Frontiers in Pharmacology
·
2025
·
IF 4.8
Yancen Li,Chengyu Wan,Fan Li,Guang Xin,Tao Wang,Qilong Zhou,Tingyu Wen,Shiyi Li,Xiaoting Chen,Wen Huang
Background: Isatidis Folium, a botanical drug widely used in traditional medicine, is known for its anti-inflammatory properties, including heat-clearing, detoxifying, and blood-cooling effects. Although its potential in sepsis treatment has been suggested, the bioactive metabolites and underlying mechanisms remain poorly understood.Methods: Network pharmacology and molecular docking were employed to identify the therapeutic effects and mechanisms of Indirubin, the major bioactive metabolite of Isatidis Folium, in sepsis treatment. In vivo, a cecal ligation and puncture (CLP)-induced mouse sepsis model was used to evaluate the protective effects of Indirubin through histopathological analysis, ELISA, and biochemical assays. In vitro, RAW264.7 cells were stimulated with LPS and treated with varying concentrations of Indirubin. The anti-inflammatory effects of Indirubin were assessed using ELISA, apoptosis assays, and Western blotting.Results: Network pharmacology analysis identified Indirubin as the major bioactive metabolite of Isatidis Folium and EGFR and SRC as its key molecular targets. Experimental validation demonstrated that Indirubin significantly improved survival rates, alleviated tissue injury, and suppressed inflammatory responses in sepsis models. Mechanistically, Indirubin inhibited LPS-induced activation of the EGFR/SRC/PI3K and NF-κB/MAPK pathways in macrophages, significantly reducing cell death and inflammation in RAW264.7 cells.Conclusion: Indirubin, the primary bioactive metabolite of Isatidis Folium, exerts protective effects against sepsis by targeting the EGFR/SRC/PI3K and NF-κB/MAPK signaling pathways in macrophages. These findings provide a mechanistic basis for the development of Indirubin as a multi-target therapeutic agent for sepsis treatment.
研究领域:
药理学
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免疫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Li Peng,Bai Chujie,Zhan Lingmin,Zhang Haoran,Zhang Yuanyuan,Zhang Wuxia,Wang Yingdong,Zhao Jinzhong
Identification of the biological targets of a compound is of paramount importance for the exploration of the mechanism of action of drugs and for the development of novel drugs. A concept of the Connectivity Map (CMap) was previously proposed to connect genes, drugs, and disease states based on the common gene-expression signatures. For a new query compound, the CMap-based method can infer its potential targets by searching similar drugs with known targets (reference drugs) and measuring the similarities into their specific transcriptional responses between the query compound and those reference drugs. However, the available methods are often inefficient due to the requirement of the reference drugs as a medium to link the query agent and targets. Here, we developed a general procedure to extract target-induced consensus gene modules from the transcriptional profiles induced by the treatment of perturbagens of a target. A specific transcriptional gene module pair (GMP) was automatically identified for each target and could be used as a direct target signature. Based on the GMPs, we built the target network and identified some target gene clusters with similar biological mechanisms. Moreover, a gene module pair-based target identification (GMPTI) approach was proposed to predict novel compound–target interactions. Using this method, we have discovered novel inhibitors for three PI3K pathway proteins PI3Kα/β/δ, including PU-H71, alvespimycin, reversine, astemizole, raloxifene HCl, and tamoxifen.
研究领域:
生物信息学
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药物研发
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系统生物学
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产品关联
DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL DESIGN
·
2023
·
IF 3.1
Chen Chao,An Na,Pang Defeng,Cheng Yuanyuan,Chen Yingjie,Feng Xuefei,Lei Haoqi,He Wenqian,Yang Baofeng,Zhang Yan,Zhao Xin
Background: Colorectal cancer (CRC) is the most common type of gastrointestinal tumor, but the
available pharmacological treatment is insufficient. As a traditional Chinese medicine, the green walnut husks
(QLY) exhibit anti-inflammatory, analgesic, anti-bacterial and anti-tumor effects. However, the effects and
molecular mechanisms of QLY extracts on CRC were not yet made known.
Objective: This study aims to provide efficient and low toxicity drugs for the treatment of CRC. The purpose of
this study is to explore the anti-CRC effect and mechanism of QLY, providing preliminary data support for clinical
research of QLY.
Methods: Western blotting, Flow cytometry, immunofluorescence, Transwell, MTT, Cell proliferation assay,
and xenograft model were used to perform the research.
Results: In this study, the potential of QLY to inhibit the proliferation, migration invasion and induce apoptosis
of the mouse colorectal cancer cell line CT26 in vitro was identified. The xenograft tumor model of CRC noted
that QLY suppressed tumor growth without sacrificing body weight in mice. In addition, QLY-induced apoptosis
in tumor cells through NLRC3/PI3K/AKT signaling pathway was revealed.
Conclusion: QLY regulates the levels of mTOR, Bcl-2 and Bax by affecting the NLRC3/PI3K/AKT pathway
to promote apoptosis of tumor cells, suppressing cell proliferation, invasion and migration, and subsequently
preventing the progression of colon cancer.
研究领域:
肿瘤学
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药理学
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中医药
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 4
·期 2
·273-281
·
IF 4.726
Lei Wang,Weimin Wu,Jingshuai Wang,Jianjun Wang,Xiaowen Tong,Qiaoling Hu,Lifeng Qi
Malignant bowel obstruction (MBO) is a serious complication which causes high death rate and low quality of life (QOL) for patients diagnosed at an advanced stage of ovarian cancer. RNA interference (RNAi) could be a promising method for the treatment of ovarian cancer and could decrease the morbidity of MBO. Gab2 gene is overexpressed in ovarian cancer compared with normal ovarian tissue, and regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells. Here, chitosan–polyethyleneimine (PEI, Mw 1800) copolymer nanoparticles were synthesized as nanocarriers to deliver Gab2 siRNA into SKOV3 cells. The silencing effects against the Gab2 gene and the antitumor effects by the chitosan–PEI–Gab2 siRNA nanoparticles (chitosan–PEI–Gab2 NPs) were studied. Results showed that highly efficient silencing effects against Gab2 expression and its downstream effector, AKT protein, at more than 90% deregulation were obtained by chitosan–PEI NP mediated Gab2 siRNA delivery, so as to exhibit obvious antitumor effects against SKOV3 cells with low cytotoxicity, and induce cell apoptosis in early and late stages. The study will provide novel strategies to overcome MBO in ovarian cancer by the efficient knockdown of Gab2 expression.
研究领域:
肿瘤学
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Yuxiao Wang,Guichun Wang,Jiaxin Li,Maomao Tang,Baoqing Jia,Zixuan Shu,Yang Ding,Chengjun Peng,Shuangying Gui,Jian Guo
Periodontitis is a chronic inflammatory disease caused by pathogenic biofilms and over-activated host immune response, leading to sustained damage to periodontal supporting tissue and even tooth loss. A key therapeutic challenge in recurrence of periodontitis is persistent existence of infiltrating monocytes and macrophages in periodontal tissues. Particularly, C-C motif ligand 2 (CCL2) is vital for monocyte recruitment and macrophage polarization in periodontitis. In this study, we developed biomimetic caffeic acid phenethyl ester-loaded nanoparticles (M−CNPs) as nanodecoys by macrophage membrane encapsulation to block CCL2-mediated inflammatory response and tissue damage. M−CNPs were distributed in the thermosensitive gel matrix (M−CNPs@Gel) to improve the retention time and sustained-release in the periodontal pocket. Our study demonstrated that M−CNPs@Gel exhibited a significant nanodecoy effect by competitively binding to CCL2 in periodontium, which inhibited monocyte/macrophages recruitment. Additionally, biomimetic nanodecoy system could reprogram macrophages phenotype through multi-step blocking CCL-CCR2-PI3K pathway and ROS elimination . M−CNPs@Gel effectively reduced the infiltration of monocytes and macrophages, and promote alveolar bone regeneration by regulating the ratio of M1/M2 macrophages in vivo . This study develops a novel CCL2-scavenging biomimetic nanodecoy hydrogel that remodel monocytes recruitment and macrophages polarization for effective periodontitis treatment.
研究领域:
牙科学
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药学
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生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
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