Scientific Reports
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2024
·Vol. 14
·期 1
·1-13
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IF 3.8
Yao Fei,Yuan Qin,Yan Yichao,Liang Guoqiang,Zhou Liang,Xu Heng,Gao Shaomei,Zou Ting,Zhang Lurong
Yu-Ping-Feng-San (YPF) is a famous classical Chinese medicine formula known for its ability to boost immunity. YPF has been applied to enhance the immune status of tumor patients in clinical practice. However, there is still a lack of research on its immune regulatory effects and mechanisms in the tumor microenvironment. This study was designed to investigate the effects and mechanism of YPF on improving the immune suppression state of hepatocellular carcinoma (HCC) microenvironment. In an orthotopic mouse model of HCC, YPF improved the immune microenvironment of HCC immunosuppression, enhanced the maturation of dendritic cells (DCs), promoted the release of IL-12, and decreased the presence of JAK2, p-JAK2, STAT3, and p-STAT3 proteins in both tumor tissue and paracancerous tissues. YPF also could promote the maturation and reduce the activation of JAK2, p-JAK2, STAT3, and p-STAT3 proteins of mouse bone marrow-derived DCs induced by culture medium or tumor supernatant in vitro . Transient transfection of siRNA-STAT3 with DCs resulted in an increase in its maturation and its secretion of IL-12. On the whole, these combined effects of YPF served to ameliorate the HCC immune suppression microenvironment, which conducive to immune cells play the role of immune surveillance and killing liver cancer cells. The mechanisms of these combined effects were, at least in part, related to its inhibition of the activated JAK2-STAT3 signaling pathway in DCs within the HCC microenvironment.
研究领域:
肿瘤学
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免疫学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-24
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IF 12.6
Yu Yang,Kong Liang,Guo Rui-bo,Zhang Ya-ni,Li Shu-tong,Zhang Feng-yuan,Wang Xin,Liu Yang,Li Xiu-Ying,Li Xue-tao
Background The imbalance of macrophage polarization plays a pivotal role in the progression of rheumatoid arthritis (RA). Reprogramming macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is considered a promising therapeutic strategy. Methods To address this challenge, Panax notoginseng polysaccharides (PNP) with varying molecular weights were chemically conjugated with deoxycholic acid (DC) to obtain amphiphilic conjugates (PNP-DC), which self-assembled into micelles (PNP-Ms). After screening for optimal molecular weight, folic acid (FA) was introduced onto the micelle surface, and Polyphyllin I (PPI) was encapsulated to form FA-modified, PPI-loaded micelles (FA-PPI-Ms) with macrophage-targeting capability. Results FA-PPI-Ms showed enhanced cellular uptake via FA receptor–mediated endocytosis and effectively eliminated reactive oxygen species (ROS), reduced inflammatory cytokine production, and exhibited good biosafety. In vivo, FA-PPI-Ms significantly alleviated joint swelling and inflammation in RA rat models. Mechanistic studies based on RNA sequencing and experimental validation revealed that FA-PPI-Ms suppressed the JAK2/STAT3 signaling pathway, thereby promoting M2 macrophage polarization and restoring the M1/M2 balance. Conclusion This study presents a novel FA-PPI-Ms delivery system for targeted macrophages. By modulating polarization through inhibition of JAK2/STAT3 signaling, the system offers a promising therapeutic strategy for RA and potentially other inflammatory diseases.
研究领域:
药理学
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免疫学
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纳米医学
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分子生物学
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炎症性疾病
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药物递送系统
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PubMed
高影响因子
Natural Products and Bioprospecting
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2024
·Vol. 14
·期 1
·1-17
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IF 4.8
Yang Suqin,Huang Jingtao,Tan Wenjing,Xia Xiankun,Gan Dali,Ren Yalei,Su Hanwen,Xiang Meixian
Xiaoyankangjun tablet (XYKJP) is a traditional Chinese medicine formulation used to treat intestinal disorders in clinical practice. However, the specific therapeutic mechanism of action of XYKJP in colitis has not yet been elucidated. This study aimed to reveal the multifaceted mechanisms of action of XYKJP in treating colitis. The model established based on DSS-induced colitis in C57BL/6 mice was employed to estimate the effect of XYKJP on colitis, which was then followed by histological assessment, 16S rRNA sequencing, RT-qPCR, ELISA, and Western blot. XYKJP alleviated the symptoms of DSS-induced colitis mainly by reducing oxidative stress, inflammatory responses, and intestinal mucosal repair in colitis tissues. In addition, XYKJP regulated the intestinal flora by increasing the relative abundance of Akkermansia and Bifidobacterium and reducing the relative abundance of Coriobacteriaceae_UCG-002 . Mechanistically, XYKJP increased the content of short-chain fatty acids (SCFAs) in the feces, particularly propanoic acid and butyric acid, activated their specific receptor GPR43/41, furthermore activated the Nrf2/HO-1 pathway, and suppressed the JAK2/STAT3 pathway. XYKJP significantly alleviated the symptoms of experimental colitis and functioned synergistically by regulating the intestinal flora, increasing the production of SCFAs, and activating their specific receptors, thereby repressing oxidative stress and inflammation. Graphical Abstract
研究领域:
药理学
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免疫学
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微生物学
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胃肠病学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
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IF 4.18
Wen-Zhen Dang,Hui Li,Bing Jiang,Kutty Selva Nandakumar,Kai-Fei Liu,Li-Xin Liu,Xiao-Chen Yu,Hui-Jing Tan,Chun Zhou
Background Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis . However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear. Purpose The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/ lpr mice and its regulatory function on Tfh cells . Study design and methods MRL/ lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/ lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2–Stat3 signaling pathway . Results Upon oral administration , ART significantly prolonged the survival of MRL/ lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment , T-cell compartment in the spleen of MRL/ lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/ lpr mice. Conclusion ART showed therapeutic effects on lupus-prone MRL/ lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2–Stat3 signaling cascade.
研究领域:
免疫学
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药理学
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自身免疫疾病
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
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IF 4.5
Xiaoqiang Huang,Guohua Ru,Hengyun Tian,Pengbo Zhang,Hongchang Zhao,Shouren Zhang,Sijie Wang,An Jia,Wanli Zhao
Background Benign prostatic hyperplasia (BPH) significantly compromises patients' quality of life, has detrimental effects on both physical and mental well-being, and poses a substantial economic burden. Current pharmacological interventions primarily focus on symptom relief; nevertheless, their associated adverse effects are evident. Rape bee pollen and maca are both homologous food products, which are not only rich in nutrition, but also have many biological activities. There is no report on the combination of rape bee pollen and maca in benign prostatic hyperplasia therapy, and no report on the molecular mechanism. This study aims to systematically investigate the therapeutic efficacy and underlying molecular mechanisms of a chewable tablet formulation containing rape bee pollen and maca in the management of BPH. Methods First, the chewable tablets were prepared from rape bee pollen and maca, and the High Performance Liquid Chromatography (HPLC) fingerprint was established. During a 4-week period, rats were subjected to subcutaneous injections of testosterone propionate solution to establish a BPH model, while simultaneously receiving orally administered chewable tablets for BPH treatment via gavage. We assessed the body weight, prostate tissue index, serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) levels in rats. Prostate tissues were collected for histopathological analysis. The protein expression levels of IL-6, phosphorylated Janus kinase 2 ( p -JAK2), and phosphorylated signal transducer and activator of transcription 3 ( p -STAT3) were determined by Western blotting. Rat feces were collected aseptically for 16S rDNA gene sequencing to assess gut microbiota levels. Additionally, our research findings demonstrate that the combined application of rape pollen and maca exhibits superior therapeutic efficacy compared to the individual use of either rape pollen or maca alone. Results We prepared the rape bee pollen and maca chewable tablets, established the HPLC fingerprint map, and quantitatively analyzed four of these main components. We found that the rape bee pollen and maca chewable tablets significantly inhibited DHT, T, E2, E2/T ratio, IL-6, TNF-α, and IL-1β and reduced MDA levels and increased SOD, GSH levels. 16S rDNA gene sequencing revealed that the chewable tablet increased the abundance of the beneficial bacteria Faecalibacterium, Collinsella, Phascolarctobacterium, Kineothrix , and Lactobacillus , and decreased that of the pro-inflammatory bacterium Prevotella . Western blot indicated that the chewable tablet could significantly inhibit the IL-6, p -JAK2, and p -STAT3 protein expression levels. Conclusion We found that rape bee pollen and maca chewable tablets had a protective effect on rats with BPH, and also found that the combination of rape bee pollen and maca was better than separate application. The mechanism may be related to the gut microbiota and IL-6/JAK2/STAT3 signaling pathway.
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高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Chen Donglai,Zhang Fuquan,Wang Jinhui,He Hua,Duan Shanzhou,Zhu Rongying,Chen Chang,Yin Lichen,Chen Yongbing
Background: Erlotinib (ELTN)-based targeted therapy as first-line treatment for epidermal growth factor receptor (EGFR)-mutant lung cancers suffers from insufficient selectivity, side effects, and drug resistance, which poses critical challenges in the clinical setting. Acquired resistance of ELTN results in extremely poor prognoses of non-small cell lung cancer (NSCLC) patients, wherein activation of the JAK2/STAT3 signaling pathway has been proven to induce acquired ELTN resistance.Methods: In this study, we developed a nanoparticle (NP) delivery system based on Food and Drug Administration (FDA)-approved poly(ethylene glycol) (PEG)-poly(lactic acid) (PLA) for the co-delivery of ELTN and fedratinib (FDTN, a small-molecular, highly selective JAK2 inhibitor). Both ELTN and FDTN could be encapsulated into the PEG-PLA NPs via optimization of the encapsulation method. The effect of NPs on NSCLC cells was evaluated by MTT assay. Western blotting was performed to study the molecular mechanisms of NPs inhibiting the downstream pathways of EGFR in vitro. The histological analysis and protein expression in vivo were assessed by hematoxylin/eosin (H&E) staining and immunohistochemistry, respectively.Results: The drug cargoes exhibited great stability, and could be released more efficiently in the acidic tumorous condition. Mechanistic study showed that FDTN notably down-regulated the expression levels of proteins in the JAK2/STAT3 signaling pathway, including p-EGFR, p-JAK2, p-STAT3 and Survivin, therefore reversing the ELTN resistance. As a result, synergistic anti-cancer effect was achieved by PEG-PLA NPs encapsulating both ELTN and FDTN in ELTN-resistant NSCLC tumors both in vitro and in vivo, and lower systemic side effect was noted for the co-delivery NPs compared to free drugs.Conclusion: This study provides a promising approach to overcome the ELTN resistance in the treatment of NSCLC, and the use of FDA-approved materials with clinically applied/investigated chemical drugs may facilitate the translation of the current delivery system.
研究领域:
药学
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肿瘤学
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纳米技术
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Yan Chen,Ming Zhang,Zhifang Liu,Ning Zhang,Qingpeng Wang
Tumor microenvironment (TME) is a pivotal factor driving the tumor metastasis and leading to the failure of tumor therapy. Here, a series of ursodeoxycholic acid platinum(IV) conjugates with potency in remodeling the TME through suppressing JAK2/STAT3 signaling was developed. A candidate was screened out, which displayed potent antiproliferative and antimetastatic performance both in vitro and in vivo. It displayed superior pharmacokinetic properties compared to cisplatin. Serious DNA injury was induced, and then mitochondria-mediated apoptosis was initiated through the Bcl-2/Bax/Caspase3 pathway. The JAK2/STAT3 and TGF-β1 signaling pathways were remarkably inhibited, and pro-death autophagy was subsequently promoted. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
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IF 7.9
Yinhuang Gao,Ke Ma,Zhibo Zhu,Yan Zhang,Qiong Zhou,Jing Wang,Xiaowen Guo,Liuting Luo,Haitao Wang,Kang Peng,Menghua Liu
Background Vascular dementia (VaD) is one of the most common clinical syndromes of progressive neurocognitive dysfunction with uncertain mechanisms. Modified Erchen decoction (MECD), developed from “Erchen decoction (ECD)” recorded in “Taiping Huimin Heji Jufang”, showed a good effect in the treatment of VaD. However, its therapeutic mechanism is still unclear. Purpose This study aimed to elucidate the multi-target mechanisms of MECD against VaD in vivo and in vitro . Methods VaD model was established by two-vessel obstruction (2-VO) in Sprague-Dawley rats. Six groups, including the control, 2-VO operation, MECD treatment (2.5, 5.0 and 10.0 g kg −1 d −1 ), donepezil hydrochloride (positive control, 0.45 g kg −1 d −1 ) were designed in the whole experiment. After oral administration for 4 weeks, the effects of MECD were verified by behavioral experiments, histological observation, and biochemical index analysis. The chemical profiling of MECD was performed by UHPLC-Orbitrap Fusion-HRMS, and a "compound-target-pathway" multivariate network was constructed to validate and elucidate its pharmacological mechanisms. Results Compared with 2-VO group, MECD treatment significantly alleviated anxiety and improved spatial memory in VaD rats according to the open field test (OFT) and Y-maze test. A significant increase in neuron number was observed from hematoxylin and eosin (H&E) stained images in cornu ammonis 1 (CA1) of the hippocampal region after MECD treatment. On the one hand, MECD reduced the plasma levels of triglyceride (TG), low-density lipoprotein (LDL), malondialdehyde (MDA), and amyloid-beta 42 (Aβ42), and inhibited mRNA expression of interleukin-1 beta ( Il-1β ) and Il-6 in the hippocampus. On the other hand, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were significantly increased after treatment with MECD. Moreover, MECD reduced the mRNA expression and protein expression of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), and BCL2-associated X (BAX) in the brain of 2-VO rats. Furthermore, 71 compounds were identified from the extract of MECD. Among them, liquiritin and isochlorogenic acid C gave inhibiting effects on the mRNA expression of Jnk . In addition, liquiritin and hesperetin were conformed with the inhibition of Jak2 transcription level in vitro experiments. Conclusion MECD has demonstrated a significant amelioration effect on cognitive dysfunction in VaD rats via JAK2/STAT3 and JNK/BAX signaling pathways , which represents an innovative insight into the “activate blood and eliminate phlegm” theory.
研究领域:
药理学
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神经科学
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中医药
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分子生物学
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行为科学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 4
·2018
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IF 6.208
Yan Zhang,Pei Ma,Zhiguang Duan,Yannan Liu,Yu Mi,Daidi Fan
Lung adenocarcinoma (LAC) is a common lung cancer with a high malignancy that urgently needs to be treated with effective drugs. Ginsenoside Rh4 exhibits outstanding antitumor activities. However, few studies reported its effects on growth, metastasis and molecular mechanisms in LAC. Here, Rh4 is certified to show a strong anti-LAC efficiency in vitro and in vivo. Results of flow cytometry and Western blot are obtained to exhibited that Rh4 markedly restrained cellular proliferation and colony formation by arresting the cell cycle in the G1 phase. Results from a wound healing assay and transwell assays demonstrated that Rh4 is active in the antimigration and anti-invasion of LAC. The analysis of Western blot, immunofluorescence and RT-qPCR confirmed that Rh4 reverses the epithelial–mesenchymal transition (EMT) through upregulating the gene expression of E-cadherin and downregulating that of snail, N-cadherin and vimentin. In vivo results from immunohistochemistry show consistent trends with cellular studies. Furthermore, Rh4 suppresses the Janus kinases2/signal transducer and activator of the transcription3 (JAK2/STAT3) signaling pathway stimulated by TGF-β1. Silencing the STAT3 signal or co-treating with AG490 both enhanced the EMT attenuation caused by Rh4, which revealed that Rh4 suppressed EMT via inhibiting the JAK2/STAT3 signaling pathway. These findings explore the capacity and mechanism of Rh4 on the antimetastasis of LAC, providing evidence for Rh4 to LAC therapy.Keywords:ginsenoside Rh4;lung adenocarcinoma;metastasis;cell cycle;JAK/STAT signaling
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2026
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IF 4.5
Jing Chen,HongYinLong Cui,MingKui Zhao,XiaoHan Du,Wen Chen
Alpk1 overexpressed in microglia of SE models. • Knockdown of Alpk1 alleviated the symptoms in epileptic rats. • Knockdown of Alpk1 represses M1-microglial activation. • Effects of Alpk1 knockdown are via suppressing JAK2/STAT3 signaling. Background Epilepsy is a chronic brain disorder characterized by recurrent, highly synchronous abnormal neuronal discharges leading to cerebral dysfunction. This study investigates the role of alpha kinase 1 (ALPK1), a pattern recognition receptor, in epilepsy. Methods ALPK1 expression and distribution were analyzed using the GSE190452 dataset and a pilocarpine-induced rat model. An adeno-associated virus delivering Alpk1 shRNA was injected intra-hippocampally into model rats, followed by seizure monitoring. Pathological changes were assessed via hematoxylin and eosin and Nissl staining. Primary microglia and BV2 cells transfected with Alpk1 siRNA were stimulated with kainic acid. Immunofluorescence, quantitative real-time polymerase chain reaction, and Western blot were used to evaluate M1 microglial marker and pro-inflammatory cytokines. Gene Set Enrichment Analysis (GSEA) was performed to identify potential signaling associated with Alpk1 function. Results ALPK1 was widely distributed and highly expressed in epileptic microglia. Alpk1 knockdown alleviated seizure symptoms in rats, including hippocampal damage, Nissl body loss, reduced Racine scores, and decreased daily seizure frequency and duration. Both in vivo and in vitro , Alpk1 knockdown downregulated the M1 marker inducible nitric oxide synthase and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6). GSEA indicated Alpk1 activates Janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) signaling. Stat3 overexpression reversed the inhibitory effects of Alpk1 knockdown on M1 activation and inflammation. Conclusion ALPK1 is highly expressed in epileptic microglia. Silencing Alpk1 alleviates M1-microglial activation and inflammation in epilepsy by inhibiting the JAK2/STAT3 signaling.
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高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Fei Jia,Yu Liu,Xinyu Dou,Chuanchao Du,Tianli Mao,Xiaoguang Liu
Osteosarcoma (OS) is the most common malignancy of bone. Liensinine exerts antitumor effects on cancers of the colon, breast, and gallbladder. However, its antitumor activity in OS remains unclear. This study is aimed at investigating the efficacy of liensinine against OS and the underlying mechanism of action. Cell proliferation, apoptosis, and cycle arrest in OS were detected using the Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays, respectively. The production of reactive oxygen species (ROS), glutathione (GSH) and glutathione disulfide (GSSG) concentrations, and mitochondrial membrane potential (MMP) of OS cells were measured by flow cytometry, colorimetry, and JC-1 staining. The expressions of factors related to apoptosis, cell cycle, and activation of the JAK2/STAT3 pathway were determined by Western blotting. To examine the potential role of ROS, an antioxidant (N-acetyl cysteine, NAC) was used in combination with liensinine. In vivo, we generated a xenograft mouse model to assess its antitumor efficacy. Tissue level expressions of factors related to apoptosis and activation of the JAK2/STAT3 pathway were assessed by immunohistochemistry or Western blotting. Liensinine inhibited the proliferation and induced G0/G1 phase arrest and apoptosis of OS cells in a dose-dependent manner. Additionally, liensinine promoted intracellular ROS production, enhanced the GSSG/GSH ratio, and induced MMP loss and ROS-mediated suppression of the JAK2/STAT3 pathway. NAC significantly attenuated the liensinine-induced antitumor activities and activated the JAK2/STAT3 pathway. In vivo, liensinine effectively inhibited the OS growth and promoted apoptosis; however, it had no negative effect on the internal organs. In conclusion, liensinine-induced ROS production could suppress the activation of the JAK2/STAT3 pathway and inhibit the OS growth both in vivo and in vitro. Our findings provided a new rationale for subsequent academic and clinical research on OS treatment.
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Xiao Zhang,Zhekai Huang,Xuejun Hu,Yu Tang,Xiaofeng Zhong,Li Li,Liujing Ni,Fang Li,Haibing Hua,Fangshi Zhu
Ethnopharmacological relevance Wendan Decoction (WDD) is a classical prescription deeply rooted in traditional Chinese medicine (TCM), originally documented by Sun Simiao in Beiji Qianjin Yaofang during the Tang Dynasty. Traditionally, it has been used to treat disorders associated with phlegm-dampness accumulation and digestive dysfunction, reflecting the TCM principle of harmonizing the stomach and resolving dampness. Within the clinical practice at Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, WDD is employed for the treatment of chronic atrophic gastritis (CAG), continuing its long-standing application in gastrointestinal disorders. Despite its widespread traditional use and cultural significance, the active constituents and precise pharmacological mechanisms of WDD have not yet been fully elucidated. Purpose This study aimed to systematically investigate the material basis and therapeutic mechanisms of WDD in CAG treatment. Methods The bioactive constituents of WDD were first identified using high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS). To evaluate its therapeutic effects, we established both in vivo and in vitro models of chronic atrophic gastritis (CAG). For the in vivo studies, a rat CAG model was generated through a multi-factor compound induction approach, whereas in vitro cellular injury was induced using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). To elucidate the underlying mechanisms, we integrated network pharmacology to predict candidate targets and signaling pathways, followed by experimental verification via immunohistochemical staining and Western blot analysis. Results HPLC-Q-TOF-MS/MS profiling revealed 34 bioactive constituents in WDD, with naringin, neohesperidin, and narirutin identified as key components. In vivo investigations demonstrated that WDD administration markedly improved gastric histopathological alterations in CAG model rats, accompanied by increased serum levels of pepsinogen I (PG I) and pepsinogen II (PG II), along with reduced gastrin-17 (G-17) and interleukin-6 (IL-6) concentrations. In vitro studies further showed that WDD treatment inhibited cell proliferation, migration, and invasive potential in MNNG-transformed MC cells. Network pharmacology-based analysis predicted that the therapeutic efficacy of WDD against CAG was primarily mediated via the JAK/STAT signaling axis. Subsequent mechanistic validation confirmed that WDD significantly attenuated the phosphorylation of JAK2 and STAT3, suggesting its inhibitory effect on the JAK2/STAT3 pathway. Conclusion This study revealed that WDD exerted therapeutic effects on CAG through suppression of the JAK2/STAT3 pathway. Our findings elucidate the pharmacological mechanisms of WDD and provide a scientific basis for its traditional use in managing CAG, highlighting its potential as a therapeutic candidate worthy of further clinical investigation.
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高影响因子
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