PHYTOMEDICINE
·
2022
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IF 6.656
Zhenhao Li,Haitao Pan,Jihong Yang,Dongjie Chen,Yu Wang,Han Zhang,Yiyu Cheng
Background Xuanfei Baidu Formula (XBF) is an effective traditional Chinese medicine (TCM) remedy for treating coronavirus disease 2019 (COVID-19) in China. This herbal medicine has shown effects in reducing clinical symptoms and shortening the average length of hospital stay for COVID-19 patients. Previous studies have demonstrated that XBF alleviates acute lung injury (ALI) by regulating macrophage-mediated immune inflammation, but the mechanisms of action remain elusive. Purpose This study aimed to evaluate the lung-protective and anti-inflammatory effects of XBF and its underlying mechanisms. Methods Here, XBF's effects were investigated in an ALI mouse model induced by inhalation of atomized lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in RAW264.7 cells was used to clarify the underlying mechanisms of XBF against ALI. Results Our results showed that XBF treatment alleviated LPS-induced lung injury, as evidenced by reduced histopathological changes, pulmonary alveoli permeability, fibrosis, and apoptosis in the lung tissues. In addition, inflammation was alleviated as shown by decreased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β in serum and bronchoalveolar lavage fluid (BALF), and reduced white blood cell (WBC) count in BALF. Furthermore, consistent with the in vivo assay, XBF inhibited LPS-induced inflammatory cytokines release and pro-inflammatory polarization in RAW264.7 cells. Mechanistically, XBF increased mitochondrial fusion by upregulating Mfn1 and attenuated NLRP3 inflammasome activation by repressing Casp11, respectively, to inhibit NF-κB and MAPK pathways, thus repressing pro-inflammatory macrophage polarization. Conclusion In this study, we demonstrate that XBF exerts anti-ALI and -inflammatory effects by recovering mitochondrial dynamics and reducing inflammasome activation, providing a biological illustration of the clinical efficacy of XBF in treating COVID-19 patients.
研究领域:
药理学
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免疫学
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细胞生物学
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中医
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
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IF 4
Rui Ge,Qikai Su,Jian Liang,Lu Zheng,Qing-shan Li,Li Tang
The identification of natural compounds with therapeutic efficacy for acute lung injury has consistently represented a critical area of research. Dulcitol, a natural product isolated from plants, is extensively used in the food and medical industries as a sweetener. Herein, we investigated whether dulcitol exerts an anti-inflammatory effect on LPS-induced acute lung injury (ALI) in mice. In our study, ICR mice were pretreated with dulcitol at dose of 6, 12 and 24 mg/kg for seven consecutive days, followed by intratracheally instilled with LPS (10 mg/kg) to induce acute lung injury. In vitro, RAW264.7 and A549 cells were incubated with LPS in the presence of dulcitol to investigate the anti-inflammatory activity and mechanism. The results demonstrated that dulcitol effectively inhibited the infiltration of inflammatory cells and reduced the excessive production of pro-inflammatory cytokines triggered by LPS to ameliorates acute lung injury in mice. Additionally, in vitro experiments indicated that dulcitol suppressed the release of NO, IL-6 and TNF-α while reducing mRNA expression levels of IL-1β, IL-6, COX-2, iNOS and TNF-α in RAW264.7 and A549 cells in a dose-dependent manner. Furthermore, dulcitol significantly decreased TLR4, MyD88, and TRIF levels and inhibited the translocation of NF-κB from the cytoplasm to the nucleus. Our finding suggested that dulcitol could serve as a protective agent against LPS-induced acute lung injury by inhibiting the TLR-4/NF-κB signaling pathway.
研究领域:
免疫学
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药理学
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分子生物学
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DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Zhaolei Peng,Yulin Wang,Kai Liu,Chunyan Cai,Dejun Yang,Jingjing Xi,Mingyi Shi,Xiaofang Li
In this work, Bletilla striata polysaccharide-modified SeNPs (BSPs-SeNPs) was prepared to address the instability of SeNPs as a result of its outstanding performance in the field of natural polymer materials. BSPs-SeNPs were synthesized using Na 2 SeO 3 as the selenium source and ascorbic acid as the reducing agent. The FTIR, XRD and EDS results demonstrated the successful synthesis of BSPs-SeNPs, which exhibited excellent nanoparticle characteristics, with a particle size of 66.9 ± 1.30 nm and Se concentration of 12.19 ± 0.62 %. Stability tests indicated that BSPs-SeNPs maintain structural integrity under various storage conditions, pH levels, temperatures, and ionic strengths. The mice acute liver injury (ALI) model was created with 300 mg/kg APAP, BSPs-SeNPs decreased serum ALT and AST values as expected. And the restored SOD, GSH and MDA values showed correlation with the in vitro antioxidant activity assay results (DPPH · , ABTS · , · O 2 − , and · OH). In general, BSPs-SeNPs is successfully synthesized, which enlightened the conjunction between natural polysaccharide and inorganic nanoparticles, but also encouraged the extensive use of BSPs in the field of pharmaceutical excipients.
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高影响因子
International Journal of Biological Sciences
·
2026
·Vol. 22
·期 13
·7427
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IF 11.7
Hong Xu,Hongyu Chen,Fengling He,Xinlan Li,Wanxin Li,Qingqing Yang,Tingting Zhang,Jin Liu,Xiaoke Shi,Shilin Chen,Defang Li,Jun Lu
Aberrant activation of macrophages and their amplification of inflammatory responses constitute the core pathological basis driving the progression of acute lung injury (ALI). Celastrol (CE), despite its potent anti-inflammatory activity, suffers from poor aqueous solubility and substantial systemic toxicity, which severely limit its clinical translation. Capitalizing on the metabolic signature of pro-inflammatory M1 macrophages, specifically their high expression of glucose transporter 1 (GLUT1), we designed a glucose-modified CE prodrug that self-assembled into carrier-free nanoparticles CG NPs. With markedly improved solubility and systemic stability, CG NPs rapidly and persistently accumulated in the inflammatory lungs of LPS-induced ALI mice facilitated by GLUT1-mediated targeting and uptake by M1 macrophages. Compared with free CE, CG NPs exhibited enhanced overall therapeutic efficacy while significantly reducing hepatorenal toxicity. Mechanistic studies revealed that by targeting Drp1, CG NPs disrupt Drp1-MiD51 interaction, thus inhibiting excessive mitochondrial fission and ROS accumulation, which blocks NF-κB-mediated inflammatory signaling and M1-driven cytokine release. Molecular docking suggested that glucose conjugation may confer CG with a superior ability to regulate mitochondrial homeostasis over CE, potentially driven by its unique U-shaped conformation that inserts into Drp1 and forms a denser hydrogen-bond network, which could contribute to enhanced binding affinity. In summary, this study proposes a nanoprodrug strategy that combines precise targeting with mitochondrial protection, offering a promising therapeutic avenue for inflammatory diseases such as ALI.
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PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Jihong Bi,Yan Li,Lin Lu,Tingting Yin,Shaohua Mao,Run Zhang,Juan He,Xing Ni,Kai Wang,Jirui Bi
Objective: To investigate the protective effects of luteolin on ALI induced by lipopolysaccharide (LPS) in male mice and to explore the underlying mechanisms.Methods: A two-sample Mendelian randomization (MR) analysis was conducted to assess the causal relationship between hepatocyte growth factor (HGF) and acute respiratory distress syndrome (ARDS). Network pharmacology analysis was employed to identify herbs that mitigate inflammation and apoptosis by upregulating HGF expression and to determine the hub active ingredients. These findings were subsequently validated through in vivo experiments using an LPS-induced ALI mouse model. Lung histopathological examination, enzyme-linked immunosorbent assay, and Western blot analysis were performed to evaluate relevant biomarkers of inflammation and apoptosis.Results: The MR analysis demonstrated a causal effect of HGF on ARDS (IVW: β = −1.120, OR = 0.326, 95% CI = 0.116–0.916, P = 0.033). Among herbs associated with upregulating HGF expression, Salvia miltiorrhiza Bunge is involved in the negative regulation of apoptotic process and positive regulation of cell population proliferation. Luteolin was identified as the hub active ingredient extracted from S. miltiorrhiza Bunge. In LPS-induced ALI mice, luteolin significantly alleviated histopatholocial damage, inflammation, and apoptosis in the lungs. However, these protective effects were abrogated by c-Met inhibition.Conclusion: Luteolin attenuates inflammation and apoptosis in the lungs of LPS-induced ALI mice via activation of the HGF/c-Met pathway.
研究领域:
免疫学
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分子生物学
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药理学
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呼吸病学
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转化医学
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DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 6
·2360
·
IF 13.3
Bin Li,Jingyi Liu,Wanyu He,Yanlin Zhou,Man Zhao,Cong Xia,Xiaoyue Pan,Zhihua Ji,Ruoyu Duan,Hui Lian,Kai Xu,Guoying Yu,Lan Wang
Rationale: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical syndrome with a mortality rate of up to 40%, and it is characterized by a prominent inflammatory cascade. The inflammasome and pyroptosis play crucial regulatory roles in regulating various inflammatory-related diseases by serving as pivotal signaling platforms for inflammatory responses and mediating the release of substantial quantities of inflammatory factors. Our previous studies confirmed that GC-1, a clinical-stage thyroid hormone analog, effectively mitigated pulmonary fibrosis by restoring mitochondrial function in epithelial cells. However, the potential effects of GC-1 on macrophage inflammasome assembly and pyroptosis in lung injury as well as the underlying mechanisms, remain unclear. Methods: The effects of GC-1 on lung injury, oxidative damage and inflammation were evaluated in two murine models of ALI (LPS- or HCl-induced models) by assessing lung pathology, the concentrations of IL-1β and IL-18 in BAL fluid, inflammasome and the levels of inflammasome- and pyroptosis-related proteins. Additionally, the impact of GC-1 on ROS-mediated inflammasome assembly and pyroptosis was investigated by examining ROS levels, Nrf2 signaling, and inflammasome adaptor protein ASC levels in mouse alveolar macrophages and human THP-1 macrophages treated with LPS and ATP. The Nrf2 inhibitor ML385 and the mitochondrial-ROS inhibitor Mito-TEMPO were used to further elucidate the effect of GC-1 on the Nrf2-p53-ASC pathway. Results: GC-1 significantly alleviated inflammation and lung injury in ALI model mice, as indicated by pulmonary pathology, inflammatory cytokine levels, ROS production and pyroptosis rates. Consistently, GC-1 inhibited ASC recruitment and oligomerization in macrophages, which suppressed the gasdermin D-mediated release of IL-1β and IL-18. These findings indicated a reduction in inflammasome assembly and pyroptosis initiation. Further research revealed that GC-1 may mitigate oxidative stress induced by mitochondrial damage through Nrf2 signaling, thereby inhibiting the expression of ROS-activated p53 and the target gene ASC. This protective effect of GC-1 could be reversed by ML385 and mimicked by Mito-TEMPO. Conclusions: This study presents a novel mechanism for treating ALI in which GC-1 inhibits macrophage ROS-mediated inflammasome assembly and pyroptosis through Nrf2-p53-ASC pathway. These findings highlight the promising potential of the use of GC-1 as an anti-inflammatory and antioxidant drug in the treatment of ALI/ARDS.
研究领域:
药理学
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免疫学
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呼吸医学
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炎症研究
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
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IF 4.18
Hongjin Chen,Yali Zhang,Wenxin Zhang,Hui Liu,Chuchu Sun,Bing Zhang,Bin Bai,Di Wu,Zhongxiang Xiao,Hazel Lum,Jianmin Zhou,Ruijie Chen,Guang Liang
Background ALI/ARDS is characterized by severe hypoxemic respiratory failure attributed to inflammatory tissue injury. There are no treatment modalities able to prevent/reverse the dire pathological sequelae in these patients . Evidence links the inflammatory lung injury to uncontrolled activation of the immune signaling complex, TLR4-MD2 (Toll-like receptor-myeloid differentiation factor 2). Baicalein , a natural flavonoid , is reported to have robust anti-inflammatory properties, but its inhibition mechanism remains unclear. Hypothesis/Purpose This study investigated the protective mechanisms of baicalein on ALI/ARDS. Methods We used two experimental mouse models of LPS-induced ALI , pulmonary infection model (intratracheal LPS), and systemic infection model (intravenous LPS). Blood, BALF , lung and liver tissues were analyzed using routine methods. In vitro studies using peritoneal mouse macrophages or recombinant proteins were designed to elucidate inhibition mechanisms of baicalein. Results Our critical new findings revealed that Baicalein was an MD2 inhibitor, directly bound to MD2, effectively suppressing TLR4-MD2 activation and the subsequent MAPK and NF-κB signaling. The inhibited MD2 prevented development of inflammatory tissue injury and improved survival. The importance of MD2 in the inflammatory injury in ALI was corroborated by data obtained from MD2 −/− mice, which did not develop the characteristic LPS-induced lung tissue damage. Thus, the findings indicated that MD2 was critical for development of ALI, functioning as an early upstream signal driving the progression of inflammatory injury. Conclusion Baicalein, as a direct and selective MD2 inhibitor, inhibited the early upstream TLR4-MD2 signaling and is a promising therapeutic agent for the treatment of ALI/ARDS.
研究领域:
免疫学
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药理学
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肺科学
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分子生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
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IF 11
Bichao Lu,Jie Su,Yu Long,Xuefeng Liu,Tongfei Fu,Ningfeng Mao,Miao Wang,Wei Guo,Ke Yi,Shuhan Zhou,Wenliang Lv
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are severe respiratory diseases with a high mortality rate, characterized by pathological lung damage induced by excessive inflammation. Current therapeutic strategies for ALI are limited; conventional treatments are associated with severe side effects and lack targeted efficacy. Hesperetin(Hes)is a natural flavanone abundant in citrus fruits that exhibits promising anti-inflammatory potential, yet its further clinical application is hindered by poor solubility and low bioavailability. Small intracellular vesicles (sIVs) derived from mesenchymal stem cells have been demonstrated to possess the advantages of high yield, rapid cellular uptake and excellent stability. In view of this, the present study constructed a Hes-loaded sIVs-liposome nanodelivery system (sIVs-LPs@Hes) for the treatment of ALI via nebulized inhalation. Our findings revealed that sIVs-LPs@Hes could be efficiently absorbed and persistently retained in the lung, and it exerted a superior protective effect by inhibiting glycolysis through the MCU-mCa 2+ -NF-κB pathway, promoting M2 polarization of macrophages, ameliorating pulmonary inflammatory status, reducing pulmonary edema and repairing pathological lung damage. In conclusion, the present study not only elucidated the specific anti-inflammatory mechanism of Hes, but also developed a novel composite nanodelivery system by integrating the merits of sIVs and liposomes, thereby providing a promising potential therapeutic strategy for ALI.
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DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2026
·
IF 2.7
Lei-lei Yang,Min Sun,Wen-wen Zhang,Hai-yan Wang,Zi-long Cheng,Mao-jun Liu,Zhi-xin Feng,Wen-liang Li
The respiratory epithelium acts as the airway's first physical barrier against invading pathogens, mainly relying on mucociliary clearance (MCC) and apical junctional complexes (tight junctions/TJs and adherens junctions/AJs) for barrier function. Primary airway epithelial cells cultured in the air-liquid interface (ALI) system can well mimic these characteristics in vitro . This study established and characterized well-differentiated ALI-cultured goat airway epithelial cells (ALI-GAECs), and developed a CPIV3 infection model therein, verifying the apical infection and release of CPIV3 in ALI-GAECs. CPIV3 infection impaired the barrier function of ALI-GAECs, as reflected by decreased trans-epithelial electrical resistance (TEER), increased FITC-Dextran permeability, and reorganization of the ZO-1 and F-actin meshwork. Mechanistically, RT-qPCR and Western blot analyses demonstrated that CPIV3 downregulated major TJ proteins (ZO-1, occludin, claudin-1) while upregulated the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-4, IL-6). The NF-κB signaling pathway, but not the MAPK pathways, was activated upon viral infection. Treatment with the NF-κB inhibitor BAY 11–7082 partially restored the expression of TJ proteins and proinflammatory cytokines. Collectively, the activation of the NF-κB pathway and subsequent production of proinflammatory cytokines is responsible for CPIV3-induced TJ disruption. In addition, the developed ALI-GAECs model provides a valuable in vitro tool for investigating the pathogenesis of CPIV3 and other caprine respiratory pathogens.
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DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2024
·
IF 7.2
Meng Cao,Jisheng Song,Haonan Ren,Fan Yang,Rong Chen
With the development of integrated circuit miniaturization, the RC delay caused by the interconnect resistance of metal wires and the capacitance of interlayer dielectric materials limits the high integration and miniaturization of electronic devices. As a promising low-k dielectric material, metal–organic frameworks (MOFs) can effectively alleviate this problem. In this work, we report an atomic regulation strategy of ultralow k MIL-53 film, achieved by converting an Al2O3 seed layer deposited via atomic layer deposition (ALD) and subsequently modifying through atomic layer infiltration (ALI). Thanks to the linear relationship between the thickness of the MIL-53 film and the Al2O3 seed layer prepared by ALD, precise nanoscale control of the MIL-53 films was realized. To meet both mechanical and dielectric property requirements, ALI modification is introduced, effectively regulating Young’s modulus and hardness of MIL-53 films from 19.5 and 0.17 GPa to 29.1 and 0.36 GPa, respectively, while the dielectric constant can be tuned from 1.93 to 2.59. The reconciliation of these properties is achieved by regulating the porosity of the MIL-53 framework through the additional Al–O clusters during the ALI. Furthermore, the superhydrophobic properties (140.7°) and the nearly constant dielectric constant after 9 months of aging reflect its potential as a dielectric insulating material. The proposed preparation and modification strategy of MOF films based on atomic regulation has broad potential for application in low-k interconnect integrated circuits.
研究领域:
材料科学
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电子工程
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纳米技术
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DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·40525
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IF 3.9
Ma Chunli,Wang Linghong,Cao Lili,Zhao Linyun,Zhang Xin,Ma Chengyou,Lian Hua,Bao Xiufang,Eerde Mutu,Buren Qiqige,Tong He,Dai Lili,Amu Guleng,Bao Yulong,Hong Mei,Wang Li
Acute liver injury (ALI) is a prevalent hepatic condition that poses significant risks to both life and overall health. Traditional Mongolian medicine utilizes Honghua Qinggan Thirteen-Flavor Pills (HHQG) as a primary formula for dispelling liver heat, illustrating both an extensive application in clinical settings and notable therapeutic effectiveness for treating liver ailments such as hepatitis and liver failure. Nevertheless, the molecular mechanisms underpinning the hepatoprotective properties of HHQG remain inadequately understood.We employed a CCl 4 -induced mouse model of liver injury alongside network pharmacology analysis, molecular docking studies, and cellular assays to dissect the effects and mechanisms of action of HHQG. Our findings demonstrated that HHQG significantly improved CCl 4 -induced liver injury in mice, reducing pathological damage and inflammatory factors. Network pharmacology identified 184 overlapping targets, 6 key genes, and 5 key active components in HHQG. Molecular docking confirmed the binding affinity of these components to RASD1. Gene expression analysis in liver tissue revealed a positive correlation between mRNA expression of RASD1 and NLRP3. Cell experiments demonstrated the role of RASD1 in regulating NLRP3 inflammasome and inflammatory factors. Pretreatment of HHQG attenuated LPS-induced inflammatory response and the activation of PKCδ-NF-κB signaling pathway. In the CCl 4 -induced liver injury model, HHQG significantly reduced NLRP3, RASD1, and PKCδ-NF-κB expression.This study revealed that HHQG effectively mitigates CCl 4 -induced liver injury by inhibiting the activation of NLRP3 inflammasome by regulating the PKCδ-NF-κB signaling pathway via RASD1. These findings provide novel theoretical support for the rational application of HHQG as a potential hepatoprotective agent.
研究领域:
药理学
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传统医学
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分子生物学
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肝脏病学
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信号转导
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Anna Gan,Haimiao Chen,Fei Lin,Ruixuan Wang,Bo Wu,Tingxu Yan,Ying Jia
Background Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated. Purpose This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI. Methods The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI. Results This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis. Conclusions This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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免疫学
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呼吸医学
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传统中医
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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）