INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
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免疫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmacognosy Magazine
·
2023
·
IF 0.7
Guiyuan Liu,Yinliang Bai,Guangxian Leng,Hanwei Ma,Yin Kong,Liuqing Guo,Fahong Wu,Fengxian Wei,Yi Pang,Youcheng Zhang
Background:Leakage of the alveolar epithelial barrier can lead to pulmonary oedema, leading to organ dysfunction.Objectives:Combination anthraquinone (CA) and free anthraquinone (FA) were extracted from Rhubarb, and the prevention and therapeutic effects of Rhubarb anthraquinones (RA) on lipopolysaccharide (LPS)-induced lung injury were investigated.Materials and Methods:The CA and FA were extracted from Rhubarb by water solvent extraction and ethanol solvent extraction. The extracted RA content was determined using spectrophotometry and high-performance liquid chromatography (HPLC). A mouse model of inflammatory lung injury was established by LPS induction to study the mechanism of RA activity. Inflammatory factors were measured using an enzyme-linked immunosorbent assay. Changes in alveolar epithelial leakage were assessed using a permeability assay. Changes in lung injury were evaluated by histopathological and ultrastructural observations. Tight junction (TJ) markers and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase 1 (ROCK1) pathway-related proteins were measured using immunohistochemistry and Western blotting. As an agonist of RhoA/Rock signalling, U46619 was used to further verify whether RA acts through this pathway.Results:RA could inhibit pulmonary inflammation by decreasing the level of inflammatory factors. The alveolar epithelial permeability was reduced, and the pathological injury of the lung tissue was alleviated after administration with RA. Furthermore, the expression of TJ proteins was up regulated and RhoA/ROCK1 signalling was inhibited in the presence of RA. The effects of RA on TJ proteins were partially reversed by U46619.Conclusion:RA effectively protects mice against inflammatory lung injury by enhancing alveolar epithelial TJ via RhoA/ROCK1 signalling.
研究领域:
药理学
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肺病学
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免疫学
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分子生物学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Shu Long,Fu Hangjie,Pi Aiwen,Feng Yuliang,Dong Hui,Si Caijuan,Li Songtao,Zhu Feiye,Zheng Peifen,Zhu Qin
Ulcerative colitis (UC) is a recurring inflammatory bowel disease, in which oxidative stress plays a role in its progression, and regulation of the oxidative/antioxidative balance has been suggested as a potential target for the treatment of UC. The aim of this study was to evaluate the protective effect of andrographolide against UC and its potential antioxidant properties by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Dextran sulfate sodium (DSS) -induced UC mice and the LPS-induced HT29 inflammatory cell model were established to uncover the potential mechanisms of andrographolide. ML385, a Nrf2 inhibitor, was used in both models to assess whether andrographolide exerts a protective effect against UC through the Nrf2/HO-1 pathway. The in vivo experiment showed that andrographolide ameliorated the symptoms and histopathology of DSS-induced mice and restored the expressions of ZO-1, Occludin-1 and Claudin-1. Meanwhile, DSS-induced oxidative stress and inflammation were suppressed by andrographolide treatment, along with the upregulation of key proteins in the Nrf2/HO-1 pathway. In vitro experiments showed that andrographolide attenuated LPS-induced excessive generation of ROS in HT29 cells, reduced inflammatory factors, and upregulated the expression of proteins related to tight junctions and Nrf2/HO-1 pathway. In addition, ML385 abolished the beneficial effect of andrographolide. In conclusion, the protective effect of andrographolide against UC may involve the suppression of oxidative stress and inflammation via the Nrf2/HO-1 pathway.
研究领域:
药理学
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炎症性肠病
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Xin Qiao,Xiaojuan Cao,Shuang Xu,Cunlin Wang,Rui Guo,Xiaojuan Yao,Qiong Zhang
Background: Dysregulated and excessive inflammatory reactions can lead to tissue damage, which is the underlying cause of most human diseases. Menisoxoisoaporphine A (MA), a novel oxoisoaporphine alkaloid, was obtained from Menispermi Rhizoma, a traditional Chinese medicinal herb used in the treatment of inflammatory conditions in clinical practice. This suggests that MA has very promising potential for the development of anti-inflammatory therapeutics. Hence, this study aims to investigate the anti-inflammatory effects and underlying mechanisms of MA.Method: The anti-inflammatory effects of MA were evaluated in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. Its underlying mechanisms were explored through RNA sequencing and Western blotting. The binding modes and interactions sites between MA and phosphodiesterase 4B (PDE4B) were predicted using molecular docking and validated by molecular dynamics simulation.Results: MA treatment significantly reduced LPS-induced morphological changes, inflammatory cytokine relesae, and proinflammatory genes expression in RAW264.7 cells compared to the LPS-induced controls. Transcriptome sequencing analysis suggested that PDE4B might be a key target for MA to exert its therapeutic effect. Mechanismly, MA directly acted on Tyr405 site of PDE4B, thus leading to a sustained elevation of the cyclic adenosine monophosphate (cAMP) levels, which subsequently inactivated NF-κB signaling pathway by phosphorylating protein kinase A (PKA). MA inhibited the NF-κB-mediated inflammatory response depending on PDE4B.Conclusion: MA, a natural and novel compound, exerted anti-inflammatory effects in LPS-induced RAW264.7 macrophage cells. It demonstrated a strong binding ability to the Tyr405 sites of PDE4B, thereby inhibiting NF-κB signaling pathway by regulating the cAMP-PKA axis. Elucidating the interaction between MA and PDE4B holds significant potential for the advancement of innovative therapeutic strategies aimed at inflammatory diseases. By strategically modulating this interaction, it may be feasible to achieve more precise regulation of inflammatory responses, thereby offering promising therapeutic benefits for conditions such as rheumatoid arthritis, asthma, and inflammatory bowel disease.
研究领域:
药理学
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免疫学
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分子生物学
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炎症性疾病
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2024
·
IF 5.1
Yajie Ma,Fan Zhang,Yujun Xie,Luyao An,Bo-Li Zhang,Bo-Yang Yu,Renshi Li
Asparagi Radix is a healthy food type with medicinal and edible homology, which is now widely used for improving pulmonary inflammation in clinical. However, the lung-protective effect and the active constituents of Asparagi Radix have yet to be elucidated. Herein, the potential pulmonary protective effect of oligosaccharides was investigated. We firstly identified eighteen oligosaccharides with different degrees of polymerization from Asparagi Radix using HPLC-QTOF MS. Oligosaccharides were found to be simultaneously determined in 20 batches of Asparagi Radix collected from various regions in China by HILIC-ELSD, and oligosaccharides stably exist in this herb. In the present study, we found that AROS significantly reduced NO production, and effectively down-regulated the mRNA expression of IL-6, IL-1β and TNF-α in RAW 264.7 cells, thereby reducing the inflammatory response induced by LPS. AROS also inhibited LPS-stimulated intracellular ROS production. A murine model of lipopolysaccharide (LPS)-induced acute lung injury was used to evaluate the in vivo anti-inflammatory and lung protective efficacy of AROS. AROS could ameliorate the damage of the pulmonary cellular architecture pathological injury and lung edema. AROS significantly decreased the levels of cytokines IL-6, TNF-α and IL-1β, as well as the levels of MPO and MDA, and superoxide dismutase consumption in vivo. This effect of oligosaccharides could explain the traditional usage of Asparagus cochinchinensis as a tonic medicine for respiratory problems and oligosaccharides from Asparagi Radix used as a natural ingredient could play an important role in protecting from lung injury.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
COPD-Journal of Chronic Obstructive Pulmonary Disease
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2023
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IF 2.2
Chuanxin Yang,Libing Deng,Fang Bao,Hui Jiang,Long Zhang
Chronic obstructive pulmonary disease (COPD) is a difficult-to-cure disease that mainly affects the respiratory system. Inhaled anesthetic drug such as sevoflurane plays a controversial role in COPD by different concentration, but the underlying epigenetic mechanism remains unclear. Here, we prepared lipopolysaccharide (LPS)-induced COPD rat model, and isolated Alveolar type II (ATII) cells. We mainly focused DNA methylation on the promoter of COPD-related genes including Sftpa1, Napsa, Ca2, Sfta2, Lamp3, Wif1, Pgc, and Etv5. We observed COPD rat treated by sevoflurane with low (0.5%) and high (2%) concentrations displayed an opposite DNA methylation pattern. These six genes' promoter were all hypomethylated by 0.5% sevoflurane whereas hypermethylated by 2% sevoflurane, accompanied with the opposite transcriptional activity. We further verified that the DNMT1 binding ability contributed to DNA methylation these six genes' promoter. Moreover, we also captured DNMT1 and identified REC8 meiotic recombination protein (REC8) as the specific binding protein only existed in ATII cells treated with 0.5% sevoflurane rather than 2% and control. The binding ability of REC8 on these target genes' promoter showed highly positive correlation with DNMT1. In summary, we uncovered a potential epigenetic role of sevoflurane with low concentration in ATII cells of COPD that may help us deeply understand the pathogenesis and treatment mechanism of inhaled anesthesia drugs in COPD via a dose-dependent manner.
研究领域:
肺病学
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分子生物学
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表观遗传学
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药理学
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DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2020
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IF 4.96
Junke Song,Li Zhang,Yanfeng Xu,Dezhi Yang,Li Zhang,Shiying Yang,Wen Zhang,Jinhua Wang,Shuo Tian,Shengqian Yang,Tianyi Yuan,Ailin Liu,Qi Lv,Fengdi Li,Hongqi Liu,Biyu Hou,Xiaozhong Peng,Yang Lu,Guanhua Du
Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 μM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form β of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1β and TNF-α in serum. In conclusion, oral administration of crystal form β of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.
研究领域:
药理学
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病毒学
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免疫学
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治疗学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
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2019
·Vol. 127
·期 6
·1716-1726
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IF 2.683
Cheng R.,Wang L.,Li J.,Fu R.,Wang S.,Zhang J.
AimsTo purify and characterize an exopolysaccharide (EPS) from an Agrobacterium strain ZCC3656 with high EPS‐secreting performance and investigate its anti‐inflammatory activity using lipopolysaccharide (LPS)‐induced macrophage cells in an acute liver injury mouse model.Methods and ResultsTwelve rhizobial strains were compared for EPS fermentation production in modified M9 salts supplemented with mannitol or sucrose as the sole carbon source. Agrobacterium sp. ZCC3656 exhibited the highest EPS yield (21·1 g l−1) and was characterized for EPS production by carbon source utilization, time course fermentation and serial subcultivation assays. The EPS, designated Riclin, was purified by deproteinization using the Sevag method. The combined results of gel permeation chromatography, monosaccharide composition, methylation analysis and nuclear magnetic resonance analyses indicated that Riclin is a succinoglycan‐like polysaccharide comprised of glucose, galactose, succinate and pyruvate at a ratio of 7·8. : 1·0 : 0·9 : 1·1 and has an molecular weight of approximately 2·5 × 106 Da. Riclin inhibited TNF‐α, IL‐1β and IL‐6 expression in LPS‐stimulated RAW 264.7 macrophage cells in a dose‐dependent manner. In addition, Riclin pretreatment increased the survival rate of D‐Gal/LPS treated mice, inhibited serum ALT and AST activities and reduced the production of the inflammatory mediators TNF‐α, IL‐1β and IL‐6.ConclusionsAgrobacterium sp. ZCC3656 is a highly stable EPS‐producing strain. The EPS Riclin from ZCC3656 is a succinoglycan‐type polysaccharide that is noncytotoxic and exhibits remarkable anti‐inflammatory effects in vivo and in vitro.Significance and Impact of the StudySuccinoglycans are well known for good rheological properties and their physiological interactions with plants. However, their potential activity towards mammals has received little attention. Our study revealed that the succinoglycan Riclin exhibited excellent anti‐inflammatory activities and could be considered as a promising reagent in anti‐inflammatory treatment.
研究领域:
微生物学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-12
·
IF 4.8
Shi Yuru,Zhang Xiaoqian,Pei Shengji,Wang Yuhua
Adenosma buchneroides Bonati, also known as fleagrass, is an important medicinal plant used by the Akha (Hani) people of China for treating inflammation-related skin swelling, acne, and diarrhoea, among other conditions. In this study, we aimed to evaluate the anti-inflammatory activities and explore the molecular mechanisms of fleagrass on treating skin swelling and acne. The results demonstrated that fleagrass inhibited the enzymatic activities of 5-LOX and COX-2 in vitro, and decreased the release of NO, IL-6, TNF-α, and IL-10 in the LPS-induced RAW264.7 macrophages. The levels of proteins associated with the nuclear factor-kappa B (NF-κB) pathway were examined by western blotting and immunofluorescence, demonstrating that fleagrass downregulated the expression of TLR4, MyD88, NF-κB/p65, and iNOS and blocked the nuclear translocation of NF-κB/p65. Furthermore, fleagrass exhibited acute anti-inflammatory activity in paw oedema models. The results confirm that fleagrass exhibits remarkable anti-inflammatory activity and can be used in alleviating inflammation, suggesting that fleagrass has the potential to be a novel anti-inflammatory agent. Graphical Abstract
研究领域:
民族药理学
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药理学
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炎症
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药用植物
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Ying Lu,Dan Xu,Jingyao Liu,Lina Gu
Sophocarpine (SOP) is a tetracyclic quinolizidine alkaloid isolated from Sophora alopecuroides L. A number of studies have shown that SOP has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The purpose of this study was to investigate the protective effects of SOP on LPS-induced acute lung injury (ALI) in mice. Lung histological alterations, edema, and MPO activity were measured in this study. Furthermore, the production of inflammatory cytokines and the expression of NF-κB and MAPKs signaling pathways were measured. The results showed that the LPS-induced lung histological alterations, edema, protein concentration, inflammatory cell level in BALF, MDA content, and MPO activity were significantly attenuated by SOP. The LPS-induced inflammatory cytokine TNF-α, IL-1β, and IL-6 were also inhibited by SOP. SOP also inhibited the LPS-induced IL-6 and IL-8 production in A549 cells. Western blot analysis demonstrated that SOP remarkably inhibited the phosphorylation of IκBα and NF-κB. LPS-induced MAPKs activation and TLR4 expression were also suppressed by treatment with SOP. In conclusion, the results indicate that SOP protects against LPS-induced ALI by inhibiting TLR4 signaling pathway.
研究领域:
药理学
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免疫学
·
肺病学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Xinhui Fan,Ke Li,Xuemei Qin,Zhenyu Li,Yuguang Du
Astragali Radix polysaccharides (APSs) exhibit a broad spectrum of biological activity, which is mainly related to immune regulation. At present, most available studies focus on total APSs or a certain component of APSs. However, structural structure study and screening for the anti-inflammatory activity of polysaccharides with different molecular weights (MW) have yet to be conducted. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of APSs and its fractions. The results revealed that fraction APS-I had better anti-inflammatory effects than APS-II. After APS-Ⅰ was hydrolyzed by trifluoroacetic acid (TFA), the resulting degradation products oligosaccharides were fully methylated. These derivatized oligosaccharides were further analyzed by MALDI-TOF-MS and UPLC-Q-Exactive-MS/MS. The results showed that APS-Ⅰ was a hetero-polysaccharide with a molecular weight of about 2.0 × 106 Da, mainly consisting of glucose (46.8%) and galactose (34.4%). The degree of polymerization of Astragali Radix oligosaccharides (APOS) was 2-16. APOS were identified as 1,4-glucooligosaccharides and 1,4-galactooligosaccharides. The findings of this study lay the foundation for further elucidation of structure-function relationships of APSs and provide guidance for the development of anti-inflammatory drugs.
研究领域:
药理学
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生物化学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
·
IF 3.6
Zhu Xiaona,Bai Bin,Ge Xiangting,Zheng Bin,Xiao Zhongxiang,Tang Yue,Fang Letong,Tang Yelin,Dai Yuanrong,Zhang Bing,Zhang Yali
Inflammation is an important pathological process of many acute and chronic diseases, such as sepsis, arthritis, and cancer. Many factors can lead to an inflammatory state of the body, among which bacterial infection plays an important role. Bacterial infection often leads to sepsis, acute lung injury (ALI), or its more serious form of acute respiratory distress syndrome, which are the main fatal diseases in intensive care units. Costunolide has been reported to possess excellent anti-inflammatory activity; however, whether it can affect inflammation induced by gram-negative bacterial is still unclear. Lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages (MPMs) to release proinflammatory cytokines was used as the cell model. The mouse model of sepsis and ALI was built through injecting intravenously and intratracheally of LPS. In the present study, costunolide inhibited LPS-induced inflammatory response through IKK/NF-κB signaling pathway in macrophages. In vivo, costunolide attenuated LPS-induced septic death in mice. Meanwhile, costunolide treatment alleviated LPS-induced lung injury and inflammation via inhibiting the infiltration of inflammatory cells and the expression of inflammatory cytokines. Taken together, these results demonstrated that costunolide could attenuate gram-negative bacterial induced inflammation and diseases and might be a potential candidate for the treatment of inflammatory diseases.
研究领域:
免疫学
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药理学
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炎症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）