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Dihydromyricetin (DMY), a natural flavonoid compound extracted from the stems and leaves of Ampelopsis grossedentata, has been found as a potential therapeutic chemical for treating atherosclerosis. This study explores the underlying mechanism of DMY repressing M1 macrophage polarization in atherosclerosis. We showed that DMY treatment markedly decreased M1 macrophage markers (e.g., Tnf-α and IL-1ß) and p65-positive macrophage numbers in the vessel wall of Apoe-deficient (Apoe-/-) mice. Overexpression of miR-9 or knockdown of SIRT1 in macrophages reversed the effect of DMY on M1 macrophage polarization. The data we presented in the study indicate that the miR-9-mediated SIRT1/NF-κB pathway plays a pivotal role in M1 macrophage polarization and is one of the molecular mechanisms underlying the anti-atherosclerosis effects of DMY. We provide new solid evidence that DMY may be explored as a potential therapeutic adjuvant for treating atherosclerosis.
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MicroARNs , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Sirtuina 1/metabolismo , Transducción de Señal , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Apolipoproteínas E/metabolismoRESUMEN
BACKGROUND: Our previous study found that hyperbaric oxygen (HBO) attenuated cognitive impairment in mice induced by cerebral ischemia-reperfusion injury (CIRI). However, its mechanism of action is not fully understood. In this study, we aimed to establish a rat model of cerebral ischemia-reperfusion, explore the possible role of ferroptosis in the pathogenesis of CIRI, and observe the effect of HBO on ferroptosis-mediated CIRI. METHODS: Sprague Dawley (SD) rats were randomly divided into control, model, Ferrostatin-1 (Fer-1), HBO and Fer-1+ HBO groups. Morris water maze, myelin basic protein (MBP) and ß-tubulin immunoreactivity were assessed to evaluate the neuroprotective effects of HBO on cerebral ischemia reperfusion injury. Ferroptosis were examined to investigate the mechanism underlying the effects of HBO. RESULTS: Our result showed that Fer-1 and HBO improved learning and memory ability in the navigation trail and probe trail of the Morris water maze and increased MBP and ß-tubulin immunoreactivity of the cortex in the model rats. The levels of ferritin, malondialdehyde (MDA) and glutathione (GSH) in the serum were also reversed by Fer-1 and HBO treatment. Mitochondrial cristae dissolution and vacuolization were observed in the model group by transmission electron microscopy and these conditions were improved in the Fer-1 and HBO groups. Furthermore, Fer-1 and HBO treatment reversed Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Iron Responsive Element Binding Protein 2 (IREB2), acyl-CoA synthetase long chain family member 4 (ACSL4) and Solute Carrier Family 7 Member 11 (SLC7A11) mRNA levels and Transferrin Receptor 1 (TFR1), ferritin light chain (FTL), ferritin heavy chain 1 (FTH1), glutathione peroxidase 4 (GPX4), Nuclear factor E2-related factor 2 (Nrf2), lysophosphatidylcholine acyltransferase 3 (LPCAT3), c-Jun N-terminal kinase (JNK), phosphorylated c-Jun N-terminal kinase (P-JNK) phosphorylated Extracellular signal-regulated protein kinase (P-ERK) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) protein levels. The above changes were more pronounced in Fer-1+ HBOGroup. DISCUSSION: The results of the present study indicated that HBO improves cerebral ischemia-reperfusion injury in rats, which may be related to inhibition of ferroptosis. This also means that ferroptosis may become a new target of HBO against CIRI.
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Isquemia Encefálica , Ferroptosis , Oxigenoterapia Hiperbárica , Daño por Reperfusión , Ratas , Ratones , Animales , Ratas Sprague-Dawley , Oxigenoterapia Hiperbárica/métodos , Tubulina (Proteína) , Oxígeno , Isquemia Encefálica/terapia , Quinasas MAP Reguladas por Señal Extracelular , Proteínas Quinasas JNK Activadas por Mitógenos , Daño por Reperfusión/patología , 1-Acilglicerofosfocolina O-AciltransferasaRESUMEN
CONTEXT: Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. OBJECTIVE: To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225. RESULTS: In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29-1.48), DCR (RR = 1.15, 95% CI 1.12-1.19), QOL (RR = 1.71, 95% CI 1.54-1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low. CONCLUSIONS: Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Neoplasias Pulmonares/patología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , GemcitabinaRESUMEN
We previously reported that Yulangsan polysaccharide (YLSP), which was isolated from the root of Millettia pulchra Kurz, attenuates withdrawal symptoms of morphine dependence by regulating the nitric oxide pathway and modulating monoaminergic neurotransmitters. In this study, we investigated the effects and mechanism of YLSP on the reinstatement of morphine-induced conditioned place preference (CPP) in rats. A CPP procedure was employed to assess the behavior of rats, and indicators of serum and four brain regions (nucleus accumbens, ventral tegmental area, hippocampus and prefrontal cortex) were determined to explore its underlying mechanism. YLSP inhibited priming morphine-induced reinstatement of CPP in a dose-dependent manner. YLSP markedly reduced nitric oxide and nitric oxide synthase levels in the brain. Moreover, YLSP significantly decreased the dopamine and norepinephrine levels in the serum and brain. Furthermore, YLSP significantly decreased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations, inhibited the expression of dopamine D1 receptors and cAMP response element binding protein mRNA, and improved the expression of dopamine D2 receptor mRNA in the four brain regions. Our findings indicated that YLSP could inhibit the reinstatement of morphine-induced CPP possibly by modulating the NO-cGMP and D1R-cAMP signaling pathways.
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Condicionamiento Clásico/efectos de los fármacos , Millettia , Dependencia de Morfina/tratamiento farmacológico , Morfina/administración & dosificación , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Condicionamiento Clásico/fisiología , Relación Dosis-Respuesta a Droga , Masculino , Dependencia de Morfina/metabolismo , Dependencia de Morfina/psicología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Polisacáridos/aislamiento & purificación , Polisacáridos/uso terapéutico , Ratas , Ratas Sprague-DawleyRESUMEN
Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system's perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS < 10 (scenario 2), and patients with PD-L1 CPS ≥ 10 (scenario 3) populations, the ICERs were $69,025/QALY, $82,533/QALY, and $75,436/QALY for serplulimab-CF. Nevertheless, the probability of serplulimab-CF becoming cost-effective based on scenarios 1, 2, and 3 is only 2.71%, 0.94%, and 2.84%, respectively, at a WTP threshold of $38,258/QALY. When serplulimab costs < $4.84/mg, serplulimab-CF may be cost-effective at the WTP threshold of $38,258/QALY; otherwise, CF was preferred. Similar results were obtained from sensitivity analyses, suggesting the robustness of these findings. There was no cost-effectiveness in general regions of China for serplulimab-CF in PD-L1-positive ESCC compared to CF, although it is probably considered cost-effective in affluent regions. Serplulimab-CF may achieve favorable cost-effectiveness by lowering the price of serplulimab.
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Protocolos de Quimioterapia Combinada Antineoplásica , Antígeno B7-H1 , Análisis Costo-Beneficio , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/economía , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Años de Vida Ajustados por Calidad de Vida , Cisplatino/uso terapéutico , Masculino , Fluorouracilo/uso terapéutico , Fluorouracilo/economía , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/economía , Persona de Mediana Edad , Análisis de Costo-EfectividadRESUMEN
BACKGROUND: Durvalumab plus etoposide-platinum (DEP) showed sustained overall survival improvements in patients with extensive-stage small-cell lung cancer (ES-SCLC) compared to etoposide-platinum (EP), but adding tremelimumab to DEP (DTEP) did not significantly improve outcomes. A third-party payer perspective is taken here to evaluate the cost-effectiveness of DTEP, DEP, and EP for ES-SCLC. METHODS: The cost-effectiveness was evaluated by partitioning survival models into 3 mutually exclusive health states. In this model, clinical characteristics and outcomes were obtained from the CASPIAN. Model robustness was evaluated through 1-way deterministic and probabilistic sensitivity analyses. Outcome measurements included costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, life-years, incremental net health benefit, and incremental net monetary benefit. The analysis was conducted with a 10-year lifetime horizon in a United States setting. RESULTS: Compared with EP, DEP, and DTEP were associated with an increment of 0.480 and 0.313 life-years, and an increment of 0.247 and 0.165 QALYs, as well as a $139,788 and $170,331 increase in cost per patient. The corresponding ICERs were $565,807/QALY and $1033,456/QALY, respectively. The incremental net health benefit and incremental net monetary benefit of DEP or DTEP were -0.685 QALYs and -$102,729, or -0.971 QALYs and -$145,608 at a willingness to pay threshold of $150,000/QALY, respectively. Compared with DTEP, DEP was dominated. DTEP and DEP were 100% unlikely to be cost-effective if the willingness to pay threshold was $150,000/QALY. DEP was cost-effective compared to EP when durvalumab was priced below $0.994/mg. Compared with EP, DEP, and DTEP were unlikely to be considered cost-effective across all subgroups. CONCLUSION: DEP and DTEP were not cost-effective options in the first-line treatment for ES-SCLC compared with EP, from the third-party payer perspective in the United States. Compared with DTEP, DEP was dominated.
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Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Estados Unidos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Etopósido/uso terapéutico , Platino (Metal)/uso terapéutico , Análisis de Costo-Efectividad , Análisis Costo-Beneficio , Años de Vida Ajustados por Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
The resolution of traffic congestion and personal safety issues holds paramount importance for human's life. The ability of an autonomous driving system to navigate complex road conditions is crucial. Deep learning has greatly facilitated machine vision perception in autonomous driving. Aiming at the problem of small target detection in traditional YOLOv5s, this paper proposes an optimized target detection algorithm. The C3 module on the algorithm's backbone is upgraded to the CBAMC3 module, introducing a novel GELU activation function and EfficiCIoU loss function, which accelerate convergence on position loss lbox, confidence loss lobj, and classification loss lcls, enhance image learning capabilities and address the issue of inaccurate detection of small targets by improving the algorithm. Testing with a vehicle-mounted camera on a predefined route effectively identifies road vehicles and analyzes depth position information. The avoidance model, combined with Pure Pursuit and MPC control algorithms, exhibits more stable variations in vehicle speed, front-wheel steering angle, lateral acceleration, etc., compared to the non-optimized version. The robustness of the driving system's visual avoidance functionality is enhanced, further ameliorating congestion issues and ensuring personal safety.
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Chitosan samples were prepared from the shells of marine animals (crab and shrimp) and the cell walls of fungi (agaricus bisporus and aspergillus niger). Fourier-transform infrared spectroscopy (FT-IR) was used to detect their molecular structures, while headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was employed to analyze their odor composition. A total of 220 volatile organic compounds (VOCs), including esters, ketones, aldehydes, etc., were identified as the odor fingerprinting components of chitosan for the first time. A principal component analysis (PCA) revealed that chitosan could be effectively identified and classified based on its characteristic VOCs. The sum of the first three principal components explained 87% of the total variance in original information. An orthogonal partial least squares discrimination analysis (OPLS-DA) model was established for tracing and source identification purposes, demonstrating excellent performance with fitting indices R2X = 0.866, R2Y = 0.996, Q2 = 0.989 for independent variable fitting and model prediction accuracy, respectively. By utilizing OPLS-DA modeling along with a heatmap-based tracing path study, it was found that 29 VOCs significantly contributed to marine chitosan at a significance level of VIP > 1.00 (p < 0.05), whereas another set of 20 VOCs specifically associated with fungi chitosan exhibited notable contributions to its odor profile. These findings present a novel method for identifying commercial chitosan sources, which can be applied to ensure biological safety in practical applications.
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This study aimed to figure out how microRNA (miR)-411-3p's impacts on methotrexate (MTX)'s cellular uptake and cytotoxicity in acute lymphoblastic leukaemia (ALL) CEM-C1 cells by targeting Yin-yang 1 (YY1). miR-411-3p and YY1 were detected by RT-qPCR or Western blot. Intracellular MTX concentration was measured by enzyme-linked immunosorbent assay. Cell viability and apoptosis were evaluated by CCK-8, clonal formation assay, and flow cytometry. Verification of miR-411-3p and YY1's targeting link was manifested. It came out that miR-411-3p mimic or si-YY1 elevated intracellular MTX, MTX-induced cytotoxicity and apoptosis rate in CEM-C1. However, the inverse results were noticed in cells introduced with miR-411-3p inhibitor or oe-YY1. Meanwhile, it was found that cell relative luciferase activity was reduced after co-transfection of miR-411-3p mimic with YY1-WT, indicating that miR-411-3p targeted YY1. Elevation of YY1 could turn around elevating miR-411-3p's impacts on MTX's cellular uptake and cytotoxicity in CEM-C1 cells. These findings convey that miR-411-3p motivated MTX's cellular uptake and cytotoxic impacts via targeting YY1 in leukemia cells. This study is helpful for learning about the mechanisms underlying MTX responses in ALL patients.
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MicroARNs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metotrexato/farmacología , Yin-Yang , Transporte Biológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , MicroARNs/genéticaRESUMEN
Comprehensive research is conducted on the design and control of the unmanned systems for electric vehicles. The environmental risk prediction and avoidance system is divided into the prediction part and the avoidance part. The prediction part is divided into environmental perception, environmental risk assessment, and risk prediction. In the avoidance part, according to the risk prediction results, a conservative driving strategy based on speed limit is adopted. Additionally, the core function is achieved through the target detection technology based on deep learning algorithm and the data conclusion based on deep learning method. Moreover, the location of bounding box is further optimized to improve the accuracy of SSD target detection method based on solving the problem of imbalanced sample categories. Software such as MATLAB and CarSim are applied in the system. Bleu-1 was 67.1, bleu-2 was 45.1, bleu-3 was 29.9 and bleu-4 was 21.1. Experiments were carried out on the database flickr30k by designing the algorithm. Bleu-1 was 72.3, bleu-2 was 51.8, bleu-3 was 37.1 and bleu-4 was 25.1. From the comparison results of the simulations of unmanned vehicles with or without a system, it can provide effective safety guarantee for unmanned driving.
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Conducción de Automóvil , Algoritmos , Recolección de Datos , Medición de Riesgo , TecnologíaRESUMEN
BACKGROUND: Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy. OBJECTIVE: To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence. RESULTS: A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia. CONCLUSIONS: Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.
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Venenos de Anfibios/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos de Platino/uso terapéutico , Venenos de Anfibios/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas/patología , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/patología , Masculino , Fitoterapia , Compuestos de Platino/administración & dosificación , Resultado del TratamientoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, was mainly used in ancient times in the treatment of urinary calculi, recurrent headache and joint pain. AIM OF THE STUDY: Our aims were to explore the potential therapeutic effect of the extract of Averrhoa carambola L. (Oxalidaceae) roots (EACR) against hepatic fibrosis in CCl4-treated rats and to understand the underlying molecular mechanism. MATERIALS AND METHODS: Six groups of male Sprague Dawley rats were treated as follows: vehicle (olive oil), CCl4 alone, CCl4+colchicine, CCl4+EACR 1.0â¯g/kg, CCl4+EACR 0.5â¯g/kg and CCl4+EACR 0.25â¯g/kg. At the end of the 12th week, biomarkers of liver function, liver fibrosis, hepatic oxidative stress and antioxidant status were assayed, and histopathological and immunohistochemical evaluation of liver tissue were conducted to investigate the liver damage and fibrosis degree. Furthermore, expressions of COL-1a1, α-SMA, TGF-ß1, Smad2, smad3, Smad4 and TIMP2 were examined by qPCR and/or western blot. The expressions of apoptosis-related proteins were also detected using western blot analysis. RESULTS: EACR treatment markedly reduced the CCl4-induced elevation of serum aminotransferase activities, liver fibrosis indexes, and the extent of oxidative stress. EACR treatment also significantly reduced the accumulation of collagen and the immunostaining of α-SMA, TGF-ß1 and Smad2, 4 and 7 in the liver of CCl4 treated rats. In addition, EACR treatment markedly reversed the CCl4-induced increase in mRNA expression of COL-1a1, α-SMA, TIMP2, TGF-ß1, Smad2 and Smad4 and suppressed the expressions of α-SMA, TIMP2, TGF-ß1, smad2, 3 and 4, BAX and cleaved caspase-3 proteins. Meanwhile, EACR treatment also significantly elevated the mRNA expression of Smad7 and the protein expression of Smad7 and Bcl-2. CONCLUSION: These results suggest that EACR has protective activity against liver fibrosis. The anti-fibrotic activity of EACR in vivo is associated with enhanced antioxidant, apoptosis-inhibition and increased MMP-2/TIMP-2 expression ratio, and with modulation of TGF-ß1/Smad signaling pathway.
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Cirrosis Hepática/tratamiento farmacológico , Oxalidaceae/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Animales , Tetracloruro de Carbono/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Masculino , Medicina Tradicional China/métodos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Yulangsan flavone (YLSF) was extracted from the root of Millettia pulchra Kurz var-laxior (Dunn) Z. Wei, which has been widely used for liver disease treatment in the Guangxi province of China. HYPOTHESIS/PURPOSE: The study was conducted to demonstrate the hepatoprotective effects of YLSF against CCl4-induced hepatic fibrosis in rats, meanwhile revealing the potential mechanism. STUDY DESIGN: Sprague-Dawley (SD) rats of both sexes were randomly divided into two groups: hepatic fibrosis group and normal control (NC) group. The rats in the hepatic fibrosis group were given 1â¯ml/kg 50% CCl4 (1:1 mixed with peanut oil), while those in the NC group were given 1â¯ml/kg normal saline (NS), both via intragastric administration. The established experimental rat model from the hepatic fibrosis group was confirmed by pathological inspection and randomly divided into five groups: three YLSF groups (20â¯mg/kg, 40â¯mg/kg and 80â¯mg/kg), a colchicine group (0.20â¯mg/kg) and a model group (10â¯ml/kg NS). All rats were treated with corresponding drugs or NS once a day for four consecutive weeks. Twenty-four hours after the last administration, blood serum and hepatic tissue were collected. METHODS: The activities of ALT and AST in the serum and the levels of SOD, MDA, GSH and GSH-Px in hepatic tissue were analysed, the indexes of liver, spleen and thymus were counted, the degree of hepatic injury was examined using HE and Masson staining, and the mRNA expression of Col-1, TIMP-1 and TGF-ß1 in hepatic tissues was detected. RESULTS: Compared with the model group, experimental results showed that YLSF and colchicine could reduce the levels of AST, ALT and MDA, increase the levels of SOD, GSH and GSH-Px, enhance rat survivability, decrease the liver, spleen and thymus index, significantly lessen collagen deposition and tissue damage and down-regulate the mRNA expression of Col-1, TIMP-1 and TGF-ß1. CONCLUSIONS: Our findings confirm that YLSF has a certain curative effect on rats with liver fibrosis induced by CCl4, and its mechanism may include attenuating free radicals, inhibiting lipid peroxidation and accelerating extracellular matrix degradation by down-regulating expression of related genes.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Flavonas/farmacología , Cirrosis Hepática/tratamiento farmacológico , Millettia/química , Animales , Tetracloruro de Carbono/efectos adversos , China , Femenino , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Although numerous studies have proven the medicinal values of Yulangsan polysaccharide (YLSP), the toxicity of this active ingredient is unknown. In the acute toxicity study, a single oral administration of 24 g/kg YLSP caused neither toxicological symptoms nor mortality, and the LD50 was estimated >24 g/kg. In the chronic toxicity study, we administered doses of 0, 0.6, 1.2 and 2.4 g/kg YLSP in rats by oral gavage for 26 weeks followed by a 3-week recovery period. There was no mortality or remarkable clinical signs observed during this 26-week study. Additionally, there were no toxic differences in the following parameters: body weight, food consumption, hematology, clinical biochemistry, organ weight, and macroscopic ï¬ndings. There were no adverse effects on histopathology observed in males or female rats treated with YLSP. Based on the results, the no-observed-adverse-effect-level of YLSP in rats is greater than 2.4 g/kg when administered orally for 26 consecutive weeks.