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1.
Saudi Pharm J ; 32(7): 102124, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38933713

RESUMEN

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

2.
Molecules ; 29(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38893287

RESUMEN

Psoriasis is a common chronic immune-mediated inflammatory skin disorder. Sophora flavescens Alt. (S. flavescens) has been widely acknowledged in the prevention and treatment of psoriasis. Kushenol F (KSCF) is a natural isopentenyl flavonoid extracted from the root of S. flavescens. We aimed to investigate the effect and mechanism of KSCF on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. A mouse model of psoriasis was induced with 5% IMQ for 5 days, and the mice were given KSCF dermally for 5 days. Changes in skin morphology, the psoriasis area, the severity index (PASI), and inflammatory factors of psoriasis-like skin lesions were evaluated. Metabolites in the psoriasis-like skin lesions were analyzed with ultra-high-performance liquid chromatography/mass spectrometry followed by a multivariate statistical analysis to identify the differential metabolites and metabolic pathway. The results of the present study confirmed that KSCF significantly reduced PASI scores, epidermal thickening, and epidermal cell proliferation and differentiation. KSCF also reduced the levels of interleukin (IL)-1ß, IL-6, IL-8, IL-17A, IL-22, IL-23, and tumor necrosis factor (TNF)-α in the injured skin tissues while increasing IL-10 content. KSCF significantly regulated metabolites in the skin samples, and a total of 161 significant metabolites were identified. These differential metabolites involved sphingolipid and linoleic acid metabolism and steroid hormone biosynthesis. Collectively, KSCF inhibited the inflammatory response to prevent IMQ-induced psoriasis-like skin lesions in mice by call-backing the levels of 161 endogenous metabolites and affecting their related metabolic pathways. KSCF has the potential to be developed as a topical drug for treating psoriasis symptoms.


Asunto(s)
Modelos Animales de Enfermedad , Imiquimod , Metabolómica , Psoriasis , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Psoriasis/patología , Animales , Imiquimod/toxicidad , Ratones , Cromatografía Líquida de Alta Presión , Metabolómica/métodos , Metaboloma/efectos de los fármacos , Citocinas/metabolismo , Flavonoides/farmacología , Espectrometría de Masas , Piel/metabolismo , Piel/efectos de los fármacos , Piel/patología , Masculino
3.
Saudi Pharm J ; 31(4): 597-604, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37063439

RESUMEN

A third of the world's population suffers from unexplained fatigue, hugely impacting work learning, efficiency, and health. The fatigue development may be a concomitant state of a disease or the side effect of a drug, or muscle fatigue induced by intense exercise. However, there are no authoritative guides or clinical medication recommendations for various fatigue classifications. Traditional Chinese medicines (TCM) are used as dietary supplements or healthcare products with specific anti-fatigue effects. Thus, TCM may be a potential treatment for fatigue. In this review, we outline the pathogenesis of fatigue, awareness of fatigue in Chinese and western medicine, pharmacodynamics mechanism, and substances. Additionally, we offer a comprehensive summary of fatigue and forecast the potential effect of novel herbal-based medicines against fatigue.

4.
Biomed Pharmacother ; 162: 114584, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36989710

RESUMEN

Jiuzhuan Huangjing Pills (JHP) composed of Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR) remedied mitochondria to cure metabolic dysfunction-associated fatty liver disease (MAFLD). However, a comparison of the anti-MAFLD ability between JHP prescription and PR and ASR single-medicines in MAFLD has not been performed, and the action mechanisms and substances remain unknown. Our results show that JHP, PR and ASR decreased serum and liver lipid levels. The effects of JHP were stronger than those of PR and ASR. JHP, PR and ASR afforded protection to mitochondrial ultrastructure, and regulated oxidative stress and energy metabolism in mitochondria. JHP also regulated the expression of ß-oxidation genes, which were not regulated by PR and ASR. JHP-, PR- and ASR-derived components in mitochondrial extracts regulated oxidative stress, energy metabolism, and ß-oxidation gene expression and alleviated cellular steatosis. Four, six and eleven compounds were identified in mitochondrial extracts from PR-, ASR- and JHP-treated rats, respectively. The data suggest that JHP, PR and ASR alleviated MAFLD by remedying mitochondria, while the ability of JHP was stronger than that of PR and ASR, which was involved with the ß-oxidation promotion. The compounds identified may be the main ingredients in the three extracts active in MAFLD improvement.


Asunto(s)
Medicamentos Herbarios Chinos , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Medicamentos Herbarios Chinos/farmacología , Rizoma/química , Ácidos Grasos/análisis
5.
Heliyon ; 9(3): e14353, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36967867

RESUMEN

Background: Hypoxia is an essential cause of fatigue and aging, and is associated with the occurrence and development of many diseases. Polygonatum kingianum (PK) is a deficiency-nourishing Chinese herbal medicine utilized as both medicine and food, and it has long been used to ameliorate human conditions associated with fatigue and aging over 2000 years in China. PK is an important genuine-medicinal-materials cultivated in Yunnan, China, and is used by the Bai, Wa, and Zhuang nationalities as a traditional medicine for enhancing immunity, anti-fatigue, and anti-aging, while the preventive effect of PK on hypoxia-induced injury and the underlying mechanism are indefinite. Aim of the study: The present study aimed to evaluate the anti-hypoxia efficacy and understand the corresponding mechanism of PK water extract. Materials and methods: The main active ingredients and targets of PK were predicted using network pharmacology, and the anti-hypoxia activities of Gracillin and Liquiritigenin were verified by in vitro experiments. The pharmacodynamic experiments were conducted to evaluate the major signal pathways of PK for detecting anti-hypoxia activity. Results: Fifty active ingredients and 371 potential targets were screened by network pharmacology, then, we confirmed that Gracillin and Liquiritigenin were the main active components of PK to exert anti-hypoxia effect in vitro. The pharmacodynamic experiments revealed that PK enhanced the extension rate of the survival time (ERST) and regulated the targets-related biochemical parameters of rats under hypoxia, showing significant anti-hypoxia effects on rats. Conclusion: The network pharmacology results suggested that PK exerts its anti-hypoxia effect through a multi-component and multi-target manner. Simultaneously, we also observed that Gracillin (saponins) and Liquiritigenin (flavonoids) are the main active components of PK to play a role in anti-hypoxia. The anti-hypoxia effect of PK could be associated with scavenging excess free radicals, maintaining the activities of antioxidant enzymes, and inhibiting oxidative stress due to lipid peroxidation. These findings provide insight into the Polygonatum kingianum as promising medicines or healthcare products for preventing and treating hypoxia.

6.
World J Gastroenterol ; 29(1): 171-189, 2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36683716

RESUMEN

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a severe threat to human health. Polygonum multiflorum (PM) has been proven to remedy mitochondria and relieve MAFLD, but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear. AIM: To research the active ingredients of PM adjusting mitochondria to relieve high-fat diet (HFD)-induced MAFLD in rats. METHODS: Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms. The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry (mitochondrial pharmacochemistry). The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model, respectively. RESULTS: PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the liver mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated. CONCLUSION: PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD. Thus, PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction. Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.


Asunto(s)
Fallopia multiflora , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratas , Ratones , Animales , Emulsiones/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado/metabolismo , Mitocondrias/metabolismo
7.
J Biosoc Sci ; 55(5): 921-930, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36519311

RESUMEN

This article reports the results of a study investigating the impact of family orientation, the number of years spent working, and their interaction on childbearing age among women who have recently completed their childbearing.We find that a traditional family orientation and a higher number of working years contribute to delaying the childbearing age. People with a traditional family orientation can delay childbearing because they want to make elaborate material preparations for raising their children. Women who have worked many years are more aware of gender inequality in the domestic sphere (having been exposed to gender equality in the workplace). This is especially the case for women with a modern family orientation. However, this does not necessarily lead people with a modern family orientation to delay childbearing. They may advance their childbearing in an effort to escape an oppressive domestic environment in their families of origin.


Asunto(s)
Empleo , Estructura Familiar , Conducta Reproductiva , Mujeres , Femenino , Humanos , China
8.
Nat Commun ; 13(1): 7931, 2022 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-36566233

RESUMEN

There are growing demands for multimaterial three-dimensional (3D) printing to manufacture 3D object where voxels with different properties and functions are precisely arranged. Digital light processing (DLP) is a high-resolution fast-speed 3D printing technology suitable for various materials. However, multimaterial 3D printing is challenging for DLP as the current multimaterial switching methods require direct contact onto the printed part to remove residual resin. Here we report a DLP-based centrifugal multimaterial (CM) 3D printing method to generate large-volume heterogeneous 3D objects where composition, property and function are programmable at voxel scale. Centrifugal force enables non-contact, high-efficiency multimaterial switching, so that the CM 3D printer can print heterogenous 3D structures in large area (up to 180 mm × 130 mm) made of materials ranging from hydrogels to functional polymers, and even ceramics. Our CM 3D printing method exhibits excellent capability of fabricating digital materials, soft robots, and ceramic devices.

9.
Biomed Pharmacother ; 156: 113849, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36252355

RESUMEN

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that currently lacks approved pharmacological treatment options. The mechanisms and active ingredients of Polygonum cuspidatum (PC) that regulate the mitochondria to relieve MAFLD have not been assessed. Thus, this study was designed to explore the bioactive components of PC extract in regulating mitochondria to alleviate high-fat diet-induced MAFLD using mitochondrial pharmacology and pharmacochemistry. Our results demonstrate that PC protected the mitochondrial ultrastructure and inhibited oxidative stress and energy metabolism disorder in the liver mitochondria. Furthermore, PC-derived components in the liver mitochondria attenuated oxidative stress and restored the energy metabolism of fat emulsion-induced steatosis in L02 cell. Sixteen compounds were identified in the liver-mitochondrial extracts of PC-treated rats. The antisteatotic effects of three identified monomers and anti-MAFLD ability of the monomer group were confirmed. Collectively, our data suggest that the extract of PC can alleviate lipid metabolism disorder in MAFLD by protecting the mitochondrial ultrastructure, reducing oxidative stress injury, and promoting energy metabolism. The sixteen identified compounds were potentially the main effective ingredients of PC in treating MAFLD. Thus, PC shows potential in treating MAFLD and related mitochondrial dysfunction. The proposed strategy to identify the ingredients of herbal medicines based on mitochondrial pharmacology and pharmacochemistry presents a new approach in exploring the pharmacodynamic components of herbal medicines that regulate mitochondria in preventing and treating diseases.


Asunto(s)
Fallopia japonica , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Fallopia japonica/química , Mitocondrias , Estrés Oxidativo , Hígado , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico
10.
Molecules ; 27(19)2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36234924

RESUMEN

(1)Objective: In this study, a quantitative analysis of chemical groups (the triterpenoids, water-soluble polysaccharides, and acidic polysaccharides) and quantitative high liquid performance chromatography (HPLC) fingerprint of Poria cocos (Schw.) Wolf (PC) for quality control was developed. (2) Methodology: First, three main chemical groups, including triterpenoids, water-soluble polysaccharides, and acidic polysaccharides, in 16 batches of PC were evaluated by ultraviolet spectrophotometry. Afterward, the quantitative fingerprint of PC was established, and the alcohol extract of PC was further evaluated. The method involves establishing 16 batches of PC fingerprints by HPLC, evaluating the similarity of different batches of PC, and identifying eight bioactive components, including poricoic acid B (PAB), dehydrotumulosic acid (DTA), poricoic acid A (PAA), polyporenic acid C (PAC), 3-epidehydrotumulosic acid (EA), dehydropachymic acid (DPA), dehydrotrametenolic acid (DTA-1), and dehydroeburicoic acid (DEA), in PC by comparison with the reference substance. Combined with the quantitative analysis of multi-components by a single marker (QAMS), six bioactive ingredients, including PAB, DTA, PAC, EA, DPA, and DEA, in PC from different places were established. In addition, the multivariate statistical analyses, such as principal component analysis and heatmap hierarchical clustering analysis are more intuitive, and the visual analysis strategy was used to evaluate the content of bioactive components in 16 batches of PC. Finally, the analysis strategy of three main chemical groups in PC was combined with the quantitative fingerprint strategy, which reduced the error caused by the single method. (3) Results: The establishment of a method for the quantification of chemical groups and quantitative HPLC fingerprint of PC was achieved as demonstrated through the quantification of six triterpenes in PC by a single marker. (4) Conclusions: Through qualitative and quantitative chemical characterization, a multi-directional, simple and efficient routine evaluation method of PC quality was established. The results reveal that this strategy can provide an analytical method for the quality evaluation of PC and other Chinese medicinal materials.


Asunto(s)
Medicamentos Herbarios Chinos , Poria , Triterpenos , Wolfiporia , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales , Poria/química , Triterpenos/química , Agua , Wolfiporia/química
11.
Sensors (Basel) ; 22(18)2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36146322

RESUMEN

Domestic trash detection is an essential technology toward achieving a smart city. Due to the complexity and variability of urban trash scenarios, the existing trash detection algorithms suffer from low detection rates and high false positives, as well as the general problem of slow speed in industrial applications. This paper proposes an i-YOLOX model for domestic trash detection based on deep learning algorithms. First, a large number of real-life trash images are collected into a new trash image dataset. Second, the lightweight operator involution is incorporated into the feature extraction structure of the algorithm, which allows the feature extraction layer to establish long-distance feature relationships and adaptively extract channel features. In addition, the ability of the model to distinguish similar trash features is strengthened by adding the convolutional block attention module (CBAM) to the enhanced feature extraction network. Finally, the design of the involution residual head structure in the detection head reduces the gradient disappearance and accelerates the convergence of the model loss values allowing the model to perform better classification and regression of the acquired feature layers. In this study, YOLOX-S is chosen as the baseline for each enhancement experiment. The experimental results show that compared with the baseline algorithm, the mean average precision (mAP) of i-YOLOX is improved by 1.47%, the number of parameters is reduced by 23.3%, and the FPS is improved by 40.4%. In practical applications, this improved model achieves accurate recognition of trash in natural scenes, which further validates the generalization performance of i-YOLOX and provides a reference for future domestic trash detection research.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Ciudades
12.
Curr Pharm Des ; 28(21): 1738-1744, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35619320

RESUMEN

Mitochondria regulate a range of important physiological and biochemical cellular processes including apoptotic cell death, energy production, calcium homeostasis, oxidative stress, and lipid metabolism. Given their role as the 'engines' of cells, their dysfunction is associated with a variety of disease states. Exploring the relationship between mitochondrial function and disease can reveal the mechanism(s) of drug activity and disease pathology. In this review, we summarized the methods of evaluating the structure and function of mitochondria, including the morphology, membrane fluidity, membrane potential, opening of the membrane permeability transition pore, inner membrane permeabilization, mitochondrial dynamics, mitophagy, oxidative stress, energy metabolism-related enzymes, apoptotic pathway related proteins, calcium concentration, DNA copy number, oxygen consumption, ß-oxidation-related genes and proteins, cardiolipin content, and adenosine triphosphate content. We believe that the information presented in this review will help explore the pathological processes of mitochondria in the occurrence and development of diseases, as well as the activity and mechanism of drugs, and the discovery of new drugs.


Asunto(s)
Calcio , Mitocondrias , Calcio/metabolismo , Cardiolipinas/metabolismo , Humanos , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Mitofagia , Estrés Oxidativo
13.
Oxid Med Cell Longev ; 2022: 3260243, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35087614

RESUMEN

Parkin is a crucial E3 ubiquitin ligase for initiating mitophagy through the PINK1/Parkin pathway. Regulating the expression and activity of parkin can remedy mitophagy and human disease. We developed an efficient method to isolate natural parkin ligands from herbal medicines by combining centrifugal ultrafiltration and liquid chromatography/mass spectrometry. The heterologous expression technology identified functionally active and pure parkin proteins. After evaluating the reliability of the method using DL-selenomethionine and DL-dithiothreitol as positive controls, this method was successfully applied to capture parkin ligands from Polygoni Cuspidati Rhizoma et Radix and Sophorae Flavescentis Radix. LC/MS identified seven novel parkin-targeting compounds, namely, 7,4'-dihydroxy-5-methoxy-8-(γ, γ-dimethylallyl)-flavanone, kushenol I, kurarinone, sophoraflavanone G, torachrysone-8-O-glucoside, apigenin, and emodin, supported by the molecular docking analysis. Five of the seven novel compounds (kushenol I, kurarinone, sophoraflavanone G, apigenin, and emodin) can activate parkin in in vitro autoubiquitination assays. Meanwhile, kushenol I and kurarinone had antisteatosis activity in fat emulsion-damaged human hepatocytes. These results confirmed the effectiveness of the method for identifying parkin ligands from complex preparations, useful to advance drug discovery from medicinal herbs.


Asunto(s)
Medicina de Hierbas/métodos , Ubiquitina-Proteína Ligasas/uso terapéutico , Humanos , Ubiquitina-Proteína Ligasas/farmacología
14.
Curr Pharm Des ; 28(6): 488-496, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34620055

RESUMEN

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.


Asunto(s)
Medicina Tradicional China , Mitofagia , Anciano , Homeostasis , Humanos , Mitocondrias/metabolismo , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
15.
Front Microbiol ; 12: 758870, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34867887

RESUMEN

Polysaccharide is one of the main active ingredients of Polygonatum kingianum, which has been proven to regulate the balance of gut microbiota. For the first time, this study focused on the regulation of polysaccharides from Polygonatum kingianum (PS) on Lactobacillus faecis, a specific probiotic in the intestinal tract. PS effectively promoted the biomass, biofilm and acetic acid production in L. faecis 2-84, and enhanced quorum sensing (QS) signaling. The characteristics of gene sequence were analyzed using genomics approaches, and L. faecis 2-84 was found to encode 18 genes that are closely related to QS and 10 genes related to short-chain fatty acids (SCFAs). Additionally, transcriptome and proteome analysis demonstrated that PS could promote the QS system of L. faecis by enhancing the transcription of oppA gene and expression of oppD protein. PS also regulated the production and metabolism of SCFAs of L. faecis by upregulating the expression of ldh and metE gene and adh2 protein, and downregulating the expression of mvK gene. In conclusion, it was speculated that PS could affect intestinal SCFAs production by affecting the QS system and SCFAs production in L. faecis. The present study implied that PS might have a role in promoting the growth of intestinal probiotics, where the QS system and SCFAs might be two of the important mechanisms for the probiotic activity of PS.

16.
Front Pharmacol ; 12: 740528, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34776961

RESUMEN

Objectives: Polygonatum kingianum is a medicinal herb used in various traditional Chinese medicine formulations. The polysaccharide fraction of P. kingianum can reduce insulin resistance and restore the gut microbiota in a rat model of aberrant lipid metabolism by down regulating miR-122. The aim of this study was to further elucidate the effect of P. kingianum on lipid metabolism, and the roles of specific miRNAs and the gut microbiota. Key findings: P. kingianum administration significantly altered the abundance of 29 gut microbes and 27 differentially expressed miRNAs (DEMs). Several aberrantly expressed miRNAs closely related to lipid metabolism were identified, of which some were associated with specific gut microbiota. MiR-484 in particular was identified as the core factor involved in the therapeutic effects of P. kingianum. We hypothesize that the miR-484-Bacteroides/Roseburia axis acts as an important bridge hub that connects the entire miRNA-gut microbiota network. In addition, we observed that Parabacteroides and Bacillus correlated significantly with several miRNAs, including miR-484, miR-122-5p, miR-184 and miR-378b. Summary: P. kingianum alleviates lipid metabolism disorder by targeting the network of key miRNAs and the gut microbiota.

17.
Biomed Res Int ; 2021: 4045819, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34751247

RESUMEN

PINK1, also known as PARK6, is a PTEN-induced putative kinase 1 that is encoded by nuclear genes. PINK1 is ubiquitously expressed and regulates mitochondrial function and mitophagy in a range of cell types. The dysregulation of PINK1 is associated with the pathogenesis and development of mitochondrial-associated disorders. Many natural products could regulate PINK1 to relieve PINK1-associated diseases. Here, we review the structure and function of PINK1, its relationship to human diseases, and the regulation of natural products to PINK1. We further highlight that the discovery of natural PINK1 regulators represents an attractive strategy for the treatment of PINK1-related diseases, including liver and heart diseases, cancer, and Parkinson's disease. Moreover, investigating PINK1 regulation of natural products can enhance the in-depth comprehension of the mechanism of action of natural products.


Asunto(s)
Productos Biológicos/farmacología , Proteínas Quinasas/efectos de los fármacos , Proteínas Quinasas/metabolismo , Animales , Productos Biológicos/metabolismo , Enfermedad , Quimioterapia/métodos , Humanos , Mitocondrias/metabolismo , Enfermedades Mitocondriales/tratamiento farmacológico , Mitofagia , Mutación , Proteínas Quinasas/genética , Proteínas Quinasas/fisiología , Ubiquitina-Proteína Ligasas/metabolismo
18.
Biomed Pharmacother ; 142: 112092, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34449316

RESUMEN

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common global chronic liver disease. Jiuzhuan Huangjing Pills (JHP) have been used for the treatment of human disease for over a thousand years, but their efficacy and underlying mechanism(s) of action against MAFLD are unknown. We investigated the alleviating effects of JHP on high-fat diet (HFD)-induced MAFLD. METHODS: In vitro and in vivo methods were used to evaluate the effects of JHP on MAFLD. L02 adipocyte models were induced by fat emulsion and adipocytes were treated with JHP for 24 h. MAFLD rat models were induced by HFD-feeding and were intragastrically administered JHP for 12 weeks. Changes in fat accumulation, L02 cell damage, body weight, food intake, histological parameters, organ indexes, biochemical parameters, and mitochondrial indicators including ultrastructure, oxidative stress, energy metabolism, and fatty acid metabolism were investigated. RESULTS: JHP attenuated the increase in levels of total cholesterol, triglyceride, low density lipoprotein cholesterol, alanine transaminase, and aspartate transaminase levels, and significantly increased high density lipoprotein cholesterol. JHP up-regulated levels of glutathione (GSH) and superoxide dismutase (SOD), and down-regulated malondialdehyde (MDA). JHP afforded protection to the mitochondrial ultrastructure, and inhibited the HFD-induced increase in MDA and the reduction of SOD, GSH, ATP synthase, and complex I and II, in liver mitochondria. JHP regulated the expression of ß-oxidation genes, including acyl-CoA dehydrogenase, cyl-CoA dehydrogenase long chain, carnitine palmitoyltransferase 1A, carnitine palmitoyltransferase 1B, peroxisomal proliferator-activated receptor-gamma coactivator-1α and peroxide proliferator activated receptor α. CONCLUSION: JHP alleviates HFD-induced MAFLD through the protection of mitochondrial function.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Mitocondrias/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Línea Celular , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Masculino , Mitocondrias/patología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
19.
Can J Gastroenterol Hepatol ; 2021: 5527315, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34222135

RESUMEN

Metabolic associated fatty liver disease (MAFLD) is a multifactorial systemic disorder that occurs in the absence of excessive alcohol consumption. The disease is characterized by fatty degeneration and fat accumulation in liver parenchymal cells, the incidence of which is increasing annually, particularly in younger adults. MAFLD is caused by genetic and metabolism related disorders, of which mitochondrial dysfunction is the major contributor. Natural products can relieve MAFLD through restoring mitochondrial function. In this article, we describe the relationship between mitochondria and MAFLD and discuss the beneficial effects of natural products as a future anti-MAFLD strategy. Significance Statement. We herein propose that the development of mitochondrial regulators/nutrients from natural products can remedy mitochondrial dysfunction which represents an attractive strategy for the treatment of MAFLD. Furthermore, the mitochondrial regulation of natural products can provide new insight into the underlying mechanisms of action of natural products used for future MAFLD therapeutics.


Asunto(s)
Productos Biológicos , Enfermedad del Hígado Graso no Alcohólico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Hepatocitos , Humanos , Mitocondrias , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico
20.
Micromachines (Basel) ; 12(6)2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34208519

RESUMEN

Wire electrical discharge machining (WEDM), widely used to fabricate micro and precision parts in manufacturing industry, is a nontraditional machining method using discharge energy which is transformed into thermal energy to efficiently remove materials. A great amount of research has been conducted based on pulse characteristics. However, the spark image-based approach has little research reported. This paper proposes a discharge spark image-based approach. A model is introduced to predict the discharge status using spark image features through a synchronous high-speed image and waveform acquisition system. First, the relationship between the spark image features (e.g., area, energy, energy density, distribution, etc.) and discharge status is explored by a set of experiments). Traditional methods have claimed that pulse waveform of "short" status is related to the status of non-machining while through our research, it is concluded that this is not always true by conducting experiments based on the spark images. Second, a deep learning model based on Convolution neural network (CNN) and Gated recurrent unit (GRU) is proposed to predict the discharge status. A time series of spark image features extracted by CNN form a 3D feature space is used to predict the discharge status through GRU. Moreover, a quantitative labeling method of machining state is proposed to improve the stability of the model. Due the effective features and the quantitative labeling method, the proposed approach achieves better predict result comparing with the single GRU model.

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