INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Linlin Li,Hualin Wang,Chongyang Jin,Minmin Chen,Suwei Jiang,Junfeng Cheng,Shaotong Jiang
Zn (II) coordination compounds have aroused growing attentions as antibacterial entities. In the present work, we fabricated a new antibacterial complex of l ‑phenylalanine‑oxidized starch-coordinated zinc (II) ( l ‑Phe-OSt → Zn (II)) by successive reactions of oxidization, Maillard and coordination. Maillard reaction occurred between l ‑Phe and OSt to form l ‑Phe-OSt, which was then coordinated with Zn (II) by carboxyl groups for l ‑Phe-OSt → Zn (II). The complex showed good antibacterial activity and the antibacterial activity against E. coli was slightly poorer than B. subtilis . The presence of complex favored the generation of reactive oxygen species (ROS) in bacteria and the ROS level in B. subtilis was higher than that in E. coli . Furthermore, the toxicity of l ‑Phe-OSt → Zn (II) towards HT-29 cells was very low. The characteristics of better antibacterial activity and less cytotoxicity endow l ‑Phe-OSt → Zn (II) a great potential of application as a food additive.
研究领域:
材料科学
·
生物技术
·
食品科学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Tao Xie,Gao-Yao Cao,Shize Zhang,Meng-Ke Li,Xin Jin,Liu Liu,Guangji Wang,Le Zhen
Inflammatory bowel disease (IBD) is a clinically heterogeneous disease demanding more therapeutic targets and intervention strategies. Vanin-1, an oxidative stress-regulating protein, has emerged as a promising target for alleviating inflammation and oxidative stress. In this study, a series of thiazole carboxamide derivatives as vanin-1 inhibitors were designed and synthesized. The preferred compound, X17, demonstrated potent inhibition against vanin-1 at the protein, HT-29 cell, and tissue levels, whose binding mode with the target was confirmed via the cocrystal structure. X17 achieved a high bioavailability of 81% in rats, accompanied by concentration-dependent inhibition of serum vanin-1. In a DSS-induced mouse colitis model, X17 exhibited potent anti-inflammatory and antioxidant activities, repressing the inflammatory factor expressions and myeloperoxidase activity, elevating the colonic glutathione reserve, and restoring the intestinal barrier. Collectively, these findings depict the discovery of a potent vanin-1 inhibitor, providing an opportunity for further drug candidate development for treating IBD.
研究领域:
药理学
·
药物化学
·
炎症
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Lan Wang,Jin Mao,Qi Zhou,Qianchun Deng,Lei Zheng,Jie Shi
Curcumin is a hydrophobic substance with various beneficial biological activities. Its weak solubility and instability, however, now restrict its usage as a functional food. Herein, the purpose of this work is to fabricate curcumin-loaded bovine serum albumin/carboxymethylpachymaran nanoparticles (BMCNPs) to overcome these challenges. Under optimal conditions, the BMCNPs were spherically shaped with a surface charge of −31.4 mV, polydispersity index of 0.16 and particle size of 158.3 nm were characterized by electron microscopy and dynamic light scattering. The interactions between curcumin, bovine serum albumin (BSA), and carboxymethylpachymaran (CMP) were investigated. BMCNPs had a much better curcumin encapsulation efficiency (74.1%) as well as strong antioxidant activity, storage stability, and ionic strength tolerance. The in vitro release revealed that curcumin was more successfully sustained in the small intestine stage (68.7%) and that BMCNPs were able to prevent it from releasing too early in the stomach (21.4%). Not to mention, the results of the cytotoxicity test performed on the HT-29 and IEC-6 cell lines demonstrated the acceptable biocompatibility of BMCNPs.
研究领域:
药学
·
纳米技术
·
食品科学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
Asian Pacific Journal of Tropical Medicine
·
2019
·
IF 1.772
Ni Pan-Li,Tian Shu-Hong,Yang Zhao-Xin,Zhang Jun-Qing,Yang Fan,Zhong Li-Fan,Gan Lian-Fang,Huang Mian-Qing,Huang Ling
Objective: To explore the effect of Feng-liao-chang-wei-kang ( FLCWK ) on acute and chronic gastroenteritis, synergistic effect on the growth inhibitory effect with 5-fluorouracil (5-FU) on colorectal cancer and its underlying mechanisms. Methods: In the in vitro study, HT-29 cells were divided into 5-FU alone, FLCWK alone and coadministration groups. The MTT assay was used to analyze the proliferation of HT-29 cells at 24 h. Flow cytometry was used to observe the apoptosis, cycle of colorectal cancer HT-29 cells at 24 h. In the in vivo experiment, The subcutaneous transplantation tumor model of colorectal cancer HT-29-Luc was established with nude mice. All mice were randomly divided into 5-FU alone, FLCWK alone and coadministration groups according to body weight. During administration, the Interactive Video Information System small animal live imaging system was used to monitor the growth of subcutaneous transplantation in nude mice. The model of colitis-associated colorectal cancer (CACC) was established with BALB/c mice. BALB/c mice were randomly divided into the normal control group, the model control group, and the FLCWK group. At the end of the administration, the pathological status was detected by HE staining. Cell apoptosis of tumor tissue tumor and colon tissues were observed by TUNEL staining and TUNEL green fluorescence. The protein expression of Caspase 3, p-STAT3, Bcl-2, Bax and P-gp in tumor tissues tumor and colon tissues were tested by using immunohistochemical assay. Results: FLCWK and 5-FU coadministration suppressed HT-29 cell viability and induced S phase arrest and apoptosis compared to treatment with 5-FU alone. Furthermore, compared to treatment with 5-FU alone, coadministration of FLCWK and 5-FU obviously reduced tumor volume and weight and induced apoptosis through decreasing p-STAT3 and P-gp and increasing Caspase 3 protein expression in a murine xenograft tumor model. Moreover, the result revealed decreased number and size of tumors following FLCWK protective administration, downregulated p-STAT3 and Bcl-2 levels and upregulated Bax and Caspase 3 expression in mice with CACC. Conclusions: FLCWK has synergistic effects with 5-FU on colorectal cancer by suppressing the STAT3 pathway and downregulating P-gp expression. Furthermore, FLCWK administration suppresses CACC tumorigenesis by inhibiting the STAT3 pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Bin Xu,Guohua Jiang,Weijiang Yu,Depeng Liu,Yongkun Liu,Xiangdong Kong,Juming Yao
To improve insulin bioavailability and overcome multiple barriers for oral delivery of insulin, the composite nanocarriers (PLGA/FA-CS) prepared from poly(lactide- co -glycoside) (PLGA) and folic acid modified chitosan (FA-CS) were fabricated via electrostatic self-assembly method. The resultant composite nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that the as-prepared composite nanocarriers may be a promising drug delivery system for oral administration of insulin and other biomacromolecules.
研究领域:
药学
·
纳米技术
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Feng Huixia,Chen Guilin,Zhang Yongli,Guo Mingquan
Podophyllum sinense (P. sinense) has been used as a traditional herbal medicine for ages due to its extensive pharmaceutical activities, including antiproliferative, anti-inflammatory, antiviral, insecticidal effects, etc. Nevertheless, the specific bioactive constituents responsible for its antiproliferative, anti-inflammatory, and antiviral activities remain elusive, owing to its complicated and diversified chemical components. In order to explore these specific bioactive components and their potential interaction targets, affinity ultrafiltration with multiple drug targets coupled with high performance liquid chromatography/mass spectrometry (UF–HPLC/MS) strategy was developed to rapidly screen out and identify bioactive compounds against four well-known drug targets that are correlated to the application of P. sinense as a traditional medicine, namely, Topo I, Topo II, COX-2, and ACE2. As a result, 7, 10, 6, and 7 phytochemicals were screened out as the potential Topo I, Topo II, COX-2, and ACE2 ligands, respectively. Further confirmation of these potential bioactive components with antiproliferative and COX-2 inhibitory assays in vitro was also implemented. Herein, diphyllin and podophyllotoxin with higher EF values demonstrated higher inhibitory rates against A549 and HT-29 cells as compared with those of 5-FU and etoposide. The IC50 values of diphyllin were calculated at 6.46 ± 1.79 and 30.73 ± 0.56 μM on A549 and HT-29 cells, respectively. Moreover, diphyllin exhibited good COX-2 inhibitory activity with the IC50 value at 1.29 ± 0.14 μM, whereas indomethacin was 1.22 ± 0.08 μM. In addition, those representative constituents with good affinity on Topo I, Topo II, COX-2, or ACE2, such as diphyllin, podophyllotoxin, and diphyllin O-glucoside, were further validated with molecular docking analysis. Above all, the integrated method of UF–HPLC/MS with multiple drug targets rapidly singled out multi-target bioactive components and partly elucidated their action mechanisms regarding its multiple pharmacological effects from P. sinense, which could provide valuable information about its further development for the new multi-target drug discovery from natural medicines.
研究领域:
药理学
·
药物化学
·
传统医学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2018
·Vol. 18
·期 12
·1800321
·
IF 3.392
Minmin Chen,Suwei Jiang,Feng Zhang,Linlin Li,Hailiang Hu,Hualin Wang
Graphene oxide (GO)/poly (lactide-co-glycolic acid) (PLGA) scaffolds have promising applications in the biomedical field. However, greater attention is focused on the incorporated system and its applications in normal cells. In this work, a novel GO immobilized PLGA nanofibrous scaffold assisted by polydopamine (PLGA-PDA-GO) is developed for growth inhibition of HT-29 colon cancer cells. The interactions between GO and PDA are attributed to a π–π conjugate interaction and electrostatic attraction. In addition to the enhancement of thermal stability and mechanical strength, the surface roughness, hydrophilicity, and electro-activity of the scaffolds are significantly improved by immobilization of GO. The scaffolds show good inhibition of HT-29, and immobilized GO is observed to be in contact with but not internalized in HT-29 cells. The cytotoxicity mechanism of scaffolds toward HT-29 is attributed to intracellular activated reactive oxygen species that result from the physical interaction of the sharp GO edges and electrical signals of π–π stacking between PDA and GO.
研究领域:
生物医学工程
·
材料科学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Shuai Wang,Jian-Tao Shi,Xing-Rong Wang,Hong-Xia Mu,Xue-Ting Wang,Kai-Yan Xu,Qing-Shan Wang,Shi-Wu Chen
The PI3K/AKT/mTOR signaling pathway is one of the most common abnormal activation pathways in tumor cells, and has associated with multiple functions such as tumor cell growth, proliferation, migration, invasion, and tumor angiogenesis. Here, a series of 3-amino-1 H -indazole derivatives were synthesized, and their antiproliferative activities against HT-29, MCF-7, A-549, HepG2 and HGC-27 cells were evaluated. Among them, W24 exhibited the broad-spectrum antiproliferative activity against four cancer cells with IC 50 values of 0.43–3.88 μM. Mechanism studies revealed that W24 inhibited proliferation by affecting the DNA synthesis, induced G 2 /M cell cycle arrest and apoptosis by regulating Cyclin B1, BAD and Bcl-xL, meanwhile induced the change of intracellular ROS and mitochondrial membrane potential in HGC-27 cells. Moreover, W24 inhibited the migration and invasion of HGC-27 cells by decreasing EMT pathway related proteins and reducing the mRNA expression levels of Snail, Slug and HIF-1α. Furthermore, W24 displayed low tissue toxicity profile and good pharmacokinetic properties in vivo . Therefore, 3-amino-1 H -indazole derivatives might serve as a new scaffold for the development of PI3K/AKT/mTOR inhibitor and anti-gastric cancer reagent.
研究领域:
肿瘤学
·
药理学
·
化学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2023
·
IF 3.4
Yajing Wang,Tao Zhang,Jie Liu,Xianfeng Huang,Xiaojing Yan
The clinical treatment of ulcerative colitis (UC) faces great challenges due to lifetime medication. In this study, Gingerol oil was extracted and purified by the process easily scale-up and cost effective, with productivity 2.72 ± 0.38% ( w /w, versus crude drugs). The quality control of gingerol oil was fully established by HPLC fingerprint with 4 common peaks identified as 6-gingerol, 8-gingerol, 6-shogaol and 10-gingerol. The similarities of 6 batches of gingerol oil are within 0.931–0.999. The protective effects of gingerol oil are equivalent to or even stronger than that of 6-gingerol on inflammation and oxidative stress of HT-29 cells induced by lipopolysaccharide and H 2 O 2 , as well as on UC in mice caused by dextran sulfate sodium salt (DSS). Our research conclusions coincide well with the holistic view of Traditional Chinese Medicine and network pharmacology . The absorption kinetics of gingerol oil were conducted using the in situ intestinal perfusion in rats and comparable absorption were achieved in the jejunum , ileum and colon segments within 2 h. Thus, gingerol oil colon targeting pellets were prepared by extrusion-spherization technique. The cumulative dissolution behaviors and mechanisms were observed and analyzed by fitting to dissolution model. Our studies provided reliable theoretical and experimental support for the gingerol oil as reliable therapeutic choice of UC.
研究领域:
药理学
·
胃肠病学
·
传统中药
·
药物递送系统
✓ 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）