PHYTOMEDICINE
·
2026
·
IF 11.3
Qiaomei Zheng,Xia Zhang,Shaozhan Chen,Shaoyu Wang,Lihong Chen,Jinhua Wang
Purpose This study investigated indirubin's effects on ovarian cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), both in vitro and in vivo, while exploring its underlying mechanisms. Methods The anti-tumor activity of indirubin was evaluated using ovarian cancer cell lines (A2780, SKOV-3, OVCAR-3) through MTT, colony formation, wound healing, and Transwell assays. Patient-derived organoids and a nude mouse xenograft model were employed for further validation. Mechanistic studies integrated bioinformatics analysis (SymMap database and transcriptome sequencing) with experimental assessment of EMT markers and PI3K/AKT pathway activity, including the use of specific inhibitors (MK2206, SB 216763). Results Indirubin significantly suppressed ovarian cancer cell proliferation, colony formation, migration, and invasion, as well as inhibited patient-derived organoid growth. In a xenograft model, indirubin effectively attenuated tumor growth without inducing pathological changes in major organs. Through SymMap database and transcriptomic analyses, indirubin was shown to modulate multiple signaling pathways, particularly impairing cell adhesion. Mechanistically, indirubin downregulated AKT and GSK-3β phosphorylation in the PI3K/AKT pathway, and upregulated E-cadherin while suppressing Vimentin and N-cadherin, thereby inhibiting EMT. Notably, indirubin, the PI3K/AKT inhibitor MK2206, and the GSK-3β inhibitor SB216763 all exhibited strong antitumor efficacy in vivo. Conclusion Indirubin exerts broad anti-ovarian cancer effects by inhibiting proliferation, migration, invasion as well as EMT, with demonstrated efficacy in xenograft models and no observed organ toxicity. Its mechanistic overlap with PI3K/AKT inhibitors underscores its potential as a multitargeted therapeutic agent.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2026
·
IF 2.9
Zihan Zhou,Fanxing Zhou,Xudong Xing,Zuguo Zheng,Guangji Wang,Hua Yang
QGJZF reduces aortic plaque in AS mice with PCSK9 overexpression induced by HFD. • 16 blood-absorbed components and 23 metabolites identified from QGJZF in vivo . • Network pharmacology and omics reveal QGJZF modulates lipid metabolism via PI3K-AKT. • QGJZF suppresses macrophage foam cell formation. • QGJZF activates PI3K-AKT pathway and upregulates ABCA1 for cholesterol export. Objective Qigui Jiangzhi Formula (QGJZF) is a traditional Chinese medicine formulation developed based on the principles of regulating Qi, warming Yang, and resolving dampness. All of its herbs have historically been used to treat obesity, hypertension, and hyperlipidemia. However, its therapeutic mechanism in atherosclerosis (AS)-related cardiovascular disease remains unclear. This study aimed to investigate the anti-atherosclerotic activity and explain the mechanism of QGJZF. Methods PCSK9 overexpressing mice induced by high-fat diet were used to establish an in vivo model. Aortic pathology and inflammation were assessed via histology, immunofluorescence, and Enzyme-linked immunosorbent assay. Chemical characterisation was performed by LC-MS. Network pharmacology and multi-omics were combined to elucidate the mechanism of QGJZF, validated by molecular docking and surface plasmon resonance (SPR). An in vitro foam cell model using ox-LDL-induced RAW264.7 macrophages was analysed by qPCR and Western blot. Results QGJZF effectively reduced aortic lipid plaque deposition, ameliorated plaque pathology, and suppressed macrophage infiltration in AS mice. LC-MS identified 93 non-volatile components, including 16 blood-entering constituents and 23 metabolites. Network pharmacology and multi-omics analyses indicated QGJZF regulates lipid metabolism via the PI3K-AKT pathway. Molecular docking and SPR confirmed strong binding of five major blood-entering components to PI3K/AKT proteins. In vitro , QGJZF activates the PI3K-AKT pathway, upregulated ABCA1 expression, inhibited macrophage foam cell formation, and improved lipid metabolism. Conclusion QGJZF inhibits the formation of foam macrophages through the PI3K-AKT-ABCA1 signalling pathway, thereby improving AS. This provides a scientific foundation for the clinical application of QGJZF in AS-related cardiovascular disease. Download: Download high-res image (195KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
ALLERGOLOGY INTERNATIONAL
·
2025
·
IF 6.7
Maoxin Huang,Liping Dong,Yue He,Xinying Cai,Yun Lu,Jinlei Xu,Fengli Xiao
Background YTHDF1, a critical regulator of cellular processes, has attracted attention for its involvement in some inflammatory diseases. However, its specific association with atopic dermatitis (AD) remains unclear. The objective is to investigate the functional roles and underlying mechanisms of YTHDF1 in AD. Methods The expression of YTHDF1 was investigated by bioinformatics analysis and skin lesions of AD patients. The functional role and upstream and downstream regulatory mechanisms of YTHDF1 were examined through a series of in vitro and in vivo experiments. Adeno-associated virus (AAV)-mediated delivery of YTHDF1 in the AD mouse model was evaluated for its therapeutic potential. Results Bioinformatics analysis revealed that the YTHDF1 mRNA level in the skin lesions of AD was significantly higher than that in healthy people. YTHDF1 expression was significantly elevated in AD skin lesions, the DNCB-induced AD mouse model, and primary human keratinocytes and HaCaT cells stimulated with interleukin (IL)-4/IL-13, compared to controls. Both in vitro and in vivo experiments revealed that upregulation of YTHDF1 in AD exacerbated cell proliferation and inhibited keratinization by activating the PI3K/AKT pathway, which was modulated via the IL-4/IL-13/STAT3 axis. Moreover, topical application of AAV-YTHDF1 significantly improved AD-like lesions in the mouse model. Conclusions This study identifies YTHDF1 as a contributor to AD pathogenesis by influencing keratinocyte proliferation and differentiation. It also suggests that YTHDF1 could be a potential therapeutic target for AD treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2022
·Vol. 52
·期 1
·48-59
·
IF 1.18
Guomin Lv,Yan Chen,Zhengyue Cheng,Lixiang Lin,Huasong Shen
Objective Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation mayserve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 onosteoporosis. Methods Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expressiondata. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools(starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression,cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP)staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expressionof RNAs and proteins after transfection or during osteoblastic differentiation. Results circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experimentsrevealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblasticdifferentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 spongedmiR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescueassay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenicmarkers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTENto inhibit osteoblastic differentiation. Conclusion Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulationof Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8.2
Yi Chen,Zhaoyu Liu,Zesen Mai,Yongbing Zhou,Huiwen Wen,Gaowen Qu,Runhao Zeng,Jianfu Zhao,Dongmei Zhu,Yuxiong Lai,Xue Liang
Non-small cell lung cancer (NSCLC) remains a lethal malignancy due to therapy resistance and recurrence. Ferroptosis, a regulated form of cell death, is a promising strategy to overcome cancer drug resistance, yet its mechanisms remain incompletely defined. Here, we report that Immediate Early Response 3 (IER3) is significantly upregulated in NSCLC tumors and linked to advanced stage and poor prognosis. Using IER3-overexpressing and knockout models in A549 and H1299 cells, we found that IER3 promotes NSCLC cell proliferation, migration, and invasion by suppressing ferroptosis. Conversely, IER3 knockout induced ferroptosis and reduced malignancy—effects reversed by the ferroptosis inhibitor Fer-1. Mechanistically, IER3 sustained AKT phosphorylation to inactivate GSK3β, both blocking GSK3β-dependent proteasomal degradation of NRF2 and enhancing its nuclear translocation, which collectively led to the transactivation of downstream ferroptosis-suppressive gene programs. This program maintained glutathione homeostasis, sequestered labile iron, scavenged ROS, and ultimately inhibited lipid peroxidation to counter ferroptosis. Rescue assays confirmed NRF2 overexpression or AKT/GSK3β activation reversed IER3 knockout-induced ferroptosis and viability loss. Additionally, low-IER3 NSCLC tumors were more sensitive to clinical/preclinical agents targeting survival/stress pathways. Collectively, our findings establish IER3 as an NSCLC oncogenic driver—suppressing ferroptosis via AKT/GSK3β/NRF2 to sustain malignancy—highlighting its potential as a prognostic biomarker and therapeutic target for improved NSCLC outcomes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HUMAN GENETICS
·
2025
·
IF 2.5
Yin Bin,Li Mu-Jia,Sun Jia-Lin,You Yue,Zhang Si-Di,Wan Qian-Xue,Yao Mei-Lin,Yang Cheng-Wei,Sun Hua-Qin,Lin Zi-Yuan,Shi Bing,Jia Zhong-Lin
The biological interactions between genetic and environmental modifiers play critical roles in the etiology of non-syndromic orofacial cleft (NSOC), but it is rarely studied. This study selected 47 environmental related genes from the metabolic pathways of smoking, drinking, hypoxia, and vitamins (including vitamin A, vitamin B9 (folic acid), vitamin C (ascorbic acid), vitamin D, and vitamin E), and test their associations with NSOC and its subtypes. We found that a novel gene SLC23A2 , the vitamin C transporter gene is significantly associated with non-syndromic cleft palate only (NSCPO) ( p = 3.25E-07, OR = 8.45, 95%CI:3.73–19.17). SLC23A2 is expressed in the craniofacial region of zebrafish (24hpf to 120hpf), obvious craniofacial abnormalities appeared in zebrafish (48hpf) when knock down the slc23a2 ( slc23a2 -MO). Knock down SLC23A2 in human embryonic palatal mesenchymal cell line (HEPM) induced decreased intracellular ascorbic acid (AA), increased reactive oxygen species (ROS), inhibited cell proliferation and triggered apoptosis, activated the PI3K-AKT-mTOR signaling pathway and inhibited autophagy; ROS levels and apoptosis ratio significantly decreased when we supplemented AA to HEPM cells with high ROS levels induced by Sin-1 (an exogenous ROS mimic). Knocked down SLC23A2 in HEPM cells or zebrafish, they became more sensitive to Sin-1, and AA supplementation was ineffective. In conclusion, we identified a novel susceptibility gene SLC23A2 for NSCPO, it may function by decreasing AA level, increasing the ROS levels, inducing apoptosis, and inhibiting autophagy through the activation of the PI3K-AKT-mTOR pathway in etiology of cleft palate.
✓ 已验证
DOI
PubMed
高影响因子
LIVER INTERNATIONAL
·
2026
·Vol. 46
·期 6
·e70696
·
IF 6.2
Ling Liu,Jintao Zheng,Ye Wang,Chenao Yang,Yuqiang Shan,Changku Jia
Background & Aims Hepatic fibrosis (HF) is a key pathological process in the development of chronic liver disease, and the activation of hepatic stellate cells (HSCs) is its core driving factor. Although curcumin, as a natural polyphenolic compound, has therapeutic potential, its specific mechanism in HF is still unclear. Methods This study used the CCl4-induced mouse HF model and explored its mechanism through single-cell RNA sequencing (scRNA-seq) combined with in vitro and in vivo experimental systems. Results The results showed that curcumin attenuated liver injury and fibrosis levels in mice with HF in a dose-dependent way, alleviated liver pathological damage, improved liver function indicators, and inhibited the release of inflammatory factors. ScRNA-seq analysis revealed a significant reduction in the number of activated HSCs after curcumin treatment, and the key gene Crispld2 was identified through perturbation model prediction and pseudo-temporal analysis. Curcumin significantly downregulated the expression of Crispld2 and inhibited the activation of the PI3K/AKT signalling pathway. In the TGF—β—induced LX-2 cell activation model, curcumin inhibited HSC proliferation, promoted apoptosis, reduced fibrosis-related protein expression, and decreased inflammatory cytokine secretion by regulating Crispld2. Overexpression of Crispld2 reversed the anti-fibrotic effect of curcumin, while the PI3K/AKT pathway inhibitor LY294002 restored its therapeutic effect. Animal experiments further confirmed that curcumin improved HF by regulating the Crispld2/PI3K/AKT axis. Conclusions This study elucidates the molecular mechanism by which curcumin exerts anti-HF effects by inhibiting the activation of the PI3K/AKT pathway mediated by Crispld2, providing a new strategy for targeted therapy of Crispld2. Lay Summary This study investigated the ameliorative effects of curcumin, a natural compound, on hepatic injury and fibrosis in mouse models of liver fibrosis. The underlying mechanism involves the suppression of the key gene Crispld2, which subsequently blocks the aberrant activation of the PI3K/AKT signalling pathway, thereby inhibiting the activation of hepatic stellate cells and exerting hepatoprotective functions. These findings furnish novel scientific evidence supporting the therapeutic application of curcumin in patients with liver fibrosis and shed new light on the development of Crispld2-targeted pharmaceutical agents. Curcumin can alleviate liver injury and fibrosis in mice with hepatic fibrosis. The underlying mechanism is that curcumin blocks the PI3K/AKT signalling pathway by targeting and inhibiting Crispld2, thereby suppressing the activation of HSCs and ameliorating hepatic fibrosis.
✓ 已验证
DOI
PubMed
高影响因子
Biology-Basel
·
2025
·Vol. 14
·期 11
·1573
·
IF 3.5
Shize Zhang,Tian Cheng,Yuang Chen,Mengqin Wang,Guangji Wang,Jiye Aa
Based on emerging evidence linking vitamin homeostasis to inflammatory bowel disease, this study investigated the causal role and therapeutic potential of folate in ulcerative colitis. By employing Mendelian randomization and experimental models, we demonstrated that folate supplementation markedly attenuated colitis severity, suppressed inflammatory responses, and restored the structure and function of the epithelial barrier. Mechanistically, folate acts through inhibition of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis, leading to improved barrier integrity and reduced mucosal inflammation. These findings establish folate not only as a protective nutrient but also as a potential therapeutic agent, supporting its use in clinical nutritional strategies for ulcerative colitis management. Vitamin homeostasis plays a critical role in inflammatory bowel disease management, yet the protective mechanisms and clinical utility of specific vitamins remain incompletely characterized. Within this context, a two-sample Mendelian randomization analysis leveraging genetic instruments for measuring circulating vitamin levels identified folate as a protective factor against ulcerative colitis (UC). To validate these findings, a DSS-induced colitis model was established with serial serum folate measurements. Therapeutic folate supplements were subsequently administered, followed by a comprehensive evaluation of epithelial barrier modulation through in vivo and recombinant TNF-α/IFN-γ-induced in vitro models. This included assessment of junctional proteins, ultrastructural analysis by transmission electron microscopy, and functional quantification of barrier integrity using transepithelial electrical resistance with paracellular permeability assays in epithelial monolayers. Molecular mechanisms were investigated through RNA sequencing complemented by immunoblot validation of key pathway components. The results demonstrated decreased serum folate levels in DSS-induced colitis mice, whereas folate supplementation ameliorated disease severity and attenuated intestinal inflammation and histopathological damage. Crucially, folate restored epithelial barrier structural integrity and function both in vivo and in vitro. Mechanistically, folate mediated barrier restoration through suppression of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis. Collectively, the results of this study provide mechanistic insights that support the use of folate as an active therapeutic molecule in patients with UC.
研究领域:
免疫学
·
胃肠病学
·
营养科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 6
·774-781
·
IF 1.128
Su Fanfan,Guo Ming,Wang Jinhua
Using nanomaterials is a potential way to improve the accuracy and safety of chemotherapeutic drugs and avoid the toxic side effects caused by the non-selectivity of traditionally used chemotherapeutic agents. Vincristine is a commercial clinical chemotherapeutic drug with good anti-tumor
effects. However, the effects of vincristine decorated hybrid nanoparticles (VCR-HNPs) on human retinoblastoma cells have not been previously reported. In this study, we explored the impact of VCR-HNPs exposure on retinoblastoma cells and identified the corresponding mechanism involved in
their activity. Retinoblastoma WERI-Rb1 and Y-79 cell lines were treated with different concentrations of VCR-HNPs and effects on cell proliferation were analyzed using the CCK8 assay, while apoptosis was measured and analyzed by flow cytometry. To further analyze the outcome of apoptosis,
Western blot assay was used to evaluate the expression levels of proteins correlating with apoptosis. Proteins involved in the PI3K/Akt pathway were also analyzed by western blotting to identify whether this pathway was involved in the molecular response to VCR-HNPs exposure. Compared with
the control group, VCR-HNPs markedly inhibited cell proliferation and induced apoptosis, at concentrations greater than 20 mg/L. In addition, western blotting experiments confirmed that VCR-HNPs could downregulate the phosphorylation of proteins involved in the PI3K/Akt signaling pathway leading
to the inactivation of the signaling pathway. VCR-HNPs exerted tumor suppressor effects on human retinoblastoma via inhibition of the PI3K/Akt signaling pathway.
研究领域:
肿瘤学
·
纳米医学
·
分子生物学
✓ 已验证
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Jia-Mei Geng,Pei-Feng Zhu,Lu-Shuang Xu,Ji-Lai Liu,Zheng-Qing Yang,Zhu-Ya Yang,Qiong Jin,Lu Liu
The medicinal moss Rhodobryum giganteum is rich in polysaccharides, whose structural and biofunctional properties remain largely unexplored. In this study, a novel glucose-rich polysaccharide fraction (named RGP, 29.8 kDa) was isolated and characterized from R. giganteum . Structural analysis revealed a unique α -1,6-linked glucan backbone with C-2 acetylation, along with side chains composed of →4)- α - d -glucopyranosyl-(1 → and terminal α - d -glucopyranose units. RGP significantly promoted proliferation, phagocytosis, and cytokine (TNF- α , IL-6) secretion via the TLR4/PI3K-Akt/IκB α pathway in RAW264.7 cells. In immunosuppressed mice, RGP restored immune function, as shown by improved organ indices, elevated serum immunoglobulins (IgA, IgG, IgM), and alleviated splenic damage. Molecular docking revealed that RGP binds the hydrophobic pocket of the TLR4/PI3K-Akt/IκB α complex via its glucose chain, and dynamics simulations confirmed the stability of this interaction. These findings reveal the bioactivity of bryophyte polysaccharides and suggest RGP as a potential immunomodulatory agent.
✓ 已验证
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2023
·
IF 7
Zhenhua Liu,Mengke Wang,Lijun Meng,Yixiao Chen,Qiuyi Wang,Yan Zhang,Xuefeng Xi,Wenyi Kang
Patrinia scabiosaefolia , is used as wild vegetable in China for more than 2 000 years, with a variety of pharmacological activities, including anti-inflammatory, anti-tumor and hypoglycemic. Based on our ongoing research on chemical constituents and hypoglycemic activity of P. scabiosaefolia , 4 lignan compounds, (+)-isolariciresinol ( 1 ), 7 R ,7' R ,8 S ,8' S -(+)-neo-olivil-4- O - β - D -glucopyranoside ( 2 ), 4- O- methylcedrusin ( 3 ) and patrinian A ( 4 ), were isolated and identified. The hypoglycemic activity showed that compounds 2 and 3 could extremely significantly improve insulin resistance at 100 ( P < 0.001), 50 ( P < 0.001) and 25 µmol/L ( P < 0.01) in IR 3T3-L1 cells. While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100 µmol/L ( P < 0.01). Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS, PI-3K, p-AKT and glucose transporter 4 (GLUT4), and promoted the transcription of GLUT4 mRNA. Therefore, the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2022
·
IF 1.61
Wei-Wei Ye,Xiang-Ying Meng,Qian Zhao,Jian-Yang Chen,Cong Liu,Feng Chen,Yong Zhou,Yi Wang
Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）