JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
You-Zhi Wang,Yu-Long Wang,Hao-Jie Che,Yi-He Jia,Hui-Fang Wang,Lin-Fei Zuo,Kan Yang,Ting-Ting Li,Jin-Xin Wang
Ethnopharmacological relevance Sumu ( Lignum sappan ), the dry heartwood of Caesalpinia sappan L., is a traditional Chinese medicine used as an analgesic and anti-inflammatory agent. Aim of the study The study aspired to discover natural phosphodiesterase 4 (PDE4) inhibitors with dual anti-inflammatory and antioxidant activities from Sumu for the treatment of chronic obstructive pulmonary disease (COPD). Materials and methods To accurately and efficiently identify natural PDE4 inhibitors from Sumu, molecular docking and molecular dynamics (MD) analysis methods were used for structure-based virtual screening of a self-built database of primary polyphenols in Sumu. According to the previous studies of Sumu and the free radical scavenging mechanism of polyphenols, the reported antioxidant components from Sumu and the potential antioxidants with the antioxidant pharmacophore of catechol and π-conjugated moieties were selected from the potential PDE4 inhibitors predicted by docking. Sappanone A, a potential PDE4 inhibitor with antioxidant activity from Sumu, was selected, calculated and synthesized to evaluate its dual anti-inflammatory and antioxidant functions in vitro and in vivo studies. Herein sappanone A was assayed for its inhibitory effects against PDE4 enzyme activity, tumor necrosis factor-alpha (TNF-α) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and malondialdehyde (MDA) production induced by Fe 2+ in mouse lung homogenate; sappanone A was also assayed for its abilities of radical (DPPH) scavenging, reducing Fe 3+ and complexing Fe 2+ in vitro. Additionally, LPS-induced acute lung injury (ALI) in mice was used to evaluate its anti-inflammatory activity as a PDE4 inhibitor in vivo, and the levels of TNF-α and total protein in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung were assayed. Results The present study predicted and validated that sappanone A was a promising PDE4 inhibitor from Sumu with dual anti-inflammation and antioxidant activities from Sumu. In vitro, sappanone A remarkably inhibited PDE4 enzyme activity and reduced TNF-α production induced by LPS in RAW264.7 macrophages and MDA production induced by Fe 2+ in mouse lung homogenate. Meanwhile, it showed outstanding abilities of scavenging DPPH radicals, reducing Fe 3+ and complexing Fe 2+ . In vivo, sappanone A (25 mg/kg and 50 mg/kg, i.p., twice daily for 7 days) distinctly prevented LPS-induced ALI in mice by reducing the levels of TNF-α and total protein in BALF and MPO activity in the lung. Conclusion Sappanone A is a natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the traditional Chinese medicine Sumu, which may be a promising therapeutic agent to prevent the vicious cycle of COPD inflammation and oxidative stress.
研究领域:
药理学
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药物化学
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民族药理学
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炎症
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氧化应激
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呼吸系统疾病
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产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2023
·Vol. 34
·期 33
·335101
·
IF 3.5
Yu-Hang Wan,Meng-Lei Huan,Chong-Xiao Yun,Tian-Yan Han,Si-Yuan Zhou,Xiao Song,Bang-Le Zhang
Acute lung injury (ALI) can be induced by various injury factors, which is closely related to the inflammatory reaction and cellular ferroptosis reported recently. Glutathione peroxidase (GPX4) palys an important role in the inflammatory reaction, which also is the core regulatory protein of ferroptosis. Up-regulation of GPX4 can be helpful to inhibit the cellular ferroptosis and inflammatory reaction to treat ALI. mPEI/pGPX4 gene therapeutic system based on mannitol-modified polyethyleneimine (mPEI) was constructed. Compared with PEI/pGPX4 nanoparticles using commoditized gene vector PEI 25k, mPEI/pGPX4 nanoparticles achieved caveolae-mediated endocytosis and improved the gene therapeutic effect. mPEI/pGPX4 nanoparticles could up-regulate the gene expression of GPX4, inhibit inflammatory reaction and the cellular ferroptosis, thereby alleviating the ALI in vitro and in vivo. The finding indicated that gene therapy with pGPX4 is a potential therapeutic system for the effective treatment of ALI.
研究领域:
呼吸病学
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基因治疗
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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
Advanced Science
·
2025
·
IF 14.1
Doudou Lei,Lin Liao,Tao Qin,Xiaoxuan Guan,Kunpeng Duan,Zhiwei Gao,Weiqian Jin,Mingjing Yin,Ke Zhang,Yan Liu,Yin Chen,Huyang Gao,Jiaxiao Li,Feifei Huang,Wenjing Liu,Chengde Xia,Bailei Wang,Hualin Huang,Shengqiu Lv,Qiang Zhi,Jiahao Huang,Ming Gao,Junyu Lu
Acute lung injury (ALI) refers to damage to lung related cells, typically caused by an uncontrollable inflammatory response, and over-generated reactive oxygen species (ROS). Increasing evidence suggests that reprogramming lung redox homeostasis holds significant potentials for the clinical treatment of ALI. Herein, the simple synthesis of ultra-small Pd loaded covalent organic framework (COF) (TP@Pd) is reported, which, when combined with near infrared (NIR) irradiation, exhibits nanozyme functionalities, including multiple enzyme mimicking activities and broad spectrum ROS scavenging, thereby promoting tissue repair for ALI immunotherapy. Mechanistically, through the therapeutic strategy of TP@Pd+NIR, the damaged cells and tissues are ameliorated by decreasing intracellular ROS levels (total ROS, ·OH and ·O 2 − ), downregulating inflammatory cytokines levels (IL-6, TNF-α and IL-1β), upregulating antioxidant factor level (SOD2), inducing macrophage M2 directional polarization (downregulation of iNOS and CD86, and upregulation of IL-10 and CD206), activating immunoregulation (CD4 + /CD8 + ratio increase), promoting tissue repair factor levels (upregulation of HSP70 and CD31), and suppressing the NF-κB signaling pathway (downregulation of phosphorylated p65 and IκBα). Furthermore, following intravenous (IV) injection in rats, TP@Pd accumulated in lung tissue for 6 h, indicating the promising therapeutic efficacy via this administration route. Notably, the TP@Pd+NIR strategy demonstrated the excellent synergistic effects in alleviating lung inflammation storms, reducing diffuse alveolar damage, and accelerating lung tissue repair. Summarily, this work has designed a novel TP@Pd+NIR strategy for the synergistic enhancement of ALI amelioration, which may serve as a promising therapeutic approach for other ROS related diseases.
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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肺科学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Fan Su,Chong Zhang,Qianyun Zhang,Yi Shen,Saiqi Li,Jianlin Shi,Ya-Xuan Zhu,Han Lin,Bin He
The sepsis-induced acute lung injury (ALI) still represents one of the leading causes of death in critically ill patients, underscoring the need for novel therapies. Excessive activation of immune cells and damage of reactive oxygen species (ROS) are the main factors that exacerbate lung injury. Here, the multifaceted immunomodulatory nanocomplexes targeting the proinflammatory neutrophilic activation and ROS damage are established. The S100A8/9 inhibitor, ABR2575, is loaded in the nanocomplexes, which effectively blocks the neutrophils-S100A8/A9- toll-like receptors (TLRS)-Inflammasome signaling in ALI. Synergically, the SiH nanosheets are encapsulated together with ABR2575 into the core of poly(lactic- co -glycolic acid) (PLGA) nanosponges, to achieve sustainable hydrogen release for the alleviation of ROS-induced lung tissue injury, and also promote the M2 polarization of macrophages. This novel combination strategy is proven to significantly suppress the infiltration of neutrophils and pro-inflammatory macrophages into the lungs, decrease the activation of neutrophils and pro-inflammatory monocytes in the blood, facilitate the anti-inflammatory polarization of macrophages and monocytes, and reduce the expression of pro-inflammatory cytokines in both the lung and blood circulation, all of which alleviate the lung injuries in preclinical murine ALI models. The current investigations offer a novel nanomedicine for the treatment of ALI with great potential in clinical invention.
研究领域:
纳米医学
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免疫学
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肺科学
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药理学
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重症医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Xia Liu,Nannan Wang,Tingting Cai,Hua Chen,Chunhui Dai,Wanping Zhu
Ethnopharmacological relevance Acute lung injury (ALI), a critical complication of severe pneumonia, lacks targeted therapies. Astilbe chinensis (Maxim.) Franch. & Sav. possesses documented anti-inflammatory and respiratory-protective properties, yet its efficacy against ALI, bioactive constituents, and mechanisms remain unexplored. Aim of the study This study sought to evaluate the therapeutic efficacy and elucidate the mechanisms of action of Astilbe chinensis in the treatment of ALI through the application of network pharmacology and experimental methodologies. Materials and methods UHPLC-MS was used to analyze plasma components absorbed after Astilbe chinensis administration in rats. Inflammation-related targets and pathway enrichment analyses were conducted via network pharmacology technique. Pulmonary function was assessed using forced lung function measurements in a LPS-induced ALI mouse model. ELISA quantified inflammatory mediators, including pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ), chemokines (CCL5, CXCL2), and the anti-inflammatory cytokine IL-10 in mouse lung tissue. Flow cytometry evaluated macrophage polarization, and HE staining examined histopathological changes. qRT-PCR determined the mRNA expression levels of genes like CCR1, IKBKB, CXCL8, STAT3, CXCR4, AKT1, CCL3, CCL5, iNOS, Arg1, YM1 and CCR5, while simple western analysis evaluated the protein expression of t-AKT, p-AKT, t-STAT3, p-STAT3, CCR1 and CCR5 in mouse lung tissues affected by Astilbe chinensis . Results In this study, 20 blood-borne components of Astilbe chinensis were identified, predicted to interact with 369 potential molecular targets, with 331 related to ALI treatment. GO and KEGG pathway analyses showed that 36 targets participate in inflammatory processes, mainly via chemokine signaling pathways. Key targets identified include CCR1, IKBKB, CXCL8, STAT3, CXCR4, AKT1, and CCR5. The principal active constituents of Astilbe chinensis with potential efficacy against ALI were identified as cyclo(phenylalanyl-prolyl), 5-(6-hydroxy-6-methyloctyl)- -2,5-dihydrofuran-2-one, nicotinamide, 3-phenyllactic acid, and phloretin. In vivo studies demonstrated that Astilbe chinensis administration significantly increased M2 macrophage populations in lung tissue while improving forced pulmonary function parameters. Furthermore Astilbe chinensis reduces the levels of inflammatory factors TNF-α, IL-6, IFN-γ, CCL5 (the ligand for CCR5 and CCR1), and the neutrophil chemokine CXCL2 in the lung tissues of ALI mice, while significantly increasing the content of the anti-inflammatory cytokine IL-10. Additionally, Astilbe chinensis significantly downregulated gene expression of chemokine receptors CCR1, CCR5 and their ligands CCL3, CCL5 in ALI mouse lung tissues, while upregulating anti-inflammatory markers Arg1 and Ym1 (M2 macrophage biomarkers). Meanwhile, it exerts a notable inhibitory effect on the protein expression of CCR1, CCR5, p-AKT, and p-STAT3. Conclusion This study demonstrates that Astilbe chinensis significantly improves lung function and pulmonary inflammation in mice with ALI. Component identification combined with network pharmacology analysis reveals that its major anti-inflammatory components are cyclo(phenylalanyl-prolyl), 5-(6-hydroxy-6- -methyloctyl)-2,5-dihydrofuran-2-one, nicotinamide, 3-phenyllactic acid, and phloretin. The anti-inflammatory mechanism may involve inhibiting the gene and protein expression of inflammatory chemokines CCR1 and CCR5, suppressing the activity of the AKT/STAT3 signaling pathway, reducing the expression of inflammatory factors, promoting M2 macrophage polarization, and thereby increasing the release of anti-inflammatory genes and cytokines, ultimately exerting anti-inflammatory effects.
研究领域:
药理学
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民族药理学
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炎症研究
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呼吸系统疾病
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网络生物学
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系统药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Yi Li,Dongfang Liu,Ting Chen,Jianwen Song,Xuya Yu,Qian Liu,Ji Qi,Wen Li
Acute lung injury (ALI) poses a significant and escalating medical challenge, where precise diagnosis and timely intervention hold utmost importance in halting its deterioration. Nevertheless, persistent obstacles arise from the lack of agents proficient in both real-time diagnosis and efficient mitigation of ALI. Here, a biocatalytic and second near-infrared (NIR-II) fluorescence-illuminating nanoplatform is designed to simultaneously facilitate real-time monitoring and robust inflammation alleviation in ALI. The study first develops a new aggregation-induced emission luminogen with trifluoromethyl substitutions, which simultaneously increase NIR-II emission wavelength and fluorescence brightness. The molecular probe is further integrated into biocatalytic hollow ceria nanostructures, and cloaked with pre-activated macrophage membranes for targeted inflammation intervention. Upon inhalation administration in ALI mice, the theranostic nanoagents leverage the bright NIR-II emission and active inflammation-tropic properties for in vivo sensitive NIR-II imaging of ALI, which also facilitates real-time tracking of the nanoagents’ distribution and dynamic fate within pneumonia milieu. Concurrently, the catalytic prowess of the nanoplatforms efficaciously scavenges excess reactive oxygen species, dampens proinflammatory cytokines, and promotes macrophage repolarization, substantially alleviating acute lung damage. The multifaceted nanoplatform integrates NIR-II bioimaging with nanocatalysis-mediated immunoregulation, offering a versatile and promising approach for addressing the intricate challenges posed by acute inflammation diseases.
研究领域:
生物医学工程
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纳米技术
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免疫学
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肺病学
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生物成像
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Weng Changmei,Li Guanhua,Zhang Dongdong,Duan Zhaoxia,Chen Kuijun,Zhang Jieyuan,Li Tao,Wang Jianmin
Acute lung injury (ALI) has high mortality and still lacks novel and efficient therapies. Zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) are highly expressed in the early stage of ALI and are positively correlated with the progression of pulmonary fibrosis. Herein, we developed a nanoscale Zr(IV)-based porphyrin metal-organic (ZPM) framework to deliver small interfering ZEB1/2 (siZEB1/2) to alleviate early pulmonary fibrosis during ALI. This pH-responsive nano-ZPM system could effectively protect siRNAs during lung delivery until after internalization and rapidly trigger siRNA release under the mildly acidic environment of the endo/lysosome (pH 4.0–6.5) for transfection and gene silencing. Furthermore, the in vivo studies confirmed that this nano-ZPM system could anchor in inflamed lungs. Moreover, the ZEB1/2 silencing led to increased E-cadherin and decreased α-SMA levels. Overall, the nano-ZPM system was an excellent non-viral vector system to deliver siRNAs to alleviate early pulmonary fibrosis during ALI.
研究领域:
药学
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分子生物学
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纳米技术
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肺科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Yin Mingjing,Lei Doudou,Liu Yalan,Qin Tao,Gao Huyang,Lv Wenquan,Liu Qianyue,Qin Lian,Jin Weiqian,Chen Yin,Liang Hao,Wang Bailei,Gao Ming,Zhang Jianfeng,Lu Junyu
Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO 2 ) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
研究领域:
纳米技术
·
药学
·
生物医学工程
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炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Wali Muhammad,Min Liang,Beiduo Wang,Jieqi Xie,Wajiha Ahmed,Changyou Gao
N-Acetyl cysteine (NAC) is an essential molecule that boosts acute lung injury (ALI) defense via its direct antioxidant capability. Nevertheless, the therapeutic use of NAC is limited due to its poor bioavailability and short half-life. In this study, NAC was grafted to the polyurethane consisting of poly(propylene fumarate), poly(thioketal), and 1,6-hexamethylene diisocyanate (PFTU) to reduce excessive oxidative stress and inflammatory factors in ALI. The NAC-grafted polymer nanoparticles (NPT@NPs) were prepared as a drug delivery system, which could effectively scavenge free radicals and reduce inflammation in vitro. The administration of NPT@NPs exhibited notable efficacy in ameliorating pulmonary edema, attenuating the presence of inflammatory cells, suppressing myeloperoxidase expression, diminishing the levels of pro-inflammatory cytokines, and reversing cell apoptosis in an ALI model induced by lipopolysaccharide (LPS). The NPT@NPs demonstrated significantly better efficacy compared to the free NAC in mitigating the deleterious effects of LPS on pulmonary tissue, thereby providing more effective protection against pulmonary inflammation.
研究领域:
药理学
·
纳米技术
·
肺科学
·
炎症研究
✓ 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）