JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Jinfeng Shang,Qiannan Li,Tingyue Jiang,Lei Bi,Yinghui Lu,Jiakang Jiao,Qi Song,Mingxue Yan,Lizha Shabuerjiang,Jingyi Wang,Xin Liu
Ethnopharmacological relevance Huanglian Jiedu Decoction (HLJDD) has the effect of clearing heat and detoxifying, and has been considered as an effective prescription for cerebral ischemia (CI) for thousands of years in traditional Chinese medicine (TCM). It can improve the quality of life of patients with ischemic stroke, but its pharmacological mechanism remains unclear. Aim of the study The study aimed to explore the pharmacological action and potential mechanism of HLJDD against CI by systems pharmacology, proteomics and in vivo experiments. Materials and methods In this study, databases such as TCMIP V2.0 and Genecards were used to predict compounds, targets and CI related targets, and network topology criteria of protein-protein interaction (PPI) network was used to screen core targets. The Database for Annotation, Visualization and Integrated Discovery database (DAVID) was used to discover biological processes and pathways. In addition, molecular docking was performed between the screened core biological active compounds and targets to verify the binding activity. Finally, proteomics and Western blot were performed on cerebral cortex tissues of middle cerebral artery occlusion (MCAO) model rats with HLJDD intervention to further verify the predicted results. Results 77 compounds and 308 targets of HLJDD were identified, 54 of which were predicted to be associated with cerebral ischemia. PPI network and enrichment results showed that 8 targets, including AKT1, PTGS2 and TLR4 , were core targets of HLJDD in CI. And 19 signaling pathways, including Rap1 signaling pathway, cAMP signaling pathway and arachidonic acid metabolism, were identified as key pathways to the therapeutic activity of HLJDD in CI. Combined with proteomics studies, we identified that Rap1 signaling pathway and upstream and downstream targets were the key mechanisms. Molecular biology experiments showed that RAP1A and AKT expression levels were significantly up-regulated in middle cerebral artery occlusion (MCAO) rats treated with HLJDD ( P < 0.0001), GRIN1 expression level was significantly down-regulated ( P < 0.0001). However, ACTB expression level was slightly down-regulated ( P > 0.05), which may be related to the biological function. Conclusion This study confirms the pharmacological effect of HLJDD on cerebral ischemia. These results indicate that HLJDD mediates various pathways such as inhibition of apoptosis , regulation of oxygen balance, inhibition of excitatory toxicity and maintenance of basic cell functions to improve CI by regulating Rap1 signaling pathway.
研究领域:
药理学
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神经科学
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中医
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Yuanyuan Li,Guangmei Yang,Yuting Wang,Yahong Li,Shu Zhang,Ruyi Li,Linxin Yang,Jian Wang,Xibo Pei,Qianbing Wan,Junyu Chen
Following the introduction of osteo-immunomodulation as a new and important strategy to enhance material osseointegration, designing an appropriate immune response after biomaterial implantation has become a significant challenge for efficient bone repair. In this study, a nanosilicate-reinforced sodium alginate (SA) hydrogel was fabricated by introducing montmorillonite (MMT) nanoparticles. Meanwhile, an immunogenically bioactive agent, harmine (HM), was loaded and released to induce macrophage differentiation into the M2 type. The fabricated SA/MMT/HM (SMH) hydrogel exhibited improved mechanical stiffness and stability, which also efficiently promoted macrophage anti-inflammatory M2 phenotype polarization and enhanced the secretion of pro-tissue healing cytokines for inducing a favorable immunomodulatory microenvironment for the osteogenic differentiation of bone marrow stromal cells (BMSCs). Furthermore, a rat air-pouch model and the critical-size bone defect model were used and the results showed that SMH hydrogel increased the proportion of M2 macrophages and markedly reduced local inflammation, while enhancing desirable new bone formation. Transcriptomic analysis revealed that the SMH hydrogel accelerated the M1-to-M2 transition of macrophages by inhibiting relevant inflammatory signaling pathways and activating the PI3K-AKT1 signaling pathway. Taken together, this high-intensity immunomodulatory hydrogel may be a promising biomaterial for bone regeneration and provide a valuable base and positive enlightenment for massive bone defect repair.
研究领域:
生物材料
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免疫学
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组织工程
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骨再生
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2024
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IF 7
Haojie Sha,Yanrong Ma,Jiaxing Li,Junying Zhao,Yunbi Xu,Dingding Su
Rice has a long history as a staple food consumed by half of the world’s population. Compared with white rice (WR), colored rice (CR) has more nutritional value because it contains rich active ingredients. In this study, the potential mechanism of CR (red rice (RR), green rice (GR), black rice (BR), and purple rice (PR)) for immunomodulation was explored by UPLC-Q-TOF, network pharmacology, and cell experiment. kuromanin, kaempferol-3-O-arabinoside, keracyanin, guajavarin, and hispidulin in CR were the critical components for improving immunity. These ingredients are mainly found in BR. Cell experiments supported that kuromanin plays a role in maintaining immune homeostasis. In the normal environment, it promotes cell proliferation and improves DNA repair; In an inflammatory environment, it binds to AKT1 and reduces the release of inflammatory factors through the MAPK and NFKB signaling pathways. The study provides a guideline for humans to utilize the precise nutrition of CR.
研究领域:
食品科学
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药理学
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免疫学
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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 BIOMOLECULAR STRUCTURE & DYNAMICS
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2023
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IF 4.4
Bing-Hui Yan,Qi-Xuan Xu,Xiao Ge,Ming-Tong Gao,Yun Li,Liang Guo,Po Hu,Yang Pan
Benign prostatic hyperplasia (BPH) is a common disease that affects the quality of life of middle-aged and older men. We investigated the therapeutical effects of Chengshi Beixie Fenqing Decoction (CBFD), a classic traditional Chinese medicine prescription, on BPH through in vivo model and network pharmacology. Bioactives in CBFD were detected through UPLC-Q-Tof-MS/MS and GC-MS, and filtered by the modified Lipinski’s rule. Target proteins associated with the filtered compounds and BPH are selected from public databases. Venn diagram identified the overlapping target proteins between the bioactives-interacted target proteins and the BPH-targeted proteins. The bioactive-protein interactive networking of BPH was analyzed through the KEGG pathway on STRING to identify potential ligand-target and visualized the rich factors on the R packet. After that, the molecular docking test (MDT) was performed between bioactives and target proteins. It showed that the mechanism of CBFD against BPH was related to 104 signaling pathways of 42 compounds. AKT1, 6-demethyl-4′-methyl-N-methylcoclaurine and relaxin signaling pathways were selected as a hub target, key bioactivitie and hub signaling pathway, respectively. In addition, three major compounds, 6-demethyl-4′-methyl-N-methylcoclaurine, isoliensinine and liensinine, had the highest affinity on MDT for the three crucial target proteins, AKT1, JUN and MAPK1. These proteins were associated with the relaxin signaling pathway, which regulated the level of nitric oxide and is implicated in both BPH development and CBFD. We concluded that the three key bioactivities found in Plumula nelumbinis of CBFD may contribute to improving BPH condition by activating the relaxin signaling pathways.Communicated by Ramaswamy H. Sarma
研究领域:
药理学
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中医
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泌尿科
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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
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2024
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IF 4.8
Mengdi Wu,Xiangli Yan,Huang Huang,Xiuhui Guo,Ming Bai,Baoying wang,Pan Su,Yucheng Li,Erping Xu
Ethnopharmacological relevance Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. Aim of the study To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro . Materials and methods UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. Results There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. Conclusions These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.
研究领域:
药理学
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神经科学
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中医
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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
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2022
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IF 5.195
Min Hao,Zhouhui Yao,Mengting Zhao,Ziyan Chen,Pingping Wang,Xianan Sang,Qiao Yang,Kuilong Wang,Xin Han,Gang Cao
Ethnopharmacological relevance Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a classic herbal pair to promote blood circulation and remove blood stasis in ancient China. However, the molecular mechanism is still unclear. Aim of study To screen out the anti-liver fibrosis active ingredients in CR-SR. Moreover, preliminary exploration the molecular mechanism of CR-SR to ameliorates liver fibrosis . Materials and methods In this research, plant taxonomy has been confirmed in the “The Plant List” database ( www.theplantlist.org ). The chemical components of CR-SR were analysed by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). “Component-Target-Pathway-Disease” network of CR-SR components were built by network pharmacology . Then, the interaction between primary components and predicted protein targets based on network pharmacology were validated by molecular docking. The pharmacological actions of CR-SR were verified by blood biochemical indexes, histopathologic examination of CCL 4 induced rats’ model. The core protein targets were verified by Western blot . The effects of screened active components by molecular autodocking were verified by HSC-T6 cell experiment. Results The result shows that 57 chemical constituents in CR-SR herbal pair were identified by UPLC-Q/TOF-MS, in which, 27 compounds were closely connected with liver fibrosis related protein targets. 55 protein targets screened out by “component-target-pathway-disease network” maybe the underlying targets for CR-SR to cure liver fibrosis. Moreover, the 55 protein targets are mainly related to RNA transcription, apoptosis , and signal transduction. The molecular autodocking predicted that ten components can bond well with PTGS2 and RELA protein targets. The blood biochemical indexes, histopathologic examination of CCL 4 induced rats experiment showed that CR-SR has well intervention effect of liver fibrosis. The Western blot analysis indicated that CR-SR could significantly inhibit RELA, PTGS2, IL-6, SRC, and AKT1 protein expression to exert the anti-fibrosis effect. The HSC-T6 cell experiment indicated that both formononetin (FNT) and curdione could significantly inhibit the activation of HSC and reduce the expression of PTGS2, and p-AKT1 which was accordance with the molecular autodocking results. Conclusion This study proved the molecular mechanism of CR-SR multi-component and multi-target anti-liver fibrosis effect through mass spectrometry, network pharmacology, and western blotting technology. The research provides a theoretical evidence for the development and utilization of CR-SR herbal pair.
研究领域:
药理学
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分子生物学
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网络药理学
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中药学
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肝病
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产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
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2025
·Vol. 82
·期 9
·1-18
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IF 2.6
Xu Wenyi,Guan Yinghua,Tian Liping,Fu Yu,Zhang Yinghui,Liu Yanhong,Hu Yanfei,Zhao Bowen,Wu Chongming
The global prevalence of type 2 diabetes mellitus (T2DM) is currently surging, posing significant health and socioeconomic burdens. Probiotics have emerged as promising interventions due to their safety and potential metabolic benefits. Gut microbiota plays a critical role in the pathophysiology of metabolic diseases in humans, offering valuable insights for therapeutic strategies such as probiotics. Here, aiming to identify novel probiotics from the human gut microbes to combat T2DM, a total of 203 human intestinal bacterial strains were screened in vitro to evaluate their enzymatic inhibition of α-glucosidase and α-amylase, in which Lacticaseibacillus paracasei Glu-07 (= QH-142 = CGMCC 23796) exhibited the highest inhibitory efficacy (81.05% and 72.56% for α-glucosidase and α-amylase, respectively). In HepG2 cells, L. paracasei Glu-07 elevated glucose uptake and consumption by 22.4% and 85.8%. Oral administration of strain Glu-07 in diabetic mice significantly improved hyperglycemia, hyperlipidemia, and restored the structure and composition of gut microbiota toward a healthier profile. Mechanistically, strain Glu-07 activated the AMPK-AKT1-GSK3β/FOXO1 signaling pathways by modulating the expression of key genes, enhanced glycolysis and fatty acid ꞵ-oxidation, and inhibited gluconeogenesis and lipogenesis. It also stimulated GLP-1 secretion, potentially via triggering the GPR41/43-GLP-1 axis, and increased the abundance of beneficial gut microbes, such as Akkermansia muciniphila (~ threefold). The dual regulations synergistically support strain Glu-07 as a promising probiotic candidate for T2DM management.
研究领域:
微生物学
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糖尿病研究
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分子生物学
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药理学
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营养科学
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代谢性疾病
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2014
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IF 3.785
Rong-Lin Xie,Yoon-jeong Jang,Lei Xing,Bing-Feng Zhang,Feng-Zhen Wang,Peng-Fei Cui,Myung-Haing Cho,Hu-Lin Jiang
The clinical successful application of gene therapy critically depends upon the development of non-toxic and efficient delivery system. Although polycationic non-viral vectors hold great promise in nanomedicine , the exploring of application in clinics still remains a big challenge. To develop a non-toxic and efficient non-viral gene delivery system, two kinds of endogenous substance, citric acid (CA) and spermine (SPE), were used to prepare a new low charge density hyperbranched polyspermine (HPSPE) by one-pot polymerization. The biocompatibility evaluated by hemolytic activity and red blood cell (RBC) aggregation indicated that HPSPE was highly biocompatible without causing hemolysis and RBC aggregation compared with PEI as well as SPE. The MTS assay also demonstrated that the cell viability of HPSPE was above 90% even at 200 μg/mL at different time (24 and 72 h), which much higher than PEI 25 K. Besides, HPSPE showed high transfection efficiency without any toxic effect after aerosol delivery to the mice. Moreover, aerosol delivery of HPSPE/Akt1 shRNA significantly reduced tumor size and numbers and efficiently suppressed lung tumorigenesis ultimately in K- ras LA1 lung cancer model mice. These results suggest that low charge density as well as endogenous substance skeleton endow HPSPE with great potential for toxicity-free and efficient gene therapy.
研究领域:
生物医学工程
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基因治疗
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纳米医学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Zhi-Xin Peng,Hui-Wen Gu,Yuan Pan,Yan Wang,Jun Yan,Wanjun Long,Haiyan Fu,Yuanbin She
In recent years, red wine drinking has become more popular in China owing to its antioxidant effects. However, the key antioxidant compounds and their action mechanisms of Chinese red wines are still unclear. Herein, the antioxidant activities and chemical compositions of 45 Chinese Cabernet Sauvignon red wine samples were determined using chemical antioxidant assays and an UHPLC-QTOF-MS-based untargeted metabolomics method. The key antioxidant compounds in red wines and potential action mechanisms were revealed by integrating network pharmacology and molecular docking approaches. Results showed that there are 8 key antioxidant compounds in the red wine samples. These compounds are involved in several metabolic pathways in the body, particularly PI3K/AKT. What's more, they bind to the core antioxidant targets through hydrogen bonding and hydrophobic interaction. Among them, myricetin, laricitrin, 2,3,8-tri- O -methylellagic acid and AKT1 have the highest binding energies. This study could provide the theoretical basis for further investigation of physiological activities and functions of Chinese red wines.
研究领域:
食品科学
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药理学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Zichen Cui,Tian He,Shuo Zhang
Polylactic acid (PLA), as a bioplastic, is extensively utilized in bone tissue engineering for its biocompatibility, adaptability and affordability. However, the toxicological research of PLA is still limited. The hydrolysis products of PLA induced inflammatory response which caused inflammatory osteolysis mediated by oxidative damage through the recruitment of macrophages and the accumulation of foreign body multinucleated giant cells, ultimately leading to the failure of bone tissue regeneration. The lack of effective treatments highlights the importance of finding new therapies. This study systematically investigated the potential molecular mechanisms of PLA-induced inflammatory osteolysis by employing network toxicology and molecular docking techniques. We first conducted a network toxicology-based assessment according to the molecular structure of PLA. The result from integrating and screening targets from multiple databases identified 126 potential targets associated with PLA-induced inflammatory osteolysis, and then an interaction network diagram of the targets was constructed. Gene ontology (GO)/KEGG enrichment analysis clarified that PLA may cause inflammatory osteolysis via metabolic pathways and pathways in cancer, as well as lipid and atherosclerosis. Further analysis by STRING and Cytoscape software screened 25 core targets including HSP90AA1, AKT1, SRC, STAT1 and FYN. We found that the enriched highly correlated pathways covered 18 of the 25 core targets, supporting the scientific hypothesis that PLA induces inflammatory osteolysis. Moreover, the results of molecular docking confirmed that PLA displayed a strong binding ability with the core targets and formed stable binding. Taken together, this study not only revealed the potential biological mechanism of PLA-induced inflammatory osteolysis, but also provided new evidence for the future prevention and treatment of PLA-induced inflammation.
研究领域:
生物医学工程
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毒理学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2022
·
IF 4.132
Shan-Shan Wu,Li-Jun Hao,Yuan-Yuan Shi,Zhuo-Jian Lu,Jia-Lin Yu,Si-Qi Jiang,Qing-Ling Liu,Ting Wang,Shi-Ying Guo,Ping Li,Fei Li
Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine–threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.
研究领域:
药理学
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中医
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风湿病学
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分子生物学
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系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2025
·
IF 5.9
Ruoxin Chen,Jiahao Ren,Zhenlong Zhou,Wenjun Zhang,Jianyu Su
Gentiana rigescens Franch. extract have demonstrated various important bioactivities, however, their potential against photoaging has yet to be evaluated. This study explored the anti-photoaging effects of Gentiana rigescens Franch. root extract (GRFR) and stem (GRFS), along with their underlying mechanisms and bioactive components, using the UVB-induced zebrafish model. GRFS demonstrated superior anti-photoaging efficacy compared to GRFR. GRFS significantly alleviated UVB-induced tail fin damage, increasing the relative tail fin area from 31.23% to 80.92% (at 1mg/mL), and reducing ROS levels from 244.80% to 150.95%. It also inhibited lipid peroxidation, lowering malondialdehyde (MDA) levels from 202.87 nmol/g to 142.83 nmol/g. Furthermore, GRFS enhanced antioxidant enzyme activities, increasing superoxide dismutase (SOD) from 80.94 U/g to 104.06 U/g. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) indicated substantial distinctions in the composition and content of major constituents between GRFR and GFRS, which may explain the differences in their anti-photoaging activities. And then network pharmacology was used to investigate possible mechanisms of GFRS, which identified five potential targets including CTNNB1, ESR1, AKT1, JUN and EGFR, as well as three key active compounds including aspartyl-phenylalanine (Asp-Phe), N-acetyl-L-phenylalanine (N-Acetyl-L-Phe), and phenylalanyl-tyrosine (Phe-Tyr). Finally, the molecular docking revealed that Phe-Tyr exhibited the strongest binding affinity for AKT1 (-8.86 kcal/mol), indicating that it may be the most potent anti-photoaging compound in GFRS. These findings suggest that G . rigescens , with its potent anti-photoaging properties, offers superior protection against UVB-induced photoaging and holds promise as a natural therapeutic agent.
研究领域:
药理学
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植物学
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皮肤科学
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生物化学
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计算生物学
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天然产物研究
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）