PHARMACEUTICAL CHEMISTRY JOURNAL
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2018
·Vol. 52
·期 2
·95-102
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IF 0.679
Xu Xiaoya,Chen Yajun,Zhang Min,Wang Dianlei,Wu Jie,Yao Zhaomin,Wu Qingqing,Fang Wei
The therapy of Huatanjiangqi capsule (HTJQ) has been used in the treatment of chronic obstructive pulmonary disease (COPD) clinically, with remarkable benefits. A lower functional activity of MRP1 is related to COPD development. However, the mechanism that contributes to MRP1 up-regulation by HTJQ was unclear. This study aimed to investigate the effects of HTJQ on the expression of Nrf2 and MRP1 in COPD rats. Rats were exposed to cigarette smoke plus lipopolysaccharide tracheal instillation to induce a COPD model. Then, Nrf2, HO-1, and MRP1 mRNA expression and their protein production in lung tissues were examined. The model group showed significant changes in the above assessments as compared to those of the control group ( p < 0.05). The lung function of model group treated with low/high dose of HTJQ was significantly strengthened (both p < 0.05), and the inflammatory cells and goblet cells were decreased in lung tissues. Treatment with low/high dose of HTJQ resulted in obvious increase in Nrf2, HO-1, and MRP1 mRNA and protein expression levels ( p < 0.05). HTJQ could up-regulate Nrf2 and MRP1 expression in lung tissues of COPD model rats. The mechanism by which HTJQ up-regulates MRP1 expression may be associated with Nrf2.
研究领域:
药理学
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呼吸病学
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分子生物学
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产品关联
DOI
高影响因子
PHARMACOLOGICAL RESEARCH
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2022
·
IF 10.334
Xiaohua Xie,Xiaofeng Wu,Dongsheng Zhao,Ying Liu,Qiyue Du,Yitian Li,Yaping Xu,Yuhang Li,Yan Qiu,Yungang Yang
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9–5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.
研究领域:
药理学
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肺科学
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免疫学
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病理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Shengnan Qiu,Xianglei Fu,Yanbin Shi,Hengchang Zang,Yunpeng Zhao,Zhilong Qin,Guimei Lin,Xiaogang Zhao
Idiopathic pulmonary fibrosis (IPF) causes worsening pulmonary function, and no effective treatment for the disease etiology is available now. Recombinant Human Relaxin-2 (RLX), a peptide agent with anti-remodeling and anti-fibrotic effects, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, due to its short circulating half-life, optimal efficacy requires continuous infusion or repeated injections. Here, we developed the porous microspheres loading RLX (RLX@PMs) and evaluated their therapeutic potential on IPF by aerosol inhalation. RLX@PMs have a large geometric diameter as RLX reservoirs for a long-term drug release, but smaller aerodynamic diameter due to their porous structures, which were beneficial for higher deposition in the deeper lungs. The results showed a prolonged release over 24 days, and the released drug maintained its peptide structure and activity. RLX@PMs protected mice from excessive collagen deposition, architectural distortion, and decreased compliance after a single inhalation administration in the bleomycin-induced pulmonary fibrosis model. Moreover, RLX@PMs showed better safety than frequent gavage administration of pirfenidone. We also found RLX-ameliorated human myofibroblast-induced collagen gel contraction and suppressed macrophage polarization to the M2 type, which may be the reason for reversing fibrosis. Hence, RLX@PMs represent a novel strategy for the treatment of IPF and suggest clinical translational potential.
研究领域:
呼吸病学
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药学
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生物技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
·
IF 10
Wei Liu,Di Liu,Tianyi Cui,Yili Wang,Sufei Zhou,Fangzhen Tian,Ke Yang,Wei Wang,Lewei Bi,Kelong Fan,Lan Li,Hao Wang,Xiao-Dong Zhang
Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au 25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the K m of Au 24 Er 1 with H 2 O 2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.
研究领域:
纳米技术
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免疫学
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2021
·
IF 4.407
Yu-bo Sun,Mo Liu,Xin-sheng Fan,Li-ping Zhou,Meng-wen Li,Fang-yuan Hu,Qin-fei Yue,Yi-ming Zhang
The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. It is worth exploring whether CS can injury TJs and aggravate asthma by activating TRPA1. The objective of this study was to investigate the aggravation of CS on ovalbumin (OVA)-induced asthma related phenotypes and TJs expression in mice, and to explore the relationship between TRPA1 and the expression of TJs protein. Female wild type (WT) C57BL/6 mice, induced by OVA, CS and OVA plus CS (OVA + CS) respectively, were used to establish a 42-day asthma model, and mice with TRPA1 knockout (TRPA1 −/− ) were treated in the same way. This study detected the number of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13 in BALF, enhanced pause (Penh) of lung function, pathological changes and the gene and protein expressions of TRPA1 and TJs (including ZO-1, Occludin and Claudin-2) in lung tissues. Compared with normal saline (NS) group, WT mice in the OVA group and OVA + CS group were significantly higher in asthma related phenotypes. The WT-OVA + CS group also showed higher Penh value, levels of IL-5 and IL-13 in BALF and lung tissue injury scores when compared with the WT-OVA group and WT-CS group. However, WT-OVA + CS group mice had significantly larger number of neutrophils in BALF than the WT-OVA group, and had larger number of eosinophils in peripheral blood and higher levels of IL-4 in BALF than the WT-CS group. Meanwhile, compared with the WT-NS group, the expressions of TRPA1 and Claudin-2 in lung tissues increased in other three groups while their expressions of ZO-1 and Occludin decreased, among which, the WT-OVA + CS group showed more remarkable changes. Compared with the WT-OVA + CS group, mice in the TRPA1 −/− -OVA + CS showed a significant decrease in the number of inflammatory cells, levels of IL-4, IL-5 and IL-13 in BALF, Penh value and lung tissue injury score, and a downregulation of Claudin-2 expression while an upregulation of ZO-1 and Occludin expressions. In addition, the airway inflammation and injury, and the expressions of ZO-1, Occluding and Claudin-2 expressions were found with no statistic differences between TRPA1 −/− -OVA group and TRPA1 −/− -OVA + CS group. These results suggest that CS has aggravated the airway inflammation, pathological damage and destruction of TJs in airway epithelium of OVA-induced asthmatic mice, the processes of which are related to the increase of TRPA1 expression.
研究领域:
免疫学
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呼吸病学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Lin Lin,Siyuan Li,Que Liu,Xingxing Zhang,Ying Xiong,Shaoyun Zhao,Liyue Cao,Jiaxuan Gong,Yaping Liu,Rong Wu
Objective: This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.Methods: Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.Results: OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.Conclusion: The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.
研究领域:
儿科学
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免疫学
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药理学
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微生物学
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肌肉骨骼系统
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Ma Xiaoyao,Liu Aina,Liu Wenjuan,Wang Zhihua,Chang Nianwei,Li Suyun,Li Jiansheng,Hou Yuanyuan,Bai Gang
Chronic obstructive pulmonary disease (COPD) has been a major public health problem and is still a formidable challenge for clinicians. It is urgent to find new compounds for minimizing the risk of disease progression and exacerbation especially in the early phase of COPD. A traditional Chinese medicine (TCM) formula, Chuan Bei Pi Pa dropping pills (CBPP), was tested in this study to investigate its potential mechanisms in preventing the exacerbation of COPD. Phosphoproteomics analysis for a smog stimulated early stage COPD mice model was employed to detect the underlying molecular mechanisms of CBPP. In addition, protein–protein interaction (PPI) and bioinformatics analyses were included to analyze the key proteins and predict the key bioactive compounds. The results indicated that peiminine (PEI) target epidermal growth factor receptor (EGFR) prevented the exacerbation of COPD by inhibiting the EGFR signaling pathway, and ursolic acid (UA) can alleviate inflammation disorders via inhibition of CASP3 on mitogen-activated protein kinase (MAPK) signaling pathway. After in vivo and in vitro evaluations, we revealed that PEI from CBPP, as a lead compound, can improve lung function and alleviate pulmonary fibrosis by acting on the EGFR and MLC2 signaling pathways. Furthermore, the approach described here is an effective way to analyze and identify the bioactive ingredients from a mixture by functional proteomics analysis.
研究领域:
药理学
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呼吸病学
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蛋白质组学
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传统中药
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 2.997
Xuejuan Zhang,Xiao Yue,Yingtong Cui,Ziyu Zhao,Ying Huang,Shihao Cai,Guanlin Wang,Wenhao Wang,Smyth Hugh,Xin Pan,Chuanbin Wu,Wen Tan
For carrier-based dry-powder inhaler (DPI) formulations, the adhesion between carrier particles and active pharmaceutical ingredients (API) particles have a significant influence on the aerosolization performance of the API-carrier complexes and the desired detachment of the API for efficient pulmonary delivery. In our previous study, nanoporous mannitol material was successfully fabricated as carriers by a one-step nonorganic solvent spray drying method with the thermal degradation of ammonium carbonate. These carriers were shown to achieve excellent aerosolization performance. In addition, no residue of ammonium carbonate was detected on the powder surface. However, the safety of nanoporous mannitol carriers (Nano-PMCs) during pulmonary administration/delivery was still unknown because the lung is vulnerable to the inhaled particles. To address this question, the present study was conducted to construct a systematic safety evaluation for DPIs carriers to investigate the safety of Nano-PMCs in the whole inhalation, which would make up for the lack of detailed and standardized method in this field. In vitro safety evaluation was carried out using respiratory and pulmonary cytotoxicity tests, hemolysis assay, and ciliotoxicity test. In vivo safety evaluation was studied by measuring inflammatory indicators in the bronchoalveolar lavage fluid, assessing the pulmonary function and observing pulmonary pathological changes. Nano-PMCs showed satisfactory biocompatibility on respiratory tracts and lungs in vitro and in vivo . It was suggested that Nano-PMCs were safe for intrapulmonary delivery and potential as DPI carriers.
研究领域:
药学
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肺科学
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毒理学
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生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2018
·
IF 2.064
Gao Zhen,Wang Jing,Jing Jing,Dan Xu,Li Zheng,Fengsen Li
Objective. In China, the Chinese medicine formula modified zhisou powder (MZP) is commonly used to treat COPD with cold-dryness syndrome (CDSCOPD) to relieve cough and sputum. However, the underlying mechanisms of MZP on treating CDSCOPD remain to be elucidated. Methods. COPD and CDSCOPD rat models were established; MZP was given to CDSCOPD rats in the last 7 days of the 97-day model establishment. Then the rats were subjected to lung function measurement. Pathological changes in lungs were observed through paraffin section and H&E staining. The mRNA and protein levels of AQP1, 4, and 5 and Muc5AC and Muc5B in lung were determined by quantitative RT-PCR and western blotting. NE levels was determined by ELISA. Results. The impaired lung functions were observed in rats exposed to cigarette smoke. Among all parameters evaluating lung functions, only tidal volume demonstrates a further decrease in CDSCOPD when compared with COPD, indicating further impaired pulmonary ventilation functions upon cold-dryness stimulation. The intervention of MZP effectively improved lung functions parameters, prevented the inflammations, and eliminated the increases of AQP4 and 5 and the decrease of Muc5AC in lung. Conclusion. MZP probably improves pulmonary functions in CDSCOPD through inhibiting lung inflammation, increasing expressions of AQPs, and decreasing Muc5AC expression in lung.
研究领域:
药理学
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肺病学
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中医药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Lifang Ye,Yu Zuo,Fang Chen,Yuetong Xu,Puli Zhang,Hongxia Yang,Qinglin Peng,Guochun Wang,Xiaoming Shu
Objective To evaluate adrenomedullin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM) as well as their correlation with the severity of interstitial lung disease (ILD). Methods A total of 41 DM patients and seven immune-mediated necrotizing myopathy (IMNM) patients were recruited, in addition to 21 healthy controls (HCs). The adrenomedullin mRNA levels in PBMCs were measured via quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR). The associations between adrenomedullin expression levels and major clinical, laboratory, pulmonary function parameters and the prognosis of patients with DM-related ILD (DM-ILD) were analyzed. Immunohistochemical analysis was performed on lung tissues of DM-ILD patients to determine adrenomedullin expression. Results Adrenomedullin mRNA levels in PBMCs were significantly higher in DM patients than in IMNM patients and HCs (p = 0.022 and p<0.001, respectively). Among DM patients, the levels were significantly higher in those with rapidly progressive ILD (RP-ILD) than in those with chronic ILD (p = 0.002) or without ILD (p < 0.001). The adrenomedullin mRNA levels in DM-ILD were positively correlated with serum ferritin (r =0.507, p =0.002), lactate dehydrogenase (LDH) (r =0.350, p =0.045), and lung visual analog scale (VAS) (r=0.392, p=0.021) and were negatively correlated with pulmonary function test parameters, including predicted forced vital capacity (FVC)% (r = −0.523, p = 0.025), forced expiratory volume in 1 s (FEV1)% (r = -0.539, p = 0.020), and diffusing capacity of carbon monoxide (DLco)% (r = -0.495, p = 0.036). Immunohistochemical analysis of adrenomedullin confirmed higher expression in the alveolar epithelial cells and macrophages of DM patients with RP-ILD. Among the DM patients with ILD, the six decedents exhibited higher adrenomedullin levels than the 28 survivors (p = 0.042). The cumulative survival rate was significantly lower (62.5% vs . 100%, P = 0.005) in patients with an adrenomedullin level > 0.053 than in those with a level <0.053. Conclusions Adrenomedullin levels are upregulated in DM patients with RP-ILD and are associated with ILD severity and poor prognosis. Adrenomedullin may be a potential prognostic biomarker in DM patients with ILD, although need further investigation.
研究领域:
风湿病学
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肺科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）