Natural Product Communications
·
2022
·
IF 1.496
Bozhan Tan,Zhiwen Qi,Guliang Yang,Haiyan Zhong
Tangeretin (Tan) possesses great anti-oxidation and anti-inflammation bioactivities; however, it is accompanied by poor water solubility, which leads to inefficient cellular internalization. To address this issue, a reactive oxygen species (ROS)-triggered poly (thioether-polyesters) micelle (PDHP, PEG-DTT) was designed and prepared via self-assembly, which consisted of poly (thioether-polyesters) as the hydrophilic shell, and the drug Tan as the hydrophobic inner core. The micelles (Tan@ PDHP), with a 63.15% loading efficiency of Tan, showed negligible cytotoxicity, high stability in phosphate-buffered saline buffer (pH = 7.4), and continuous release of Tan with the stimulation of H2O2. In addition, this Tan loading micelle was more efficient in responding to the formation of ROS in the lipopolysaccharide-stimulated RAW264.7 cells compared to that of the free Tan. In short, the strategy of encapsulating the low solubility Tan in ROS-triggered poly (thioether-polyesters) micelles provides an effective assay of enhancing Tan's antioxidative activity.
研究领域:
药学
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纳米技术
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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
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
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Ximeng Lin,Wenxia Li,Hywel Yuen,Michael Yuen,Qiang Peng
Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.
研究领域:
免疫学
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真菌学
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 19
·5583-5595
·
IF 7.59
Han Li,Jiming Xu,Jun-Feng Hu,Qing-Yun Hu,Xiaolin Fang,Zhi-Jun Sun,Zhigang Xu,Lu Zhang
Periodontitis is a prevalent chronic inflammatory disease that destroys the periodontal supporting tissues, impinges on oral health, and is correlated with an increased risk of systemic disease. Currently, the main drug treatment is antibiotic therapy; however, systemic antibiotic therapy still has various drawbacks such as bacterial resistance, low bioavailability and burst release. It is noteworthy that the local use of non-antibiotic drugs with sustained release characteristics can effectively overcome these problems. It has been documented that chlorogenic acid (CGA) has good anti-inflammatory and antioxidant properties. To achieve the sustained release of CGA, we synthesized CGA–PLGA@PVP nanomicelles by loading CGA onto poly(D,L-lactide-co-glycolide) (PLGA) and modified them with polyvinylpyrrolidone (PVP) for better dispersion. The results demonstrated that CGA–PLGA@PVP nanomicelles could prolong the release time of CGA, and could not only effectively remove reactive oxygen species (ROS) but also downregulate the overexpression of proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW264.7 cells. Moreover, CGA–PLGA@PVP nanomicelles could remain in gingival tissue for more than 24 hours after local injection, inhibit alveolar bone resorption and prevent the progression of periodontitis in a mouse model, showing good biocompatibility. Therefore, CGA–PLGA@PVP nanomicelles have great properties and are expected to be a novel therapeutic strategy for periodontitis.
研究领域:
药剂学
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牙科学
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材料科学
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药理学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 6
·1273
·
IF 6.525
Jingjing Ye,Min Gong,Jian Song,Shu Chen,Qinghan Meng,Rui Shi,Liqun Zhang,Jiajia Xue
Chronic inflammation plays a side effect on tissue regeneration, greatly inhibiting the repair or regeneration of tissues. Conventional local delivery of anti-inflammation drugs through physical encapsulation into carriers face the challenges of uncontrolled release. The construction of an inflammation-responsive prodrug to release anti-inflammation drugs depending on the occurrence of inflammation to regulate chronic inflammation is of high need. Here, we construct nanofiber-based scaffolds to regulate the inflammation response of chronic inflammation during tissue regeneration. An inflammation-sensitive prodrug is synthesized by free radical polymerization of the indomethacin-containing precursor, which is prepared by the esterification ofN-(2-hydroxyethyl) acrylamide with the anti-inflammation drug indomethacin. Then, anti-inflammation scaffolds are constructed by loading the prodrug in poly(ε-caprolactone)/gelatin electrospun nanofibers. Cholesterol esterase, mimicking the inflammation environment, is adopted to catalyze the hydrolysis of the ester bonds, both in the prodrug and the nanofibers matrix, leading to the generation of indomethacin and the subsequent release to the surrounding. In contrast, only a minor amount of the drug is released from the scaffold, just based on the mechanism of hydrolysis in the absence of cholesterol esterase. Furthermore, the inflammation-responsive nanofiber scaffold can effectively inhibit the cytokines secreted from RAW264.7 macrophage cells induced by lipopolysaccharide in vitro studies, highlighting the great potential of these electrospun nanofiber scaffolds to be applied for regulating the chronic inflammation in tissue regeneration.Keywords:enzyme-responsive drug release;anti-inflammatory;prodrug;electrospun nanofiber scaffold
研究领域:
药学
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生物材料
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组织工程
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ping Ji,Xin-Chen Deng,Xiao-Kang Jin,Shi-Man Zhang,Jia-Wei Wang,Jun Feng,Wei-Hai Chen,Xian-Zheng Zhang
Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self-assembled from Fe(II), unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll-like receptor 9, induces the production of pro-inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune-related processes to achieve optimal antitumor immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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药学
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Liu Yang,Wang Fang,Guo HuiWen,Zhang Dingkun,Zhang Xiaofei,Wu Zhenfeng,Li Huiting,Xian Yang,Yue Pengfei,Yang Ming
Asarum essential oil (AEO) has been shown to have good pharmacological activities for the anti-inflammatory and analgesic effects, but increasing the dose may cause toxicity. Therefore, we studied the toxic and pharmacodynamic components of AEO by molecular distillation (MD). Anti-inflammatory activity was assessed using RAW264.7 cells. Neurotoxicity was assessed in PC12 cells and the overall toxicity of AEO was evaluated in the mouse acute toxicity assay. The results showed that AEO is primarily composed of safrole, methyl eugenol, and 3,5-dimethoxytoluene. After MD, three fractions were obtained and contained different proportions of volatile compounds relative to the original oil. The heavy fraction had high concentrations of safrole and methyl eugenol, while the light fraction contained high concentrations of α-pinene and β- pinene. The original oil and all three fractions exhibited anti-inflammatory effects, but the light fraction demonstrated more excellent anti-inflammatory activity than the other fractions. Asarum virgin oil and MD products are all neurotoxic. The exposure of PC12 cells to high concentrations of AEO resulted in abnormal nuclei, an increased number of apoptotic cells, increased ROS formation, and decreased SOD levels. Moreover, the results of acute toxicity tests in mice revealed that the light fractions were less toxic than virgin oils and other fractions. In summary, the data suggest that the MD technology enables the enrichment and separation of essential oil components and contributes to the selection of safe concentrations of AEO.
研究领域:
药理学
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 13
·2202
·
IF 5.1
Jiasi Liu,Zhiyong Li,Huiyue Gu,Songdong Shen
Large-scale blooms ofUlva proliferaseverely impact coastal ecosystems and economic development. In addressing Ulva management, the development of high-value utilization approaches for this macroalga remains crucial. Compared to other marine algae,Ulva proliferaexhibits higher protein content with diverse amino acid profiles, and existing studies demonstrate that hydrolyzedUlva proliferaproteins can yield biologically active peptides with functional potential. Conventional methods for producing bioactive peptides are often cost-intensive. Here, we employed in silico enzymatic hydrolysis to generate small peptides fromUlva proliferaprotein. Through computer screening, molecular docking with the Keap1 protein, and molecular dynamics simulations, we identified a potential antioxidant peptide, DWS (Asp-Trp-Ser). Molecular docking and dynamics simulations revealed that DWS forms stable complexes with Keap1 by establishing hydrogen bonds and Pi bonds with conserved amino acid residues (Leu557, Gly558, Ile559, Val604, Val606, and Arg415). In vitro antioxidant assays demonstrated that DWS exhibits potent DPPH and ABTS radical scavenging activities as well as reducing power. Cellular experiments showed that DWS effectively alleviates LPS-induced oxidative stress and inflammation in RAW264.7 macrophages.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Qiang Li,Linmao Ke,Dandan Yu,Han Xu,Zixuan Zhang,Rilei Yu,Tao Jiang,Yue-Wei Guo,Mingzhi Su,Xin Jin
Mitogen-activated protein kinase-interacting protein kinases (MNKs) and phosphorylate eukaryotic initiation factor 4E (p-eIF4E) play a critical role in regulating mRNA translation and protein synthesis associated with the development of cancer, metabolism, and inflammation. This study undertakes the modification of a 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine structure, leading to the discovery of 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridine (D25) as a potent and selective MNK inhibitor. D25 demonstrated inhibitory activity, with IC50 values of 120.6 nM for MNK1 and 134.7 nM for MNK2, showing exceptional selectivity. D25 inhibited the expression of pro-inflammation cytokines in RAW264.7 cells, such as inducible NO synthase, cyclooxygenase-2, and interleukin-6 (IL-6). In the lipopolysaccharide-induced sepsis mouse model, D25 significantly reduced p-eIF4E in spleen tissue and decreased the expression of tumor necrosis factor α, interleukin-1β, and IL-6, and it also reduced the production of reactive oxygen species, resulting in improved organ injury caused by inflammation. This suggests that D25 may provide a potential treatment for sepsis and sepsis-associated acute spleen injury.
研究领域:
药理学
·
免疫学
·
传染病
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Jun Hui Li,Fang Ting Gu,Ye Yang,Zi Chen Zhao,Lin Xi Huang,Yan Yu Zhu,Shiguo Chen,Jian Yong Wu
Lentinula edodes (Shiitake) is an important edible mushroom and polysaccharides are its major constituents with proven health benefits. The study was to investigate the gut bacterial fermentation and subsequent effects on gut barrier function of a glucan-rich polysaccharide, LePS40 precipitated from the mushroom water extract with 40 % (v/v) ethanol. LePS40 consisted of a β-(1→3)-glucan main chain with substitution in the C-6 position with side chains mainly composed of (1 → 6)-linked β-Glc p residues, (1 → 6)-linked α-Gal p residues and terminal residues of β-Glc p . LePS40 was found highly resistant to digestive enzymes and gastric acid in simulated human gastrointestinal tract, but highly fermentable during in vitro human fecal fermentation. The fecal fermentation degradation of LePS40 appeared to selectively break the glucoside linkage in view of the dramatic decrease in the glucose molar ratio (12.68 to 1.07). Compared with the prebiotic reference FOS, LePS40 led to much higher levels of butyric, and propionic acid and a lower level of acetic acid. Moreover, LePS40 enhanced the abundance of some beneficial bacterial populations, but decreased the bacteria possibly linked with fatty-liver disease and colorectal cancer. Furthermore, the fecal fermentation products of LePS40 showed a potential protective effect on intestinal barrier function against inflammatory damage in Caco-2/Raw264.7 co-culture model. These findings suggest the potential of LePS40 for improvement of gut health through modulation of gut microbiota.
研究领域:
营养学
·
微生物学
·
胃肠病学
·
药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 15
·3443
·
IF 4.2
Taiping Li,Huan Wang,Wenjie Bi,Yonghui Su,Yongai Xiong,Songsong Wang,Liwen Han
Medicinal plant-derived vesicle-like nanoparticles can carry chemical components and exert intercellular activity due to the encapsulation of nanostructures. American ginseng is well known as a traditional herb and is commonly used in clinical decoctions. However, the nano-characteristics and chemical composition of American-ginseng-derived vesicle-like nanoparticles (AGVNs) in decoctions are unclear. In this study, the gradient centrifugation method was used to extract and isolate AGVNs. A metabolomic method based on high-resolution mass spectrometry was established to analyze small molecules loaded in AGVNs. Zebrafish and RAW264.7 cells were employed to investigate the anti-inflammatory effects of AGVNs. The results showed that the particle size of AGVNs was generally 243.6 nm, and the zeta potential was −14.5 mV. AGVNs were found to contain 26 ginsenosides (14 protopanaxadiols, 11 protopanaxatriols, and 1 oleanolic acid). Ginsenoside Rb1 and malonyl-ginsenoside Rb1 tended to be enriched in AGVNs. Moreover, AGVNs were found to exert anti-inflammatory effects by reducing macrophage migration in zebrafish and regulating inflammatory factor (NO, TNF-α, IL-6, IL-10) secretion in RAW 264.7 cells. The characterization and analysis of AGVNs provide references and data that support the development of nanoscale anti-inflammatory substances from medicinal plants.
研究领域:
药理学
·
纳米技术
·
分析化学
·
炎症研究
·
传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yaming Yu,Ningning Mao,Lin Yu,Fangzhu Lin,Xiaofeng Shi,Xuanqi Lu,Yang Yang,Yu Lu,Deyun Wang
Ethnopharmacological relevance Endometritis is a common reproductive disease in dairy cattle after calving, characterized by persistent inflammation of the endometrium. YiMu-QingGong San (YMQGS), a patented Chinese medicine formulation, has demonstrated efficacy in the treatment of clinical endometritis in dairy cattle. However, the potential mechanisms by which YMQGS alleviates endometritis remain unclear. Aim of the study The objective of this study is to elucidate the underlying therapeutic mechanisms of YMQGS in the context of endometritis. Materials and methods The chemical components of YMQGS were analyzed using UHPLC/MS. The anti-inflammatory capabilities of YMQGS were assessed by inducing an inflammatory response in RAW264.7 cells with lipopolysaccharide (LPS). Moreover, a clinical model of endometritis was simulated via vaginal injection of LPS into the uterine horns to investigate the therapeutic mechanisms of YMQGS. Results YMQGS could downregulate the expression of inflammatory mediators (TNF-α, IL-6, IL-1β) by suppressing the activation of the TLRs/MyD88/TRAF6/NF-κB signaling pathway in RAW264.7 cells. Additionally, YMQGS facilitated the polarization of RAW264.7 cells towards M2-like macrophages (Mφs) while inhibiting M1-like Mφs polarization, thereby exerting anti-inflammatory effects. Further investigation revealed that YMQGS could diminish ROS production, augment cellular antioxidant capacity, preserve mitochondrial membrane potential, and reduce intracellular [Ca 2+ ]i accumulation, thereby minimizing cellular damage. In the mouse model of endometritis, YMQGS similarly inhibited the activation of the NF-κB signaling pathway in uterine tissues and modulated Mφ polarization in the endometrium, leading to a decrease in the expression of inflammatory factors and subsidence of the inflammatory response in the endometrium. Histological staining results showed that YMQGS reduced endometrial fibrosis, increased the expression of endometrial ZO-1, Occludin and glycoprotein, protect the endometrial barrier function, and prevent the further development of endometritis. Conclusion Collectively, the present study confirms that YMQGS possesses notable anti-inflammatory and antioxidant properties. The suppression of the NF-κB signaling pathway and the modulation of Mφ polarization emerge as the pivotal mechanisms by which YMQGS alleviates endometritis.
研究领域:
药理学
·
免疫学
·
生殖医学
·
中医药
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）