Chinese Medicine
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2025
·Vol. 20
·期 1
·1-22
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IF 5.7
Li Xueyan,Ding Lu,Li Zirui,Cao Zhenghua,Li Min,Yin Kai,Song Siyu,Cao Liyuan,Xia Qinjing,Wang Zihan,Zhao Daqing,Tong Xiaolin,Li Xiangyan,Wang Zeyu
Background Asthma is a chronic inflammatory airway disease that remains inadequately controlled by existing conventional treatments. A traditional Chinese medicine (TCM) formula of Yangke powder (yǎng ké sǎn-YKS) has demonstrated potential in alleviating asthma symptoms and reducing its acute exacerbation. Despite clinical evidence supporting its benefit, there is still insufficient understanding of the active compounds in YKS and their underlying mechanisms, which limits its broader clinical application. Objective This study aims to identify the key active ingredients in YKS and explore their mechanisms, particularly through the PI3K/AKT/NF-κB pathways, to provide a scientific basis for its application in asthma treatment. Methods We employed UPLC-Q-Exactive Orbitrap-MS to analyze YKS constituents, identified key ingredients, and explored asthma treatment mechanisms through bioinformatics, network pharmacology, Mendelian randomization, and molecular docking. The asthma model was evaluated using ovalbumin (OVA) and pulmonary function tests, while pathological examination was conducted using hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson trichrome stains. Concentrations of IgE, IL-4, and IL-5 were measured by ELISA, and protein and mRNA expressions were confirmed via qPCR, immunohistochemistry, and Western blot analysis. Results A total of 174 compounds were identified in YKS by UPLC-MS, with 49 detected in the bloodstream, indicating their role as active ingredients. Bioinformatics analysis revealed 353 asthma-related targets and 972 potential targets for YKS. Key targets such as AKT1, TNF, and IL1B were validated by molecular docking. Our studies indicated that YKS modulates asthma primarily through the PI3K/Akt and NF-κB pathways, improving airway resistance, reducing inflammation, mucus production, and airway remodeling, and decreasing Th2 cytokines and IgE levels. Conclusion This investigation identifies Kaempferol, Norephedrine, Cynaroside, Genistein, and Rutin as critical active ingredients in YKS, impacting key biomarkers such as AKT1, TNF, and IL1B. These substances effectively modulate the PI3K/AKT/NF-κB pathway, enhancing the management of allergic asthma.
研究领域:
药理学
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免疫学
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呼吸病学
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DOI
PubMed
高影响因子
CELL CYCLE
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2022
·
IF 5.173
Tianjiao Lai,Haifeng Qiu,Lulu Si,Yu Zhen,Danxia Chu,Ruixia Guo
Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.
研究领域:
肿瘤学
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分子生物学
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基因组学
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癌症生物学
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PubMed
高影响因子
PHYTOMEDICINE
·
2024
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IF 6.7
Pingping Tuo,Risheng Zhao,Ning Li,Shuang Yan,Gege Yang,Chunmei Wang,Jinghui Sun,Haiming Sun,Mengyang Wang
Background Ang II induces hypertensive heart failure (HF) via hemodynamic and non-hemodynamic actions. Lycorine (LYC) is an alkaloid derived from Lycoris bulbs, and it possesses anti-cardiovascular disease-related activities. Herein, we explored the potential LYC-mediated regulation of Ang II-induced HF. Methods Over 4 weeks, we established a hypertensive HF mouse model by infusing Ang II into C57BL/6 mice using a micro-osmotic pump. For the final two weeks, mice were administered LYC via intraperitoneal injection. The LYC signaling network was then deduced using RNA sequencing. Results LYC administration strongly suppressed hypertrophy, myocardial fibrosis, and cardiac inflammation. As a result, it minimized heart dysfunction while causing no changes in blood pressure. The Nuclear Factor kappa B (NF-κB) network/phosphoinositol-3-kinase (PI3K)-protein kinase B (AKT) was found to be a major modulator of LYC-based cardioprotection using RNA sequencing study. We further confirmed that in cultured cardiomyocytes and mouse hearts, LYC reduced the inflammatory response and downregulated the Ang II-induced PI3K-AKT/NF-κB network. Moreover, PI3K-AKT or NF-κB axis depletion in cardiomyocytes completely abrogated the anti-inflammatory activities of LYC. Conclusion Herein, we demonstrated that LYC safeguarded hearts in Ang II -stimulated mice by suppressing the PI3K-AKT/NF-κB-induced inflammatory responses. Given the evidence mentioned above, LYC is a robust therapeutic agent for hypertensive HF.
研究领域:
心脏病学
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药理学
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分子生物学
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炎症研究
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2016
·Vol. 38
·期 6
·1871-1878
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IF 2.348
Xusheng Yuan,Junjun Chen,Min Dai
Paeonol (2'-hydroxy-4'-methoxyacetophenone) is an active component isolated from the root of Paeonia Suffruticosa Andrews. We previously found that paeonol inhibited vascular cell adhesion molecule-1 (VCAM‑1) expression, and thus may be useful for the prevention and treatment of rabbit atherosclerosis (AS); however, the underlying mechanisms are not yet well known. Recently, microRNAs (miRNAs or miRs) have been reported to play an important role in the pathogenesis of AS. In the present study, we examined the effects of paeonol on miRNA-126 (miR‑126) expression, and its ability to inhibit monocyte adhesion to oxidized low-density lipoprotein (ox-LDL)-injured vascular endothelial cells (VECs). VECs were isolated from the rat thoracic aorta and stimulated with ox-LDL (20 mg/l) in the presence of paeonol. We found that miR‑126 had a lower expression in the ox-LDL-injured VECs, and VCAM‑1 was identified as a target gene of miR‑126. Furthermore, paeonol promoted miR‑126 expression and suppressed VCAM‑1 expression at the mRNA and protein level. It also inhibited monocyte adhesion to ox-LDL-injured VECs through the promotion of miR‑126 expression. Furthermore, it was demonstrated that paeonol blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway by promoting miR-126 expression. Taken together, and to the best of our knowledge, the findings of this study provide the first evidence that paeonol promotes miR‑126 expression to inhibit monocyte adhesion to ox-LDL-injured VECs and block the activation of the PI3K/Akt/NF-κB signaling pathway. Our data suggest that miR‑126 plays a crucial role in vascular inflammation and may be an important therapeutic target in the treatment of AS with the use of paeonol.
研究领域:
药理学
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分子生物学
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心血管疾病
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PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Wenxiao Shi,Yu Feng,Jincheng Tang,Yichang Xu,Wang Wei,Lichen Zhang,Xinzhao Jiang,Zhouye Ding,Kun Xi,Liang Chen,Yong Gu
The innate immune response is crucial to the inflammation, but how neutrophils and macrophages act in bone repair and tissue engineering treatment strategies await clarification. In this study, we found N2 neutrophils release stronger “eat me” signals to induce macrophage phagocytosis which then polarize into the M2c anti-inflammatory phenotype. This is beneficial for bone repair. Guided by this biological mechanism, we filled a mesoporous bioactive glass scaffold (MBG) with HAMA hydrogel loaded with TGFβ1 adenovirus (Ad@H), constructing a genetically engineered composite scaffold (Ad@H/M). The scaffold not only has good hydrophilicity and biocompatibility, but also provides mechanical stress support for bone repair. Adenovirus infection quickly induces N2 neutrophils, upregulating NF-κB and MAPK signaling pathways through Toll-like receptor 4 (TLR4) to promote the inflammatory response and macrophage phagocytosis. Macrophages perform phagocytosis and polarize towards the M2 phenotype, mediating the inflammatory response by inhibiting the PI3K-AKT-NF-κB pathway, maintaining homeostasis of the osteogenic microenvironment. The role of Ad@H/M scaffold in regulating early inflammation and promoting long-term bone regeneration was further validated in vivo. In brief, this study focuses on the cascade of reactions between neutrophils and macrophage subtypes, and reports a composite scaffold that coordinates the innate immune response to promote bone repair. This article is protected by copyright. All rights reserved
研究领域:
生物医学工程
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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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DOI
PubMed
高影响因子
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