JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Tao He,Mingshuang Wang,Jiao Kong,Qiang Wang,Yue Tian,Chaofeng Li,Qian Wang,Chuanxin Liu,Jianmei Huang
Ethnopharmacological relevance Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases . Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. Aim of the study Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. Materials and methods Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. Results A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine , baicalin , coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications , mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine , tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. Conclusion Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.
研究领域:
民族药理学
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网络药理学
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代谢组学
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生物医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INFECTIOUS DISEASES
·
2024
·
IF 5
Tian Yu,Cao Yuwen,Liu Fang,Xia Lin,Wang Chao,Su Zhaoliang
In this study, we investigated the role of the non-canonical pyroptosis pathway in the progression of lethal sepsis. Our findings emphasize the significance of non-canonical pyroptosis in monocytes/macrophages for the survival of septic mice. We observed that inhibiting pyroptosis alone significantly improved the survival rate of septic mice, and the HMGB1 A box effectively suppressed this non-canonical pyroptosis, thereby enhancing the survival of septic mice. Additionally, our cell in vitro experiments further unveil that frHMGB1, originating from LPS-carrying histiocytes, enters macrophages via RAGE, resulting in the direct activation of caspase-11 and the induction of non-canonical pyroptosis. Notably, the A Box's competitive binding with LPS thereby impedes its entry into the cell cytosol. These findings reveal potential therapeutic strategies for slowing the progression of lethal sepsis by modulating the non-canonical pyroptosis pathway.
研究领域:
免疫学
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传染病学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 1
·e70051
·
IF 4.2
Qiwen Shi,Tao Zhou,Wenjun Hou,Yuqi Zhou,Shufen Deng,Ying Song
Diabetes nephropathy (DN) is a severe diabetic chronic microvascular complication and the major cause of end-stage renal disease (ESRD). Our study aimed to investigate the effects of isoliquiritigenin (ISL) a natural flavonoid compound on DN and to explore the underlying mechanisms. The db/db mice were received intragastric treatments of ISL (5, 10, or 20 mg/kg), vehicle or positive drug metformin (300 mg/kg) once a day for 12 weeks, and the db/m mice treated with vehicle were used as controls. ISL significantly ameliorated pathological changes and functional injury in the kidneys of db/db mice in a dose-dependent manner. The administration of 20 mg/kg ISL reduced the levels of serum creatinine (Scr; 49.0 ± 1.7 vs. 56.9 ± 2.9 μmol/L; p < 0.01), blood urine nitrogen (BUN; 9.6 ± 1.3 vs. 12.0 ± 1.1 mmol/L; p < 0.05), albumin to creatinine ratio (ACR; 1925.8 ± 798.1 vs. 4269.4 ± 925.6 μg/mg; p < 0.01) and urinary albumin (276.2 ± 39.9 vs. 576.9 ± 108.9 μg; p < 0.05). Further study identified advanced glycation end product (AGE)–receptor for AGE (RAGE) axis as a target of ISL. ISL (20 mg/kg) lowered renal AGE level (2.5 ± 0.5 vs. 3.8 ± 0.6 μg/mg; p < 0.01) and RAGE expression, leading to improvements in renal fibrosis, oxidative stress, and inflammation. To sum up, our study demonstrated that ISL displayed preventive effects on the experimental model of DN through suppressing AGE–RAGE pathway, and provided some insights into the application of ISL in DN treatment.
研究领域:
药理学
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内分泌学
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肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HEREDITAS
·
2024
·Vol. 161
·期 1
·1-17
·
IF 2.1
Zheng Jianxiu,Wang Liyan,Liu Ahui,Shen Haofei,Wang Bin,Jiang Yanbiao,Jing Panpan,Guan Defeng,Yu Liulin,Zhang Xuehong
Background Indole-3-acetic acid (IAA), an indole analog produced by intestinal microorganisms metabolizing tryptophan, has anti-inflammatory and antioxidant properties and thus has potential applications in ovarian protection, although the exact mechanism is unknown. The present study preliminarily investigated the pharmacological mechanism of IAA in alleviating diminished ovarian reserve (DOR) by network pharmacology and molecular docking. Methods Relevant target proteins of IAA were searched in SwissTargetPrediction, PharmMapper, TargetNet, BATMAN-TCM, and SuperPred databases. The potential targets of DOR were obtained from GeneCards, DisGenet, OMIM, and Drugbank databases. Both common targets were then imported into the String website to construct a PPI network, and these targets were analyzed for GO and KEGG enrichment. Finally, we utilized molecular docking to validate the possible binding conformations between IAA and the candidate targets. We used in vitro experiments to preliminarily investigate the effects of IAA on DOR. Results We obtained 88 potential targets for IAA and DOR interaction. We received 16 pivotal targets by constructed protein interaction screening. KEGG enrichment analysis mainly included the AGE-RAGE signaling pathway, IL-17 signaling pathway, Chemical carcinogenesis—reactive oxygen species in diabetic complications, etc. GO functional analysis showed that IAA treatment of DOR may involve biological processes such as response to external stimuli, hypoxia, gene expression, and regulation of enzyme activity. Molecular docking and in vitro experiments further revealed the potential effects of IAA on MMP2, TNF-α, AKT1, HSP90AA1, and NF-κ B. Conclusion We preliminarily revealed the potential protective effects of IAA against DOR through multiple targets and pathways, which provides a new research strategy for the molecular mechanism of IAA to alleviate DOR in the future. However, further studies need to demonstrate whether IAA can be used as a compound to prevent and treat DOR.
研究领域:
药理学
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分子生物学
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生殖医学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Diabetes Metabolic Syndrome and Obesity-Targets and Therapy
·
2025
·
IF 3
Shizhao Zhang,Mei Yan,Pengpeng Liang,Ye Zhang,Jiamin Liu,Hai Huang,Guiyun Li,Hongyan Wu
Objective This study aimed to investigate the active ingredients and mechanisms of Fu-Fang-Qi-Di-Hua-Yu-Tang (FFQD) in alleviating atherosclerosis and insulin resistance in diabetic macrovascular disease (DMD) mice.Methods Chemical profiling of FFQD was performed using UPLC-Q-TOF-MS. Apoe-/- mice were injected with streptozotocin and fed a high-fat diet to establish DMD. Groups included control (C57BL/6), model (normal saline), low/medium/high-dose FFQD, and western medicine (atorvastatin + metformin). After 12 weeks, aortic morphology, blood glucose/lipid profiles, inflammatory factors, and PI3K/AKT pathway-related targets were analyzed.Results FFQD contained 159 identified components. Treatment significantly reduced aortic plaque area, blood glucose, lipids, and lowered the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), oxidized low-density lipoprotein (ox-LDL), C-reactive protein (CRP), and monocyte chemoattractant protein-1 (MCP-1). It also reduced nitric oxide synthase 2 (NOS2) level, a marker of macrophage polarization, increased arginase 1 (Arg1) level, regulated macrophage polarization, and improved oxidative stress and inflammatory response. In addition, FFQD activated the receptor for advanced glycation end products (RAGE)/PI3K/AKT/mammalian target of rapamycin (mTOR) pathway in the aorta, inhibited RAGE expression, promoted PI3K, AKT, and mTOR phosphorylation, down-regulated microtubule-associated protein 1A/1B-light chain 3-II/I (LC3 II/I) and nuclear factor κB (NF-κB p65) expression, up-regulated SQSTM1 protein (p62) expression, inhibited excessive autophagy, and reduced vascular endothelial damage caused by long-term high glucose levels. In the liver, FFQD activated the Ras family small molecule G protein (RAP1)/PI3K/AKT/forkhead box protein 01 (FOX01) pathway, inhibited RAP1 expression, promoted PI3K and AKT phosphorylation, suppressed FOX01 expression, and improved insulin resistance.Conclusion FFQD may improve insulin resistance, regulate glucose and lipid metabolism, inhibit excessive autophagy, induce macrophage polarization, resist inflammation and oxidative stress, inhibit atherosclerosis, and ultimately improve DMD by activating the RAGE/PI3K/AKT/mTOR and RAP1/PI3K/AKT/FOX01 pathways. Therefore, FFQD may be a promising candidate for DMD treatment.
研究领域:
药理学
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中医药学
·
心血管疾病
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分子生物学
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代谢紊乱
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免疫学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 1
·1-10
·
IF 2.7
Ying Deng,Jing-Shu Hong,Yi-Yun Cao,Ning Kang,Deng-Yang Han,Yi-Tong Li,Lei Chen,Zheng-Qian Li,Rui Zhan,Xiang-Yang Guo,Ning Yang,Cheng-Mei Shi
Postoperative delirium (POD), which occurs in hospital up to 1‑week post‑procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood‑brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end‑products (RAGE) expression and β‑amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD‑like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD‑like behaviour. FPS‑ZM1, a specific RAGE antagonist, ameliorated POD‑like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS‑ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD.
研究领域:
神经科学
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麻醉学
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老年医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Aging-US
·
2024
·
IF 3.9
Jiahao Ye,Ruiping Yang,Lin Li,Senjie Zhong,Ruixue Jiang,Zhixi Hu
Background: Danxiong Tongmai Granules (DXTMG) are widely utilized in treating coronary heart disease (CHD) in China. This study aims to explore the molecular mechanisms underlying the therapeutic effects of DXTMG on CHD by employing a network pharmacology approach, complemented with experimental validation. Methods: Traditional Chinese Medicine (TCM) compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database was used to obtain the main target genes involved in CHD. We combined disease targets with the drug targets to identify common targets. The “TCM-compound-target” network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock software. A molecular dynamics simulation was conducted on the optimal protein-small molecule complex identified through molecular docking, using Amber18 software. The rat model for myocardial ischemia was established through pre-gavage administration of DXTMG, followed by dorsal hypodermic injection of isoprenaline. Myocardial tissues from the rats were analyzed using hematoxylin and eosin (HE) staining and Masson’s trichrome staining. Relevant targets were validated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Results: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system; 109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways ( P < 0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. The results of molecular docking and molecular dynamics simulations demonstrated the robust binding affinity between the compounds and target proteins. Animal experiment findings indicated that, compared with the model group, the DXTMG group effectively ameliorated inflammation and fibrosis in rat myocardial tissues, reduced LDH, cTn-I, and MDA levels ( P < 0.05, P < 0.01), elevated SOD and GSH-PX levels ( P < 0.05), and reduced the percentage of positive area for IL-6 and TNF-α ( P < 0.05). Conclusion: This study preliminarily suggests that DXTMG can modulate oxidative stress, inflammation response, and cardiomyocyte regulation, thereby mitigating the onset and progression of CHD.
研究领域:
药理学
·
心脏病学
·
分子生物学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2020
·
IF 3.011
Yuzhen Hou,Jie Lan,Fan Zhang,Xianggen Wu
As a damage-associated molecular pattern molecule, high-mobility group box 1 protein (HMGB1) is involved in diabetes and its complications. However, the role of HMGB1 in diabetic keratopathy is not yet understood. The purpose of this study was to investigate the potential roles of HMGB1 in the development of diabetic keratopathy as well as potential strategies to block HMGB1 in order to prompt epithelial wound healing and nerve regeneration in diabetic corneas. The results demonstrated that diabetic keratopathy developed in mice over the duration of the diabetic condition with typical symptoms, including damaged ocular surfaces and corneal nerves . The diabetic corneas had significantly increased protein expression levels of HMGB1 and its receptors—the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4)—compared to the age-matched normal corneas ( P < 0.05). Corneal HMGB1 levels significantly increased during the corneal wound healing process of the diabetic mice, peaking on the first day after the wound was created and then decreasing to the unwounded level on the seventh day. Exogenous HMGB1 peptide significantly retarded wound and nerve healing, while glycyrrhizin (an HMGB1 inhibitor) significantly prompted wound and nerve healing. Further, the western blot results confirmed that RAGE and TLR4 were also involved in corneal wound and nerve healing. In conclusion, these data showed that HMGB1 and its related receptors are highly involved in the development of diabetic keratopathy. This finding indicates that the blockage of HMGB1 might serve as a strategy to prompt diabetic corneal and nerve wound healing.
研究领域:
眼科学
·
糖尿病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Yuhong Jiang,Yuke Li,Dongmei Zheng,Xin Du,Huan Yang,Chuan Wang,Mengnan Zhao,Haihua Xiao,Lingpu Zhang,Xiaofang Li,Sanjun Shi
Metastasis as the hallmark of cancer preferentially contributes to tumor recurrence and therapy resistance, aggrandizing the lethality of patients with cancer. Despite their robust suppressions of tumor progression, chemotherapeutics failed to attenuate cancer cell migration and even triggered pro-metastatic effects. In parallel, protease-activated receptor 2 (PAR2), a member of the G protein-coupled receptor subfamily, actively participates in cancer metastasis via multiple signal transduction pathways. CRISPR/Cas9 that is a dominating genome editing tool can evoke PAR2 knockout to inhibit cancer metastasis. However, the absence of valid delivery systems largely limits its efficacy. Herein, we nanosized polymeric platinum (NanoPt) as therapeutical drug carries to deliver CRISPR/Cas9 to elicit genome editing of PAR2, which drastically augmented anti-metastatic effects and alleviated systematic toxicity of platinum-based treatment in vitro and in vivo . More importantly, the NanoPt@Cas9-PAR2 initiated PAR2 deficiency to mechanistically attenuate EMT process and ferroptosis via RAGE/ERK signalling, consequently preventing cancer cell migration. Our findings indicate that NanoPt@Cas9-PAR2 that mitigated PAR2 signalling and cytotoxic effects of platinum could be a safe and powerful all-in-one combinatorial strategy for cancer treatment.
研究领域:
肿瘤学
·
遗传学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2022
·Vol. 17
·期 1
·1-8
·
IF 2.677
Zhang Bin-Fei,Song Wei,Wang Jun,Wen Peng-Fei,Zhang Yu-Min
Objectives The lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model. Methods Seventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses. Results Nine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Conclusion The remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.
研究领域:
病理生理学
·
肺医学
·
创伤外科
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Hongwei Li,Le Kang,Shirong Dou,Yiming Zhang,Yumei Zhang,Ning Li,Yangang Cao,Mengyun Liu,Deen Han,Kai Li,Weisheng Feng
Background Gleditsiae Sinensis Fructus (GSF) is commonly used in traditional medicine to treat respiratory diseases such as bronchial asthma. However, there is a lack of research on the chemical composition of GSF and the pharmacological substance and mechanism of action for GSF in treating bronchial asthma. Purpose The chemical constituents of GSF were analyzed using ultrahigh-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). In this study, we combined network pharmacology, molecular docking techniques, and experimental validation to explore the therapeutic efficacy and underlying mechanism of GSF in the treatment of bronchial asthma. Methods Characterization of the chemical constituents of GSF was conducted using UHPLC-Q-Orbitrap HRMS. The identified chemical components were subjected to screening for active ingredients in the Swiss Absorption, Distribution, Metabolism, and Excretion (ADME) database. Relevant databases were utilized to retrieve target proteins for the active ingredients and targets associated with bronchial asthma disease, and the common targets between the two were selected. Subsequently, the protein-protein interaction (PPI) network was constructed using the String database and Cytoscape software to identify key targets. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Metascape database. The "component-common target" network was constructed using Cytoscape to identify the primary active ingredients. Molecular docking validation was conducted using AutoDock software. The bronchial asthma mouse model was established using ovalbumin (OVA), and the lung organ index of the mice was measured. Lung tissue pathological changes were observed using hematoxylin and eosin (HE), Periodic Acid-Schiff (PAS), and Masson staining. The respiratory resistance (Penh) of the mice was assessed using a pulmonary function test instrument. An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IgE, IL-4, IL-5, and IL-13 in the mouse serum. Immunofluorescence staining was performed to detect the protein expression levels of AKT and PI3K in the lung tissues. An in vitro experiment was performed to observe the effects of echinocystic acid (EA) on IL-4 stimulated Human ASMCs (hASMCs). Cell viability was measured using a CCK-8 assay to calculate the IC50 value of the EA. A wound healing test was conducted to observe the effect of EA on degree of healing. RT-qPCR was performed to detect the influence of EA on the mRNA expression levels of ALB, SRC, TNF-α, AKT1, and IL6 in the cells. Results A total of 95 chemical constituents were identified from the GSF. Of these, 37 were identified as active ingredients. There were 169 overlapping targets between the active ingredients and the disease targets. A topological analysis of the protein-protein interaction (PPI) network identified the core targets as IL6, TNF, ALB, AKT1, and SRC. An enrichment analysis revealed that the treatment of bronchial asthma with GSF primarily involved the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway, among others. The primary active ingredients included 13(s)-HOTRE, linolenic acid, and acacetin. The molecular docking results demonstrated a favorable binding activity between the critical components of GSF and the core targets. Animal experimental studies indicated that GSF effectively improved symptoms, lung function, and lung tissue pathological changes in the OVA-induced asthmatic mice, while alleviating inflammatory responses. GSF decreased the fluorescent intensity of the AKT and PI3K proteins. The IC50 value of EA was 30.02μg/ml. EA (30) significantly promoted the proliferation of IL4-stimulated hASMCs cells. EA (30) significantly increased the expression of ALB and SRC mRNA and decreased the expressions of TNF-α, AKT, and IL6 mRNA. Conclusion The multiple active ingredients found in GSF exerted their anti-inflammatory effects through multiple targets and pathways. This preliminary study revealed the core target and the mechanism of action underlying its treatment of bronchial asthma. These findings provided valuable insights for further research on the pharmacological substances and quality control of GSF.
研究领域:
药理学
·
中药学
·
呼吸系统疾病
·
分子生物学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Yang Wu,Yan Li,Liangqing Zheng,Pengcheng Wang,Yan liu,Yongning Wu,ZhiYong Gong
Nε-(carboxymethyl)lysine (CML) is a potentially noxious compound that is causing widespread concern due to its use in various food products. In this study, we investigated CML neurotoxicity via an in vivo experiment with mice, and an in vitro experiment using a 3D microvascular network model (with human brain vascular endothelial cell and human astrocyte) that simulated the blood-brain barrier. We found that CML could induce cell survival status variations, and histopathological changes to the brain. In addition, CML increased levels of oxidative stress , prompted the protein expression of the receptor for advanced glycation end-products (RAGE). CML up-regulated both the gene expression of RAGE, the activating protein-1 (AP-1), the inflammatory cytokines Interleukin-6 (IL-6), vascular cell adhesion molecule1 (VCAM-1), monocyte chemotactic protein1 (MCP-1). We, therefore, postulated that CML has the potential to deleteriously affect the nervous system through oxidative stress and that activation of the p38 MAPK-AP-1 signaling pathway might be implicated in this pathological process.
研究领域:
神经科学
·
毒理学
·
细胞生物学
·
食品科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）