NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Duan Qiong,Li Ruochen,Wang Mingxiao,Cui Zhenting,Zhu Xia,Chen Fanghong,Han Feng,Ma Jianxin
Phillyrin (PHN), derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a kind of Chinese herbal medicine with the effect of clearing heat, and has been used in China for thousands of years in treating various tumors. However, the mechanism of its main components on non-small cell lung cancer (NSCLC) remains unclear. PHN is a distinct component extracted from Forsythia suspensa with promising anti-cancer activity against various tumor types. This study sought to elucidate the promising effects of PHN on NSCLC. Based on network pharmacology results, we identified potential PHN targets and pathways for NSCLC treatment. CCK-8 assay, wound healing assay, apoptosis assay, western blot, and in vivo experiments verified the inhibitory effect of PHN on NSCLC. Network pharmacology identified 160 potential PHN targets, 955 NSCLC-related targets, and 54 common targets, along with 132 pathways and 2 core genes. Biological experiments demonstrated that PHN significantly inhibited the growth and migration of A549 and LLC cells while promoting their apoptosis. Western blot analysis revealed down-regulation of AKT, HSP90AA1, and CDC37 expression, suggesting that PHN inhibits A549 and LLC cell proliferation by down-regulating the HSP90-AKT pathway. In vivo experiments confirmed that PHN significantly inhibited NSCLC growth with low toxicity. This study, using network pharmacology and biological experiments, verified the effectiveness of PHN against NSCLC through the HSP90-AKT pathway. These findings provide a foundation for further research and analysis.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Mashiti Sha,Huansong Li,Yangsui Liu,Cong Tang,Xue Bai,Yun Wang,Bo Yuan,Kairui Liu,Xiaoning Gao,Jun Yan,Silong Wei,Jin Chang,Jun Kang
Cancer immunotherapy has improved the survival rate of patients with malignant tumors. However, the response of solid tumors to immunotherapy is quite limited. Here, we report a pH-responsive nanocomposite for augmented sonodynamic-chemodynamic immunotherapy. This Mn-CaCO 3 -2,2′-azobis[2-(2-imidazolin-2-yl) propane]-dihydrochloride (AIPH) nanosystem, Lipo@MCA, was prepared through a simple two-step reaction. It released sonosensitizer AIPH and Ca 2+ within the acidic tumor microenvironment. AIPH generated alkyl free radicals under ultrasound irradiation, and Mn 2+ produces ·OH through Fenton-like reaction. The Ca 2+ induced calcium overload in tumor cells. This induced mitochondrial dysfunction and promoted tumor cell apoptosis. Lipo@MCA also inhibited the phosphorylation of Akt and PI3K. In vitro experiments indicated that the nanoparticle inhibited tumor cell invasion and migration, and induced tumor cell apoptosis. In vivo experiments demonstrated that Lipo@MCA inhibited tumor growth by promoting cytokine secretion, stimulating dendritic cell maturation, and enhancing T-cell differentiation. In summary, this study paves the way for synergistic inhibition of tumor cell metastasis and immunotherapy in solid tumors through PI3K signaling pathway inhibition.
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Marine Drugs
·
2025
·Vol. 23
·期 1
·22
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IF 5.4
Xia Zheng,Xiaofei Liu,Zhuo Wang,Rui Li,Qiaoli Zhao,Bingbing Song,Kit-Leong Cheong,Jianping Chen,Saiyi Zhong
Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na2SeO3) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor.
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Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-21
·
IF 6.1
Guo Qinglong,Wang Yi,Yu Liangchen,Guan Liao,Ji Xuefei,Li Xiaohui,Pang Gang,Ren Zhenhua,Ye Lei,Cheng Hongwei
Background Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice.Methods MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines.Results Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis.Conclusion sThis study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.
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NanoImpact
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2025
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IF 5.5
Feng-Jie Shen,Wei-Nan Cao,Xue-Chun Han,Qiu-Yue Pan,Yuan Wang,Rong Zhang,Gang Wei,Jin-Kui Yang
Microplastics (MPs) are environmental pollutants with potential health risks. This study examined the effect of MPs on wound healing in both diabetic and non-diabetic mice. MPs exposure significantly delayed wound healing, particularly in diabetic mice, with reduced epidermal thickness and impaired collagen deposition. Mechanistically, MPs suppressed cell proliferation, angiogenesis, and increased apoptosis. Transcriptomic analysis identified dysregulation of critical wound healing pathways, especially those involved in inflammation, extracellular matrix remodeling, and lipid metabolism. Notably, the PI3K/AKT signaling pathway was inhibited. In vitro experiments using human dermal fibroblasts confirmed that MPs disrupted the PI3K/AKT pathway, reducing cell proliferation and migration. Further investigation revealed that MPs suppressed N -acetyltransferase 10 (NAT10) expression, leading to reduced ac4C-dependent stabilization of Fasn mRNA, which in turn diminished lipid synthesis and further inhibited the PI3K/AKT pathway. Our findings reveal a novel interaction between MPs and diabetes in impairing wound healing and suggest the NAT10-FASN-PI3K/AKT axis as a potential therapeutic target.
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RARE METALS
·
2025
·
IF 11
Zhu Yi-Bing,Zang Yu-Fan,Yu Jia-Nan,Li Cheng-Yu,Jia Shao-Sheng,Liang Yu-Han,Bai Ling-Chuang,Li Bin,Li Jing-An,Chen Lan
Superior vena cava syndrome (SVCS) caused by lung cancer accounts for 75% of patients with SVCS, which is one of the common complications of tumors. Interventional therapy is currently the most effective approach to relieve obstruction, but existing stents cannot inhibit or eliminate tumors, requiring postoperative radiotherapy and chemotherapy that may lead to secondary obstruction. Based on the characteristics of the tumor microenvironment and the interlayer ion replaceable properties of the layered material-montmorillonite (MMT), the composite coating (MMT/Em/PDA) of emodin (Em)-loaded MMT and dopamine was constructed on the magnesium alloy by liquid phase ion exchange technology and hydrothermal technology. The in vitro and in vivo results showed that the modified samples showed excellent corrosion resistance, the drug loading through adsorption and complexation with Zn 2+ between MMT layers, and the drug-loaded samples possessed good pH and near-infrared response-controlled release drug performances. The MMT/Em/PDA sample exhibited an excellent photothermal conversion performance. Photothermal (PTT) synergistic drug therapy of samples could significantly promote the production of ROS in lung cancer cells damage mitochondria, and further inhibit cell adhesion, proliferation, and invasion by down-regulating PI3K-AKT and EMT signaling pathways, thereby causing tumor cell death. Furthermore, the multimodal therapies of samples promoted the repolarization of tumor-associated macrophages into the M1 phenotype to re-activate tumor immunity through activating the AKT-NF-κB signaling pathway. In normal tissues, they can significantly promote the M2 phenotype polarization to promote vascular tissue repair by inhibiting the AKT-NF-κB signaling pathway. This work helps to provide a new insight into designing the modified magnesium alloy. Graphical abstract
研究领域:
生物材料
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纳米医学
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癌症治疗
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免疫治疗
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生物医学工程
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药理学
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材料科学
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Journal of Analytical Methods in Chemistry
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2025
·Vol. 2025
·期 1
·4646858
·
IF 2.2
Gui-Yu Li,Bai-Xue Li,Hong-Fei Song,Jie-Wen Gou,Li Wen,Quan-Sheng Feng
Background and Objectives: Liver fibrosis results from chronic inflammation. Qijia Rougan decoction, a traditional Chinese medicinal formulation, shows hepatoprotective potential, yet its mechanisms remain unclear. This study aims to investigate its antifibrotic effects and underlying mechanisms. Methods: Rat liver fibrosis was induced by carbon tetrachloride (CCl 4 ) and ethanol exposure. Histopathological assessment was performed using hematoxylin–eosin (HE) and Masson’s trichrome staining. Hepatic stellate cell (HSC) activation and autophagic processes were examined through western blot analysis, immunofluorescence staining, and other in vitro assays. Components of Qijia Rougan decoction were analyzed by BATMAN-TCM platform. The pharmacological network was constructed using BATMAN-TCM platform, while disease-related targets were identified through DisGeNET database. Pathway enrichment analysis was conducted using KEGG pathway database. Results: Significant reductions in hepatic index and serum biomarkers (ALT, AST, ALP, TBA, and γ-GT) were observed following Qijia Rougan decoction treatment, with maximal efficacy at 6 weeks. The decoction downregulated of LC3B and α-SMA expression in fibrotic tissues. In vitro, it suppressed LPS-induced α-SMA expression and autophagosome formation in HSC-T6 cells. Network pharmacology analysis of Qijia Rougan decoction identified 274 bioactive compounds and 12,883 potential targets, with pathway analysis indicating PI3K/AKT signaling as the predominant regulatory mechanism. Conclusion: Qijia Rougan decoction alleviates liver fibrosis, potentially by inhibiting HSC activation and autophagy processes via PI3K/AKT/mTOR pathway.
研究领域:
药理学
·
肝脏病学
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Heliyon
·
2023
·Vol. 9
·期 7
·e17393
·
IF 4
Kang Kai,Jiang Han-bing,Cheng Bing-lin,Zhang Shu-jun
Gastric cancer (GC) is a deadly malignant tumor with a high fatality rate and limited curative options. A growing body of research suggests that network pharmacology can replace traditional methods for determining the precise mechanism of action of medicinal substances in conditions such as cancer. The goal of this study was to clarify the biological mechanism of chelerythrine (CHE) and develop a prediction target for CHE against GC using network pharmacology. First, the genes related to GC were identified from the databases Genecards, Disgenet, Online Mendelian Inheritance in Man, Therapeutic Target Database, and Drugbank, and the targets of CHE were obtained from the SwissTargetPrediction database. Fifty linked targets were identified as anti -GC targets of CHE. Functional enrichment and pathway analyses revealed important biological mechanisms mediated by these targets. The core target PIK3CA of CHE anti -GC was obtained using the protein-protein interaction network, CytoHubba plug-in, and Human Protein Atlas. Molecular docking studies revealed that CHE has a strong affinity for PIK3CA (-10.5 kcal/mol). In addition, we used MTT, colony formation, wound-healing, Transwell®, and flow cytometry experiments to confirm that CHE inhibited the proliferation and migration of GC cells and induced cell cycle arrest and apoptosis. Finally, western blotting results showed that CHE downregulated the expression of the PIK3CA protein and inhibited the activation of the PI3K/AKT signaling pathway. Therefore, we concluded that CHE inhibited GC cell proliferation and migration and induced cell cycle arrest and apoptosis by targeting the PIK3CA protein to inhibit the PI3K/AKT pathway activity.
研究领域:
药理学
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肿瘤学
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分子生物学
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ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
·
2024
·
IF 1.9
Chunshan Wei,Zhulin Wu,Xiaoya Yang,Xiaoyan Jiang,Lianan Wang,Jinsong He,Guangdong Tong
Background: In China, traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese herb formulas with the effect of "yiqi jianpi jiedu huayu" (replenishing qi, strengthening spleen, and removing toxicity and blood stasis) are the common and efficient treatments for HCC. However, the mechanism of these formulas in treating HCC remain unclear. Objective: In this paper, our goal is to explore the potential mechanism of Phyllanthus urinaria L anti-neoplastic decoction (PAD), the representative formula of "yiqi jianpi jiedu huayu", in treating HCC. Design: The research team performed the network pharmacology and in vitro experiment (preparation of PAD aqueous extract, cell cultures and MTT assay, cell apoptosis assay, wound healing assay, transwell assays, western blot). Setting: The study took place in the Department of Hepatology, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), China. Outcome measures: The active components and targets of PAD and HCC targets were screened by five Chinese herbs and two disease databases respectively. The network pharmacology was utilized to construct the relationship network between PAD and HCC, and the mechanism was predicted by pathway enrichment analysis. The experiment was performed to verify the intervention effect of PAD on HCC and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. Results: The relationship network between PAD and HCC suggested that PAD mainly regulated the potential therapeutic targets of HCC by key active components such as quercetin, luteolin, calycosin, wogonin, and pinocembrin. Pathway analysis demonstrated PAD could play an anti-HCC effect via multiple pathways (e.g., PI3K/Akt). Results of the experiment showed that PAD could effectively inhibit the proliferation and migration of HCC cells, and promote HCC cells apoptosis in a concentration-dependent behavior. Additionally, PAD could decrease the protein expression of phosphorylated PI3K/Akt. Conclusion: PAD mainly exerts an anti-HCC effect through multiple active components represented by quercetin and multiple pathways represented by the PI3K/Akt pathway. This study provided an experimental basis for the clinical application of PAD.
研究领域:
肿瘤学
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中医药学
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分子生物学
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Current Computer-Aided Drug Design
·
2023
·Vol. 21
·期 1
·50-66
·
IF 1.7
Hongyi Liang,Guoliang Yin,Guangxi Shi,Xiaofei Liu,Zhiyong Liu,Jingwei Li
AimsBreast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC).ObjectivesTo analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC.Materials and MethodsNetwork pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC.ResultsAccording to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels.ConclusionThe study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.
研究领域:
肿瘤学
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网络药理学
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分子生物学
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TOXICOLOGY LETTERS
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2026
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IF 3.1
Lele Zhou,Lingbin Chen,Cailin Zheng,Jinneng Wu,Meihua Zhong,Zhixiong Huang,Zhiming Xin,Zhou Chen
Tripchlorolide, a low-toxicity derivative of the natural product triptolide, exhibits significant therapeutic potential for inflammatory and autoimmune diseases; however, its profile of male reproductive toxicity remains a major concern for clinical translation. To address this, we first established its median lethal dose at 33.13 mg/kg in mice to guide safe exposure levels. We then systematically evaluated its reproductive toxicity in male rats following 8-week intraperitoneal administration (2.5, 5, and 10 μg/kg/day). Our results demonstrated a clear dose-dependent toxicity, characterized by significant reductions in testicular and epididymal coefficients, impaired sperm count and motility, disrupted testosterone, follicle-stimulating hormone, and luteinizing hormone levels, and evident histopathological damage in the testes and epididymides. Encouragingly, these adverse effects showed signs of reversal after a 4-week recovery period, suggesting that the impairment is reversible. Through an integrated approach combining network pharmacology prediction and molecular docking, we identified the inhibition of the PI3K/Akt/mTOR signaling pathway as the pivotal molecular event. This mechanism was conclusively validated by our in vivo rescue experiment, where co-administration of the Akt activator SC79 markedly attenuated the tripchlorolide-induced reproductive impairments. Our study provides a comprehensive toxicological profile, defining the dose-response, reversibility, and mechanistic basis of tripchlorolide's male reproductive toxicity, thereby offering critical insights for its risk assessment and potential repurposing.
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International Journal of Nanomedicine
·
2026
·
IF 8.7
Mengqi Wang,Mengxuan Jia,Rongrong Zhang,Caixia Xue,Xue Ma,Mingjun Song,Gang Liu
Background: The theranostic potential of glycine-derived carbon dots (Gly/CDs) against arsenic-induced hepatotoxicity remains largely unexplored. This study aimed to synthesize Gly/CDs via a green, microwave-assisted method and to systematically evaluate their hepatoprotective efficacy and underlying mechanisms in a sodium arsenite (NaAsO2)-induced hepatic injury model.Methods: Gly/CDs were synthesized using citric acid, urea, and glycine as precursors. Their physicochemical properties were characterized using transmission electron microscopy (TEM), fluorescence spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Following in vivo biocompatibility assessment, a murine model of NaAsO2-induced hepatotoxicity was established to evaluate therapeutic efficacy. Comprehensive biochemical assays, histopathological examinations, and transcriptomic analyses were conducted to assess oxidative stress, inflammatory responses, DNA damage, apoptosis, fibrosis, and the involved molecular pathways.Results: Gly/CDs exhibited excellent biocompatibility and demonstrated significant hepatoprotective effects, including restoration of redox homeostasis, suppression of pro-inflammatory cytokines, and attenuation of hepatocellular DNA damage, apoptosis, and fibrotic remodeling. Transcriptomic profiling suggested the involvement of the PI3K/AKT signaling pathway as a key molecular axis associated with the observed therapeutic effects. Overall, Gly/CDs preserved hepatic structure and function under chronic arsenic exposure.Conclusion: This study provides the first comprehensive evidence that Gly/CDs function as biologically active nano-antioxidants capable of mitigating arsenic-induced hepatotoxicity through redox modulation and modulation of PI3K/AKT signaling activity. Given their low toxicity, ease of synthesis, and multifunctional properties, Gly/CDs represent a promising nanotherapeutic platform for applications in redox biology, toxicology, and environmental health.
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