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BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disease caused by previous acute lung injury (ALI), but there is currently no satisfactory therapy available. Aerosol inhalation of medicine is an effective way for treating PF. Total ginsenosides (TG) shows potential for the treatment of ALI and PF, but the effects of inhaled TG remain unclear. PURPOSE: To determine the therapeutic effects of TG in ALI and PF, to assess the superiority of the inhaled form of TG over the routine form, and to clarify the mechanism of action of inhaled TG. METHODS: Ultrahigh-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UPLC-QE-MS) was applied to determine the chemoprofile of TG. A mouse model of ALI and PF was established to evaluate the effects of inhaled TG by using bronchoalveolar lavage fluid (BALF) analysis, histopathological observation, hydroxyproline assay, and immunohistochemical analysis. Primary mouse lung fibroblasts (MLF) and human lung fibroblast cell line (HFL1) were applied to determine the in vitro effects and mechanism of TG by using cell viability assay, quantitative real time PCR (qPCR) assay, and western blot (WB) analysis. RESULTS: The UPLC-QE-MS results revealed the main types of ginsenosides in TG, including Re (14.15 ± 0.42%), Rd (8.42 ± 0.49%), Rg1 (6.22 ± 0.42%), Rb3 (3.28 ± 0.01%), Rb2 (3.09 ± 0.00%), Rc (2.33 ± 0.01%), Rg2 (2.09 ± 0.04%), Rb1 (1.43 ± 0.24%), and Rf (0.13 ± 0.06%). Inhaled TG, at dosages of 10, 20, and 30 mg/kg significantly alleviated both ALI and PF in mice. Analyses of BALF and HE staining revealed that TG modulated the levels of IFN-γ, IL-1ß, and TGF-ß1, reduced inflammatory cell infiltration, and restored the alveolar architecture of the lung tissues. Furthermore, HE and Masson's trichrome staining demonstrated that TG markedly decreased fibroblastic foci and collagen fiber deposition, evidenced by the reduction of blue-stained collagen fibers. Hydroxyproline assay and immunohistochemical analyses indicated that TG significantly decreased hydroxyproline level and down-regulated the expression of Col1a1, Col3a1, and α-sma. The inhaled administration of TG demonstrated enhanced efficacy over the oral route when comparable doses were used. Additionally, inhaled TG showed superior safety and therapeutic profiles compared to pirfenidone, as evidenced by a CCK8 assay, which confirmed that TG concentrations ranging from 20 to 120 µg/ml were non-cytotoxic. qPCR and WB analyses revealed that TG, at concentrations of 25, 50, and 100 µg/ml, significantly suppressed the phosphorylation of smad2 induced by TGF-ß1 and down-regulated the expression of fibrotic genes and proteins, including α-sma, Col1a1, Col3a1, and FN1, suggesting an anti-fibrotic mechanism mediated by the smad2 signaling pathway. In vitro, TG's safety and efficacy were also found to be superior to those of pirfenidone. CONCLUSIONS: This study demonstrates, for the first time, the therapeutic efficacy of inhaled TG in treating ALI and PF. Inhaled TG effectively inhibits inflammation and reduces collagen deposition, with a particular emphasis on its role in modulating the Smad2 signaling pathway, which is implicated in the anti-fibrotic mechanism of TG. The study also highlights the superiority of inhaled TG over the oral route and its favorable safety profile in comparison to pirfenidone, positioning it as an ideal alternative for ALI and PF therapy.
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BACKGROUND: The pathogenesis of psoriasis involves the interaction between keratinocytes and immune cells, leading to immune imbalance. While most current clinical treatment regimens offer rapid symptom relief, they often come with significant side effects. Tetrastigma hemsleyanum polysaccharides (THP), which are naturally nontoxic, possess remarkable immunomodulatory and anti-inflammatory properties. METHODS: In this study, we utilized an imiquimod (IMQ)-induced psoriasis mouse model and a LPS/IL-6-stimulated HaCaT model. The potential and mechanism of action of THP in psoriasis treatment were assessed through methods including Psoriasis Area Severity Index (PASI) scoring, histopathology, flow cytometry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Percutaneous administration of THP significantly alleviated symptoms and manifestations in IMQ-induced psoriatic mice, including improvements in psoriatic skin appearance (erythema, folds, scales), histopathological changes, decreased PASI scores, and spleen index. Additionally, THP suppressed abnormal proliferation of Th17 cells and excessive proliferation and inflammation of keratinocytes. Furthermore, THP exhibited the ability to regulate the JAK/STAT3 signaling pathway. CONCLUSION: Findings from in vivo and in vitro studies suggest that THP can inhibit abnormal cell proliferation and excessive inflammation in lesional skin, balance Th17 immune cells, and disrupt the interaction between keratinocytes and Th17 cells. This mechanism of action may involve the modulation of the JAK/STAT3 signaling pathway, offering potential implications for psoriasis treatment.
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BACKGROUND: The traditional Chinese medicine Tetrastigma Hemsleyanum (TH) is employed in treating respiratory diseases; however, the aerial parts by which its total flavonoids alleviate acute lung injury (ALI) are still unknown. This study investigated the protective effect and mechanism of Tetrastigma Hemsleyanum flavonoids (THF) in lipopolysaccharide (LPS)-induced ALI in mice. METHODS: Firstly, the total flavonoids from the above-ground part of TH were extracted. Subsequently, the composition of THF was analyzed using LC-MS. In vivo, the impact of THF on ALI mice was assessed through lung histopathology and the evaluation of various inflammatory factors' expression in mice. After treating RAW264.7 cells with THF in vitro, changes in inflammatory markers were examined upon LPS stimulation, and mRNA expression levels of inflammatory factors were detected using RT-qPCR. Finally, Western blot analysis was performed to determine TLR4/NF-κB pathway-associated proteins expression. RESULTS: In summary, a total of 24 flavonoids have been identified in THF. In vivo and vitro results show that THF effectively reduces the damage caused by LPS inflammation by blocking the expression and release of inflammatory factors. THF alleviates inflammatory injury by modulating the TLR4/NF-KB pathway. CONCLUSION: The results suggest that flavonoids exhibit a potent anti-inflammatory effect and effectively mitigate LPS-induced injury both in vivo and in vitro. We suggested that these flavonoids exert their therapeutic effects by modulating the TLR4/NF-KB pathway. In conclusion, the development of THF is anticipated to represent a promising new pharmaceutical for treatingALI.
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The absence of effective therapeutic targets poses considerable obstacles to the treatment of triple-negative breast cancer (TNBC). This study aimed to explore the function and mechanism of polysaccharides derived from the aerial parts of Tetrastigma hemsleyanum (THP) for the treatment of TNBC. THP exerts notable anti-TNBC effects when used alone, and its combination with Doxorubicin (DOX) effectively augments the sensitivity of TNBC cells to DOX. Through RNA sequencing, Fe2+ assays, western blotting, and transmission electron microscopy, THP was identified as a natural inducer of ferroptosis and ferritinophagy through the xCT/GSH/GPX4 and Nrf2/NCOA4/FTH1 pathways. Further research revealed that the THP branched-chain hexose directly binds to the xCT protein to inhibit its expression and promotes ferroptosis. In vivo experiments confirmed the role of THP in inducing ferroptosis and showed that THP improves the tumor microenvironment and immune function by increasing the ratio of CD4+ and CD8+ T cells to regulatory T cells and modulating cytokine levels. As demonstrated by electrocardiography, blood chemistry, and histological analyses, THP alleviates organ toxicity caused by DOX. Overall, these results suggest that THP has significant clinical potential as a natural macromolecular drug and may provide a safe and effective treatment strategy for TNBC when combined with DOX.
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Doxorrubicina , Ferroptosis , Polisacáridos , Neoplasias de la Mama Triple Negativas , Ferroptosis/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Humanos , Doxorrubicina/farmacología , Polisacáridos/farmacología , Polisacáridos/química , Animales , Femenino , Ratones , Línea Celular Tumoral , Vitaceae/química , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ulcerative colitis (UC) is characterized by a chronic and protracted course and often leads to a poor prognosis. Patients with this condition often experience postoperative complications, further complicating the management of their condition. Tetrastigma hemsleyanum polysaccharide (THP) has demonstrated considerable potential as a treatment for inflammatory bowel disease. However, its underlying mechanism in the treatment of UC remains unclear. This study systematically and comprehensively investigated the effects of THP on dextran sulfate-induced UC mice and illustrated its specific mechanism of action. The colon and spleen in UC mice were restored after THP treatment. The levels of key markers, such as secretory immunoglobulin A, ß-defensin, and mucin-2 were increased, collagen deposition and epithelial cell apoptosis were decreased. Notably, THP administration led to increased levels of Ki67 and tight junction proteins in colon tissue and reduced colon tissue permeability. THP contributed to the restored balance of intestinal flora. Furthermore, THP downregulated the expressions of the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17 and promoted those of the regulatory factors forkhead box protein P3. It also exerted anti-inflammatory effects by promoting suppressor of cytokine signaling (SOCS1) expression and inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our results demonstrated that THP had an efficacy comparable to that of JAK inhibitor in treating UC. In addition, THP might play a role in UC therapy through modulation of the SOCS1/JAK2/STAT3 signaling pathway and remodeling of the intestinal mucosal barrier.
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Colitis Ulcerosa , Funcion de la Barrera Intestinal , Mucosa Intestinal , Polisacáridos , Transducción de Señal , Vitaceae , Animales , Masculino , Ratones , Antiinflamatorios/farmacología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colon/efectos de los fármacos , Colon/patología , Citocinas/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Funcion de la Barrera Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Janus Quinasa 2/metabolismo , Ratones Endogámicos C57BL , Polisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/genética , Vitaceae/químicaRESUMEN
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an disease characterized by pulmonary edema and widespread inflammation, leading to a notably high mortality rate. The dysregulation of both pro-inflammatory and anti-inflammatory systems, results in cytokine storm (CS), is intricately associated with the development of ALI/ARDS. Tetrastigma hemsleyanum polysaccharide (THP) exerts remarkable anti-inflammatory and immunomodulatory effects against the disease, although its precise role in pathogenesis remains unclear. In the present study, an ALI/ARDS model was established using bacterial lipopolysaccharides. THP administration via aerosol inhalation significantly mitigated lung injury, reduced the number of inflammatory cells, and ameliorated glycerophospholipid metabolism. Furthermore, specific CS-related pathways were investigated by examining the synergy between tumor necrosis factor-α and interferon-γ used to establish CS models. The results indicated that THP effectively decreased inflammatory damage and cell death. The RNA sequencing revealed the involvement of the Janus kinase (JAK) 2-signal transducers and activators of transcription (STAT) signaling pathway in exerting the mentioned effects. Additionally, THP inhibited the activation of the JAK-STAT pathway, thereby alleviating the CS both in vivo and in vitro. Overall, THP exhibited marked therapeutic potential against ALI/ARDS and CS, primarily by targeting the IFN-γ-JAK2/STAT signaling pathway.
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Síndrome de Liberación de Citoquinas , Interferón gamma , Polisacáridos , Transducción de Señal , Vitaceae , Animales , Humanos , Masculino , Ratones , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Modelos Animales de Enfermedad , Interferón gamma/metabolismo , Janus Quinasa 2/metabolismo , Lipopolisacáridos , Polisacáridos/farmacología , Polisacáridos/química , Transducción de Señal/efectos de los fármacos , Factores de Transcripción STAT/metabolismo , Vitaceae/químicaRESUMEN
The management of diabetic ulcers poses a significant challenge worldwide, and persistent hyperglycemia makes patients susceptible to bacterial infections. Unfortunately, the overuse of antibiotics may lead to drug resistance and prolonged infections, contributing to chronic inflammation and hindering the healing process. To address these issues, a photothermal therapy technique was incorporated in the preparation of wound dressings. This innovative solution involved the formulation of a self-healing and injectable hydrogel matrix based on the Schiff base structure formed between the oxidized Bletilla striata polysaccharide (BSP) and hydroxypropyltrimethylammonium chloride chitosan. Furthermore, the introduction of CuO nanoparticles encapsulated in polydopamine imparted excellent photothermal properties to the hydrogel, which promoted the release of berberine (BER) loaded on the nanoparticles and boosted the antibacterial performance. In addition to providing a reliable physical protection to the wound, the developed hydrogel, which integrated the herbal components of BSP and BER, effectively accelerated wound closure via microenvironment regulation, including alleviated inflammatory reaction, stimulated re-epithelialization, and reduced oxidative stress based on the promising results from cell and animal experiments. These impressive outcomes highlighted their clinical potential in safeguarding the wound against bacterial intrusion and managing diabetic ulcers.
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Quitosano , Hidrogeles , Polisacáridos , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Terapia Fototérmica/métodos , Ratones , Humanos , Berberina/farmacología , Berberina/química , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Cobre/química , Cobre/farmacología , Masculino , Polímeros/química , Polímeros/farmacología , Indoles/química , Indoles/farmacología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Nanopartículas/química , Staphylococcus aureus/efectos de los fármacos , Nanopartículas del Metal/químicaRESUMEN
The anti-inflammatory activity of polysaccharides derived from Melastoma dodecandrum Lour. was evaluated in pyretic mice and HEK-Blue™ hTLR4 cells. The testing led to the identification of MDP2-1, which was then investigated for its structural characteristics and anti-inflammatory effects. Results showed that MDP2-1 had a molecular weight of 29.234 kDa and primarily consisted of galactose, arabinose, rhamnose, glucose, glucuronic acid, and galacturonic acid. Its main backbone was composed of â4)-α-D-GalpA-(1â, â2)-α-L-Rhap-(1â, â3,4)-α-D-GalpA-(1â, â2,4)-α-D-GlcpA-(1â, and its side chains were connected by â4)-α-D-Galp-(1â, α-D-Galp-(1â, â4)-ß-D-Glcp-(1â, and α-L-Araf-(1â. In vivo experiments on mice demonstrated that MDP2-1 attenuated LPS-induced acute lung injury, and in vitro experiments on RAW264.7 cells showed that MDP2-1 reduced the levels of inflammatory mediators and mitigated LPS-induced inflammatory damage by inhibiting the activation of the TLR4 downstream NF-κB/MAPK pathway. These findings suggest that MDP2-1 is a novel anti-inflammatory agent for therapeutic interventions.
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Lipopolisacáridos , Polisacáridos , Ratones , Animales , Polisacáridos/farmacología , Polisacáridos/química , Galactosa , Glucosa , Antiinflamatorios/farmacologíaRESUMEN
A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 105 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.
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Receptor Toll-Like 4 , Vitaceae , Animales , Ratones , Vitaceae/química , Polisacáridos/química , Macrófagos , Células RAW 264.7RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata polysaccharides (BSP) extracted from the B. striata tuber, have been demonstrated to possess anti-inflammatory properties. However, their potential protective effect against ARDS and their role in regulating cell pyroptosis remained unexplored. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic effect of BSP in the alleviation of lipopolysaccharide (LPS)-induced ARDS, and to explore its mechanism of action. METHODS: The effect of BSP was assessed by LPS injection into the intraperitoneal cavity in vivo; pathological changes of ARDS mice were gauged by immunohistochemical, hematoxylin and eosin staining, and immunofluorescence assays. MH-S cells were used to model the pyroptosis in vitro. Finally, the pyroptosis of alveolar macrophage was detected by western blots, qPCR, and flow cytometry for NLRP3/caspase1/GSDMD and HMGB1/TLR4 pathway-associated proteins and mRNA. RESULTS: BSP could significantly increase the weight and survival rate of mice with ARDS, alleviate the cytokine storm in the lungs, and reduce lung damage in vivo. BSP inhibited the inflammation caused by LPS/Nigericin significantly in vitro. Compared with the control group, there was a remarkable surge in the incidence of pyroptosis observed in ARDS lung tissue and alveolar macrophages, whereas BSP significantly diminished the pyroptosis ratio. Besides, BSP reduced NLRP3/caspase1/GSDMD and HMGB1/TLR4 levels in ARDS lung tissue and MH-S cells. CONCLUSIONS: These findings proved that BSP could improve LPS-induced ARDS via inhibiting pyroptosis, and this effect was mediated by NLRP3/caspase1/GSDMD and HMGB1/TLR4, suggesting a therapeutic potential of BSP as an anti-inflammatory agent for ARDS treatment.
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Proteína HMGB1 , Síndrome de Dificultad Respiratoria , Animales , Ratones , Macrófagos Alveolares , Lipopolisacáridos/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Receptor Toll-Like 4 , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , PulmónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown. AIM OF THE STUDY: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism. METHODS: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway. RESULTS: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators. CONCLUSIONS: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases.
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Antipiréticos , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Antipiréticos/farmacología , Antipiréticos/uso terapéutico , Saccharomyces cerevisiae , Receptor Toll-Like 4/metabolismo , Transducción de Señal , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Fiebre/tratamiento farmacológico , Metabolismo EnergéticoRESUMEN
Triclosan (TCS) is a broad-spectrum antibacterial chemical widely presents in people's daily lives. Epidemiological studies have revealed that TCS exposure may affect female puberty development. However, the developmental toxicity after low-dose TCS continuous exposure remains to be confirmed. In our study, 8-week-old ICR female mice were continuously exposed to TCS (30, 300, 3000 µg/kg/day) or vehicle (corn oil) from 2 weeks before mating to postnatal day 21 (PND 21) of F1 female mice, while F1 female mice were treated with TCS intragastric administration from PND 22 until PND 56. Vaginal opening (VO) observation, hypothalamic-pituitary-ovarian (HPO) axis related hormones and genes detection, and ovarian transcriptome analysis were carried out to investigate the effects of TCS exposure on puberty onset. Meanwhile, human granulosa-like tumor cell lines (KGN cells) were exposed to TCS to further explore the biological mechanism of the ovary in vitro. The results showed that long-term exposure to low-dose TCS led to approximately a 3-day earlier puberty onset in F1 female mice. Moreover, TCS up-regulated the secretion of estradiol (E2) and the expression of ovarian steroidogenesis genes. Notably, ovarian transcriptomes analysis as well as bidirectional validation in KGN cells suggested that L-type calcium channels and Pik3cd were involved in TCS-induced up-regulation of ovarian-related hormones and genes. In conclusion, our study demonstrated that TCS interfered with L-type calcium channels and activated Pik3cd to up-regulate the expression of ovarian steroidogenesis and related genes, thereby inducing the earlier puberty onset in F1 female mice.
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Pubertad Precoz , Triclosán , Animales , Femenino , Humanos , Ratones , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Estradiol/metabolismo , Ratones Endogámicos ICR , Pubertad , Pubertad Precoz/inducido químicamente , Triclosán/efectos adversos , Triclosán/toxicidad , Fosfatidilinositol 3-Quinasa Clase I/efectos de los fármacosRESUMEN
Cerebral ischemia (CI) is the main cause of stroke morbidity and disability. This study aims to identify the early molecular regulation responsible for the therapeutic effectiveness of the Herb pair Danshen-Honghua (DH) for CI. The major targets of DH were identified by searching the public database of traditional Chinese medicine (TCM). In addition, GeneCards, Disgenet, and GeneMap databases in OMIM were used to determine the disease targets of CI. A total of 88 common targets of DH and CI were selected, a protein-protein interaction (PPI) network was established by Cytoscape, and 19 core targets were screened. These genes were primarily enriched in biological processes including wound healing, reaction to oxidative stress, and response to peptides, lipid and atherosclerosis, Age-rage signaling pathway, and TNF signaling pathway by KEGG and GO enrichments. The effective components of DH had stable binding to these key targets by molecular docking. Finally, it was verified that the mechanism of DH on CI treatment may be related to the activation of the TNF-α/JNK signaling pathway by establishing the middle cerebral artery occlusion (MCAO) rat model.
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Carthamus tinctorius , Medicamentos Herbarios Chinos , Daño por Reperfusión , Salvia miltiorrhiza , Animales , Ratas , Simulación del Acoplamiento Molecular , Infarto Cerebral , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
IMPORTANCE: The use of plant extracts is increasing as an alternative to synthetic compounds, especially antibiotics. However, there is no sufficient knowledge on the mechanisms and potential risks of antibiotic resistance induced by these phytochemicals. In the present study, we found that stable drug resistant mutants of E. coli emerged after repetitive exposure to sanguinarine and demonstrated that the AcrB efflux pump contributed to the emerging of induced and intrinsic resistance of E. coli to this phytochemical. Our results offered some insights into comprehending and preventing the onset of drug-resistant strains when utilizing products containing sanguinarine.
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Benzofenantridinas , Proteínas de Escherichia coli , Escherichia coli , Isoquinolinas , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Farmacorresistencia Bacteriana Múltiple , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genéticaRESUMEN
The healing process of a diabetic wound (DW) is often impeded by a series of interrelated factors, including severe infection, persistent inflammation, and excessive oxidative stress. Therefore, it is particularly crucial to develop a medical dressing that can address these issues simultaneously. To this end, different ratios of Bletilla striata polysaccharide (BSP) and berberine (BER) were physically blended with Carbomer 940 (CBM940) to develop a composite hydrogel as a medical dressing. The BSP/BER hydrogel was characterized using SEM, FTIR, rheological testing and other techniques. The anti-inflammatory, antioxidant, and antibacterial properties of the hydrogel were evaluated using cell and bacterial models in vitro. A DW model of ICR mice was established to evaluate the effect of the hydrogel on DW healing in vivo. The hydrogel exhibited excellent biocompatibility and remarkable antibacterial, anti-inflammatory, and antioxidant properties. In addition, animal experiments showed that the BSP/BER hydrogel significantly accelerated wound healing in DW mice. Among the different formulations, the LBSP/BER hydrogel (2% BSP, mBER:mBSP = 1:40) demonstrated the most remarkable efficacy. In conclusion, the BSP/BER hydrogel developed exhibited immense properties and great potential as a medical dressing for the repair of DW, addressing a crucial need in clinical practice.
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Berberina , Diabetes Mellitus , Animales , Ratones , Hidrogeles/farmacología , Berberina/farmacología , Berberina/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ratones Endogámicos ICR , Cicatrización de Heridas , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Vendajes , Antibacterianos/farmacología , Antiinflamatorios/farmacologíaRESUMEN
Diabetic wounds impose enormous distress and financial burden on patients, and finding effective dressings to manage wounds is critical. As a Chinese herbal medicine with a long history of Clinical application, Bletilla striata has significant medicinal effects in the therapy of various wounds. In this study, PLA and the pharmacodynamic substances of Bletilla striata were prepared into fibrous scaffolds by emulsion electrospinning technology for the management of diabetic wounds in mice. The results of scanning electron microscopy showed that the core-shell structure fibre was successfully obtained by emulsion electrospinning. The fibre membrane exhibited excellent water absorption capability and water vapor transmission rate, could inhibit the growth of Staphylococcus aureus and Pseudomonas aeruginosa, had good compatibility, and achieved excellent healing effect on diabetic wounds. Especially in the in vivo wound healing experiment, the wound healing rate of composite fibre membrane treatment reached 98.587 ± 2.149% in 16 days. This work demonstrated the good therapeutic effect of the developed fibrous membrane to diabetic wound, and this membrane could be potentially applied to chronic wound healing.
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Diabetes Mellitus , Nanofibras , Animales , Ratones , Emulsiones , Nanofibras/uso terapéutico , Cicatrización de Heridas , Microscopía Electrónica de Rastreo , Pseudomonas aeruginosaRESUMEN
In this study, the therapeutic effects of Tetrastigma hemsleyanum polysaccharide (THP) on inflammatory bowel disease (IBD) and its possible mechanisms were investigated based on the IBD mouse model induced by dextran sodium sulfate (DSS) and the lipopolysaccharide (LPS)-stimulated Caco-2 cell model. THP significantly alleviated the signs and symptoms of DSS-induced IBD mice, including the reduced weight, shortened colonic length, and increased colitis disease activity index. In vivo, THP significantly reduced inflammatory cell infiltration and oxidative damage, promoted intestinal mucus secretion, and restored the integrity of the intestinal epithelial barrier and mucus barrier. Furthermore, THP reversed the changes in the intestinal flora of colonized mice and restored the levels of short-chain fatty acids (SCFAs) by increasing the abundance of potentially beneficial bacteria and increasing the abundance of butyrate-producing bacteria. In addition, THP upregulated the expression of G-protein-coupled receptors (GPR41 and GPR43) both in vivo and in vitro. In summary, the current investigation showed that THP effectively protected against intestinal inflammation and impairment in the intestinal barrier in the setting of DSS-induced IBD, possibly by regulating gut microbiota structure and corresponding SCFA metabolites, and the pathway of SCFAs action may be related to SCFA-GPR41/43 signaling pathway.
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Cerebral ischemia-reperfusion (CIR) injury occurs as a secondary injury during the treatment of ischemic stroke (IS). There is a high death rate and morbidity due to IS throughout the world. Even though Naoxintong Capsule (NXT) is effective in the treatment of CIR, its mechanisms of action are unclear. The study aims to explore the clear mechanism associated with NXT therapy for CIR. We established the model of middle cerebral artery occlusion to evaluate the neurological function and assess the infarct size. Brain tissue metabolomics was used to identify different metabolites, and metabolic profiling systems enriched metabolic pathways. Then, the potential targets of NXT in the treatment of CIR were explored by proteomic, transcriptomic, and metabolomic methods. NXT improves CIR symptoms. We found potential 11 proteins and corresponding metabolites involved in NXT treatment of CIR. Most of these metabolites are regulated to restore after treatment. According to network pharmacology, we found 6 hub genes, including Glb1, Gmps, Pfas, Atic, Gaa, and Acox1, and their associated core metabolites and pathways. This study reveals the complex mechanism of NXT in treating CIR, and provides a new strategy for future researchers to screen related targets and pathways.
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Isquemia Encefálica , Medicamentos Herbarios Chinos , Daño por Reperfusión , Humanos , Proteómica , Multiómica , Medicamentos Herbarios Chinos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/genéticaRESUMEN
Thermal processing is one of the important techniques for most of the plant-based food and herb medicines before consumption and application in order to meet the specific requirement. The plant and herbs are rich in amino acids and reducing sugars, and thermal processing may lead to Maillard reaction, resulting as a high risk of acrylamide pollution. Acrylamide, an organic pollutant that can be absorbed by the body through the respiratory tract, digestive tract, skin and mucous membranes, has potential carcinogenicity, neurological, genetic, reproductive and developmental toxicity. Therefore, it is significant to conduct pollution determination and risk assessment for quality assurance and security of medication. This review demonstrates state-of-the-art research of acrylamide focusing on the toxicity, formation, contamination, determination, and mitigation in taking food and herb medicine, to provide reference for scientific processing and ensure the security of consumers.
Asunto(s)
Acrilamida , Calor , Acrilamida/toxicidad , Reacción de Maillard , Manipulación de Alimentos/métodos , Extractos Vegetales , Contaminación de Alimentos/análisisRESUMEN
The intestinal mucosal barrier is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. This study investigated the reparative effect and possible mechanism of Tetrastigma hemsleyanum polysaccharides (THP) on ceftriaxone-induced intestinal mucosal damage. Our results suggested that THP repaired the mechanical barrier damage of intestinal mucosa by enhancing the expression of intestinal tight junction proteins, reducing intestinal mucosal permeability and improving the pathological state of intestinal epithelial cells. Intestinal immune and chemical barrier was further restored by THP via the increment of the body's cytokine levels, intestinal SIgA levels, intestinal goblet cell number, intestinal mucin-2 levels, and short-chain fatty acid levels. In addition, THP increased the abundance of probiotic bacteria (such as Lactobacillus), reduced the abundance of harmful bacteria (such as Enterococcus) to repair the intestinal biological barrier, restored intestinal mucosal barrier function, and maintains intestinal homeostasis. The possible mechanisms were related to sphingolipid metabolism, linoleic acid metabolism, and D-glutamine and D-glutamate metabolism. Our results demonstrated the potential therapeutic effect of THP against intestinal flora disorders and intestinal barrier function impairment caused by antibiotics.