Polymers
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2022
·Vol. 14
·期 12
·2470
·
IF 4.967
Jing Yang,Xujiao Tang,Qingqing Wu,Panpan Ren,Yishu Yan,Wei Liu,Chun Pan
Heparin has shown benefits in severe acute pancreatitis (SAP) therapy, but the underlying mechanisms were unknown. Extracellular high-mobility group protein-1 (HMGB-1) has been regarded as a central mediator contributing to inflammation exacerbation and disease aggravation. We hypothesized heparin attenuated the disease by targeting HMGB-1-related pathways. In the present study, the possible therapeutic roles of heparin and its non-anticoagulant derivatives, 6-O-desulfulted heparin and N-acylated-heparin, were determined on mouse models induced by “Two-Hit” of L-arginine. The compounds exhibited potent efficiency by substantially decreasing the pancreatic necrosis, macrophage infiltration, and serum inflammatory cytokine (IL-6 and TNF-α) concentration. Moreover, they greatly reduced the rapidly increasing extracellular HMGB-1 levels in the L-arginine injured pancreases. As a result, multiple organ failure and mortality of the mice were inhibited. Furthermore, the drugs were incubated with the RAW264.7 cells activated with damaged pancreatic tissue of SAP mice in vitro. They were found to inhibit HMGB-1 transfer from the nucleus to the plasma, a critical step during HMGB-1 active secretion from macrophages. The results were carefully re-examined with a caerulein and LPS induced mouse model, and similar results were found. The paper demonstrated heparin alleviated SAP independent of the anti-coagulant functions. Therefore, non-anticoagulant heparin derivatives might become promising approaches to treat patients suffering from SAP.Keywords:heparin;severe acute pancreatitis;HMGB-1;macrophage
研究领域:
药理学
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免疫学
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炎症
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胃肠病学
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DOI
PubMed
高影响因子
FITOTERAPIA
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2023
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IF 3.4
Yang Liu,Limei Ran,Yahong Wang,Peng Wan,Hongli Zhou
The polysaccharides from Sea buckthorn leaves (SBLPs) were extracted by hot water and purified by DEAE cellulose , then separated into six polysaccharides (SBLP-S) by DEAE-52 column. Six separated polysaccharides were characterized by Ultraviolet Spectroscopy, Infrared Spectrum, High Performance Liquid Chromatographic and Congo red analysis. The antioxidant activity and immunological activity were investigated in vitro . The results revealed that the monosaccharide composition of SBLP-S-1, SBLP-S-2, SBLP-S-3, SBLP-S-5 and SBLP-S-6 contained Man , GlcN , Rib , Rha , GluA , GalA , Glu, Gal, Xyl , Ara and Fuc , among them, rare glucosamine was found. And SBLP-S-4 contained all above components except GlcN and GluA. FT-IR showed that SBLP-S were sulfated polysaccharide containing uronic acid . Molecular weights of SBLP-S were 338.659, 401.305, 599.849, 393.904, 626.895 and 176.862 kDa. The Congo-red test indicated that SBLP-S-2, SBLP-S-4, SBLP-S-5, and SBLP-S-6 had triple helix conformation. Crude polysaccharides had the strong scavenging activities on DPPH radicals, ABTS radicals and hydroxyl radicals . The six polysaccharides had the activity of immune stimulation on RAW264.7 cell. SBLP-S-2 promoted the phagocytosis best and SBLP-S-6 promoted the NO production best. The results suggested that SBLPs could be used as potential antioxidants and immunomodulatory agents in pharmaceutical and functional food fields.
研究领域:
药理学
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食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Hua Fang,Xiumei Wang,Mengyu Li,Mengxian Huang,Yiping Zhang,Taige Zhao,Cuiling Sun,Min Xu,Wenhui Jin,Weizhu Chen,Meijuan Fang
In this study, twenty-five novel carboxylic acid DHA-alkanolamine derivatives were synthesized by the reaction of cis -docosa-4,7,10,13,16,19-hexaenoic acid-alkanolamine (DHA-AA) with various carboxylic acids, including Naproxen (S1), Ibuprofen (S2), Ferulic acid (S3), Mefenamic acid (S4), and Aspirin (S5). Their molecular structures were characterized using 1 H/ 13 C NMR and HRMS techniques. To evaluate the anti-inflammatory activities of synthesized compounds, RAW264.7 macrophage cells pretreated with or without these compounds, were stimulated by LPS, and the levels of pro-inflammatory cytokines (NO, TNF-α, IL-1β, and IL-6) were then measured by ELISA, qPCR, and Western Blot. The cell-based assays showed that compound 11 had marked anti-inflammatory activity. In addition, the molecular docking study and SPR assay demonstrated that compound 11 exhibited good Nur77-binding affinity (K D = 3.61 × 10 −6 M). Moreover, compound 11 was found to inhibit NF-κB activation in a Nur77-dependent manner. Notably, compound 11 could attenuate LPS-induced inflammation in the mouse acute lung injury (ALI) model. In conclusion, these derivatives are potential Nur77-targeting anti-inflammatory agents against versatile inflammatory and autoimmune disorders.
研究领域:
药理学
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炎症研究
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药物化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Yaozhong Lv,Yajun Yang,Ying Chen,Dongfan Wang,Yipeng Lei,Mingyue Pan,Zhenzhong Wang,Wei Xiao,Yujie Dai
In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides , a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography . PCP-2 is a heteropolysaccharide composed of glucose, galactose , mannose , and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3- β -D-Glc and 1,6- β -D-Glc as the backbone glucans and 1,6- α -D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF- α . In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3 + CD4 + T cells , increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.
研究领域:
免疫学
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药理学
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生物化学
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真菌学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Yi Zhang,Xiujin Shi,Jialun Han,Wenxing Peng,Zhenwei Fang,Yang Zhou,Xiaoyu Xu,Jie Lin,Fucheng Xiao,Limin Zhao,Yang Lin
Introduction As the primary immune cells, macrophages play a key role in atherosclerotic progression. M2 macrophage polarization has been reported to promote tissue repair and attenuate plaque formation upon the expression of anti-inflammatory factors. Convallatoxin (CNT) is a natural cardiac glycoside with anti-inflammatory pharmacological properties. However, whether CNT protects against atherosclerosis (AS) and underlying mechanisms is unknown. This work was designed to explore the potential effects of CNT on atherosclerosis.Methods In this study, Apolipoprotein E deficiency (ApoE−/-) mice fed with high-fat diet were established, and CNT (50 or 100 μg/kg) were intragastrically administrated for 12 weeks every day. In vitro, RAW264.7 macrophages stimulated with ox-LDL were treated with CNT (50 or 100 nM) for 24 h. The specific PPARγ antagonist, GW9662, was used to block the PPARγ signaling pathway in vitro. Then, the atherosclerotic lesions, macrophage polarization markers, inflammatory cytokines and PPARγ signaling pathway were examined in further examinations.Results Our results showed that the atherosclerotic lesions were reduced by CNT, as demonstrated by the downregulation of serum lipid level and aortic plaque area in AS mice. Furthermore, we found that CNT treatment promoted the expression of M2 macrophage markers (Arg1, Mrc1, Retnla and Chi3l3), and decreased the levels of pro-inflammatory cytokines (IL-6 and TNF-α), accompanied by the increase of anti-inflammatory factor (IL-10) in aortic vessels of AS mice. In ox-LDL-induced RAW264.7 cells, CNT administration also facilitated macrophages polarizing towards M2 subtype and inhibited inflammatory responses. Furthermore, both the in vivo and in vitro experiments showed CNT could increase the expression of PPARγ, Integrin αv and Integrin β5, and GW9662 could block CNT-induced M2 macrophage polarization.Conclusion Taken together, these data suggest that CNT may promote M2 macrophage polarization to exert an anti-atherosclerotic effect, partially through activating PPARγ-Integrin αvβ5 signaling pathway.
研究领域:
心血管疾病
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免疫学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Hongbo Wang,Jiawei Zuo,Liang Zha,Xia Jiang,Caixia Wu,Yong-An Yang,Wenjian Tang,Tianlu Shi
To develop new anti-inflammatory drugs for the prevention and treatment of acute kidney injury, a series of novel glycyrrhetic ureas were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Compounds 5r-5u (2.04, 2.50, 3.25 and 2.48 μM, respectively) with acidic or neutral amino acid showed potent anti-inflammatory activity (IC 50 = 2–3 μM for NO inhibition), amongst them, compound 5r also inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner. In cisplatin-induced AKI mice model, compound 5r significantly reduced the level of pro-inflammatory factors, ameliorated the pathological damage of kidney tissue, and maintained the normal metabolic capacity.
研究领域:
药理学
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药物化学
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炎症研究
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肾病学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2019
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IF 3.579
Wei Xu,Nan Zhang,Zhentao Zhang,Pu Jing
Anthocyanins exist likely as complexes with flavones/metal ions in some plants. However, few studies indicate the complexation effects on bioactivities, i.e. antioxidant activities. The aim of this study was to evaluate effects of complexes of cyanidin-3-diglucoside-5-glucoside (CY3D5G) with rutin/Mg(II) on intrinsic antioxidant enzymes and mRNA expressions. All complexes exhibited cellular antioxidant activity in RAW264.7 cells, whereas half maximal effective concentration (EC 50 ) values of CY3D5G complexes were significantly lower than its alone. Combination indexes of CY3D5G-rutin, CY3D5G-Mg(II), and CY3D5G-rutin-Mg(II) complexes were < 1 ( p < .05), indicating of synergistic effects. Additionally, CY3D5G-Mg(II) rather than others significantly enhanced total antioxidant capacity, superoxide dismutase activity, and glutathione peroxidase activity while reducing malonic dialdehyde contents in H 2 O 2 -induced RAW264.7 cell model ( p < 0.05), which were further confirmed with the up-regulated mRNA expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and the down-regulated p21 ( p < 0.05). Our results demonstrated that CY3D5G and its complexes might enhance cellular antioxidant activities via the Nrf2/HO-1 signaling pathway. Additionally, a synergistic antioxidant effect of CY3D5G in the present of rutin/ Mg(II) as regular food components was evident, suggesting anthocyanin might interact with dietary components such as Mg(II) or rutin in food matrix or biological systems and exhibit a stronger antioxidant activity than it alone. The Mg (II) that exhibited no antioxidant activities alone shows potential as a co-adjuvant for the anthocyanin antioxidant activity.
研究领域:
药理学
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生物化学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Hao Dan-Li,Wang Ya-Jie,Yang Jia-Ying,Xie Ran,Jia Ling-Yu,Cheng Jin-Tang,Ma Hai,Tian Ji-Xiang,Guo Shan-Shan,Liu Ting,Sui Feng,Zhao Yu,Chen Yan-Jun,Zhao Qing-He
Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30–40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.
研究领域:
药学
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纳米技术
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炎症研究
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肺医学
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产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 10
·1226
·
IF 4.8
Wenjuan Quan,Taoli Sun,Bo Hu,Quanye Luo,Yancheng Zhong,Wen Chen,Qinhui Tuo
Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and foam cell formation in the arterial wall. Promoting macrophage autophagy has emerged as a promising therapeutic strategy against atherosclerosis. Dipsacoside B (DB) is an oleanane-type pentacyclic triterpenoid saponin extracted from Lonicerae flos with potential anti-atherosclerotic properties. In this study, we investigated the effects of DB on atherosclerosis progression in ApoE −/− mice fed a high-fat diet and explored the underlying mechanisms in oxidized low-density lipoprotein (ox-LDL)-induced foam cells. DB treatment significantly reduced atherosclerotic lesion size, improved plaque stability, and regulated lipid metabolism without impairing liver and kidney function in ApoE −/− mice. In vitro studies revealed that DB dose-dependently inhibited ox-LDL internalization and intracellular lipid accumulation in RAW264.7 macrophages. Mechanistically, DB induced autophagy, as evidenced by increased autophagosome formation and upregulated expression of autophagy markers LC3-II and p62 both in vivo and in vitro. Inhibition of autophagy by chloroquine abolished the antiatherosclerotic and pro-autophagic effects of DB. Furthermore, DB treatment increased LC3-II and p62 mRNA levels, suggesting transcriptional regulation of autophagy. Collectively, our findings demonstrate that DB exerts anti-atherosclerotic effects by inhibiting foam cell formation via autophagy induction, providing new insights into the pharmacological actions of DB and its potential as a therapeutic agent against atherosclerosis.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2024
·
IF 5.6
Hu Xu,Gen Li,Cheng Wan,Xiao-Yi Wei,Tao Zhou
In order to improve the extraction yield of lotus leaf polysaccharide (LLP) and offer scientific foundation for utilization of LLPs in the food and pharmaceutical industries, pectinase-assisted extraction method was employed for the preparation of LLP. The chemical composition, physicochemical properties (e.g. rheological and thermal properties etc.), antioxidant and anti-inflammatory effects of LLP and its two purified fractions (LLP1 and LLP3) obtained using DEAE-52 and subsequent Sephadex G-100 column chromatography were also investigated. Antioxidant assays indicated that the polysaccharides had remarkable DPPH• and ABTS +• scavenging activities. In H 2 O 2 -induced RAW264.7 cells, LLPs showed marked protective effect on oxidative stress, reducing the MDA and ROS contents and increasing the CAT and SOD activities. LLPs were also found to effectively modulate the expressions of CAT, SOD1, Nrf-2, HO-1, NQO1 and Keap1 mRNA. Thus, the potent antioxidant effects of LLPs were achieved possibly by regulating the Keap1/Nrf-2/HO-1 signaling pathways. In lipopolysaccharide-treated RAW264.7 macrophages, LLPs reduced phagocytic ability, decreased release of NO, TNF-α, IL-1β and IL-6, and increased release of IL-10 and TGF-β1, indicating their potent anti-inflammatory effect. LLPs downregulated expressions of iNOS, IL-1β, IL-6, TNF-α, COX-2, and TLR-4 mRNA. Therefore, modulation of NF-κB signaling pathway is possibly the important anti-inflammatory mechanism of LLPs.
研究领域:
食品科学
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药理学
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生物化学
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分子生物学
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Wenliang Sun,Chao Han,Ruirui Ge,Xiaotong Jiang,Yu Wang,Yingchao Han,Ning Wang,Yanzhi Song,Mingshi Yang,Guoliang Chen,Yihui Deng
Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand–receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.
研究领域:
药学
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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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
·
药物化学
·
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
✓ 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）