RSC Medicinal Chemistry
·
2024
·
IF 4.1
Die Zhang,Wenping Wang,Huiping Ou,Jinhua Ning,Yingxun Zhou,Jin Ke,Anguo Hou,Lingyun Chen,Peng Li,Yunshu Ma,Wenbin Jin
To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of novel chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds has been evaluated by screening inhibitory effects of the NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected to further investigated by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, IL-6, and PGE2 release. The further study also indicated that 3h and 3l could significantly suppress expressions of iNOS and COX-2 through NF-κB/JNK signaling pathway. Furthermore, compounds 3h and 3l could also remarkably inhibit the mRNAs expressions of inflammation-related genes. Docking simulation was conducted to position compounds 3h and 3l into the iNOS binding site to predict the probable binding mode. In conclusion, a series of chalcone analogues with reasonable drug-likeness obtained by in silico rapid prediction could be used as promising lead candidates.
研究领域:
药理学
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炎症研究
·
药物发现
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Jing Qin,Hui-yang Wang,Dan Zhuang,Fan-cheng Meng,Xing Zhang,He Huang,Guang-ping Lv
A neutral polysaccharide (ALP-1) and an acidic polysaccharide (ALP-3) were purified from Atractylodes lancea (Thunb.) DC. ALP-1 exhibited a linear backbone composed of (2 → 1)-linked β - d -fructofuranose. The backbone of ALP-3 was elucidated as →4)-GalA p -(1 → 3,4)-Rha p -(1→, and with branch chain substituted at O-3 position of →3,4)-Rha p -(1→. The branch chain consists of →3,5)-Ara f -(1→, →5)-Ara f -(1→, and Ara f -(1→. Particularly, ALP-3 could significantly stimulate macrophage proliferation in a dose-dependent manner, and stimulate phagocytic, NO and cytokines production than ALP-1 on RAW264.7 cells. Besides, both ALP-1 and ALP-3 could activate T-cells in Peyer's patch cells and enhance the production of colony stimulation factors. While the ALP-3 also showed better intestinal immune system modulating activity than ALP-1. The result of this study indicated that the structure diversity of polysaccharide is crucial for its bioactivity. And also provided evidence for that carbohydrate polymers in A. lancea definitely contributed to its pharmaceutical effects.
研究领域:
药理学
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免疫学
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植物化学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Yuan-Xin Qian,Feng-Feng Zhou,Qiang Chen,Fen Dong,Han-Ying Xu,Yu-Long Sun,Ji-Teng Wang,Tao Han
Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass ( Micropterus salmoides ), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo . In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro . By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes ( tumor necrosis factor-alpha , tnfα ; interleukin ( il ) 8 and il10 ) and apoptotic genes ( caspase 3 , caspase 8 , and caspase 9 ) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced ( cd4-like ) cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 ( nod1 ) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.
研究领域:
免疫学
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水产养殖
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Yidan Chen,Yao Zhang,Wenjun Dai,Yunxin Xue,Jiawei Li,Ke Zhang,Rongjun Tang,Chun Mao,Mimi Wan
Innovative treatments for peritoneal metastatic cancer have attracted widespread attention from researchers. Here, we propose a drug-loaded nanomotor (PSBMA/ l -Arg/DOX, PLD) based on zwitterionic materials for the treatment of peritoneal metastatic cancer through intraperitoneal injection. Zwitterionic polymer nanocarriers (PSBMA NPs) are obtained by radical polymerization with zwitterionic SBMA as the polymerization monomer and N,N’-Bis(acryloyl)cystamine (BAC) as the cross-linking agent. The zwitterionic substrate of this nanomotor has the ability to resist non-specific protein adsorption in ascites. The loaded l -arginine enables the nanomotor to have the ability to chemotaxis towards high concentrations of ROS/iNOS in tumors and be catalyzed to produce NO, achieving deep penetration into tumor tissue. Furthermore, the disulfide bond (S S) carried by the crosslinking agent used in the preparation of the nanomotor can respond to the high expression of reducing glutathione in the tumor microenvironment and undergo degradation, releasing a large amount of loaded drug DOX. Cell and animal disease model experiments confirme the good therapeutic effect of this drug-loaded nanomotor, providing new therapeutic concepts and strategies for the treatment of peritoneal metastatic cancer.
研究领域:
癌症研究
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纳米技术
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药学
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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
PHYTOCHEMISTRY
·
2021
·
IF 4.072
Lanlan Nie,Rui Li,Jie Huang,Lingling Wang,Mengjie Ma,Chunyue Huang,Tong Wu,Renjie Yan,Xiao Hu
Five undescribed abietane diterpenoids , dracocephalumoids A–E, together with six known analogues were isolated from the aqueous EtOH extract of aerial parts of Dracocephalum moldavica L.. The structures were elucidated through extensive analysis of spectroscopic data , and their absolute configurations were established by Mosher's method and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Cell-based anti-inflammatory assays displayed that dracocephalumoid A, uncinatone, trichotomone F and caryopterisoid C showed potent suppressive effects against TNF- α , IL-1 β or NO production in LPS-induced RAW 264.7 cells, with IC 50 values ranging from 1.12 to 5.84 μM. The structure-activity relationship of these compounds was also discussed.
研究领域:
药理学
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有机化学
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生物化学
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药物化学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·607-624
·
IF 6.331
Andy Wijaya,Yi Wang,Dan Tang,Yuan Zhong,Boyan Liu,Meng Yan,Quhui Jiu,Wei Wu,Guixue Wang
Nitric oxide (NO) is an exceptional endogenous biological gas that mediates and regulates physiological and pathological processes in the human body. However, its synthesis process is impaired during athero-progression and formation. Hence, a strategy to boost NO production and target endothelial nitric oxide synthase (eNOS) is crucial and intriguing in atherosclerosis (AS) management. Herein, we prepare L-arginine (LA) and lovastatin (LV) co-loaded PLGA nanomedicine to achieve sustainable release for enhancing NO production. The utilization of LA reveals that LA has dual contributions, acting as a NO donor and enhancing the solubility of LV by stabilizing PLGA NPs. PLGA-LA/LV demonstrated its potential to boost NO in vitro and in vivo confirmed using DAF-FM DA, augment eNOS and p-eNOS mRNA and protein levels, and suppress the ki67 proliferation marker in VSMCs; in addition, it lowers the total cholesterol level of blood plasma in C57BL/6 mice. Moreover, PLGA can protect the compound delivered and enhance the bioavailability to reach and get released in the blood circulation after oral administration. Collectively, our results endow a safe and efficient nanomedicine outcome, specifically with potential for AS management.
研究领域:
药学
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心血管疾病
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Jiameng Zhang,Yanfang Wu,Chenyu Wang,Weidong Xu,Zichen Zhang,Suya Zhang,Xinyi Guan,Xinsheng Wang
Ethnopharmacological relevance Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa . Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. Aim of the study: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro . The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. Methods HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and β-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro . The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo . The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo . In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1β) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. Results HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1β were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. Conclusion The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.
研究领域:
药理学
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民族药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2022
·Vol. 87
·期 7
·3223-3234
·
IF 3.693
Youxian Zhou,Yue Gong,Zhengqi Liu,Lilong Wang,Chunqing Ai,Chengrong Wen,Taihai Zhu,Shuang Song
Although numerous polysaccharides have demonstrated potential immunostimulatory activities in in vitro models, only a few of them successfully stimulate the immune system in vivo. In order to explore the possible reasons for the activity loss of polysaccharides in in vivo models, the immunostimulatory activities in vitro and in vivo and the digestion behavior of a polysaccharide from Cyclina sinensis (CSP) were investigated in the present study. CSP showed obvious immunostimulatory activity in a RAW 264.7 cell model. In in vitro experiment, CSP did not exhibit cytotoxicity at concentrations of ≤10 µg/ml, and significantly increased NO production at concentrations of 0.4–10 µg/ml, suggesting CSP processes immunostimulatory activity in vitro. Further investigation using simulated digestion model indicated that CSP could bind with the protein in the digestive fluids to form precipitate in both the stomach and small intestine, and it could be seriously degraded by amylase during the digestion in the small intestine. Furthermore, the in vivo immunostimulatory activity evaluation demonstrated CSP had no effect on immunosuppressed mice as indicated by the body weight, thymus and spleen indexes, and TNF-α, IL-1β, IL-6, and IL-10 mRNA expression. Thus, the present study indicates that the degradation and precipitation of CSP in the digestive tract are the possible reasons for the activity loss of CSP after digestion. Practical Application Cyclina sinensis is the common aquatic shellfish in China and plays an important role in the marine aquaculture industry. Cyclina sinensis polysaccharide (CSP) is the main active component of C. sinensis . The structure characterization and immunostimulatory activity of a purified fraction of CSP (CSP-1) and the effect of digestion on CSP and its immunostimulatory activity were studied. The result of this study promotes the understanding of the nutritional function effects and provides a scientific reference for the rational development and high-value utilization of C. sinensis .
研究领域:
免疫学
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营养科学
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海洋生物学
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药学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2018
·
IF 2.642
Hong-Bo Xu,Tong-Hua Yang,Pei Xie,Zhi-Shu Tang,Xiao Song,Huai-Li Xu,Yan-Hong Li,Dong-Bo Zhang,Yan-Ru Liu,Yan-Ni Liang,Yu Zhang,Shi-Jun Liu,Si-Min Wei,Chen Sun,Hong-Bo Liu,Chong Deng,Wei Wang
Gracilistones A ( 1 ) and B ( 2 ), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH • and ABTS •+ ) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 μM.
研究领域:
药用植物学
·
药物化学
·
炎症研究
·
天然产物化学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Qingfeng Guo,Shenyu Shen,Xinyang Wang,Lei Shi,Yuwei Ren,Dandan Li,Zhenhua Yin,Juanjuan Zhang,Baocheng Yang,Xuewei Wang,Gang Ding,Lin Chen
The chemical engineering of natural extracts has emerged as an effective strategy for the production of diverse libraries of chemicals, making it integral to drug discovery. A chemical engineering strategy based on the epoxidation and ring-opening reactions was used to prepare diversity-enhanced extracts of Chaetomium madrasense 375. Eleven unnatural cytochalasan derivatives ( 1–11 ) with unique functional groups, such as amine and isoxazole, were isolated and characterized from these chemically engineered extracts of C. madrasense 375. The identification of these new structures was accomplished through comprehensive spectroscopic analysis, supplemented by synthetic considerations. Notably, compounds 5 and 13 – 16 displayed potent phytotoxic effects on Arabidopsis thaliana , while compounds 1 , 2 , 5 , 10 , and 12 demonstrated inhibitory activities on LPS-induced NO production in RAW264.7 cells. Among them, compound 1 was found to be able to inhibit the upregulated expression of the inducible nitric oxide synthase (iNOS) protein induced by LPS, while also decreasing the production of pro-inflammatory cytokines (IL-6) and influencing the phosphorylation of p38, ERK1/2, and JNK at 100 μM. Our findings demonstrate that the chemical engineering of natural product extracts can be an efficient technique for the generation of novel bioactive molecules.
研究领域:
药理学
·
化学工程
·
天然产物化学
·
免疫学
·
植物科学
✓ 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）