Journal of Functional Foods
·
2026
·
IF 3.9
Jiaqian Yang,Wenqi Wang,Kaiyuan Feng,Biying Ma,Liying Liu,Lanxi Xu,Lin Li,Xiangjiao Yi,Bo Yang,Yiqi Wang
Angelica keiskei (Miq.) Koidz. [Apiaceae] is a botanical drug with dual-purpose as food and medicine and its improvement in acute cerebral ischemic injury has not been studied. In the present study, we investigated the anti-neuroinflammatory and protective effects of the ethyl acetate extract of Angelica keiskei (EEAK) on acute cerebral ischemic injury. EEAK dose-dependently suppressed the production of inflammatory cytokines in lipopolysaccharide-activated BV2 microglia, with IC₅₀ values of 21.8 μg/mL for TNF-α and 7.9 μg/mL for IL-6, and also reduced NO and ROS levels at non-cytotoxic concentrations. In addition, EEAK inhibited the activation of the NF-κB and MAPK signaling pathways. In vivo, preventive oral administration of EEAK (50 and 100 mg/kg) significantly reduced infarct volume and improved neurological deficits in mice subjected to MCAO/R. EEAK also suppressed the mRNA expression of TNF-α, IL-6, IL-1β, and iNOS, as well as microglial activation, in ischemic brain tissues. These findings suggest that EEAK may protect against acute ischemic brain injury by inhibiting microglial activation and neuroinflammatory responses. Notably, as the treatment was administered preventively prior to acute ischemic brain injury, the therapeutic potential of EEAK in acute ischemic brain injury remains to be determined.
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高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 5
·e70420
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IF 4.2
Min Zhu,Xiaofang Fan,Nan Zhang,Hui Wang,Jianshe Ma,Xianghong Yin,Junyan Cai,Linjing Cong,Ran Chen,Junming Fan,Xiaoxia Kong,Bin Geng,Yongsheng Gong,Congkuo Du
Endothelial pyroptosis, a pro-inflammatory programmed cell death, promotes endothelial inflammation and is a pivotal process in the initial stage of acute lung injury (ALI). Hydrogen sulfide (H 2 S), a gasotransmitter primarily dependent on cystathionine γ-lyase (CSE) in the cardiovascular and respiratory systems, plays a protective role during ALI. Nonetheless, the modulatory role and precise molecular mechanism of endothelial endogenous CSE/H 2 S in the pathogenesis of ALI remain elusive. Herein, we prepared an ALI mouse model using intratracheal administration of LPS (5 mg/kg), and lung injury was assessed by evaluating pulmonary edema, inflammatory response, and endothelial pyroptosis. In this model, H 2 S production from pulmonary tissues declined in a time-dependent manner, accompanied by a compensatory elevation of CSE protein levels. Treatment with the H 2 S donor (NaHS) attenuated pulmonary edema, inflammatory cell infiltration, endothelial pyroptosis, and reduced serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Meanwhile, the inducible deletion of CSE in endothelial cells exacerbated these changes. The blocking effect of CSE/H 2 S on endothelial pyroptosis (evidenced by caspase-11 activation and GSDMD-NT formation) was also confirmed in cultured pulmonary microvascular endothelial cells (PMECs). Mechanistically, H 2 S-mediated regulation of sirtuin-1 (SIRT1) expression and activation (via sulfhydration) contributed to the modulatory process. Collectively, we uncovered that endothelial endogenous CSE/H 2 S alleviates endothelial pyroptosis by activating SIRT1, thereby preventing LPS-induced acute lung injury. Graphical In the LPS-induced ALI model, caspase-1-independent pyroptosis was activated. The expression of activated caspase-11 and GSDMD-NT was increased, accompanied by pulmonary edema and inflammatory infiltration. Endothelial CSE/H 2 S deficiency aggravated endothelial pyroptosis and acute lung injury. Mechanistically, endothelial endogenous CSE/H 2 S mediated the expression and activation of sirtuin-1 (SIRT1) via sulfhydration, one of the post-translational modifications. Activated SIRT1 inhibited the activation of caspase-11 and GSDMD-NT to inhibit endothelial pyroptosis, thereby alleviating acute lung injury.
研究领域:
医学
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分子生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Siyuan Liu,Jincheng Lv,Peng Peng,Xianshu Song,Pengyu Dai,Fangle Liu,Yufeng Yao,Chenchen Zhu,Chaozhan Lin
Ethnopharmacological relevance Recurrent or persistent respiratory tract infection may progress to chronic pneumonia or other debilitating sequelae in the absence of appropriate therapeutic interventions, seriously compromising the patients' quality of life. LianZhiXiaoYan Formula (LZXYF), a Chinese prescription composed of Chinese medical herbs Andrographis herba (ChuanXinLian) and Radix helicteris (ShanZhiMa), possesses efficiency of clearing heat and detoxifying, and shown a good therapeutic effect on respiratory infectious diseases, but its mechanism of action is not clear. Aim of the study Aim to evaluate the therapeutic efficacy of LZXYF in treatment of CP and investigate its molecular and physiological mechanisms. Materials and methods The therapeutic effects of LZXYF on CP was evaluated in an LPS-induced murine model by assessing the pulmonary function, lung histopathology, and biochemical indicators. To explore the mechanism of LZXYF, the lung metabolomics and the components of LZXYF distributed in lung were analyzed by UHPLC-Q-TOF-MS/MS. The impact of LZXYF on SIRT3-SDH-SCUNR1 pathway was investigated using RT-qPCR and Western blot, and the interaction between LZXYF and SIRT3 was verified via CETSA. LPS-induced LLC cell and succinate-induced RAW264.7 cell were employed to investigate the effect and mechanism of LZXYF on metabolic reprogramming and inflammation regulation, with selective inhibition of SIRT3 and SUCNR1, respectively. Results LZXYF treatment improved pulmonary function as demonstrated by increased Tidal volume, enhanced Minute ventilation, elevated Peak expiratory flow rate, and reduced Timed inspiration ( P < 0.05). Moreover, histopathological analysis revealed that LZXYF treatment attenuated emphysema and airway remodeling, concomitant with reduced the levels of TGF-β and HYP ( P < 0.01). Metabolomics demonstrated that LZXYF treatment restored 38 dysregulated metabolites in CP mice, primarily involving tryptophan, histidine, lysine and arginine metabolic pathways. Correlation analysis of 16 lung-distributed components and the 38 differential metabolites further indicated that LZXYF alleviated CP through SIRT3 signaling pathway mediated metabolic reprogramming. We further demonstrated that LZXYF could up-regulate SIRT3 to enhance the activities of SDH ( P < 0.01), a metabolic enzyme in TCA cycle, thereby regulating metabolic reprogramming and inhibiting the activation of SUCNR1 to prevent succinate-induced inflammation responses ( P < 0.01). Furthermore, we elucidated that the active components of LZXYF exerted ameliorated effects by up-regulating SIRT3 expression in LPS or 3-TYP induced LLC cell metabolic reprogramming, which revealed SIRT3 as a critical molecular target for LZXYF to improve metabolic reprogramming and suppress inflammatory responses induced by succinate. Conclusion LXZYF could ameliorate CP through up-regulating SIRT3, which enhances TCA cycle and suppresses succinate-mediated inflammation. This study provides new insight into the therapeutic potential of LZXYF for CP treatment.
研究领域:
呼吸病学
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中药药理学
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代谢生物学
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炎症免疫学
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分子药理学
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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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PubMed
高影响因子
International Journal of Chronic Obstructive Pulmonary Disease
·
2024
·
IF 2.7
Liguo Lu,Chengdong Zhu,Jian Xu,Yulan Hu,Juxiang Dai,Sheng Wang,Tao Wei
Introduction The Lifei Decoction (LD) is a commonly utilized Chinese medicine for the treatment of sepsis and bronchial inflammation. However, its therapeutic potential in chronic obstructive pulmonary disease (COPD) remains unknown. Therefore, the objective of this study was to investigate the therapeutic efficacy and underlying mechanism of LD in a mouse model of COPD induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS).Methods Hematoxylin-eosin (H&E) staining was employed to observe the pathological alterations in lung tissue, while ELISA was utilized for the detection of levels of inflammatory factors in both lung tissue and bronchoalveolar lavage fluid (BALF). Additionally, Western blot analysis was conducted to assess the expression of p-NF-κB, GDF11, ZO-1, and Occludin-1 proteins. The changes in intestinal flora were evaluated using the viable bacteria count method.Results The administration of LD demonstrates significant efficacy in mitigating pulmonary tissue damage in a murine model, while concurrently inhibiting the activation of the inflammatory pathway NF-κB to attenuate the levels of pro-inflammatory factors. Moreover, LD exhibits the capacity to enhance the expression of intestinal functional proteins ZO-1 and Occludin-1, thereby rectifying dysbiosis within the gut microbiota.Conclusion The LD shows great promise as a potential treatment for COPD.
研究领域:
药理学
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呼吸病学
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免疫学
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微生物学
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PubMed
高影响因子
Annals of Translational Medicine
·
2020
·
IF 3.297
Li-Xuan Yang,Fang-Yu Chen,Hai-Long Yu,Pin-Yi Liu,Xin-Yu Bao,Sheng-Nan Xia,Yue Gu,Yun Xu,Xiang Cao
Background Based on accumulating evidence, excessive activation of microglia-mediated inflammatory responses plays an essential role in ischemic stroke. Poncirin (Pon) exerts anti-hyperalgesic, anti-osteoporotic and anti-tumor effects on various diseases. However, the roles of Pon in microglial activation and the underlying mechanism have not been elucidated. This study aimed to explore whether Pon inhibits lipopolysaccharide (LPS)-induced microglial neuroinflammation and protects against brain ischemic injury in experimental stroke in mice. Methods Primary microglia cells were prepared from the cerebral cortices of 1- to 2-day-old C57BL/6J mice. Murine BV2 cells and primary microglia were stimulated with LPS and the effects of a non-cytotoxic concentration of Pon on LPS-stimulated pro-inflammatory factors were measured using real-time PCR and enzyme-linked immunosorbent assays (ELISAs). Western blot analyses were used for mechanistic studies. In an in vivo study, 8-week-old male C57BL/6J mice were subjected to focal cerebral ischemia through middle cerebral artery occlusion (MCAO). Pon (30 mg/kg, i.p.) or the same volume of saline was administered after the MCAO model was established, and the infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. We also evaluated animal behaviours, the expression of pro-inflammatory cytokines and microglial activation in the ischemic hemisphere. Results Pon prevented the release of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) in both BV2 cells and primary microglia stimulated with LPS. The inhibitory effects of Pon were associated with the regulation of the ERK1/2, JNK and nuclear factor kappa B (NF-κB) signaling pathways. In mice that underwent MCAO, Pon administration decreased the lesion size and improved neurological deficits. Furthermore, Pon attenuated the production of inflammatory cytokines mainly by restraining microglial activation after ischemic stroke. Conclusions Based on the findings from the present study, Pon provides neuroprotection through its anti-inflammatory effects on microglia and it may be a useful treatment for ischemic stroke.
研究领域:
神经科学
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药理学
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免疫学
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神经病学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Jingjing Wen,Hongfa Lin,Mengshu Zhao,Liang Tao,Yunxia Yang,Xi Xu,Aiqun Jia,Jianfa Zhang,Dan Weng
Piceatannol , a natural derivative of resveratrol , has been shown to exert similar anti-oxidant and anti-inflammatory effects as resveratrol. However, it remains unknown whether piceatannol has hepatoprotective effect against acute liver injury. In this study, we investigated the in vivo effect of piceatannol on D-GalN/LPS-induced fulminant hepatic failure (FHF), and its in vitro effect on ER stress-inducing drug thapsigargin (TG)-induced proinflammatory cytokines production and ROS release. Our results indicated that piceatannol markedly decreased the mortality rate, reduced the serum levels of alanine transaminase and aspartic aminotransferase, ameliorated the liver damage induced by D-GalN/LPS in mice. In addition, piceatannol reduced the expression of proinflammatory cytokines, including TNF-α, IL-1β and IL-6, the expression of ER stress markers CHOP and phosphorylated-IRE1α, and the generation of oxidative stress in D-GalN/LPS-treated mouse liver. In vitro results were consistent with in vivo observations, demonstrating that piceatannol suppressed the secretion of proinflammatory cytokines, inflammasome activation and the production of ROS induced by TG with or without LPS priming in J774A.1 macrophages. Our study proposes piceatannol as a promising medication for preventing acute liver failure and the mechanisms may be related to its inhibitory effects on ER stress, inflammation and oxidative stress.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
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PubMed
高影响因子
Agriculture-Basel
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2023
·Vol. 13
·期 12
·2192
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IF 3.6
Hao Zhu,Wendi Cao,Yicai Huang,Niel A. Karrow,Zhangping Yang
Pyocyanin (PCN) is an extracellular toxin secreted byPseudomonas aeruginosa(PA), which has redox capacity and disrupts the redox balance of host cells, affecting cell function and leading to cell death. The aim of this experiment was to compare the degree of apoptosis, inflammation, and oxidative stress of bovine mammary epithelium cells (bMECs) induced by lipopolysaccharide (LPS) and pyocyanin (PCN) and to examine whether PCN can promote the apoptosis, inflammation, and oxidative stress of bMECs induced by LPS. In this study, 1 µg/mL LPS and 1 µg/mL PCN were finally selected for subsequent experiments through dose-dependent experiments. In this study, cells were not given any treatment and were used as the control group (NC). The cells were treated with PCN or LPS individually for 6 h as the PCN group (PCN) or the LPS group (LPS), and the combination of LPS and PCN challenge for 6 h as the LPS + PCN (LPS + PCN) group. Compared with the control and LPS groups, PCN resulted in a significantly upregulated expression of genes related to pro-inflammatory (IL-6, TNF-α, MyD88), apoptotic (Bax, Caspase3, Caspase9), as well as protein expression of components in the TLR4/NF-κB signaling pathway (TLR4, p-p65, p65), and p53 signaling pathway (p-p53, p53, Caspase9) (p< 0.05). Moreover, the expression of genes and proteins was significantly upregulated after PCN treatment combined with LPS compared to either LPS or PCN challenge alone (p< 0.05). The stimulation of PCN combined with LPS significantly increased reactive oxygen species (ROS) and malondialdehyde (MDA) production in bovine mammary epithelial cells (bMECs), as well as decreased glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC). Moreover, cells in the LPS + PCN group aggravated oxidative stress and antioxidant inhibition in cells. In addition, the expression of the corresponding genes and proteins related to the Nrf2 pathway (Nrf2, HO-1) was significantly down-regulated in the PCN group as compared to the control group (p< 0.05). Altogether, PCN stimulation exacerbates inflammatory reactions, apoptosis, and oxidative stress reactions, as well as when combined with LPS challenge in bMECs. Therefore, this study indicates that PCN manifests a role in promoting apoptosis, inflammation, and oxidative stress and interacting with LPS to enhance more serious biological stress responses.Keywords:pyocyanin;LPS;apoptosis;cellular inflammation;oxidative stress
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BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2024
·
IF 1.4
Chen Xue,Kang Yulai,Tang Chunhua,Zhang Lili,Guo Lu
Foam cells are primarily formed through scavenger receptors that mediate the uptake of various modified low-density lipoproteins (LDL) into cells. In addition to the receptor-dependent pathway, macropinocytosis is an essential non-receptor endocytic pathway for vascular smooth muscle cells (VSMCs) to take up lipids. However, the molecular mechanisms underlying this process remain unclear. Primary cultured VSMCs were stimulated with 200 ng/ml lipopolysaccharide (LPS) and 200 μg/ml native LDL (nLDL). We observed a significant increase in TLR4 protein expression and a significant activation of macropinocytosis, which correlated with the highest uptake of nLDL and intracellular lipid deposition in WT VSMCs. However, macropinocytosis was inhibited and lipid accumulation decreased after treatment with macropinocytosis inhibitors and Syk inhibitors in WT VSMCs. Consistently, TLR4 knockout significantly suppressed macropinocytosis and lipid droplets accumulation in VSMCs. Taken together, our findings suggest a critical role of TLR4/Syk signaling in promoting receptor-independent macropinocytosis leading to VSMC-derived foam cells formation.
研究领域:
心血管生物学
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细胞生物学
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免疫学
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PubMed
高影响因子
INFLAMMATION
·
2020
·Vol. 44
·期 2
·746-757
·
IF 3.212
Gao Yang,Kang Kai,Liu Yan-song,Li Na-na,Han Qiu-yuan,Liu Hai-tao,Kong Wei-lan,Zhang Xing,Huang Rui,Yang Zhen-yu,Qi Zhi-dong,Zheng Jun-bo,Li Ming,Wang Hong-liang,Li Jia-yu,Liu Rui-jin,Wang Si-cong,Zhang Wei-hua,Zhao Ming-yan,Yu Kai-jiang
This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.
研究领域:
肾病学
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免疫学
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药理学
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PubMed
高影响因子
Frontiers in Immunology
·
2019
·
IF 4.716
Zong Xin,Cao Xiaoxuan,Wang Hong,Xiao Xiao,Wang Yizhen,Lu Zeqing
The molecular mechanisms underlying the cellular uptake of long-chain fatty acids and the regulation of this process have been debated in recent decades. Here, we established an intestinal barrier dysfunction model in mice and Caco2 cell line by Lipopolysaccharide (LPS), and evaluated the fatty acid uptake capacity of the intestine. We found that LPS stimulation restricted the absorption of long chain fatty acid (LCFA), while Cathelicidin-WA (CWA) pretreatment facilitated this physiological process. At the molecular level, our results demonstrated that the stimulatory effects of CWA on intestinal lipid absorption were dependent on cluster determinant 36 and fatty acid transport protein 4, but not fatty acid–binding protein. Further, an enhanced intestinal barrier was observed in vivo and in vitro when CWA alleviated the fatty acid absorption disorder induced by LPS stimulation. Mechanistically, peroxisome proliferator-activated receptor (PPAR-γ) signaling was considered as a key pathway for CWA to enhance LCFA absorption and barrier function. Treatment with a PPAR-γ inhibitor led to impaired intestinal barrier function and suppressed LCFA uptake. Moreover, once PPAR-γ signaling was blocked, CWA pretreatment could not maintain the stability of the intestinal epithelial cell barrier or LCFA uptake after LPS stimulation. Collectively, these findings suggested that PPAR-γ may serve as a target for specific therapies aimed at alleviating fatty acid uptake disorder, and CWA showed considerable potential as a new PPAR-γ agonist to strengthen intestinal barrier function against fatty acid malabsorption.
研究领域:
胃肠病学
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分子生物学
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免疫学
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PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Yali Zhang,Chengguang Zhao,Wenfei He,Zhe Wang,Qilu Fang,Bing Xiao,Zhiguo Liu,Guang Liang,Shulin Yang
Sepsis is a systemic inflammatory response syndrome and is mainly caused by lipopolysaccharides (LPS) – a component of the cell walls of gram-negative bacteria, via toll-like receptor 4–mitogen-activated protein kinases/nuclear factor-kappa B-dependent proinflammatory signaling pathway. Here, we synthesized 26 asymmetric monocarbonyl analogs of curcumin and evaluated their anti-inflammatory activity by inhibiting the LPS-induced secretion of tumor necrosis factor-α and interleukin-6 in mouse RAW264.7 macrophages. Five active compounds (3a, 3c, 3d, 3j, and 3l) exhibited dose-dependent inhibition against the release of tumor necrosis factor-α and interleukin-6, and they also showed much higher chemical stability than curcumin in vitro. The anti-inflammatory activity of analogs 3a and 3c may be associated with their inhibition of the phosphorylation of extracellular signal-regulated kinase and the activation of nuclear factor-kappa B. In addition, 3c exhibited significant protection against LPS-induced septic death in vivo. These results indicate that asymmetrical monocarbonyl curcumin analogs may be utilized as candidates for the treatment of acute inflammatory diseases.
研究领域:
药理学
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免疫学
·
药物化学
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PubMed
高影响因子
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