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Pharmacology Research & Perspectives · 2020 ·Vol. 8 ·期 5 ·e00660 · IF 2.052

Arctigenin protects mice from thioglycollate-induced acute peritonitis

Jingyi Zhao,Ying Chen,Lijun Dong,Xin Li,Ruijie Dong,Dongmei Zhou,Chengzhi Wang,Xiangdong Guo,Jieyou Zhang,Zhenyi Xue,Qing Xi,Lijuan Zhang,Guangze Yang,Yan Li,Rongxin Zhang

Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa . In recent years, there have been an increasing number of studies on the anti-inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti-inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in mice. ATG significantly reduced the percentage of CD11b + Ly6G + neutrophils and F4/80 + macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b-positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS-stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG-induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG-induced acute peritonitis in mice.

CAS / MDL: 7770-78-7
研究领域: 药理学 · 免疫学 · 炎症性疾病
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Food & Function · 2018 ·Vol. 9 ·期 12 ·6155-6164 · IF 3.289

Chlorogenic acid methyl ester exerts strong anti-inflammatory effects via inhibiting the COX-2/NLRP3/NF-κB pathway

Lang Zhang,Ya Fan,Hanwen Su,Li Wu,Yuying Huang,Lei Zhao,Bing Han,Guangwen Shu,Meixian Xiang,Jin-Ming Yang

The objective of this study was to investigate the anti-inflammatory effect of chlorogenic acid methyl ester (CME) and the molecular mechanism involved, through using non-infectious inflammation and infectious inflammation animal models as well as lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cell models. Our results demonstrated that CME markedly inhibited ear swelling, paw swelling and granuloma swelling, and decreased intraperitoneal capillary permeability in non-infectious inflammation. Moreover, CME significantly alleviated the pathological damage of the lung tissue, reduced the levels of PGE2 and IL-1β in the serum and the protein expression levels of related-inflammatory factors in the lung tissue of LPS-induced mice with acute lung injury (ALI). In addition, CME affected the RAW264.7 cell cycle and inhibited the protein expressions of COX-2 and NLRP3 and prevented the phosphorylation of NF-κB p65 in RAW264.7 cells treated with LPS. These observations not only validated the anti-inflammatory effects of CME, but also revealed the underlying molecular basis, which involves the down-regulation of the expression of inflammatory factors and blockade of the COX-2/NLRP3/NF-κB signaling pathway.

研究领域: 药理学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Sensors · 2020 · IF 7.333

Miniaturized Paper-Supported 3D Cell-Based Electrochemical Sensor for Bacterial Lipopolysaccharide Detection

Hui Jiang,Jun Yang,Kai Wan,Donglei Jiang,Changhai Jin

Sensitive detection of lipopolysaccharides (LPSs), which are present on the outer wall of Gram-negative bacteria, is important to reflect the degree of bacterial contamination in food. For indirect assessment of the LPS content, a miniaturized electrochemical cell sensor consisting of a screen-printed paper electrode, a three-dimensional cells-in-gels-in-paper culture system, and a conductive jacket device was developed for in situ detection of nitric oxide released from LPS-treated mouse macrophage cells (Raw264.7). Nafion/polypyrrole/graphene oxide with excellent selectivity, high conductivity, and good biocompatibility functionalized on the working electrode via electrochemical polymerization could enhance sensing. Raw264.7 cells encapsulated in the alginate hydrogel were immobilized on a Nafion/polypyrrole/graphene oxide/screen-printed carbon electrode in paper fibers as a biorecognition element. Differential impulse voltammetry was employed to record the current signal as-influenced by LPS. Results indicated that LPS from Salmonella enterica serotype Enteritidis caused a significant increase in peak current, varying from 1 × 10–2 to 1 × 104 ng/mL, dose-dependently. This assay had a detection limit of 3.5 × 10–3 ng/mL with a linear detection range of 1 × 10–2 to 3 ng/mL. These results were confirmed by analysis of nitric oxide released from Raw264.7 via the Griess method. The miniaturized sensor was ultimately applied to detect LPSs in fruit juice samples. The results indicated that the method exhibited high recovery and relative standard deviation lower than 2.65% and LPSs in samples contaminated with 102–105 CFU/mL bacteria could be detected, which proved the practical value of the sensor. Thus, a novel, low-cost, and highly sensitive approach for LPS detection was developed, providing a method to assess Gram-negative bacteria contamination in food.

CAS / MDL: 109-97-7
研究领域: 生物化学 · 分析化学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

The structures of two glucomannans from Bletilla formosana and their protective effect on inflammation via inhibiting NF-κB pathway

Qinghui Gu,Yaping Liu,Li Zhen,Tianrui Zhao,Lan Luo,Junyin Zhang,Tuo Deng,Mingyi Wu,Guiguang Cheng,Jiangmiao Hu

Bletilla formosana is a traditional Chinese herbal medicine and is widely consumed as foods and medicines in China. However, the chemical structure and bioactivity of its polysaccharides remain unknown. Herein, two new polysaccharides, BFP60 and BFP80, with molecular weights of 3.99 kDa and 10.07 kDa, respectively, were isolated and purified from dried tuber of B. formosana . Structural analysis suggested that BFP60 and BFP80 may have backbone consisted of →4)-β- d -Man-(1→,→4)-β- d -Glc-(1→,→4)-2- O -acetyl-β- d -Man-(1→, and →4)-3- O -acetyl-β- d -Man-(1→. Inflammation assay in LPS-induced RAW264.7 cells showed that the productions of NO and pro-inflammatory cytokines including IL-6, IL-1β, TNF-α, and IFN-γ were significantly reduced, and the expression of iNOS , COX-2, and target proteins in the NF-κB pathway were suppressed after BFP60 and BFP80 pretreatment. These findings indicated that this novel polysaccharide had significant inflammatory protective effects in vitro.

CAS / MDL: 76-05-1
研究领域: 药理学 · 免疫学 · 生物化学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2022 · IF 5.895

Comparative Mass Spectrometry Analysis and Immunomodulatory Effects of Casein Glycomacropeptide O-Glycans in Bovine and Caprine Whey Powder

Yu Lu,Jie Liu,Zhenhua Li,Wenqing Li,Jing Liu,Linjuan Huang,Zhongfu Wang

Casein glycomacropeptide carries various O-glycan modifications, which, together with variations in the amino acid composition of the glycopeptide, may result in different biological activities. In this study, O-glycans of casein glycomacropeptide from bovine and caprine whey powder were qualitatively and quantitatively analyzed by LC-UV-ESI-MS/MS, and their immune activities and regulatory mechanisms were compared. O-Glycans’ total content was 1.54 times higher in bovine than in caprine glycomacropeptide. The glycoform H1N1S2 (H: hexose; N: N-acetylgalactosamine; and S: N-acetylneuraminic acid) accounted for nearly 50% of total glycomacropeptide O-glycans in bovine milk but less than 20% in caprine milk. Bovine glycomacropeptide glycosylation promoted the immune activity of RAW264.7 cells, which may be linked to a higher content of disialylated O-glycans. Glycomacropeptide from both milk sources significantly upregulated the mRNA expression of IL-1α, TNF-α, and IL-10 in RAW264.7 cells and activated the MAPK immunomodulatory signaling pathway. This study demonstrates the possible use of casein glycomacropeptide as an immunomodulatory agent.

CAS / MDL: 89-25-8
研究领域: 食品科学 · 免疫学 · 生物化学 · 分子生物学
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CHEMISTRY & BIODIVERSITY · 2021 ·Vol. 18 ·期 7 ·e2100229 · IF 2.408

Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815

Wenjuan Ding,Fangfang Wang,Qingwen Li,Yaxin Xue,Zhitong Dong,Danmei Tian,Mei Chen,Youwei Zhang,Kui Hong,Jinshan Tang

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid ( 1 ) and fourteen known compounds ( 2 – 15 ) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids ( 1 – 11 ) using cultured macrophage RAW264.7 cells. The results show that compound 9 , and to a lesser degree compound 5 , significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.

研究领域: 药理学 · 微生物学 · 化学
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH · 2024 · IF 1.3

Two new quinazolinone alkaloids from Aspergillus udagawae

Lin Liang,Xi Yuan,Xiao-Ya Xian,Xian-Li Zhou,Tong-Dong Kuang,Jin-Tao Gao,Li-Sheng Wang,Cheng-Qin Liang

Two new quinazolinone alkaloids, benzomalvin F (1), and quinadoline C (2), along with four known quinazolinones (3-6), were isolated from cultures of the wetland-soil-derived fungus Aspergillus udagawae from the Huixian wetland in Guilin. Their structures were elucidated based on detailed spectroscopic analysis, including 1D, 2D NMR, mass spectrometry, and IR spectra. In addition, the anti-inflammatory results showed that compounds 1, 2, 4, and 5 had significant inhibitory effects on NO production in RAW264.7 cells activated by lipopolysaccharide (LPS), with IC50 values of 24.5 ± 0.1, 29.7 ± 0.1, 29.4 ± 0.1, and 31.0 ± 0.1 µM respectively, compared with the positive control indomethacin (IC50 = 31.6 ± 0.4 μM).

CAS / MDL: 53-86-1
研究领域: 药理学 · 化学 · 微生物学
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CURRENT ISSUES IN MOLECULAR BIOLOGY · 2025 ·Vol. 47 ·期 9 ·748 · IF 3

Resina Draconis Promotes Diabetic Wound Healing by Regulating the AGE-RAGE Pathway to Modulate Macrophage Polarization

Xin Jin,Ang Li,Zhaoyuan Dai,Yi Li,Xinchi Feng,Feng Qiu

Resina Draconis (RD), a traditional Chinese medicine, has been widely used in treating diabetic foot ulcers. However, its specific mechanisms of action remain incompletely understood. First, network pharmacology combined with GEO clinical sample data mining was employed to systematically analyze the therapeutic targets of RD in promoting diabetic wound healing. Second, an AGEs-induced RAW264.7 cell model was utilized to investigate the regulatory effects of RD and its primary active components on the AGE-RAGE signaling pathway, along with their anti-inflammatory and antioxidant activities. Finally, a diabetic wound mouse model was established to validate the efficacy of RD and further explore its underlying molecular mechanisms. Integrated analysis of network pharmacology and GEO database mining identified 492 potential therapeutic targets of RD in diabetic wound healing, primarily involving the AGE-RAGE pathway. In vitro, RD (6.25 μg/mL) significantly suppressed AGE-induced inflammatory factors and ROS production while downregulating AGE-triggered RAGE protein overexpression. In vivo, RD hydrogel accelerated diabetic wound healing by modulating the AGE-RAGE axis and regulating macrophage polarization. RD effectively promotes diabetic wound healing through synergistic regulation of the AGE-RAGE pathway, oxidative stress suppression, and macrophage polarization modulation, providing a novel therapeutic strategy for diabetic wound management.

CAS / MDL: 504-63-2 75-80-9
研究领域: 中医中药 · 药理学 · 创伤愈合 · 糖尿病并发症 · 免疫调节 · 分子生物学
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FOOD RESEARCH INTERNATIONAL · 2021 · IF 6.475

Structural characterization and immunomodulatory activity of intracellular polysaccharide from the mycelium of Paecilomyces cicadae TJJ1213

Juanjuan Tian,Cangping Zhang,Xiaomeng Wang,Xin Rui,Qiuqin Zhang,Xiaohong Chen,Mingsheng Dong,Wei Li

Two intracellular polysaccharide fractions (IPS1 and IPS2) were obtained from the mycelium of Paecilomyces cicadae TJJ1213, and the structures were conducted. Results showed that they were homogenous with the average molecular weight of 2.40 × 10 6 Da and 6.79 × 10 5 Da. Two fractions were composed of mannose, glucose and galactose with molar ratios of 1.35: 6.93: 1.0 and 2.04: 1.0: 1.87, respectively. The backbone of IPS1 was → 4)-α-D-Glc p (1 → and → 3,4)-α-D-Man p (1 → residues with a side chain consisted of T-α-D-Gal p . IPS2 was consisted of → 4)-α-D-Glc p -(1→, →3,4)-α-D-Man p -(1 → and → 2,6)-α-D-Man p -(1 → residues and the branches were also consisted of T-α-D-Gal p . In addition, the scanning electron microscope and atomic force microscope images presented different features of IPS1 and IPS2, respectively. Furthermore, two fractions exhibited better immunomodulatory effects. They could markedly promote the proliferation of RAW264.7 cells and enhance phagocytosis, nitric oxide release and cytokines production. These results indicated that IPS1 and IPS2 had potential to enhance immune responses.

研究领域: 微生物学 · 免疫学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Efficient gene delivery by multifunctional star poly (β-amino ester)s into difficult-to-transfect macrophages for M1 polarization

Tao Bo,Chenfei Wang,Dingjin Yao,Qiuyu Jiang,Yitong Zhao,Feifei Wang,Wei He,Weiyi Xu,Hao Zhou,Ming Li,Si Zhang,Ruyi Xue

Gene delivery to macrophages holds great promise for cancer immunotherapy. However, traditional gene delivery methods exhibit low transfection efficiency in macrophages. The star -shaped topological structure of polymers is known to encapsulate genes inside their cores, thereby facilitating sustained release of the genetic material. Herein, combining the structural advantages of star polymers and the transfection advantages of poly (β-amino ester)s (PAEs), we developed a novel linear oligomer grafting-onto strategy to synthesize a library of multi-terminal star structured PAEs (SPAEs), and evaluated their gene delivery efficiency in various tissue cells. The transfection with human hepatocellular carcinoma cells (HepG2, HCC-LM3 cells and MHCC-97H cells), rat normal liver cells (BRL-3 A cells), human ovarian cancer cells (A2780 cells), African green monkey kidney cells (Vero cells), human cervical cancer cells (HeLa cells), human chondrosarcoma cells (SW1353 cells), and difficult-to-transfect human epidermal keratinocytes (HaCaT cells) and normal human fibroblast cells (NHF cells) showed that SPAEs exhibited superior transfection profile. The GFP transfection efficiency of top-performing SPAEs in HeLa cells (96.1%) was 2.1-fold, and 3.2-fold higher compared to jetPEI and Lipo3000, respectively, indicating that the star-shaped topological structure can significantly enhance the transfection efficiency of PAEs. More importantly, the top-performing SPAEs could efficiently deliver Nod2 DNA to difficult-to-transfect RAW264.7 macrophages, with a high transfection efficiency of 33.9%, which could promote macrophage M1 polarization and enhanced CD8+ T cell response in co-incubation experiments. This work advances gene therapy by targeting difficult-to-transfect macrophages and remodeling the tumor immune microenvironment.

研究领域: 生物技术 · 药学 · 免疫学 · 癌症研究
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2019 · IF 3.17

Structure characteristics of flavonoids for cyclooxygenase-2 mRNA inhibition in lipopolysaccharide-induced inflammatory macrophages

Hui Li,Siyi Pan,Xiaoyun Xu

Flavonoids are natural active components. They distribute widely in edible plants with high activity of anti-inflammation. Inhibition of cyclooxygenase-2(COX-2) was determined by real-time fluorescent quantitative olymerase chain reaction (RTFQ-PCR). And structure characteristics of flavonoids for COX-2 inhibition were mainly analyzed by a quantitative structure activity relationship (QSAR) model. Descriptors such as SMR_VSA5, vsurf_DD12, reactive were the top three important independent variables to COX-2 mRNA inhibiton in RAW264.7. Low SMR_VSA5 value meant a lower molecular refractivity resulting in a lower COX-2 mRNA inhibition. High vsurf_DD12 value related to poor molecular balance and showed profound adverse to COX-2 mRNA inhibition. Reactive group in this paper referred to C2–C3 double bond contributed negatively to COX-2 mRNA inhibition. Glycosidic and C3–OH substitutions may lower SMR_VSA5 value. It indicated that flavanones such as hesperetin , naringenin , liquiritigenin were efficient to repress COX-2 mRNA and they were potential anti-inflammatory natural products. Further, substitution with a glucopyranosyl at C-6 resulted in a poorer molecule balance than that at C-8 and a lower COX-2 mRNA inhibiton accordingly. This may expain why orientin and vitexin exhibited better anti-inflammatory activity than their isomers homoorientin and isovitexin . Also, methoxyl groups at C-4’ may also be a favorable flavonoid structural characteristic for COX-2 mRNA inhibiton. These results provide valuable information on understanding the high anti-inflammatory activity of flavonoids.

研究领域: 药理学 · 分子生物学 · 化学
✓ 已验证 DOI PubMed 高影响因子
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Food & Function · 2021 ·Vol. 13 ·期 3 ·1393-1407 · IF 5.396

Role of genistein on the yield, structure and immunomodulatory activity of Monascus exopolysaccharides

Liuming Xie,Zhibing Huang,Hui Meng,Zhibing Fan,Xiaoyi Shi,Jianhua Xie

Manipulating the structures, physicochemical properties, and monosaccharide compositions of exopolysaccharides (EPS) isolated from microorganisms has been reported to enhance their biological activities. Hence, the aim of this work was to examine the effects of genistein addition during fermentation on the amount, physicochemical properties, and immunomodulatory activity of EPS secreted by M. purpureus. Results showed that genistein addition significantly increased M. purpureus biomass and EPS yield to 2.42 g L−1 and 6.08 g L−1, respectively, and affected the physicochemical properties and structures of EPS. Furthermore, EPS produced by genistein-treated M. purpureus (G-EMP) improved the immunomodulatory activity of RAW264.7 macrophages by increasing the secretion of nitric oxide and cytokines. Moreover, phospho-Jun N-terminal kinase (p-JNK), phospho-extracellular regulated protein kinase (p-ERK), phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) phospho-p65 (p65) proteins were remarkably upregulated by G-EMP stimulation, blocking Toll-like receptor 4 (TLR4) that dramatically reduced the pinocytic and phagocytic capacities. Overall, these findings provide potential rationales for the application of genistein in improving the EPS yield of M. purpureus.

CAS / MDL: 446-72-0
研究领域: 微生物学 · 免疫学 · 生物技术
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