PHYTOMEDICINE
·
2025
·
IF 8.3
Tong Chen,Lijun Ai,Ruonan Shuang,Jichen Diao,Xinyi Yuan,Weiwei Tao,Ling He,Chang Chen
Background Cognitive impairment is the common complication of diabetes, while its etiology remains not fully understood. Gardenia jasminoides is used in traditional Chinese medicine for clearing heat and detoxification. Its effective components Geniposide and Genipin have been found to show protective effect on diabetic cognitive impairment in our previous study. Whereas the effect and mechanism of Shanzhiside methyl ester (SME), another major component of Gardenia jasminoides , on cognitive impairment has been scarcely reported. Purpose The present study was conducted to evaluate the effect of SME on cognitive impairment symptom in diabetic mice. Methods Diabetes was induced by HFD/STZ. HG/PA induced BV2 cells were used as the in vitro model. Results Network pharmacology and bioinformatic analyses showed that HSP90AA1 might be the target of SME. As a result, SME attenuated cognitive impairment-related behavior in Morris water maze and passive avoidance tests. The treatment with SME inhibited inflammation, glycolysis via HSP90AA1/HIF1A/STAT1 signaling both in vivo and in vitro. SME regulated the transcriptions of inflammation, glycolysis, oxidative phosphorylation, oxidative stress, lipid metabolism, and mitochondrial stress related genes. The transfection with HSP90AA1 SiRNA or overexpression plasmid, the treatment with HIF1A inhibitor PX478, STAT1 inhibitor Fludarabine suggested that HSP90AA1/HIF1A/STAT1 signaling was required for the anti-inflammatory and anti-glycolytic effects of SME. The treatment with glycolysis agonist oligomycin, hexokinase inhibitor 2-DG, PKM2 activator TEPP46, PKM2 inhibitor Shikonin displayed that glycolysis was critical for the anti-inflammatory effect of SME. It was found that SME might combine with HSP90AA1. Conclusion SME attenuated cognitive impairment symptom of diabetic mice possibly via HSP90AA1/HIF1A/STAT1 mediated anti-inflammatory and anti-glycolytic effects.
研究领域:
药理学
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神经科学
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分子生物学
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生物信息学
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内分泌学
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中医药学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Ling Jiang,Cai-Bo Tian,Rui-Han Ye,Nian Shi,Xing-Chao He,Yun-Li Zhao,Xiao-Dong Luo
Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro . In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.
研究领域:
药理学
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分子生物学
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毒理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Luna Zhang,Qianqian Li,Yufang Ni,Zhaoyang Li,Honglian Wang,Lifeng Meng,Li Wang,Jianchun Li
Background Renal fibrosis represents a common and critical pathological process underlying chronic kidney disease (CKD), invariably leading to progressive renal dysfunction and ultimately end-stage renal disease. Purpose This investigation sought to determine anti-fibrotic efficacy of Deacetyl Asperulosidic Acid Methyl Ester (DA), in ameliorating renal fibrosis, focusing on its interaction with heat shock protein 90 (Hsp90aa1) and its downstream effects on TGF-β/Smad signaling. Study design The anti-fibrotic efficacy of DA was evaluated in vivo using two murine models of CKD (unilateral ureteral obstruction and adenine-induced nephropathy) and in vitro using TGF-β1-stimulated NRK-49F fibroblasts and TCMK-1 tubular cells. Molecular targets were identified and validated through quantitative proteomics, Specific Pupylation as Identity Reporter (SPIDER) assay, and biophysical interaction analyses. Methods Renal function and histological changes were assessed by biochemical analysis, H&E, and Masson's trichrome staining. The expression of fibrotic markers and signaling pathway proteins was determined using IHC, Western blot, and qRT-PCR. The interaction between DA and Hsp90aa1 was verified by Cellular Thermal Shift Assay (CETSA), Drug Affinity Responsive Target Stability (DARTS), and Co-immunoprecipitation (Co-IP). Results Our data demonstrated that DA administration substantially ameliorated renal dysfunction and attenuated fibrotic progression in both animal and cellular models. Quantitative proteomic profiling results revealed a prominent suppression of extracellular matrix components and TGF-β type I receptor (TGFβRI) following DA treatment. Furthermore, biotin-labeled DA binding combined with SPIDER experiments identified Hsp90aa1 as a direct target of DA. Mechanistically, the binding of DA to Hsp90aa1 disrupts the interaction between Hsp90aa1 and TGFβR1, thereby destabilizing TGFβR1 and promoting its degradation. This regulation effectively impedes the transduction of the downstream TGF-β/Smad signaling cascade, ultimately mitigating renal fibrosis. Conclusion Our findings demonstrate that DA is a potent anti-fibrotic agent that targets Hsp90aa1 to modulate TGFBR1 stability and inhibit the TGF-β/Smad pathway. Download: Download high-res image (359KB) Download: Download full-size image
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Meng-ya Zhang,Li-juan Ma,Ling Jiang,Li Gao,Xian Wang,Yue-bo Huang,Xiang-ming Qi,Yong-gui Wu,Xue-qi Liu
Ethnopharmacological relevance Paeonia lactiflora Pall has been used in Chinese Medicine for thousands of years, especially having anti-inflammatory, sedative, analgesic and other ethnic pharmacological effects. Moreover, Paeoniflorin is the main active ingredient of the Paeonia lactiflora Pall , and most are used in the treatment of inflammation-related autoimmune diseases. In recent years, studies have found that Paeoniflorin has a therapeutic effect on a variety of kidney diseases. Aim of the study Cisplatin (CIS) is limited in clinical use due to its serious side effects, such as renal toxicity, and there is no effective method for prevention. Paeoniflorin (Pae) is a natural polyphenol which has a protective effect against many kidney diseases. Therefore, our study is to explore the effect of Pae on CIS-induced AKI and the specific mechanism. Materials and methods Firstly, CIS induced acute renal injury model was constructed in vivo and in vitro , and Pae was continuously injected intraperitoneally three days in advance, and then Cr, BUN and renal tissue PAS staining were detected to comprehensively evaluate the protective effect of Pae on CIS-induced AKI. We then combined Network Pharmacology with RNA-seq to investigate potential targets and signaling pathways. Finally, affinity between Pae and core targets was detected by molecular docking, CESTA and SPR, and related indicators were detected in vitro and in vivo . Results In this study, we first found that Pae significantly alleviated CIS-AKI in vivo and in vitro . Through network pharmacological analysis, molecular docking, CESTA and SPR experiments, we found that the target of Pae was Heat Shock Protein 90 Alpha Family Class A Member 1 (Hsp90AA1) which performs a crucial function in the stability of many client proteins including Akt. RNA-seq found that the KEGG enriched pathway was PI3K-Akt pathway with the most associated with the protective effect of Pae which is consistent with Network Pharmacology. GO analysis showed that the main biological processes of Pae against CIS-AKI include cellular regulation of inflammation and apoptosis. Immunoprecipitation further showed that pretreatment with Pae promoted the Hsp90AA1-Akt protein-protein Interactions (PPIs). Thereby, Pae accelerates the Hsp90AA1-Akt complex formation and leads to a significant activate in Akt, which in turn reduces apoptosis and inflammation. In addition, when Hsp90AA1 was knocked down, the protective effect of Pae did not continue. Conclusion In summary, our study suggests that Pae attenuates cell apoptosis and inflammation in CIS-AKI by promoting Hsp90AA1-Akt PPIs. These data provide a scientific basis for the clinical search for drugs to prevent CIS–AKI.
研究领域:
药理学
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肾病学
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分子生物学
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民族药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
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IF 11.3
Zhuolin Guo,Xuemei He,Bing Chen,Zhiheng Zhang,Jingtao Yu,Wei Zhao,Xiangdong Chen,Yunguang Hu,Jianping Zuo,Linzhong Yu,Chunlin Fan,Junshan Liu
Objective Dengue virus (DENV) remains a significant public health threat, yet no effective antiviral therapies are currently available. Based on TCM theory, the treatment of dengue emphasizes the principles of clearing heat and detoxifying, cooling blood and dissipating blood stasis. Yinqiao Powder (YQS), a famous clearing heat and detoxifying formula, has a good curative effect on the virus-induced diseases, and theoretically has potential value in the treatment of dengue. Purpose This study aims to investigate the antiviral mechanism of YQS against DENV. Methods Time-of-drug-addition assay elucidated phase-specific antiviral target of YQS in dengue infection, while plaque, cytopathic effect (CPE), quantitative real-time PCR, Western blot, and immunofluorescence assays were employed to assess the antiviral efficacy of YQS. Network pharmacology analysis was performed to identify convergent molecular targets between YQS constituents and DENV pathophysiological cascades. The interactions between wogonin and HSP90AA1 were characterized using cellular thermal shift assay, drug affinity responsive target stability, molecular docking, and surface plasmon resonance. Immunofluorescence and co-immunoprecipitation assays were implemented to interrogate whether wogonin modulates E/HSP90AA1 interaction. Ultimately, the in vivo protective activity of YQS was assessed in DENV-2-infected AG129 mice. Results YQS inhibited DENV-2 infection with an IC 50 value of 468.5 μg/ml. YQS reduced progeny virus by over 75% and CPE, suppressed expression of viral RNA and proteins during the adsorption phase across multiple cell lines. The active component wogonin was identified through network pharmacology. Similarly, wogonin exhibited potent inhibition of DENV adsorption, reducing plaque formation by over 45%. Further target study demonstrated that wogonin targeted HSP90AA1 and blocked its interaction with viral E protein. In vivo findings revealed YQS mitigated weight loss, extended survival, diminished serum viral load, and conferred hepatoprotective effects in AG129 mice. Conclusion YQS potently inhibits DENV infection in vitro and in vivo . The antiviral activity of its component wogonin may contribute to this effect, potentially through binding to the host receptor HSP90AA1 and reducing DENV adsorption.
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DOI
PubMed
高影响因子
ACS Sensors
·
2025
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IF 9.1
Xue-Bo Hu,Yu-Ling Wang,Jing-Lu Lv,Meng-Yuan Zheng,Shu-Hui Ma,Jun-Tao Cao,Yan-Ming Liu
To advance the biological understanding of heat shock protein (HSP) in different types of cancers, it is crucial to achieve its accurate determination. Herein, a dual-mode self-powered photoelectrochemical (PEC) and colorimetric platform was proposed by integrating enzymatic catalysis and a chemical redox cycling amplification strategy. In this system, ascorbic acid (AA), as the signal reporter for PEC and colorimetric assay, can be regenerated during the tris(2-carboxyethyl) phosphine-mediated chemical redox cycling process. For PEC detection, the reproduced electron donor AA could repeatedly combine with holes generated by the Bi2S3/Bi2O3 photoanode to effectively separate the photogenerated electron–hole. Besides, an AA-involved color reaction was evoked during the colorimetric assay to reduce colorless tris(bathophenanthroline) iron(III) to red tris(bathophenanthroline) iron(II). Owing to the ingenious signal amplification strategy, the developed dual-mode assay achieved the PEC and colorimetric determination of HSP90AA1 (one subtype of HSP family) in real samples. It is believed that this work will offer a new strategy to fabricate a dual-mode biosensor, which has great application prospects in the detection of various tumor biomarkers.
研究领域:
生物化学
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分析化学
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生物医学工程
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癌症生物学
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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
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2022
·
IF 5.37
Renzheng Zhang,Xian Guo,Chunnian Liang,Jie Pei,Pengjia Bao,Mancai Yin,Fude Wu,Min Chu,Ping Yan
To achieve fertilization, mammalian spermatozoa must undergo capacitation and the acrosome reaction (AR) within the female reproductive tract. However, the effects of cryopreservation on sperm maturation and fertilizing potential have yet to be established. To gain insight into changes in protein levels within sperm cells prepared for use in the context of fertilization, a comprehensive quantitative proteomic profiling approach was used to analyze frozen–thawed Ashidan yak spermatozoa under three sequential conditions: density gradient centrifugation-based purification, incubation in a capacitation medium, and treatment with the calcium ionophore A23187 to facilitate AR induction. In total, 3280 proteins were detected in these yak sperm samples, of which 3074 were quantified, with 68 and 32 being significantly altered following sperm capacitation and AR induction. Differentially abundant capacitation-related proteins were enriched in the metabolism and PPAR signaling pathways, while differentially abundant AR-related proteins were enriched in the AMPK signaling pathway. These data confirmed a role for superoxide dismutase 1 (SOD1) as a regulator of sperm capacitation while also offering indirect evidence that heat shock protein 90 alpha (HSP90AA1) regulates the AR. Together, these findings offer a means whereby sperm fertility-related marker proteins can be effectively identified. Data are available via Proteome Xchange with identifier PXD035038.
研究领域:
生殖生物学
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蛋白质组学
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动物科学
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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
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zijie Wang,Anan Jiang,Hongmei Xiao,Xiaofan Yuan,Shaoru Zhang,Xinyue Qin
Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments.Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue.Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis—multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2.Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.
研究领域:
药理学
·
神经科学
·
分子生物学
·
生物信息学
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实验医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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