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1.
BMC Complement Med Ther ; 24(1): 329, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232773

RESUMO

BACKGROUND: Breast cancer is one of the most common diseases globally that may have side effects on liver and renal function. Pharmacological treatments to reduce adverse liver and renal effects are still limited. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the hepatorenal protective efficacy of silymarin supplementation in cancer patients receiving chemotherapy in an outpatient setting. METHOD: This is a randomized, placebo-controlled clinical trial that recruited female breast cancer patients. Participants were randomly assigned to one placebo group and two intervention groups. The control group received 140 mg of placebo daily, while the two intervention groups received 140 mg silymarin daily. Follow-up assessments were conducted at baseline, 3 weeks, and 6 weeks. At the beginning of the study, the patients were subjected to a computed tomography (CT) scan, and the liver and renal parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, Blood urea nitrogen (BUN) and Creatinine (Cr) were examined through laboratory tests. RESULTS: Despite two deaths and three dropouts, 100 patients completed the study. Silymarin showed significant effects on liver enzymes in the levels of ALP and bilirubin (P < 0.05), with no significant impact on renal function in the levels of Blood urea nitrogen (BUN) and Creatinine (Cr) (P > 0.05). The medication was well-tolerated, with minimal reported side effects (P > 0.05). DISCUSSION: The study suggests that silymarin may have hepato-renal protective potential in breast cancer patients and improve patient tolerance to chemotherapy. The data presented on the efficacy and safety of silymarin may provide stronger foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION INFORMATION: Registration Number: IRCT20201123049474N2, First Trial Registration: 16/08/2021, Access: https://www.irct.behdasht.gov.ir/trial/57641.


Assuntos
Neoplasias da Mama , Silimarina , Humanos , Silimarina/farmacologia , Silimarina/uso terapêutico , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Adulto , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Idoso , Fígado/efeitos dos fármacos
2.
Cell Mol Biol Lett ; 29(1): 119, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244559

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. PURPOSE: This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. METHODS: C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. RESULTS: The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. CONCLUSIONS: Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin.


Assuntos
Acetaminofen , Autofagia , Doença Hepática Induzida por Substâncias e Drogas , Glucosídeos , Hepatócitos , Camundongos Endogâmicos C57BL , Monoterpenos , Serina-Treonina Quinases TOR , Animais , Autofagia/efeitos dos fármacos , Glucosídeos/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Monoterpenos/farmacologia , Masculino , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Camundongos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Acetaminofen/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1571-1581, 2024 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-39276053

RESUMO

OBJECTIVE: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice. METHODS: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-Ⅳ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting. RESULTS: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-Ⅳ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues. CONCLUSION: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Doxorrubicina , Interleucina-6 , Lonicera , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Animais , Doxorrubicina/efeitos adversos , Camundongos , Lonicera/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Proteína Supressora de Tumor p53/metabolismo , Substâncias Protetoras/farmacologia , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Farmacologia em Rede
4.
Redox Rep ; 29(1): 2395779, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39221774

RESUMO

OBJECTIVES: Alcohol and its metabolites, such as acetaldehyde, induced hepatic mitochondrial dysfunction play a pathological role in the development of alcohol-related liver disease (ALD). METHODS: In this study, we investigated the potential of nobiletin (NOB), a polymethoxylated flavone, to counter alcohol-induced mitochondrial dysfunction and liver injury. RESULTS: Our findings demonstrate that NOB administration markedly attenuated alcohol-induced hepatic steatosis, endoplasmic reticulum stress, inflammation, and tissue damage in mice. NOB reversed hepatic mitochondrial dysfunction and oxidative stress in both alcohol-fed mice and acetaldehyde-treated hepatocytes. Mechanistically, NOB restored the reduction of hepatic mitochondrial transcription factor A (TFAM) at both mRNA and protein levels. Notably, the protective effects of NOB against acetaldehyde-induced mitochondrial dysfunction and cell death were abolished in hepatocytes lacking Tfam. Furthermore, NOB administration reinstated the levels of hepatocellular NRF1, a key transcriptional regulator of TFAM, which were decreased by alcohol and acetaldehyde exposure. Consistent with these findings, hepatocyte-specific overexpression of Nrf1 protected against alcohol-induced hepatic Tfam reduction, mitochondrial dysfunction, oxidative stress, and liver injury. CONCLUSIONS: Our study elucidates the involvement of the NRF1-TFAM signaling pathway in the protective mechanism of NOB against chronic-plus-binge alcohol consumption-induced mitochondrial dysfunction and liver injury, suggesting NOB supplementation as a potential therapeutic strategy for ALD.


Assuntos
Flavonas , Transdução de Sinais , Animais , Camundongos , Flavonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Masculino , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Etanol/toxicidade , Etanol/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Fator 1 Nuclear Respiratório/metabolismo , Fator 1 Nuclear Respiratório/genética , Substâncias Protetoras/farmacologia , Fator 1 Relacionado a NF-E2/metabolismo , Fator 1 Relacionado a NF-E2/genética , Proteínas de Grupo de Alta Mobilidade
5.
Nutrients ; 16(17)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39275153

RESUMO

Aging is the result of the accumulation of a wide variety of molecular and cellular damages over time, meaning that "the more damage we accumulate, the higher the possibility to develop age-related diseases". Therefore, to reduce the incidence of such diseases and improve human health, it becomes important to find ways to combat such damage. In this sense, geroprotectors have been suggested as molecules that could slow down or prevent age-related diseases. On the other hand, nutraceuticals are another set of compounds that align with the need to prevent diseases and promote health since they are biologically active molecules (occurring naturally in food) that, apart from having a nutritional role, have preventive properties, such as antioxidant, anti-inflammatory and antitumoral, just to mention a few. Therefore, in the present review using the specialized databases Scopus and PubMed we collected information from articles published from 2010 to 2023 in order to describe the role of nutraceuticals during the aging process and, given their role in targeting the hallmarks of aging, we suggest that they are potential geroprotectors that could be consumed as part of our regular diet or administered additionally as nutritional supplements.


Assuntos
Envelhecimento , Suplementos Nutricionais , Humanos , Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Substâncias Protetoras/farmacologia , Animais
6.
Int J Biol Macromol ; 277(Pt 3): 134305, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39094884

RESUMO

Anoectochilus roxburghii polysaccharides exhibit notable hepatoprotective effects, but the underlying substance basis and mechanisms remain unknown. In this study, four new polysaccharides named ARP-1a, ARP-1b, ARP-2a and ARP-2b, were isolated from A. roxburghii. Their structural characteristics were systematically analyzed using HPGPC, HPLC, GC-MS, IR and NMR analysis. ARP-1a, the leading polysaccharide isolated from A. roxburghii, was further evaluated for its hepatoprotective effects on acute liver injury mice induced by CCl4. ARP-1a significantly reduced the serum ALT, AST, TNF-α, IL-1ß and IL-6 levels, liver MDA content, and increased the SOD and CAT activities and GSH level in liver. H&E staining revealed that ARP-1a pretreatment could markedly relieve liver injury. Further mechanism exploration indicated that ARP-1a could relieve CCl4-induced oxidative damage through activating the Nrf2 signaling. In addition, metabolomics, lipidomics and 16S rRNA amplicon sequencing were used to elucidate the underlying mechanisms of ARP-1a. Multi-omics analysis indicated that ARP-1a exerted hepatoprotective effect against CCl4-induced acute liver injury by regulating lipid metabolism and modulating the gut microbiota. In conclusion, the above results suggest that ARP-1a can be considered a promising and safe candidate for hepatoprotective drug, as well as a potential prebiotic for maintaining intestinal homeostasis and promoting human intestinal health.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Orchidaceae , Polissacarídeos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos , Metabolismo dos Lipídeos/efeitos dos fármacos , Orchidaceae/química , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Estresse Oxidativo/efeitos dos fármacos
7.
Int J Biol Macromol ; 277(Pt 3): 134489, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111493

RESUMO

Chitooligosaccharides (COS) has attracted increasing attention due to the various promising bioactivities, tremendous potential in agricultural, environmental nutritional and functional food fields. COS as the major degradation product from chitosan or chitin is prepared via enzymatic, chemical and physical methods. Further obtained COS generally possesses different structural characteristics, such as molecular weight, degree of acetylation and degree of polymerization. Innovations into COS modification has also broadened application of COS in nutrition as well as in agricultural safety. Due to the affinity between structure and bioactivity, diversity of structural characteristics endows COS with various bioactivities like antitumor, antioxidant and anti-inflammatory effects, especially hepatoprotective activity. Therefore, the present review narrates the recent developments in COS physicochemical properties, while paying considerable attention to preparation strategies of COS and their advantages and disadvantages. Moreover, the modification of COS is also discussed including alkylation, quaternization and sulfation, herein the structure-activity relationship of COS was highlighted. Additionally, we summarize the latest research on hepatoprotective activity and mechanisms of COS. Eventually, the future directions of research on COS were discussed, which would provide a new appreciation for the future use of COS.


Assuntos
Quitina , Quitosana , Oligossacarídeos , Quitosana/química , Quitosana/farmacologia , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Quitina/química , Quitina/análogos & derivados , Quitina/farmacologia , Humanos , Animais , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Relação Estrutura-Atividade , Antioxidantes/química , Antioxidantes/farmacologia
8.
Int J Mol Sci ; 25(16)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39201451

RESUMO

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 µM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin.


Assuntos
Sobrevivência Celular , Fumonisinas , Quercetina , Espécies Reativas de Oxigênio , Células de Sertoli , Quercetina/farmacologia , Fumonisinas/toxicidade , Masculino , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Substâncias Protetoras/farmacologia
9.
Life Sci ; 354: 122949, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39127318

RESUMO

Vital organ injury is one of the leading causes of global mortality and socio-economic burdens. Current treatments have limited efficacy, and new strategies are needed. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor that protects multiple organs by reducing inflammation and preventing cell death. However, its exact mechanism is not yet fully understood. Understanding the underlying molecular mechanisms of its protective effects is crucial as it could provide a basis for designing highly targeted and more effective drugs. Ferroptosis is the primary mode of cell death during organ injury, and recent studies have shown that DEX can protect vital organs from this process. This review provides a detailed analysis of preclinical in vitro and in vivo studies and gains a better understanding of how DEX protects against vital organ injuries by inhibiting ferroptosis. Our findings suggest that DEX can potentially protect vital organs mainly by regulating iron metabolism and the antioxidant defense system. This is the first review that summarizes all evidence of ferroptosis's role in DEX's protective effects against vital organ injuries. Our work aims to provide new insights into organ therapy with DEX and accelerate its translation from the laboratory to clinical settings.


Assuntos
Dexmedetomidina , Ferroptose , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Ferroptose/efeitos dos fármacos , Humanos , Animais , Substâncias Protetoras/farmacologia , Ferro/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Antioxidantes/farmacologia
10.
Reprod Toxicol ; 129: 108679, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121979

RESUMO

This study aimed to investigate the protective effects of glucose selenol on cadmium (Cd)-induced testicular toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into four groups. Cd was administered orally at a dose of 40 mg/L or in combination with orally administered glucose selenol at doses of 0.15 mg/L and 0.4 mg/L for 30 days. The results showed that sperm quality decreased and testicular tissue was damaged in the Cd group; Glucose selenol significantly attenuated the negative effects by improving sperm quality and reducing testicular damage. Transcriptome sequencing analysis showed that Cd stress affected spermatogenesis, sperm motility, oxidative stress, blood-testis barrier and protein metabolism. Four clusters were obtained using the R Mfuzz package, which clustered highly expressed genes under different administrations, and 36 items were enriched. Notably, protein phosphorylation was enriched in the Cd group and is considered to play a key role in the response to Cd stress. We identified fifty-six target selenium (Se) and Cd co-conversion differentially expressed genes (DEGs), including three genes relating to spermatogenesis (Dnah8, Spata31d1b, Spata31d1c). In addition, the obtained DEGs were used to construct a protein-protein interaction network, co-processed with Se and Cd, and 5 modules were constructed. Overall, the analyses of rat testicular physiology and gene expression levels offer new insights into the reproductive toxicity of Cd in rats, and provide potential application prospects for glucose selenol in alleviating the impact of Cd-induced testicular damage.


Assuntos
Cádmio , Glucose , Ratos Sprague-Dawley , Testículo , Animais , Masculino , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Cádmio/toxicidade , Glucose/metabolismo , Ratos , Espermatogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espermatozoides/efeitos dos fármacos
11.
Toxicol In Vitro ; 100: 105916, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127087

RESUMO

Aberrant accumulation of dysfunctional mitochondria in renal cells during hyperglycemia signifies perturbed autophagy and mitochondrial turnover. This study aims to focus on the underlying mechanism involved in autophagy and mitophagy inducing efficacy of Berberine (isoquinoline alkaloid) in hyperglycemic NRK-52E cells. Berberine mediated protection to hyperglycemic cells prevented alteration in mitochondrial structure and function. Treatment with SRT-1720 (Sirt1 activator) enhanced autophagy, decreased apoptosis, upregulated expression of downstream moieties (FoxO3a and Bnip3) and ameliorated mitochondria related anomalies while nicotinamide (Sirt1 inhibitor) treatment exhibited reversal of the same. GFP reporter assay ascertained enhanced transcriptional activity of FoxO in Berberine-treated hyperglycemic cells, which was found to be correlated to increased expression of downstream protein Bnip3. Knocking down FoxO3a disrupted autophagy and stimulated apoptosis. N-acetyl-L-cysteine pre-treatment confirmed that generation of ROS intervened high glucose induced toxicity in NRK-52E cells. Berberine co-treatment resulted in differential expressions of key proteins involved in autophagy and mitophagy like LC3B, ATGs, Beclin1, Sirt1, Bnip3, FoxO3a and Parkin. Further, enhanced mitophagy in Berberine-treated cells was confirmed by transmission electron microscopy. Thus, our findings give evidence that the protection accorded by Berberine against hyperglycemia in renal proximal tubular cells (NRK-52E) involves instigation of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitophagy induction.


Assuntos
Autofagia , Berberina , Proteína Forkhead Box O3 , Hiperglicemia , Proteínas de Membrana , Mitocôndrias , Sirtuína 1 , Animais , Berberina/farmacologia , Proteína Forkhead Box O3/metabolismo , Sirtuína 1/metabolismo , Sirtuína 1/genética , Ratos , Autofagia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linhagem Celular , Hiperglicemia/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Espécies Reativas de Oxigênio/metabolismo , Glucose , Mitofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Proteínas Mitocondriais
12.
Int J Biol Macromol ; 277(Pt 4): 134523, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111492

RESUMO

The present study reports the green synthesis of pectin-fabricated silver nanocomposites (Pectin-AgNPs) using Carpesium nepalense leaves extract, evaluating their bactericidal kinetics, in vivo hepatoprotective, and cytotoxic potentials along with possible mechanisms. GC/MS and LC/MS analyses revealed novel phytochemicals in the plant extract. The Pectin-AgNPs were characterized using UV/Vis, AFM, SEM, TEM, DLS, FTIR, and EDX techniques, showing a spherical morphology with a uniform size range of 50-110 nm. Significant antibacterial activity (P < 0.005) was found against four bacterial strains with ZIs of 4.1 ± 0.15 to 27.2 ± 3.84 mm. AFM studies revealed significant bacterial cell membrane damage post-treatment. At 0.05 mg/kg, the nanocomposites showed significant (P < 0.005) hepatoprotective activity in biochemical and histopathology analyses compared to the CCl4 control group. Pectin-AgNPs significantly reduced (P < 0.005) LDH, AST, ALT, ALP, and DB levels. qPCR analysis showed ameliorative effects on PPARs and Nrf2 gene expression, restoring gene alterations caused by CCl4 intoxication. In vivo acute toxicity studies confirmed low toxicity of Pectin-AgNPs in major organs. Pectin-AgNPs exhibited cytotoxic activity against HeLa cell lines at higher doses with an LC50 of 223.7 µg/mL. These findings demonstrate the potential of Pectin-AgNPs as promising antibacterial, hepatoprotective, and cytotoxic agents.


Assuntos
Antibacterianos , Química Verde , Nanocompostos , Pectinas , Prata , Nanocompostos/química , Prata/química , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Pectinas/química , Pectinas/farmacologia , Humanos , Animais , Asteraceae/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cinética , Nanopartículas Metálicas/química , Masculino , Células HeLa , Ratos , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/síntese química , Testes de Sensibilidade Microbiana , Camundongos , Tetracloreto de Carbono
13.
Part Fibre Toxicol ; 21(1): 30, 2024 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-39118174

RESUMO

Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.


Assuntos
Barreira Hematotesticular , Desoxiadenosinas , Nanopartículas , Poliestirenos , Espermatogênese , Testículo , Animais , Masculino , Desoxiadenosinas/farmacologia , Barreira Hematotesticular/efeitos dos fármacos , Poliestirenos/toxicidade , Nanopartículas/toxicidade , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Simulação de Acoplamento Molecular , Microplásticos/toxicidade , Receptor 4 Toll-Like/metabolismo , Apoptose/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Substâncias Protetoras/farmacologia
14.
Food Funct ; 15(18): 9149-9164, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39157920

RESUMO

The hepatoprotective effects of kiwifruit seed oil (KSO) were evaluated on acute liver injury (ALI) induced by carbon tetrachloride (CCl4) in vivo. Network pharmacology was used to predict active compounds and targets. Metabolomics and gut microbiota analyses were used to discover the activity mechanism of KSO. KSO improved the liver histological structure, significantly reduced serum proinflammatory cytokine levels, and increased liver antioxidant capacity. The metabolomics analysis showed that KSO may have hepatoprotective effects by controlling metabolites through its participation in signaling pathways like tryptophan metabolism, glycolysis/gluconeogenesis, galactose metabolism, and bile secretion. The gut microbiota analysis demonstrated that KSO improved the composition and quantity of the gut flora. Network pharmacological investigations demonstrated that KSO operated by altering Ptgs2, Nos2, Ppara, Pparg and Serpine1 mRNA levels. All evidence shows that KSO has a hepatoprotective effect, and the mechanism is connected to the regulation of metabolic disorders and intestinal flora.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Fígado , Metabolômica , Óleos de Plantas , Sementes , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Tetracloreto de Carbono/efeitos adversos , Masculino , Óleos de Plantas/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Sementes/química , Camundongos , Substâncias Protetoras/farmacologia , Ratos
15.
Food Funct ; 15(18): 9298-9314, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39163024

RESUMO

High Fischer ratio oligopeptides derived from Antarctic krill (HFOPs-AK) were screened, and their hepatoprotective effects and potential mechanisms were investigated. Herein, HFOPs-AK, with a Fischer ratio of 29 g/g (40.22 mol/mol) (MW < 1000 Da), were prepared via two-step enzymatic hydrolysis using chymotrypsin and flavourzyme and aromatic amino acid removal. Seventy-eight characteristic peptides were identified from HFOPs-AK through UHPLC-Q/TOF, with peptides containing Leu, Val, or Ile accounting for 79%. High hepatoprotective peptides were purified using GFC and RP-HPLC and identified as SDELGW and LLGWDDM. Furthermore, a murine model of acute liver injury induced by alcohol was successfully established. It was demonstrated that the oral administration of HFOPs-AK (800 mg per kg bw per d) remarkably increased the contents of ADH and ALDH compared with the model group, reaching 3.40 and 5.10 U mg-1 prot, respectively. Further, it was revealed that HFOPs-AK could effectively mitigate hepatic oxidative stress by increasing the levels of GSH-Px (p < 0.01) and decreasing the level of MDA (p < 0.05). Additionally, HFOPs-AK (800 mg per kg bw per d) attenuated liver inflammation by down-regulating the mRNA levels of TNF-α, IL-1ß, and IL-6 by 40.45%, 38.48%, and 35.83%, respectively. Therefore, HFOPs-AK may have the potential as a new nutritional supplement for the treatment of alcoholic liver injury.


Assuntos
Euphausiacea , Fígado , Oligopeptídeos , Estresse Oxidativo , Animais , Euphausiacea/química , Camundongos , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Regiões Antárticas
16.
Bioorg Chem ; 152: 107732, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39178702

RESUMO

Phytochemical analysis of the peeled stems of Syringa pinnatifolia Hemsl. led to the discovery of 13 undescribed lignans, namely helanols A and B (1 and 2) and alashanenols W-G1 (3-13), as well as four known analogues, of which helanols A and B were lignans with novel skeleton of α-ß' linkage. The structures were unambiguously established by extensive spectroscopic analyses, NMR calculations, ECD calculations, and single crystal X-ray crystallography. Five lignans (1, 2, 5, 11 and 13) exhibited a moderate protective effect against H2O2-induced oxidative injuries in H9c2 cells with the protective rates of 11.3-20.6 % at the concentration of 0.3-20 µM, while the positive control quercetin showed protective rates of 58.7 % at 10 µM. Further mechanism investigation suggested that 1 and 2 exerted the protective effect by regulating the expression of Nrf2/HO-1.


Assuntos
Peróxido de Hidrogênio , Lignanas , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Syringa , Lignanas/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Fator 2 Relacionado a NF-E2/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Syringa/química , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Animais , Relação Dose-Resposta a Droga , Heme Oxigenase-1/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos
17.
Fish Shellfish Immunol ; 153: 109824, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127393

RESUMO

Plantago asiatica seeds (PS) are commonly used as a medicinal plant. This study investigates the efficacy of PS against heavy metal toxicity in white shrimp (Penaeus vannamei). After feeding PS diet (5 g/kg) or basal diet (control group) for 7 days, shrimps were exposed to sublethal concentrations of heavy metals in seawater (As: 12 mg/L, Pb: 250 mg/L, Hg: 0.4 mg/L). The 7-day survival observation showed that the survival in groups fed with PS were significantly higher than that in the control group, revealing that dietary PS had the efficacy to mitigate heavy metal toxicity in white shrimp. Under the same feeding condition, white shrimps were exposed to safety dose of heavy metals (1/10 of sublethal concentrations) to understand the mechanism of mitigation. The metal accumulations in haemolymph, gills, hepatopancreas, and muscle tissues as well as the immune, anti-oxidative, stress related gene expressions in haemocytes, gills and hepatopancreas were measured for 14 days. The As accumulation in gills and hepatopancreas of groups fed with PS were significantly lower than those of control group on day 7 and 14, respectively; The Pb concentration in haemolymph of group fed with PS was significantly lower than that of control group on day 7 and 14; The Hg concentration in hepatopancreas of the group fed with PS was significantly lower than that of control group on day 7. Dietary PS could mitigate heavy metal-induced immune suppression, oxidative stress, and stress response by positively regulating immune (proPO I, Toll, IMD), antioxidant (SOD, GST, Trx), and negatively regulating stress response genes (HSP70, MT). The present study demonstrated that dietary PS could protect white shrimp against metal toxicity by reducing metal accumulations and regulating the immune, antioxidant, and stress response gene expressions in specific tissue. Therefore, PS may serve as a beneficial feed additive in the aquaculture.


Assuntos
Ração Animal , Dieta , Penaeidae , Plantago , Sementes , Poluentes Químicos da Água , Animais , Penaeidae/imunologia , Penaeidae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Sementes/química , Ração Animal/análise , Dieta/veterinária , Plantago/química , Metais Pesados/toxicidade , Suplementos Nutricionais/análise , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Arsênio/toxicidade , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Brânquias/imunologia
18.
Plant Physiol Biochem ; 215: 109059, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39178802

RESUMO

Industrialization-driven surface ozone (O3) pollution significantly impairs plant growth. This study evaluates the effectiveness of exogenous protectants [3 mg L⁻1 abscisic acid (ABA), 400 mg L⁻1 ethylenediurea (EDU), and 80 mg L⁻1 spermidine (Spd)] on Trifolium repens subjected to O3 stress in open-top chambers, focusing on plant growth and dynamics of culturable endophytic fungal communities. Results indicate that O3 exposure adversely affects photosynthesis, reducing root biomass and altering root structure, which further impacts the ability of plant to absorb essential nutrients such as potassium (K), magnesium (Mg), and zinc (Zn). Conversely, the application of ABA, EDU, and Spd significantly enhanced total biomass and chlorophyll content in T. repens. Specifically, ABA and Spd significantly improved root length, root surface area, and root volume, while EDU effectively reduced leaves' malondialdehyde levels, indicating decreased oxidative stress. Moreover, ABA and Spd treatments significantly increased leaf endophytic fungal diversity, while root fungal abundance declined. The relative abundance of Alternaria in leaves was substantially reduced by these treatments, which correlated with enhanced chlorophyll content and photosynthesis. Concurrently, EDU and Spd treatments increased the abundance of Plectosphaerella, enhance the absorption of K, Ca, and Mg. In roots, ABA treatment increased the abundance of Paecilomyces, while Spd treatment enhanced the presence of Stemphylium, linked to improved nitrogen (N), phosphorus (P), and K uptake. These findings suggest that specific symbiotic fungi mitigate O3-induced stress by enhancing nutrient absorption, promoting growth. This study highlights the potential of exogenous protectants to enhance plant resilience against O3 pollution through modulating interactions with endophytic fungal communities.


Assuntos
Ozônio , Trifolium , Trifolium/microbiologia , Trifolium/efeitos dos fármacos , Trifolium/crescimento & desenvolvimento , Ozônio/farmacologia , Endófitos/efeitos dos fármacos , Endófitos/fisiologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Folhas de Planta/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Clorofila/metabolismo , Fotossíntese/efeitos dos fármacos , Fungos/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Biomassa , Compostos de Fenilureia
19.
J Nutr Biochem ; 133: 109719, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39103108

RESUMO

This study investigated the protective effect of dulcitol on LPS-induced intestinal injury in piglets and explored the underlying molecular mechanisms. A total of 108 piglets were divided into three groups: CON, LPS, and DUL. The CON and LPS groups were fed a basal diet, the DUL group was fed a diet supplementation with 500 mg/kg dulcitol. On day 29, 6 piglets in the LPS and DUL groups were injected with 100 µg/kg BW of LPS. At 4 h postchallenge, all pigs were slaughtered, and colonic samples were collected. Results showed that dulcitol supplementation boosted intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, and increasing the gene expression of zonula occludens-1, claudin-1, and occludin in the colonic mucosa (P <0.05). Metabolomics showed DUL supplementation mainly increased (P <0.05) the metabolites related to steroid and vitamin metabolism (Cholesterol and Vitamin C). Proteomics showed that dulcitol supplementation altered the protein expression involved in maintaining barrier integrity (FN1, CADM1, and PARD3), inhibiting inflammatory response (SLP1, SFN, and IRF3), and apoptosis (including FAS, ING1, BTK, MTHFR, NOX, and P53BP2) in LPS-challenged piglets (P <0.05). Additionally, dulcitol addition also suppressed the TLR4/NF-κB signaling pathway and apoptosis in mRNA and protein levels. Dulcitol increased the abundance of short-chain fatty acid-producing bacteria (Lactobacillus, Blautia, and Faecalibacterium) at the genus level, but decreased the relative abundance of Proteobacteria at the phylum level and Pseudomonas and Delftia at the genus level in piglets (P<.05). In conclusion, these results suggested that the addition of dulcitol alleviated LPS-induced intestinal barrier injury in piglets, probably by maintaining its integrity, inhibiting the TLR4/NF-κB signaling pathways and apoptosis, and modulating the gut microbiota. Therefore, dulcitol can be considered a potential dietary additive for improving intestinal health in pig models.


Assuntos
Suplementos Nutricionais , Mucosa Intestinal , Lipopolissacarídeos , Animais , Lipopolissacarídeos/toxicidade , Suínos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Enteropatias/induzido quimicamente , Enteropatias/prevenção & controle , Enteropatias/metabolismo , Intestinos/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Apoptose/efeitos dos fármacos , Masculino
20.
J Agric Food Chem ; 72(34): 18918-18929, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39140375

RESUMO

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'-O-gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.


Assuntos
Biflavonoides , Catequina , Proantocianidinas , Substâncias Protetoras , Vitis , Proantocianidinas/química , Proantocianidinas/farmacologia , Biflavonoides/química , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Catequina/análogos & derivados , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Animais , Vitis/química , Ratos , Sementes/química , Humanos , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Linhagem Celular , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Polímeros/química , Polímeros/farmacologia
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