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Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase ⠡ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.
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Medicamentos de Ervas Chinesas , Ginsenosídeos , Lesões por Radiação , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Farmacologia em Rede , Ginsenosídeos/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fator A de Crescimento do Endotélio Vascular , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
OBJECTIVE: To observe the effect of Modified Xijiao Dihuang Decoction (, MXDD) on rats with radiation enteritis, and explore its action mechanism. METHODS: Thirty female Sprague Dawley rats were divided into the control, model, dexamethasone (DXM), golden bifid (GB) and MXDD groups using random number table, 6 rats in each group. Except the control group, the other rats were developed into radiation enteritis model by exposing to a single 60Co-γ ray at a dose of 11 Gy. The rats in the DXM, GB and MXDD groups were treated with DXM (1.425 mg/kg), GB (0.8 g/kg) and MXDD (36.0 g/kg) for 3 days, respectively. Body weight and diarrhea condition of rats were evaluated daily. On day 3, the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected. Bacterial species annotation, alpha and beta diversities as well as composition of intestinal flora were detected and compared. The protein and mRNA expressions of interleukin 17 (IL-17), retinoid-related orphan nuclear receptor gamma t (ROR-γt) and forkhead/ winged helix transcription factor p3 (FoxP3) were determined by Western blot and polymerase chain reaction, respectively. The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing. Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method. RESULTS: On day 1 to 3 after radiation, compared with the control group, the body weight in model group was decreased (P<0.05 or P<0.01). Compared with the model group, MXDD could alleviate weight loss and diarrhea caused by irradiation. At the phylum level, MXDD cause a significant increase in Firmicutes, and a decrease in Proteobacteria (P<0.05 or P<0.01). At the genus level, MXDD reduced the proportion of Escherichia Shigella (P<0.01). In addition, IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment (P<0.05). Besides, Firmicutes and Lactobacillus were positively correlated with FoxP3 (r=0.73, 0.79, respectively; P<0.01), negatively correlated with IL-17 (r=0.66, 0.64, respectively; P<0.01 or P<0.05) and ROR-γt (r0.73, 0.81, respectively; P<0.01). Proteobacteria and Escherichia Shigella both had positive correlation with IL-17 (r 0.77, 0.57, respectively; P<0.01 or P<0.05 ) and ROR-γt (r=0.94, 0.79, respectively; P<0.01) and negative correlation with FoxP3 (r0.74, 0.65; P<0.01). CONCLUSION: MXDD could improve the survival status of irradiated rats by regulating the richness, diversity and composition of intestinal flora, and restoring the balance of Th17/Treg.
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Enterite , Microbioma Gastrointestinal , Animais , Enterite/tratamento farmacológico , Feminino , Fatores de Transcrição Forkhead , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley , Linfócitos T Reguladores , Células Th17RESUMO
BACKGROUND: The carrier of hydroxyethyl starch (HES) may play a critical role in kidney injury in fluid resuscitation. This study aimed mainly to compare effects of pyruvate-enriched saline with normal saline (NS) and acetate Ringer's (AR) solution as a carrier in HES130/0.4 on kidney function in rats subjected to severe burns. METHODS: Using a lethal burn model, 140 rats were randomly allocated in seven groups (n = 20): sham group (group S); no fluid after burn (group N); burn resuscitated with NS (group NS); burn resuscitated with pyruvate saline (group PS); burn resuscitated with AR plus pyruvate-HES (group SP); burn resuscitated with AR plus acetate-HES (group SA), and burn resuscitated with AR plus NS-HES (group SN). A low volume (18.75 mL·kg-1 during 12 h) of HES130/0.4 was infused with the ratio of 1:1 to crystalloids. Renal surface blood flow, blood creatinine and blood urea nitrogen, early sensitive indicators of kidney function: alpha-1 microglobulin, cystatin-C, and neutrophil gelatinase-associated lipocalin in blood and urine, and kidney tissue water contents were determined. Renal histopathological alterations with Paller scores were also measured at 8 h and 24 h after burn (n = 10), respectively. RESULTS: The results showed in a comparable manner that group SP was the best in three HES groups and group PS was superior to group NS in renal preservation; group SP appeared significantly beneficial compared with group PS in renal surface blood flow, cystatin-C, neutrophil gelatinase-associated lipocalin, water contents, and Paller scores at 8-h or both time points after burn, respectively (all P < 0.05). CONCLUSIONS: The carrier of HES130/0.4 played a crucial role in kidney injury in fluid resuscitation of rats subjected to severe burns. Pyruvate-enriched HES130/0.4 was superior and HES130/0.4, per se, might be not renocytotoxic, but renoprotective. Further studies are warranted.
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Injúria Renal Aguda/terapia , Queimaduras/terapia , Portadores de Fármacos/química , Hidratação/métodos , Derivados de Hidroxietil Amido/administração & dosagem , Substâncias Protetoras/administração & dosagem , Ácido Pirúvico/química , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Queimaduras/complicações , Estado Terminal/terapia , Modelos Animais de Doenças , Humanos , Infusões Intravenosas , Soluções Isotônicas/administração & dosagem , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Astragalus membranaceus and Salvia miltiorrhiza (AM/SM) are well used in Traditional Chinese Medicines (TCM) for nourishing Qi and activating blood circulation method. From TCM theory, the pathogenesis of acute lung injury (ALI) was determined as Qi deficiency and blood stagnation. In this study, we are aiming to investigate the protective and therapeutic effects of AM/SM on a rat model of lipopolysaccharide- (LPS-) induced ALI in rats and to elucidate potential molecular mechanisms. ALI was induced by intratracheal instillation of LPS (5 mg/kg) in Sprague-Dawley rats. SM/AM was given orally before and after LPS administration. Results demonstrated that AM/SM attenuated lung histopathological changes induced by LPS, decreased wet/dry weight ratios and protein concentrations, and inhibited the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in BALF. Moreover, AM/SM significantly downregulated protein and mRNA expression of toll-like receptors 4 (TLR-4), interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear factor-kappa B (NF-κB/p65). These findings suggest that AM/SM showed protective and therapeutic effects in LPS-induced ALI rat through modulating TLR-4 signaling pathways. Nourishing Qi and activating blood circulation may be a beneficial treatment for ALI.
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OBJECTIVE: To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. METHODS: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated. RESULTS: The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01). CONCLUSIONS: XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.
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Queimaduras/tratamento farmacológico , Queimaduras/patologia , Permeabilidade Capilar , Medicamentos de Ervas Chinesas/uso terapêutico , Pulmão/irrigação sanguínea , Pulmão/patologia , Animais , Queimaduras/sangue , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Selectina E/sangue , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Injeções , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Pulmão/efeitos dos fármacos , Masculino , Microvasos/patologia , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue , Água/metabolismoRESUMO
OBJECTIVE: To study the supplementing Qi and activating blood circulation herbs on lung protection in acute lung injury (ALI) ventilation patients. METHODS: 67 cases of ALI patients were enrolled and randomly divided into two groups. Routine treatment was for 32 cases of control group while treatment with adding supplementing Qi and activating blood circulation herbs was for 35 cases of treatment group, by 60 mL per time for 14 consecutive days with each day three times. Hemodynamics, changes of arterial blood gas, assay of pdymorphonuclears (PMN) value and the image of bronchoscopes between two groups in T0, T3, T7 and T14 were compared. RESULTS: PMN, HR, SVR, PaO2 , PO2/FiO2 and pH of treatment group were significantly improved compared with control group during T0, T3, T7 and T14 (P <0. 05). The compared differences were remarkable on hemodynamics, changes of arterial blood gas and assay of PMN value between treatment group and control group. The image of bronchoscopes in treatment group was improved significantly. CONCLUSIONS: The intervention of supplementing Qi and activating blood circulation herbs can effectively protect the lung function from ALI patients who received ventilation.
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Lesão Pulmonar Aguda/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pulmão/efeitos dos fármacos , Qi , Respiração Artificial/efeitos adversos , Broncoscopia , Hemodinâmica , Humanos , Pulmão/patologia , RespiraçãoRESUMO
OBJECTIVE: To observe the effect of Liangxuehuoxue Recipe (LXHXF), a compound traditional Chinese medicinal preparation, on the expressions of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) in the lung tissue of rats exposed to X-ray radiation. METHODS: Seventy-two Wistar rats were randomized into exposure group (group A, without treatment) and small-, middle- and high-dose LXHXF groups (groups B, C, and D treated with LXHXF at the daily doses of 9, 18, and 36 g/kg, respectively). After X-ray exposure of the right lung at 3 Gy twice a week for 5 consecutive weeks, the rats were sacrificed at the end of the 5th, 12th and 26th weeks, and the lung tissues were taken for immunohistochemistry of the expressions of TNF-α and TGF-ß. RESULTS: In group A, the expression of TNF-α reached the peak level at 5 weeks and TGF-ß expression was the highest at 12 and 26 weeks. LXHXF, especially at the middle and high doses, obviously inhibited the expression of TNF-α at 5 weeks; the treatments also resulted in significantly lowered expressions of TGF-ß at all the time points of observation as compared with those in group A (P<0.01). The high- and middle-dose groups exhibited no significant difference in the expression levels of TNF-α and TGF-ß in the experiment (P>0.05). CONCLUSION: Treatment with LXHXF can effectively inhibit TNF-α expression in the lung tissue in the early stage following radiation exposure, causing even more obvious inhibitory effect on TGF-ß in the later stages. A higher dose of LXHXF produces more significant inhibitory effects on TNF-α and TGF-ß expressions.
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Medicamentos de Ervas Chinesas/farmacologia , Pulmão/efeitos da radiação , Lesões por Radiação/prevenção & controle , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Pulmão/metabolismo , Masculino , Lesões por Radiação/metabolismo , Protetores contra Radiação/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Radiation pneumonitis is one of the most common complications during radiotherapy of thoracic tumors. It impacts the quality of life of the patients and has life-threatening danger. However, there is a lack of drugs for prevention and treatment of this disease. OBJECTIVE: To evaluate the efficacy of Liangxue Jiedu Huoxue Decoction, a compound traditional Chinese herbal medicine, in prevention of radiation pneumonitis. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A prospective randomized clinical study was conducted. A total of 100 patients diagnosed with lung cancer from Department of Radiotherapy, Chinese PLA General Hospital, who were planning to receive radiotherapy, were randomly assigned into treatment group and control group, with 50 patients in each group. In the treatment group 3 cases were lost to follow-up and one case was excluded, while in the control group 6 cases were lost to follow-up and 2 cases were excluded. Patients in the treatment group were treated with Liangxue Jiedu Huoxue Decoction in addition to radiotherapy, while patients in the control group were treated with radiotherapy alone. MAIN OUTCOME MEASURES: The incidence rates of radiation pneumonitis in the two groups were calculated. Acute radiation injury scoring criteria by Radiation Therapy Oncology Group (RTOG), clinical-radiographic-physiologic (CRP) score system, and Karnofsky Performance Status Scale (KPS) were used to evaluate the status of the patients. RESULTS: The incidence rate of radiation pneumonitis was lower in the treatment group than in the control group (13.04% versus 33.33%, P<0.05). According to the RTOG scale, the extent of lung injury was improved in the treatment group as compared with that in the control group (P<0.05). The CRP score in the treatment group was significantly lower than that in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.05). CONCLUSION: Liangxue Jiedu Huoxue Decoction can decrease the incidence rate of radiation pneumonitis, reduce the extent of the lung injury, alleviate the symptoms of radiation pneumonitis, and improve life quality of the patients.
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Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Pneumonite por Radiação/prevenção & controle , Adenocarcinoma/radioterapia , Adenocarcinoma de Pulmão , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the efficacy of compound Dixiong Decoction (å°è汤, a Chinese herbal decoction) on early prevention of radiation pneumonitis. METHODS: Forty-six patients with non-small cell lung cancer who were planning to receive radiotherapy were randomly assigned to the treatment group treated with the compound Dixiong Decoction and the control group treated with a commonly used herbal decoction which has the effects of supplementing qi and nourishing yin, clearing heat and detoxifying at the time of radiotherapy. Primary measure was the incidence of radiation pneumonitis after radiotherapy. Secondary outcomes included Watters clinical radiographic physiologic (CRP) dyspnea score, the Radiation Therapy Oncology Group (RTOG) grading score, Karnofsky Performance Status (KPS) score, and the application of corticosteroids. RESULTS: The incidence of radiation pneumonitis in the treatment group was 10.0%, while that in the control group was 26.3% (P=0.0032). The Watters CRP dyspnea score and RTOG grading score in the treatment group were significantly =lower than those in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.01). The dosage of corticosteroids was smaller with a shorter duration of therapy in the treatment group than that in the control group. CONCLUSION: The early application of the Chinese herbal decoction compound Dixiong Decoction can decrease the incidence of radiation pneumonitis, reduce the injury of the lung, and improve the life quality of the patients.
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Corticosteroides/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Pneumonia/terapia , Humanos , Incidência , Pneumonia/etiologia , Estudos Prospectivos , Radioterapia/efeitos adversosRESUMO
OBJECTIVE: To investigate the effect of blood-cooling and promoting drugs (BCPD) on the dy-namic changes of collagens and the expressions of interleukin-6 (IL-6) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation-induced lung injury (RILI) to explore the effects and action mech-anism of BCPD in preventing and treating RILI. METHODS: One hundred and sixty Wistar female rats were ran-domly divided into the radiation group, the treatment group, the blank control group and the drug control group. The rats in the first two groups received right hemithoracic fractionated radiation, and those in the treatment group were given BCPD. Rats in the other two groups were not irradiated and BCPD was given to rats in the drug control group. The rats were sacrificed in batches (8 of each group in every batch) at the 3rd, 5th, 8th, 12th and 26th week of the experimental period, and their lung was taken for observing the dynamic changes and distribution of collagen and the expressions of IL-6 and TGF-beta with HE staining, picrosirius red staining and immunohistochemical staining respectively. RESULTS: The fibroblast proliferated obviously from the 3rd week after the first radiation in the radiation group, and the type I collagen and the proportion of type I and III collagen were significantly elevated along the time going and the radiation dose increasing, became significantly higher than those in the treatment group at all the time points (P <0.01). In the radiation group the expression of IL-6 and TGF-beta reached their peaks at the 8th and 12th week, respectively, and the levels was significantly lower in the treatment than that in the radiation group at any detecting time points (P <0.01). CONCLUSION: BCPD applied in the early stage of radiation can suppress the inflammatory and fibrogenic cytokine expressions, inhibit the synthesis of collagens and adjust the proportion of type I and III collagen, so as to re-lieve the early-stage inflammatory reaction and the anaphase lung fibrosis in RILI rats.
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Medicamentos de Ervas Chinesas/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Lesões Experimentais por Radiação/tratamento farmacológico , Animais , Feminino , Imuno-Histoquímica , Interleucina-6/biossíntese , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Fitoterapia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/biossínteseRESUMO
OBJECTIVE: To observe the pathological changes and the expression of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation injury for exploring the mechanism of blood-activating and stasis-dissipating drugs in radiation injury prevention and treatment. METHODS: One hundred and thirty SD female rats were randomly allocated into the simple irradiation group (n=60), the TCM herbs treatment group (n=60) and the blank control group (n=10). The right lung of all rats except those in the blank control group were irradiated by linear accelerator, 3 Gy each time, twice weekly, the maximum accumulated dose being 30 Gy. Ten rats in the two groups were randomly sacrificed at each of the 6 time points (1, 3, 5, 8, 12 and 26 weeks after repeated irradiation), their lung was harvested out, sliced and dyed with HE stain. The histological changes, levels of TNF-alpha and TGF-beta expression in the lung tissue were then observed by immunohistochemical technique. RESULTS: The most serious acute radiation pneumonia was seen in the 5th week and pulmonary fibrosis was remarkable in the 26th week in the simple irradiation group, with the expressions of TNF-alpha and TGF-beta at different time phases enhanced significantly (P < 0.01). While in the TCM herbs treatment group, the pneumonia was milder, pulmonary fibrosis in late stage was not so obvious, and the expressions of TNF-alpha and TGF-beta significantly lower than those in the simple irradiation group (P < 0.01). CONCLUSION: Blood-activating and stasis-dissipating drugs can inhibit expression of inflammation-inducing factors and fibrosis-inducing factors to lessen the inflammatory reaction of early radiation pneumonia, prolong the progression of radiation lung fibrosis, showing preventive and treating action on radiation lung injury.