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Trilobatin, a novel natural food additive, exerts a protective effect on acute liver injury. However, whether Trilobatin can protect against alcoholic liver disease (ALD) has not been elucidated. This research is intended to ascertain the impact of Trilobatin on ALD in mice and decipher the potential underlying mechanisms. Lieber-DeCarli liquid alcohol diet was used to induce ALD in mice, followed by administration of Trilobatin (10, 20, 40 mg·kg-1·d-1) for 15 days. The results suggested that Trilobatin significantly alleviated ethanol-induced hepatic injury in mice. Furthermore, RNA-Seq analysis revealed that yes-associated protein (YAP) downregulation occurred in the liver after Trilobatin treatment. Mechanistically, Trilobatin directly bound to YAP and hindered its nuclear translocation, which activated the Nrf2 pathway to reduce pro-inflammatory cytokines and oxidative stress. Intriguingly, 16S rDNA analysis results revealed that Trilobatin reshaped the gut microbiota, reducing harmful bacteria and increasing beneficial bacteria. It also enhanced tight junction proteins, defending against damage to the intestinal barrier. These findings not only highlight the microbiota-gut-liver axis and YAP/Nrf2 pathway as crucial potential targets to treat ALD but also reveal that Trilobatin effectively protects against ALD, at least partly, through modulating the microbiota-gut-liver axis and YAP/Nrf2 pathway.
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N6-methyladenosine (m6A) is one of the most common modifications of RNA in eukaryotic cells and is involved in mRNA metabolism, including stability, translation, maturation, splicing, and export. m6A also participates in the modification of multiple types of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, thereby affecting their metabolism and functions. Increasing evidence has revealed that m6A regulators, such as writers, erasers, and readers, perform m6A-dependent modification of ncRNAs, thus affecting cancer progression. Moreover, ncRNAs modulate m6A regulators to affect cancer development and progression. In this review, we summarize recent advances in understanding m6A modification and ncRNAs and provide insights into the interaction between m6A modification and ncRNAs in cancer. We also discuss the potential clinical applications of the mechanisms underlying the interplay between m6A modifications and ncRNAs in acute myeloid leukemia (AML). Therefore, clarifying the mutual regulation between m6A modifications and ncRNAs is of great significance to identify novel therapeutic targets for AML and has great clinical application prospects.
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Adenosina , Leucemia Mieloide Aguda , RNA não Traduzido , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , AnimaisRESUMO
Plant-microbe interactions are pivotal for ecosystem dynamics and sustainable agriculture, and are influenced by various factors, such as host characteristics, environmental conditions, and human activities. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, have revolutionized our understanding of these interactions. Genomics elucidates key genes, transcriptomics reveals gene expression dynamics, proteomics identifies essential proteins, and metabolomics profiles small molecules, thereby offering a holistic perspective. This review synthesizes diverse microbial-plant interactions, showcasing the application of omics in understanding mechanisms, such as nitrogen fixation, systemic resistance induction, mycorrhizal association, and pathogen-host interactions. Despite the challenges of data integration and ethical considerations, omics approaches promise advancements in precision intervention and resilient agricultural practices. Future research should address data integration challenges, enhance omics technology resolution, explore epigenomics, and understand plant-microbe dynamics under diverse conditions. In conclusion, omics technologies hold immense promise for optimizing agricultural strategies and fortifying resilient plant-microbe alliances, paving the way for sustainable agriculture and environmental stewardship.
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Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.
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BACKGROUND: Aging is associated with learning and memory disorder, affecting multiple brain areas, especially the hippocampus. Previous studies have demonstrated trilobatin (TLB), as a natural food additive, can extend the life of Caenorhabditis elegans and exhibit neuroprotection in Alzheimer's disease mice. However, the possible significance of TLB in anti-aging remains elusive. PURPOSE: This study aimed to delve into the physiological mechanism by which TLB ameliorated aging-induced cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: 6-month-old SAMP8 mice were administrated with TLB (5, 10, 20 mg/kg/day, i.g.) for 3 months. The therapeutic effect of TLB on aging-induced cognitive impairment was assessed in mice using behavioral tests and aging score. The gut microbiota composition in fecal samples was analyzed by metagenomic analysis. The protective effects of TLB on blood-brain barrier (BBB) and intestinal barrier were detected by transmission electron microscope, H&E staining and western blot (WB) assay. The inhibitive effects of TLB on inflammation in brain and intestine were assessed using immunofluorescence, WB and ELISA assay. Molecular docking and surface plasma resonance (SPR) assay were utilized to investigate interaction between TLB and sirtuin 2 (SIRT2). RESULTS: Herein, the findings exhibited TLB mitigated aging-induced cognitive impairment, neuron injury and neuroinflammation in hippocampus of aged SAMP8 mice. Moreover, TLB treatment repaired imbalance of gut microbiota in aged SAMP8 mice. Furthermore, TLB alleviated the damage to BBB and intestinal barrier, concomitant with reducing the expression of SIRT2, phosphorylated levels of c-Jun NH2 terminal kinases (JNK) and c-Jun, and expression of MMP9 protein in aged SAMP8 mice. Molecular docking and SPR unveiled TLB combined with SIRT2 and down-regulated SIRT2 protein expression. Mechanistically, the potential mechanism of SIRT2 in TLB that exerted anti-aging effect was validated in vitro. As expected, SIRT2 deficiency attenuated phosphorylated level of JNK in HT22 cells treated with d-galactose. CONCLUSION: These findings reveal, for the first time, SIRT2-mediated brain-gut barriers contribute to aging and aging-related diseases, and TLB can rescue aging-induced cognitive impairment by targeting SIRT2 and restoring gut microbiota disturbance to mediate the brain-gut axis. Overall, this work extends the potential application of TLB as a natural food additive in aging-related diseases.
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Envelhecimento , Eixo Encéfalo-Intestino , Disfunção Cognitiva , Microbioma Gastrointestinal , Sirtuína 2 , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Camundongos , Envelhecimento/efeitos dos fármacos , Sirtuína 2/metabolismo , Masculino , Eixo Encéfalo-Intestino/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Simulação de Acoplamento Molecular , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de DoençasRESUMO
Rosa roxburghii Tratt (RRT), known as chestnut rose, has been a subject of growing interest because of its diverse chemical composition and wide range of traditional uses. This comprehensive review aimed to thoroughly examine RRT, including its traditional applications, chemical diversity, and various bioactivities. The chemical profile of this plant is characterized by the presence of essential nutrients such as vitamin C (ascorbic acid), flavonoids, triterpenes, organic acids, tannins, phenolic compounds, polysaccharides, carotenoids, triterpenoids, volatile compounds, amino acids, and essential oils. These constituents contribute to the medicinal and nutritional value. Additionally, we explore the multifaceted bioactivities of RRT, including its potential as an anticancer agent, antioxidant, antiaging agent, antiatherogenic agent, hypoglycemic agent, immunoregulatory modulator, radioprotective agent, antimutagenic agent, digestive system regulator, anti-inflammatory agent, cardioprotective agent, and antibacterial agent, and its intriguing role in modulating the gut microbiota. Furthermore, we discuss the geographical distribution and genetic diversity of this plant species and shed light on its ecological significance. This comprehensive review provides a holistic understanding of RRT, bridges traditional knowledge with contemporary scientific research, and highlights its potential applications in medicine, nutrition, and pharmacology.
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Rosa , Humanos , Rosa/química , Animais , Extratos Vegetais/farmacologia , Medicina Tradicional/métodos , Compostos Fitoquímicos/farmacologiaRESUMO
Dendrobium nobile is the largest species of the Orchidaceae family and produces dendrobine, a compound with medicinal properties (Sarsaiya et al., 2020a; Sarsaiya et al., 2024; Qian et al., 2024). The accumulation of dendrobine in D. nobile is regulated by various pathogenic fungi, which directly and indirectly influence dendrobine biosynthesis (Sarsaiya et al., 2019a; Sarsaiya et al., 2019b). In a field planted with D. nobile in Guizhou Province, China, small lesions were initially observed on the upper part of the leaves from May to June 2019, which later developed into larger brown necrotic leaf lesions. Over time, these lesions greatly impacted the medicinal value (dendrobine) and productivity of the plant. A pure culture of Xylaria flabelliformis from infected wild D. nobile leaves was recovered and subsequently cultured on potato dextrose agar (PDA) at 25 °C for 5 days. Xylaria flabelliformis grew slowly and was composed of white mycelia. Colonies were initially white, with a regular margin, and formed stromata that consisted of mycelia sterilia without ascospores. We identified the strain as Xylaria flabelliformis based on its morphological characteristics (Liu et al., 2007) and by sequencing elongation factor-1α (EF-1α). The length of the DNA sequence of EF-1α that was used for the analysis of Xylaria flabelliformis was 1188 bp. BLASTx (nucleotide 6-frame translation-protein) analysis using the National Center for Biotechnology Information database showed that the obtained protein sequence (BLASTx protein accession no.: UTS95822.1, BLASTn nucleotide sequence accession no.: MW508334.1) had the highest similarity (98.21%) with the X. flabelliformis hypothetical protein (TRX95197.1) based on a thorough phylogenetic comparison with other Xylaria species. Healthy D. nobile seedlings were planted in pots and sterilized. The terminal leaves were excised from all pre-sterilised D. nobile seedlings and inoculated with Xylaria flabelliformis mycelial plugs, whereas sterile PDA plugs and moist cotton plugs were used as controls. All seedlings were maintained under optimum temperature and humidity conditions (25 °C and 80%, respectively) for seven days for observation and analysis. All experiments were performed in triplicate. After the incubation period, brown leaf rot lesions were observed for the first time on the inoculated D. nobile leaves, but no symptoms were observed on the leaves of the two control groups (sterile PDA plugs and moist cotton plugs). To complete Koch's postulates, Xylaria flabelliformis was re-isolated and identified from all diseased tissues by DNA sequencing of the EF-1α. It was determined for the first time that Xylaria flabelliformis can cause brown leaf lesions in D. nobile. Moreover, the pathogenicity of Xylaria flabelliformis in D. nobile has not been previously reported (Mead et al., 2019; Meng et al., 2019; Sarsaiya et al., 2019a; Sarsaiya et al., 2020b; Chen et al., 2023; Rinchen, 2023; Cao et al., 2024). To the best of our knowledge, this is the first report of BLRS lesions in D. nobile leaves caused by Xylaria flabelliformis in Guizhou Province, China. Identification of Xylaria flabelliformis as a pathogen of D. nobile is crucial for advancing effective management and control practices against brown leaf rot disease. This discovery provides valuable insights into the development of targeted strategies to mitigate the impact of Xylaria flabelliformis on D. nobile, safeguard medicinal properties such as dendrobine, and enhance overall productivity.
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Introduction: Dendrobine, a valuable alkaloid found in Dendrobium nobile, possesses significant pharmaceutical potential. Methods: In this study, we explored innovative approaches to enhance dendrobine production by utilizing endophytic fungi in a Temporary Immersion Bioreactor System (TIBS, Nanjing BioFunction Co. Ltd., China) and traditional test bottles. Dendrobine was unequivocally identified and characterised in D. nobile co-culture seedlings through UHPLC analysis and LC-MS qTOF analysis, supported by reference standards. Results: The CGTB (control group) and EGTB (experimental group) 12-month-old D. nobile seedlings exhibited similar peak retention times at 7.6±0.1 minutes, with dendrobine identified as C16H25NO2 (molecular weight 264.195). The EGTB, co-cultured with Trichoderma longibrachiatum (MD33), displayed a 2.6-fold dendrobine increase (1804.23 ng/ml) compared to the CGTB (685.95 ng/ml). Furthermore, a bioanalytical approach was applied to investigate the mono-culture of T. longibrachiatum MD33 with or without D. nobile seedlings in test bottles. The newly developed UHPLC-MS method allowed for dendrobine identification at a retention time of 7.6±0.1 minutes for control and 7.6±0.1 minutes for co-culture. Additionally, we explored TIBS to enhance dendrobine production. Co-culturing D. nobile seedlings with Trichoderma longibrachiatum (MD33) in the TIBS system led to a substantial 9.7-fold dendrobine increase (4415.77 ng/ml) compared to the control (454.01 ng/ml) after just 7 days. The comparative analysis of dendrobine concentration between EGTB and EGTIBS highlighted the remarkable potential of TIBS for optimizing dendrobine production. Future research may focus on scaling up the TIBS approach for commercial dendrobine production and investigating the underlying mechanisms for enhanced dendrobine biosynthesis in D. nobile. The structural elucidation of dendrobine was achieved through 1H and 13C NMR spectroscopy, revealing a complex array of proton environments and distinct carbon environments, providing essential insights for the comprehensive characterization of the compound. Discussion: These findings hold promise for pharmaceutical and industrial applications of dendrobine and underline the role of endophytic fungi in enhancing secondary metabolite production in medicinal plants.
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BACKGROUND AND PURPOSE: Blood-brain barrier (BBB) breakdown is one of the crucial pathological changes of cerebral ischaemia-reperfusion (I/R) injury. Trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effects against cerebral I/R injury as demonstrated in our previous study. This study was designed to investigate the effect of TLB on BBB disruption after cerebral I/R injury. EXPERIMENTAL APPROACH: Rats with focal cerebral ischaemia caused by transient middle cerebral artery occlusion were studied along with brain microvascular endothelial cells and human astrocytes to mimic BBB injury caused by oxygen and glucose deprivation/reoxygenation (OGD/R). KEY RESULTS: The results showed that TLB effectively maintained BBB integrity and inhibited neuronal loss following cerebral I/R challenge. Furthermore, TLB increased tight junction proteins including ZO-1, Occludin and Claudin 5, and decreased the levels of apolipoprotein E (APOE) 4, cyclophilin A (CypA) and phosphorylated nuclear factor kappa B (NF-κB), thereby reducing proinflammatory cytokines. TLB also decreased the Bax/Bcl-2 ratio and cleaved-caspase 3 levels along with a reduced number of apoptotic neurons. Molecular docking and transcriptomics predicted MMP9 as a prominent gene evoked by TLB treatment. The protective effects of TLB on cerebral I/R-induced BBB breakdown was largely abolished by overexpression of MMP9, and the beneficial effects of TLB on OGD/R-induced loss of BBB integrity in human brain microvascular endothelial cells and astrocyte co-cultures was markedly reinforced by knockdown of MMP9. CONCLUSIONS AND IMPLICATIONS: Our findings reveal a novel property of TLB: preventing BBB disruption following cerebral I/R via targeting MMP9 and inhibiting APOE4/CypA/NF-κB axis.
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Isquemia Encefálica , Flavonoides , Polifenóis , Traumatismo por Reperfusão , Ratos , Humanos , Animais , Barreira Hematoencefálica/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Aditivos Alimentares/metabolismo , Aditivos Alimentares/farmacologia , Células Endoteliais/metabolismo , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Isquemia Encefálica/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismoRESUMO
Naturally derived alkaloids belong to a class of quite significant organic compounds. Coptisine, a benzyl tetrahydroisoquinoline alkaloid, is one of the major bioactive constituents in Coptis chinensis Franch., which is a famous traditional Chinese medicine. C. chinensis possesses many kinds of functions, including the ability to eliminate heat, expel dampness, purge fire, and remove noxious substances. In Asian countries, C. chinensis is traditionally employed to treat carbuncle and furuncle, diabetes, jaundice, stomach and intestinal disorders, red eyes, toothache, and skin disorders. Up to now, there has been plenty of research of coptisine with respect to its pharmacology. Nevertheless, a comprehensive review of coptisine-associated research is urgently needed. This paper was designed to summarize in detail the progress in the research of the pharmacology, pharmacokinetics, safety, and formulation of coptisine. The related studies included in this paper were retrieved from the following academic databases: The Web of Science, PubMed, Google scholar, Elsevier, and CNKI. The cutoff date was January 2023. Coptisine manifests various pharmacological actions, including anticancer, antimetabolic disease, anti-inflammatory disease, and antigastrointestinal disease effects, among others. Based on its pharmacokinetics, the primary metabolic site of coptisine is the liver. Coptisine is poorly absorbed in the gastrointestinal system, and most of it is expelled in the form of its prototype through feces. Regarding safety, coptisine displayed potential hepatotoxicity. Some novel formulations, including the [Formula: see text]-cyclodextrin-based inclusion complex and nanocarriers, could effectively enhance the bioavailability of coptisine. The traditional use of C. chinensis is closely connected with the pharmacological actions of coptisine. Although there are some disadvantages, including poor solubility, low bioavailability, and possible hepatotoxicity, coptisine is still a prospective naturally derived drug candidate, especially in the treatment of tumors as well as metabolic and inflammatory diseases. Further investigation of coptisine is necessary to facilitate the application of coptisine-based drugs in clinical practice.
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Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Coptis , Medicamentos de Ervas Chinesas , Neoplasias , Humanos , Coptis chinensis , Estudos Prospectivos , Coptis/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: Fulminant hepatic failure (FHF) lacks efficient therapies notwithstanding increased comprehending of the inflammatory response and oxidative stress play crucial roles in the pathogenesis of this type of hepatic damage. Trilobatin (TLB), a naturally occurring food additive, is endowed with anti-inflammation and antioxidant properties. PURPOSE: In current study, we evaluated the effect of TLB on FHF with a mouse model with d-galactosamine/lipopolysaccharide (GalN/LPS)-induced FHF and LPS-stimulated Kupffer cells (KCs) injury. METHODS: Mice were randomly divided into seven groups: control group, TLB 40 mg/kg + control group, GalN/LPS group, TLB 10 mg/kg + GalN/LPS group, TLB 20 mg/kg + GalN/LPS group, TLB 40 mg/kg + GalN/LPS group, bifendate 150 mg/kg + GalN/LPS group. The mice were administered intragastrically TLB (10, 20 and 40 mg/kg) for 7 days (twice a day) prior to injection of GalN (700 mg/kg)/LPS (100 µg/kg). The KCs were pretreated with TLB (2.5, 5, 10 µM) for 2 h or its analogue (10 µM) or COX2 inhibitor (10 µM), and thereafter challenged by LPS (1 µg/ml) for 24 h. RESULTS: TLB effectively rescued GalN/LPS-induced FHF. Furthermore, TLB inhibited TLR 4/NLRP3/pyroptosis pathway, and caspase 3-dependent apoptosis pathway, along with reducing excessive cellular and mitochondrial ROS generation and enhancing mitochondrial biogenesis. Intriguingly, TLB directly bound to COX2 as reflected by transcriptomics, molecular docking technique and surface plasmon resonance assay. Furthermore, TLB failed to attenuate LPS-induced inflammation and oxidative stress in KCs in the absence of COX2. CONCLUSION: Our findings discover a novel pharmacological effect of TLB: protecting against FHF-induced pyroptosis and apoptosis through mediating ROS/TLR4/NLRP3 signaling pathway and reducing inflammation and oxidative stress. TLB may be a promising agent with outstanding safety profile to treat FHF.
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Falência Hepática Aguda , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Ciclo-Oxigenase 2 , Espécies Reativas de Oxigênio , Receptor 4 Toll-Like , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/tratamento farmacológico , Transdução de SinaisRESUMO
Nuclear factor erythroid 2-related factor 2 (Nrf2)/silent mating type information regulation 2 homolog 3 (SIRT3) signaling pathway plays a pivotal role in regulating mitochondrial dynamics and oxidative stress, which are considered to be the principal pathogenesis of myocardial infarction (MI). Our previous study proved that pretreatment with icariside II (ICS II), a major active ingredient of Herbal Epimedii, exerts cardioprotective effect on MI, however, whether post-treatment with ICS II can alleviate MI and its underlying mechanism are still uncertain. Therefore, the present study was designed to investigate the therapeutic effect and the possible mechanism of ICS II on MI both in vivo and in vitro. The results revealed that post-treatment with ICS II markedly ameliorated myocardial injury in MI-induced mice and mitigated oxygen and glucose deprivation (OGD)-elicited cardiomyocyte injury. Further researches showed that ICS II promoted mitochondrial fusion, and suppressed mitochondrial fission and oxidative stress, which were achieved by facilitating the nuclear translocation of Nrf2 and activation of SIRT3. In summary, our findings indicate that ICS II mitigates MI-induced mitochondrial dynamics disorder and oxidative stress via activating the Nrf2/SIRT3 signaling pathway.
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Infarto do Miocárdio , Sirtuína 3 , Camundongos , Animais , Dinâmica Mitocondrial , Sirtuína 3/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Estresse Oxidativo , Transdução de Sinais , ApoptoseRESUMO
Ulcerative colitis (UC) is a chronic aspecific gut inflammatory disorder that primarily involves the recta and colons. It mostly presents as a long course of repeated attacks. This disease, characterized by intermittent diarrhoea, fecal blood, stomachache, and tenesmus, severely decreases the living quality of sick persons. UC is difficult to heal, has a high recurrence rate, and is tightly related to the incidence of colon cancer. Although there are a number of drugs available for the suppression of colitis, the conventional therapy possesses certain limitations and severe adverse reactions. Thus, it is extremely required for safe and effective medicines for colitis, and naturally derived flavones exhibited huge prospects. This study focused on the advancement of naturally derived flavones from edible and pharmaceutical plants for treating colitis. The underlying mechanisms of natural-derived flavones in treating UC were closely linked to the regulation of enteric barrier function, immune-inflammatory responses, oxidative stress, gut microflora, and SCFAs production. The prominent effects and safety of natural-derived flavones make them promising candidate drugs for colitis treatment.
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Calcium-sensing receptor (CaSR) is a G protein-coupled receptor, widely distributed in various tissues, including vascular endothelial cells and smooth muscle cells, which plays an important role in the migration and homing of stem/progenitor cells and the proliferation of tissue cells. Restenosis after Percutaneous coronary intervention (PCI) seriously affects its prognosis and application. Our previous research has found that ginsenoside Rg1 (GS-Rg1) can inhibit the occurrence of restenosis after balloon injury of the common carotid artery in rats, but the mechanism is still unclear. In this study, it was found that GS-Rg1 (4, 8, 16 mg/kg) inhibited vascular restenosis caused by balloon injury, and mobilize endothelial progenitor cells (EPCs) to promote reendothelialization and inhibit intimal hyperplasia, which significantly reduced after administration of CaSR antagonist NPS 2143. Interestingly, CaSR and its downstream JNK, P38 were highly expressed in the proliferative intima and participated in the abnormal proliferation of vascular smooth muscle cells mediated by smooth muscle progenitor cells (SMPCs). GS-Rg1 inhibited intimal hyperplasia, while it decreased the expression of CaSR, JNK, and P38. This might relate to the distribution of CaSR and the facilitation of GS-Rg1 on the vascular endothelial repair. It is concluded that CaSR plays a key role in GS-Rg1 promoting reendothelialization to inhibit intimal hyperplasia after balloon Injury.
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Células Progenitoras Endoteliais , Intervenção Coronária Percutânea , Ratos , Animais , Hiperplasia , Receptores de Detecção de Cálcio , Constrição PatológicaRESUMO
Cerebral ischemia/reperfusion causes exacerbated neuronal damage involving excessive neuroinflammation and oxidative stress. ROS is considered a signal molecule to activate NLRP3; thus, the ROS/NLRP3/pyroptosis axis plays a vital role in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI). Therefore, targeting the inhibition of the ROS/NLRP3/pyroptosis axis may be a promising therapeutic tactic for CIRI. Epimedium (EP) contains many active ingredients (ICA, ICS II, and ICT), which have a wide range of pharmacological activities. However, whether EP can protect against CIRI remains unknown. Thus, in this study, we designed to investigate the effect and possible underlying mechanism of EP on CIRI. The results showed that treatment with EP dramatically mitigated brain damage in rats following CIRI, which was achieved by suppressing mitochondrial oxidative stress and neuroinflammation. Furthermore, we identified the ROS/NLRP3/pyroptosis axis as a vital process and NLRP3 as a vital target in EP-mediated protection. Most interestingly, the main compounds of EP directly bonded with NLRP3, as reflected by molecular docking, which indicated that NLRP3 might be a promising therapeutic target for EP-elicited cerebral protection. In conclusion, our findings illustrate that ICS II protects against neuron loss and neuroinflammation after CIRI by inhibiting ROS/NLRP3-mediated pyroptosis.
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INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.
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Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Derrame Pleural Maligno , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Tradicional Chinesa , Derrame Pleural Maligno/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Cisplatino/uso terapêuticoRESUMO
Arsenic resistance protein 2 (Ars2) is a nuclear protein that plays a critical role in the regulation of microRNA (miRNA) biogenesis. Ars2 is required for cell proliferation and for the early stages of mammalian development through a possible effect on miRNA processing. Increasing evidence reveal that Ars2 is highly expressed in proliferating cancer cells, suggesting that Ars2 may be a potential therapeutic target for cancer. Therefore, development of the novel Ars2 inhibitors could represent the novel therapeutic strategies for treatment of cancer. In this review, we briefly discuss the mechanisms by which Ars2 regulates miRNA biogenesis and its impact on cell proliferation and cancer development. Particularly, we mainly discuss the role of Ars2 in the regulation of cancer development and highlight pharmacological targeting of Ars2 as a promising cancer therapeutic strategy.
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Arsênio , MicroRNAs , Neoplasias , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proliferação de Células , Mamíferos/genética , Mamíferos/metabolismoRESUMO
BACKGROUND AND PURPOSE: Astrocytic nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a potential therapeutic target of ischaemic preconditioning (IPC). Icariside II (ICS II) is a naturally occurring flavonoid derived from Herba Epimedii with Nrf2 induction potency. This study was designed to clarify if exposure to ICS II mimicks IPC neuroprotection and if Nrf2 from astrocytes contributes to ICS II preconditioning against ischaemic stroke. EXPERIMENTAL APPROACH: Mice with transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischaemia and primary astrocytes challenged with oxygen-glucose deprivation (OGD) were used to explore the neuroprotective effect of ICS II preconditioning. Additionally, Nrf2-deficient mice were pretreated with ICS II to determine whether ICS II exerts its neuroprotection by activating Nrf2. KEY RESULTS: ICS II pretreatment mitigated cerebral injury in the mouse model of ischaemic stroke along with improving long-term recovery. Furthermore, proteomics screening identified Nrf2 as a crucial gene evoked by ICS II treatment and required for the anti-oxidative effect and anti-inflammatory effect of ICS II. Also, ICS II directly bound to Nrf2 and reinforced the transcriptional activity of Nrf2 after MCAO. Moreover, ICS II pretreatment exerted cytoprotective effects on astrocyte cultures following lethal OGD exposure, by promoting Nrf2 nuclear translocation and activating the OXPHOS/NF-κB/ferroptosis axis, while neuroprotection was decreased in Nrf2-deficient mice and Nrf2 siRNA blocked effects of ICS II. CONCLUSION AND IMPLICATIONS: ICS II preconditioning provides robust neuroprotection against ischaemic stroke via the astrocytic Nrf2-mediated OXPHOS/NF-κB/ferroptosis axis. Thus, ICS II could be a promising Nrf2 activator to treat ischaemic stroke.
Assuntos
Isquemia Encefálica , Ferroptose , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Camundongos , Animais , NF-kappa B/metabolismo , Neuroproteção , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/prevenção & controle , Isquemia Encefálica/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Cardiovascular diseases (CVD) are a group of cardiac and vascular disorders including myocardial ischemia, congenital heart disease, heart failure, hypertension, atherosclerosis, peripheral artery disease, rheumatic heart disease, and cardiomyopathies. Despite considerable progress in prophylaxis and treatment options, CVDs remain a leading cause of morbidity and mortality and impose an extremely high socioeconomic burden. Oxidative stress (OS) caused by disequilibrium in the generation of reactive oxygen species plays a crucial role in the pathophysiology of CVDs. Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor of endogenous antioxidant defense systems against OS, is considered an ideal therapeutic target for management of CVDs. Increasingly, natural products have emerged as a potential source of Nrf2 activators with cardioprotective properties and may therefore provide a novel therapeutic tool for CVD. Here, we present an updated comprehensive summary of naturally occurring products with cardioprotective properties that exert their effects by suppression of OS through activation of Nrf2 signaling, with the aim of providing useful insights for the development of therapeutic strategies exploiting natural products.