin, etc.). Specifically, it examines how they can promote autocrine secretion of vascular endothelial cells, enhance cell paracrine interactions, and regulate endothelial progenitor cell function. The activation of these effects may be closely related to PI3K, AMPK, and other pathways. Overall, these exogenous compounds have promising therapeutic potential for PAD. This study aims to summarize the potential active compounds, provide a variety of options for the search for drugs for the treatment of PAD, and bring light to the treatment of patients.


Assuntos
Produtos Biológicos , Diabetes Mellitus , Doença Arterial Periférica , Humanos , Células Endoteliais , Produtos Biológicos/farmacologia , Diabetes Mellitus/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico
9.
Pharmacol Res ; 196: 106919, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37722517

RESUMO

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

10.
Carbohydr Polym ; 304: 120491, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36641178

RESUMO

BACKGROUND: Chitosan-based particles are one of the most promising Pickering emulsions stabilizers due to its cationic properties, cost-effective, biocompatibility, biodegradability. However, there are currently no comprehensive reviews analyzing the role of chitosan to develop Pickering emulsions, and the bioavailability and multiple uses of these emulsions. SCOPE AND APPROACH: This review firstly summarizes the types, preparation and functional properties of chitosan-based Pickering emulsion stabilizers, followed by in vivo and in vitro bioavailability, main regulations, and future application and trends. KEY FINDINGS AND CONCLUSIONS: Stabilizers used in chitosan-based Pickering emulsions include 6 categories: chitosan self-aggregating particles and 5 types of composites (chitosan-protein, chitosan-polysaccharide, chitosan-fatty acid, chitosan-polyphenol, and chitosan-inorganic). Chitosan-based Pickering emulsions improved the bioavailability of different compounds compared to traditional emulsions. Current applications include hydrogels, microcapsules, food ingredients, bio-based films, cosmeceuticals, porous scaffolds, environmental protection agents, and interfacial catalysis systems. However, due to current limitations, more research and development are needed to be extensively explored to meet consumer demand, industrial manufacturing, and regulatory requirements. Thus, optimization of stabilizers, bioavailability studies, 3D4D printing, fat substitutes, and double emulsions are the main potential development trends or research gaps in the field which would contribute to increase adoption of these promising emulsions at industrial level.


Assuntos
Quitosana , Emulsões , Disponibilidade Biológica , Tamanho da Partícula
11.
Pharmacol Res ; 187: 106635, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36581167

RESUMO

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future.


Assuntos
Produtos Biológicos , Osteoporose , Plantas Medicinais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoclastos/metabolismo , Morte Celular
12.
J Ethnopharmacol ; 301: 115806, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36216198

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qushi Huayu Decoction (QHD) is a traditional Chinese medicine formula consisting of five herbs, which has been used for non-alcoholic fatty liver disease (NAFLD) treatment in clinic for decades in China and validated in several NAFLD animal models. The hepatic de novo lipogenesis (DNL) is enhanced greatly to contribute to steatosis in NAFLD. The spliced form of X-box binding protein 1 (XBP1s) initiates DNL independently of sterol regulatory element-binding protein (SREBP) and carbohydrate-responsive element-binding protein (ChREBP). AIM OF THE STUDY: To disclose the mechanism of inhibition on hepatic DNL by QHD and the responsible compounds. METHODS: The effects of QHD on hepatic DNL were evaluated in mice induced by high-fructose diet (HFru). The effects of the serum-absorbed compounds of QHD on XBP1s were evaluated in HepG2 cells induced by tunicamycin. Hepatic histology, triglyceride (TG) and nonesterified fatty acids were observed. Hepatic apolipoprotein B100 and very low-density lipoprotein were measured to reflect lipid out-transport. The mRNA expression of XBP1s and its target genes were detected by real-time polymerase chain reaction. The protein expression of TG synthetases and DNL enzymes, and inositol requirement enzyme 1 alpha (IRE1α), phosphorylated IRE1α and XBP1s were detected in liver tissue and HepG2 cells by western-blot. The binding activity of SREBP1, protein expression of ChREBP and XBP1s were detected in the nuclear extracts of liver tissue. RESULTS: Dynamical observing suggested feeding with HFru for 2 weeks was sufficient to induce hepatic lipogenesis and XBP1s. QHD ameliorated liver steatosis without enhancing out-transport of lipids, accompanied with more inhibitory effects on DNL enzymes than TG synthetases. QHD inhibits the nuclear XBP1s without affecting ChREBP and SREBP1. In QHD, chlorogenic acid, geniposide and polydatin inhibit lipogenesis initiated by XPB1s. CONCLUSION: QHD probably decreases hepatic DNL by inhibiting XBP1s independent of SREBP1 and ChREBP. Chlorogenic acid, geniposide and polydatin are the potential responsible compounds.


Assuntos
Lipogênese , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Ácido Clorogênico/farmacologia , Endorribonucleases/metabolismo , Endorribonucleases/farmacologia , Endorribonucleases/uso terapêutico , Frutose , Ligases/metabolismo , Ligases/farmacologia , Ligases/uso terapêutico , Fígado , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Serina-Treonina Quinases , Triglicerídeos/metabolismo
13.
J Ethnopharmacol ; 302(Pt A): 115870, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36341819

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus idaeus Linnaeus (RI) is a Chinese herbal medicine that has been widely used in China for a long time to reinforce the kidney, nourish the liver, improve vision, and arrest polyuria. AIM OF THE STUDY: This work aims to evaluate the recent progress of the chemical composition, pharmacological activity, pharmacokinetics, metabolism, and quality control and of Rubus idaeus, which focuses on the insufficiency of existing research and will shed light on future studies of Rubus idaeus. METHODS: Literatures about "Rubus idaeus","Red raspberry" and "Fupenzi"are retrieved by browsing the database, such as Web of Science (http://www.webofknowledge.com/wos), Pubmed (https://pubmed.ncbi.nlm.nih.gov/), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn). In addition, related textbooks and digital documents are interrogated to provide a holistic and critical review of the topic. The period of the literature covered from 1981 to 2022. RESULTS: Approximately 194 compounds have been isolated from Rubus idaeus, which is rich in phenols, terpenoids, alkaloids, steroids, and fatty acids. Numerous investigations have demonstrated that Rubus idaeus exhibits many pharmacological activities, including hypoglycemic and hypolipidemic, anti-Alzheimer effect, anti-osteoporosis, hepatoprotective, anti-cancer, neuroprotective, anti-bacteria and skin care, etc. However, it is worth noting that most of the research is not associated with the conventional effect, such as reducing urination and treating opacity of the cornea. CONCLUSION: The effectiveness of Rubus idaeus has been proved by its long-term clinical application. The research on the pharmacological activity of Rubus idaeus has flourished. In many pharmacological experiments, only the high-dose group can achieve the corresponding efficacy, so the efficacy of Rubus idaeus needs to be further interrogated. Meanwhile, the relationship between pharmacological activity and specific compounds of Rubus idaeus has not been clarified yet. Last but not least, studies involving toxicology and pharmacokinetics are very limited. Knowledge of bioavailability and toxicological behavior of Rubus idaeus can help understand the herb's pharmacodynamic and safety profile.


Assuntos
Etnobotânica , Rubus , Etnofarmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Controle de Qualidade , Fitoterapia
14.
Food Chem ; 404(Pt B): 134641, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36323014

RESUMO

Thermal transformations of polyphenols from the lignan and stilbene families were investigated at temperatures ranging from 200 °C to 250 °C, in polyethylene glycol (PEG-400), dimethylformamide (DMF) and in sunflower oil (SO). The polyphenols showed varying degrees of thermal stabilities and in some cases intramolecular transformations were observed. The formed products were isolated and characterized. Oligomerization of the polyphenols at thermo-oxidative conditions was also investigated. Finally, the antioxidative activity of the polyphenols against thermo-oxidative degradation α-linoleic acid was investigated at 200 °C. The results suggested that the studied substrates retained their antioxidative properties at elevated temperatures, with stilbenes showing most efficient protection against thermo-oxidative degradation of polyunsaturated fatty acids.


Assuntos
Lignanas , Estilbenos , Humanos , Antioxidantes/química , Polifenóis/química , Temperatura
15.
Food Chem ; 404(Pt A): 134603, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444021

RESUMO

This study investigated the effects of different maceration techniques on the colour parameters, phenolic content and antioxidant activity of grape juice. Maceration techniques influenced colour parameters, and a* and Hue ranged from -0.77 to 0.55 and 60.90 to 104.40, respectively. The microwave and microwave and sonication combination increased the total monomeric anthocyanin, phenolic and flavonoid contents. Malvidin 3-O-glucoside increased more than twofold, and delphinidin 3-O-glucoside and cyanidin 3-O-glucoside increased one fold according to the enzymatic method in the microwave treatments. The microwave technique was the most effective technique for antioxidant capacity, but sonication, cold and thermosonication results were lower than enzymatic treatment. The microwave and microwave and sonication enhanced the polyphenols with strong antioxidant power, such as catechin from 0.87 to 37.40 and trans-resveratrol from 0.09 to 0.23 mg/100 g, by comparison with the enzymatic technique. The findings suggested these two techniques were the most effective techniques for maceration.


Assuntos
Polifenóis , Vitis , Antioxidantes , Cor , Glucosídeos , Fenóis , Mudanças Depois da Morte
16.
Pharmacol Res ; 184: 106420, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36049664

RESUMO

Glycosylation is a critical post-translational modification (PTM) that affects the function of proteins and regulates cell signaling, thereby regulating various biological processes. Protein oxygen-N-acetylglucosamine (O-GlcNAc) glycosylation modifications are glycochemical modifications that occur within cells in the signal transduction and are frequently found in the cytoplasm and nucleus. Due to the rapid and reversible addition and removal, O-GlcNAc modifications are able to reversibly compete with certain phosphorylation modifications, immediately regulate the activity of proteins, and participate in kinds of cellular metabolic and signal transduction pathways, playing a pivotal role in the regulation of tumors, diabetes, and other diseases. This article provided a brief overview of O-GlcNAc glycosylation modification, introduced its role in altering the progression and immune response regulation of gastrointestinal tumors, and discussed its potential use as a marker of tumor neogenesis.


Assuntos
Acetilglucosamina , Neoplasias Gastrointestinais , Glicosilação , Humanos , N-Acetilglucosaminiltransferases/metabolismo , Oxigênio/metabolismo , Processamento de Proteína Pós-Traducional
17.
Pharmacol Res ; 183: 106377, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35926806

RESUMO

Spinal cord injury (SCI) can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research has shown that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. We thus investigate the alteration in gut microbiota and the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&E, Nissl, and immunofluorescence stainings. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and analyzed with 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolites indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and butyrate suppressed the expression of pro-inflammatory genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate.


Assuntos
Microbioma Gastrointestinal , Traumatismos da Medula Espinal , Animais , Anti-Inflamatórios/farmacologia , Butiratos/farmacologia , Disbiose , Ácidos Graxos Voláteis/metabolismo , Camundongos , Microglia/metabolismo , RNA Ribossômico 16S , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico
18.
Pharmacol Res ; 183: 106361, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35882295

RESUMO

There are numerous prescription drugs and non-prescription drugs that cause drug-induced liver injury (DILI), which is the main cause of liver disease in humans around the globe. Its mechanism becomes clearer as the disease is studied further. For an instance, when acetaminophen (APAP) is taken in excess, it produces N-acetyl-p-benzoquinone imine (NAPQI) that binds to biomacromolecules in the liver causing liver injury. Treatment of DILI with traditional Chinese medicine (TCM) has shown to be effective. For example, activation of the Nrf2 signaling pathway as well as regulation of glutathione (GSH) synthesis, coupling, and excretion are the mechanisms by which ginsenoside Rg1 (Rg1) treats APAP-induced acute liver injury. Nevertheless, reducing the toxicity of TCM in treating DILI is still a problem to be overcome at present and in the future. Accumulated evidences show that hydrogel-based nanocomposite may be an excellent carrier for TCM. Therefore, we reviewed TCM with potential anti-DILI, focusing on the signaling pathway of these drugs' anti-DILI effect, as well as the possibility and prospect of treating DILI by TCM based on hydrogel materials in the future. In conclusion, this review provides new insights to further explore TCM in the treatment of DILI.


Assuntos
Produtos Biológicos , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Acetaminofen , Produtos Biológicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Hidrogéis , Medicina Tradicional Chinesa
19.
Food Chem X ; 14: 100343, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35634221

RESUMO

Pickled radish is a general source of natural bioactive compounds that include phenols. Here, we used molecular docking, fluorescence quenching, circular dichroism spectroscopy and molecular dynamics simulations to identify potential inhibitors against xanthine oxidase from a library of pickled radish compounds. The most effective compounds were selected for validation through in vitro experiments including enzyme activity inhibition tests, and cell-based assays. Molecular docking results revealed that 2,6-Dihydroxyacetophenone, 4-Hydroxyphenethyl alcohol, and 4-Hydroxybenzaldehyde exhibited significant effects on xanthine oxidase inhibition. Three phenols have varying degrees of inhibition on xanthine oxidase, which is driven by hydrophobic interactions and hydrogen bonds and affects the secondary structure and hydrophobic homeostasis of xanthine oxidase. The stability of xanthine oxidase inhibition by three phenols was analyzed by molecular dynamics simulation. Finally, cellular experiments confirmed that three phenols reduced uric acid levels by inhibiting the xanthine oxidase enzyme activity of BRL 3A cells.

20.
Pharmacol Res ; 178: 106175, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35283301

RESUMO

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.


Assuntos
Tecido Adiposo Branco , Medicamentos de Ervas Chinesas , Suplementos Nutricionais , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Obesidade/tratamento farmacológico
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