JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Ping Chen,Cheng Lin,Qi Jin,Baibai Ye,Xinxu Liu,Keke Wang,Han Zhang,Jiahui Liu,Runan Zhang,Hao Huang,Chenning Zhang,Linfu Li
Ethnopharmacological relevance In TCM opinion, most of pneumonia is related to "lung heat". Sophora davidii (Franch.) Skeels flower was first documented in "Guizhou Herbal Medicine", and was recorded as having functions of clearing heat, detoxifying, and cooling blood. It can be used to treat lung heat cough. Aim of the study To investigate main mechanisms of Sophora davidii flower extract (SDFE) in Treating LPS-induced acute Pneumonia. Materials and methods Acute pneumonia models on BEAS-2B cells and rats were established using LPS. The rat model was used to verified the protective effects of SDFE through HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test. Network pharmacology was applied to predict the active compounds, core targets and main pathways of SDFE in treating acute pneumonia. Western Blot and ELISA kits were employed to validate representative proteins in selected pathway in vivo and in vitro . Results HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test showed SDFE could improve pathological features (leukocyte infiltration, pulmonary edema, lung injury and cough). Network pharmacology indicated MAPK/NF-κB pathway was the most relevant pathway. SDFE could significantly inhibit the expression of Fos and Jun, and the phosphorylation levels of p38, ERK, JNK, NF-κB and IκB. It also down-regulated the expression of pro-inflammatory factors (TNF-α, IL-6 and IL-1β). Conclusions SDFE can exert protective effects against acute pneumonia through the MAPK/NF-κB signaling pathway.
研究领域:
药理学
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免疫学
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中医药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Pulmonary Medicine
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2020
·Vol. 20
·期 1
·1-12
·
IF 2.813
Guo Jing,Li Min,Yang Yi,Zhang Lin,Zhang Li-wei,Sun Qian-yun
Background The complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Atorvastatin (ATR) is a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor approved for control of plasma cholesterol levels. This inhibitor can reduce the acute pulmonary inflammatory response. However, the ability of ATR in treating acute lung inflammation caused by complement activation is still unknown. Therefore, we investigated the effect of ATR on lung inflammation in mice induced by activation of the complement alternative pathway in this study.Methods ATR (10 mg/kg/day via oral gavage) was administered for 7 days before tail vein injection of CVF (25 μg/kg). On the seventh day, all mice were sacrificed 1 h after injection. The lung lobe, bronchoalveolar lavage fluid (BALF), and blood samples were collected. The myeloperoxidase (MPO) activity of the lung homogenate, the leukocyte cell count, and the protein content of BALF were measured. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), P-selectin, and Intercellular cell adhesion molecule-1 (ICAM-1) in BALF and serum were determined by enzyme-linked immunosorbent assay. The pathological change of the lung tissue was observed by hematoxylin and eosin staining. The deposition of C5b-9 in the lung tissue was detected by immunohistochemistry. The phosphorylation of NF-κB p65 in the lung tissues was examined by immunohistochemistry and western blotting.Results The lung inflammation levels were determined by measuring the leukocyte cell numbers and protein content of BALF, the lung MPO activity, and expression and staining of the inflammatory mediators (IL-6 and TNF-α), and adhesion molecules (P-selectin and ICAM-1) for lung lesion. A significant reduction in the lung inflammation levels was observed after 7 days in ATR pre-treated mice with a CVF-induced lung disease. Deposition of C5b-9 was significantly alleviated by ATR pretreatment. Early intervention with ATR significantly reduced the development of acute lung inflammation on the basis of phosphorylation of NF-κB p65 in the lung.Conclusion These findings suggest the identification of ATR treatment for the lung inflammation induced by activating the complement system on the basis of its anti-inflammatory response. Together with the model replicating the complement activating characteristics of acute lung injury, the results may be translatable to the overactivated complement relevant diseases.
研究领域:
药理学
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免疫学
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病理学
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2024
·Vol. 16
·期 10
·1384
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IF 4.7
Kai Wang,Dagui Chen,Chenxi Zhang,Lu Lu,Fusheng Shang,Yinghua Li
Acute pneumonia (AP), triggered primarily by pathogens like bacteria and viruses, is a leading cause of human mortality. Ribavirin, a broad-spectrum antiviral agent, plays a pivotal role in the treatment of AP. However, its therapeutic use is hindered by the need for high dosages and the associated cardiac and hepatic toxicities. In this study, we synthesized polyethylene glycol-modified cationic liposomes to encapsulate ribavirin (RBV-PCL) and formulated it into a spray, aiming to enhance the effectiveness of RBV through respiratory administration. Lipopolysaccharide (LPS), a compound known to induce AP models in animals, was utilized in our research. Successfully, we established an acute pneumonia model in mice using aerosol inhalation. Through animal experiments, we investigated the therapeutic effects of RBV-PCL on mice with AP. In vivo studies revealed promising results. RBV-PCL effectively prolonged the survival of mice with AP, significantly reduced the levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibited the infiltration of neutrophils in the lungs and spleens of mice. These findings suggest that RBV-PCL can effectively suppress the inflammatory response in mice with AP, thus holding significant potential as a novel therapeutic approach for the treatment of acute pneumonia.
研究领域:
药学
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纳米技术
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传染病学
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肺科学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2025
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IF 9.6
Jie Li,Ji- Yu Che,Hong- Yu Wang,Rui-Yao Wang,Si-Yuan Huang,Zhong-Ming Wu,Xin-Ge Zhang
Pattern recognition receptors on immune cells play essential roles in detecting pathogen-associated molecular patterns and initiating downstream immune defense cascades. Toll-like receptor-4, a key member of the PRR family, regulates macrophage-mediated innate immune responses; however, its dysregulation due to excessive activation often exacerbates inflammatory processes. Herein, we report a Toll-like receptor-4-targeted nano-extinguisher designed to combat acute pneumonia caused by multidrug-resistant Pseudomonas aeruginosa infection. This innovative nanoplatform integrates bacterial capture ligands, a photothermal agent, and a Toll-like receptor-4 signaling inhibitor. Upon near-infrared light irradiation, the nano-extinguisher generates localized hyperthermia, leading to bacterial death through disruption of membrane integrity. Moreover, the heat-triggered release of the Toll-like receptor-4 signaling inhibitor enables dual immunomodulation by simultaneously regulating macrophage polarization and scavenging reactive oxygen species. The nano-extinguisher significantly alleviated the pathological progression of infection-induced acute pneumonia in our experiments. By combining photothermal antibacterial activity with spatiotemporal immunomodulation, this nanoengineered system offers a promising translational strategy for the treatment of acute bacterial infections and concurrent mitigation of Toll-like receptor-4-mediated immunopathology. Statement of Significance TLR4, which is crucial for initiating innate immunity via pathogen detection, often exacerbates inflammation when hyperactivated. We developed TLR-4-targeted nano-extinguishers to combat multidrug-resistant Pseudomonas aeruginosa -induced pneumonia. This system integrates bacterial capturing, photothermal therapy, and TLR-4 inhibition. Photo-driven localized hyperthermia disrupts bacterial membranes while thermally releasing the inhibitor, thereby achieving simultaneous macrophage polarization modulation and reactive oxygen species scavenging, effectively mitigating infection-induced pneumonia. By integrating precision photothermal sterilization with spatiotemporal immunoregulation, our nanoengineered strategy addresses both bacterial eradication and TLR-4-mediated immunopathology, offering translational potential for the treatment of acute infections.
研究领域:
免疫学
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纳米医学
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感染性疾病
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转化医学
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分子免疫学
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呼吸系统疾病
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抗菌治疗
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Jinxue Cao,Yaping Xiu,Siqi Wang,Fangling Wu,Ji Li,Dongkai Wang
Andrographolide (AG) is known as a "natural antibiotic". It has been clinically developed into capsules, dropping pills, disperse tablets, etc., for the treatment of viral and bacterial upper respiratory tract infections. It has poor water solubility, obvious P-glycoprotein efflux, and low bioavailability, so its wide application in clinical practice is limited. In this work, a novel AG dry powder inhaler (AG-DPI) was developed using experimental design to optimize the prescription and spray-drying process to obtain higher local concentrations in the lungs while lowering the administered dose; avoiding hepatic first-pass effects and gastrointestinal p-glycoprotein efflux. The short-term local anti-inflammatory effects in the lungs were evaluated using a rat model of acute pneumonia compared with oral administration. The prepared AG-DPI showed that (1) it had good aerosolization properties and was suitable for pulmonary administration, with emitted doses >90%, and fine particle fractions >60%; (2) it was superior to oral administration in the assessment of local anti-inflammatory effects in the lungs by acting on acute pneumonia. This study provides some theoretical value and reference for the inhalable dry powder of AG as a potential targeted treatment modality for lung diseases and infections.
研究领域:
药剂学
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药理学
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呼吸病学
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药物递送系统
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2022
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IF 10.383
Chang Liu,Yihan Liu,Long Xi,Yuan He,Yingmin Liang,Judith Choi Wo Mak,Shirui Mao,Zhenping Wang,Ying Zheng
Since most current studies have focused on exploring how phagocyte internalization of drug-loaded nanovesicles by macrophages would affect the function and therapeutic effects of infiltrated neutrophils or monocytes, research has evaluated the specificity of the inhaled nanovesicles for targeting various phagocytes subpopulations. In this study, liposomes with various charges (including neutral (L1), anionic (L2), and cationic at inflammatory sites (L3)) were constructed to investigate how particle charge determined their interactions with key phagocytes (including macrophages and neutrophils) in acute lung injury (ALI) models and to establish correlations with their biofate and overall anti-inflammatory effect. Our results clearly indicated that neutrophils were capable of rapidly sequestering L3 with a 3.2-fold increase in the cellular liposome distribution, compared to that in AMs, while 70.5% of L2 were preferentially uptaken by alveolar macrophages (AMs). Furthermore, both AMs and the infiltrated neutrophils performed as the potential vesicles for the inhaled liposomes to prolong their lung retention in ALI models, whereas AMs function as sweepers to recognize and process liposomes in the healthy lung. Finally, inhaled roflumilast-loaded macrophage or neutrophil preferential liposomes (L2 or L3) exhibited optimal anti-inflammatory effect because of the decreased AMs phagocytic capacity or the prolonged circulation times of neutrophils. Such findings will be beneficial in exploiting a potential pathway to specifically manipulate lung phagocyte functions in lung inflammatory diseases where these cells play crucial roles.
研究领域:
药理学
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免疫学
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肺科学
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纳米技术
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Junyan Li,Yuanfu Ding,Qian Cheng,Cheng Gao,Jianwen Wei,Ziyi Wang,Qiaoxian Huang,Ruibing Wang
Acute pneumonia is an inflammatory syndrome often associated with severe multi-organ dysfunction and high mortality. The therapeutic efficacy of current anti-inflammatory medicines is greatly limited due to the short systemic circulation and poor specificity in the lungs. New drug delivery systems (DDS) are urgently needed to efficiently transport anti-inflammatory drugs to the lungs. Here, we report an inflammation-responsive supramolecular erythrocytes-hitchhiking DDS to extend systemic circulation of the nanomedicine via hitchhiking red blood cells (RBCs) and specifically “drop off” the payloads in the inflammatory lungs. β-cyclodextrin (β-CD) modified RBCs and ferrocene (Fc) modified liposomes (NP) were prepared and co-incubated to attach NP to RBCs via β-CD/Fc host-guest interactions. RBCs extended the systemic circulation of the attached NP, meanwhile, the NP may get detached from RBCs due to the high ROS level in the inflammatory lungs. In acute pneumonia mice, this strategy delivered curcumin specifically to the lungs and effectively alleviated the inflammatory syndrome.
研究领域:
药学
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药物递送
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炎症研究
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纳米医学
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肺病学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2020
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IF 0
Zhicheng Le,Zhijia Liu,Lilong Sun,Lixin Liu,Yongming Chen
Dysregulated inflammation is considered as an essential pathological process in inflammation-associated diseases, which would be aggravated by high levels of reactive oxygen species (ROS) generation inducing oxidative stress. Currently, extensive attention has been paid to polyphenolic compounds owing to their broad spectrum biological activities, such as antioxidant and anti-inflammatory effects, while their therapeutic potential has been compromised by the poor stability, short plasma half-life, and low bioavailability. Given that polyphenols have a wide range of structural characteristics and various physicochemical properties, there remains a real challenge toward green, mass production of universal nanocarriers for effective entrapment of these active pharmaceutical ingredients. In this study, we adopted a flash nanocomplexation (FNC) platform to prepare nanocomplexes comprising polyphenols and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) enabled by hydrogen bonding. We confirmed that the molecular structure of polyphenols has a great influence on their complexation with TPGS, and stable nanocomplexes were formed when the number of phenolic hydroxyl groups of polyphenols was above the value of 8. These hydrogen-bonded nanocomplexes produced by an FNC apparatus exhibited well-controlled quality with uniform size, good colloidal stability, and high batch-to-batch repeatability, thus improving the druggability as potent nanotherapeutics for antioxidant and anti-inflammatory applications. In vivo experiments indicated that the optimal nanocomplex (EGCG-NC) can be applied to ameliorate acute lung injury in a mice model after nasal administration. These results proved that polyphenols formulated with TPGS for nanocomplex formation through hydrogen-bonding complexation could augment their therapeutic potential for modulating hyperactive inflammation in the treatment of acute lung inflammation.
研究领域:
药理学
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纳米技术
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炎症
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药物递送系统
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产品关联
DOI
PubMed
JOURNAL OF PROTEOME RESEARCH
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2025
·
IF 3.6
Yi Wu,Yang Wang
In this study, we present an improved metabolomics methodological framework that synergistically integrates untargeted data acquisition with targeted data analysis using chemical derivatization combined with ultrahigh performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS) analysis. Data-independent acquisition (DIA)-based mass spectrometry (MS1) data were used to conduct conventional untargeted analysis for biomarker discovery. The data-dependent acquisition (DDA) method was applied to obtain high-quality tandem mass spectrometry (MS2) information for quantitative data analysis. 1-Aminopiperidine (1AP) served as the derivatization reagent for sample preparation, which selectively reacts with carboxyl-containing compounds. Fatty acid (FA) standards were used to examine the derivatization reaction, and the results of LC-MS analysis showed that protonated FA + 1AP-H2O was the precursor. The ion at m/z 84.08, along with the product ion from a neutral loss of 45.02 Da, emerged as characteristic fragments, facilitating compound annotation and quantitative analysis. Method validation results demonstrated the proposed method with excellent repeatability, stability, and linearity. The lung tissue samples were successfully analyzed using this method, which was further employed to evaluate the therapeutic efficacy of Zhuye Shigao Decoction (ZSD) against lipopolysaccharide (LPS)-induced acute pneumonia in mice.
研究领域:
代谢组学
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分析化学
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质谱分析
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药理学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-17
·
IF 14.7
Gao Cheng,Wang Qingfu,Ding Yuanfu,Kwong Cheryl H. T.,Liu Jinwei,Xie Beibei,Wei Jianwen,Lee Simon M. Y.,Mok Greta S. P.,Wang Ruibing
Membrane-camouflaged nanomedicines often suffer from reduced efficacy caused by membrane protein disintegration and spatial disorder caused by separation and reassembly of membrane fragments during the coating process. Here we show that intracellularly gelated macrophages (GMs) preserve cell membrane structures, including protein content, integration and fluidity, as well as the membrane lipid order. Consequently, in our testing GMs act as cellular sponges to efficiently neutralize various inflammatory cytokines via receptor-ligand interactions, and serve as immune cell-like carriers to selectively bind inflammatory cells in culture medium, even under a flow condition. In a rat model of collagen-induced arthritis, GMs alleviate the joint injury, and suppress the overall arthritis severity. Upon intravenous injection, GMs efficiently accumulate in the inflammatory lungs of acute pneumonia mice for anti-inflammatory therapy. Conveniently, GMs are amenable to lyophilization and can be stored at ambient temperatures for at least 1 month without loss of integrity and bio-activity. This intracellular gelation technology provides a universal platform for targeted inflammation neutralization treatment.
研究领域:
药理学
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免疫学
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
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