JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
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高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 32
·79423-79436
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IF 5.8
Zhang Jingni,Wang Hongjuan,Chen Huan,Liu Yong,Wang An,Hou Hongwei,Hu Qingyuan
Long-term use of alcohol and cigarettes is associated with millions of deaths each year, directly or indirectly. The carcinogen acetaldehyde is both a metabolite of alcohol and the most abundant carbonyl compound in cigarette smoke, and co-exposure of them is usual and primarily leads to liver and lung injury, respectively. However, few studies have explored the synchronic risk of acetaldehyde on the liver and lung. Here, we investigated the toxic effects and related mechanisms of acetaldehyde based on normal hepatocytes and lung cells. The results showed that acetaldehyde caused significant dose-dependent increases of cytotoxicity, ROS level, DNA adduct level, DNA single/double-strand breakage, and chromosomal damage in BEAS-2B cells and HHSteCs, with similar effects at the same doses. The gene and protein expression and phosphorylation of p38MAPK, ERK, PI3K, and AKT, key proteins of MAPK/ERK and PI3K/AKT pathways regulating cell survival and tumorigenesis, were significantly upregulated on BEAS-2B cells, while only protein expression and phosphorylation of ERK were upregulated significantly, the other three decreased in HHSteCs. When either the inhibitor of the four key proteins was co-treated with acetaldehyde, cell viabilities were almost unchanged in BEAS-2B cells and HHSteCs. Thus, acetaldehyde could synchronically induce similar toxic effects in BEAS-2B cells and HHSteCs, and MAPK/ERK and PI3K/AKT pathways seem to be involved in different regulatory mechanisms.
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高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4815
·
IF 3.267
Minmin Sun,Yaoting Ji,Zhen Li,Rourong Chen,Shuhui Zhou,Chang Liu,Minquan Du
Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 onPorphyromonas gingivalisLPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 amelioratedPorphyromonas gingivalisLPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.Keywords:anti-inflammatory agents;chronic periodontitis;ginsenoside;lipopolysaccharides
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Frontiers in Pharmacology
·
2020
·
IF 4.225
Li Shaoguang,Wang Xuewen,Wang Gang,Shi Peiying,Lin Shilan,Xu Dafen,Chen Bing,Liu Ailin,Huang Liying,Lin Xinhua,Yao Hong
Colorectal cancer is one type of cancer with high incidence rate and high mortality worldwide. Thus, developing new chemotherapeutic drugs is important. The Selaginella doederleinii Hieron ethyl acetate (SDEA) extract showed good anti-colon cancer effect in vitro and in vivo, but its mechanism is unclear. This study aimed to further reveal the anti-colon cancer effect of SDEA and its possible mechanism. The effects on cell viability, apoptosis, autophagy, and cell cycle in colorectal cells (HT29 and HCT116) were studied using MTT assay, fluorescence microscopy, transmission electron microscopy, and flow cytometry. The mechanisms were further studied using cell transfection, Western blot, and real-time quantitative polymerase chain reaction assay. The effect of xenotransplantation in vivo was observed using immunohistochemistry. Results showed that SDEA inhibited cell proliferation and induced cell morphological changes, cell cycle arrest, autophagy, and apoptosis. It also induced loss of mitochondrial membrane potential, increased the autophagic flux, raised the ratio of Bax/Bcl-2, activated caspases, and inhibited PI3K-Akt-mTOR signaling pathways. Furthermore, SDEA inhibited the growth of xenograft tumors in a dose-dependent manner. Immunohistochemistry analysis confirmed the alteration of autophagy- and apoptosis-related proteins and immunohistochemical microvascular density in xenografts, which were consistent with the results in vitro. Therefore, SDEA is important for developing candidate drugs against colorectal cancers.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2020
·
IF 1.863
Yuanguo Xiong,Hao Lu,Hanlin Xu
Hepatic fibrosis (HF) is a common disease, with currently no available treatment. Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of α-SMA and collagen I were markedly downregulated. Galangin also inhibited the PI3K/Akt and Wnt/β-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.
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JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
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2021
·Vol. 26
·期 7
·793-808
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IF 3.358
Chen Jincan,Deng Yuanyuan,Wang Jie,Chen Suxiang,Peng Fa,He Xuerong,Liu Meijun,Luo Hui,Zhang Jingjing,Chen Lanmei
Abstract Two new cyclometalated Ru(II)-β-carboline complexes, [Ru(dmb) 2 (Cl-Ph-βC)](PF 6 ) (dmb = 4,4′-dimethyl-2,2′-bipyridine; Cl-Ph-βC = Cl-phenyl-9H-pyrido[3,4-b]indole; RuβC-3 ) and [Ru(bpy) 2 (Cl-Ph-βC)](PF 6 ) (bpy = 2,2′-bipyridine; RuβC-4 ) were synthesized and characterized. The Ru(II) complexes display high cytotoxicity against HeLa cells, the stabilized human cervical cancer cell, with IC 50 values of 3.2 ± 0.4 μM ( RuβC-3 ) and 4.1 ± 0.6 μM ( RuβC-4 ), which were considerably lower than that of non-cyclometalated Ru(II)-β-carboline complex [Ru(bpy) 2 (1-Py-βC)] (PF 6 ) 2 (61.2 ± 3.9 μM) by 19- and 15-folds, respectively. The mechanism studies indicated that both Ru(II) complexes could significantly inhibit HeLa cell migration and invasion, and effectively induce G0/G1 cell cycle arrest. The new Ru(II) complexes could also trigger apoptosis through activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP), and inducing cytochrome c release from mitochondria. Further research revealed that RuβC-3 could deactivate the ERK/Akt signaling pathway thus inhibiting HeLa cell invasion and migration, and inducing apoptosis. In addition, RuβC-3 -induced apoptosis in HeLa cells was closely associated with the increase of intracellular ROS levels, which may act as upstream factors to regulate ERK and Akt pathways. More importantly, RuβC-3 exhibited low toxicity on both normal BEAS-2B cells in vitro and zebrafish embryos in vivo. Consequently, the developed Ru(II) complexes have great potential on developing novel low-toxic anticancer drugs. Graphic Abstract
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JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yang Wang,Shi-Yang Shen,Lei Liu,Xiao-Dong Zhang,Dan-Yang Liu,Na Liu,Bing-Hua Liu,Lei Shen
Ethnopharmacological relevance The diterpenoids extracted from Euphorbia kansui S.L. Liou ex S.B.Ho, Euphorbia fischeriana Steud. have good antitumor effects. Jolkinolide B has anti-breast cancer effect, but it is unclear whether it has different therapeutic effects between luminal A subtype and luminal B subtype breast cancer. Aim of the study This study investigated the Jolkinolide B has different therapeutic, important targets and pathways effects between luminal A subtype and luminal B subtype breast cancer. Materials and methods We used bioinformatics to predict the biological process and molecular mechanism of Jolkinolide B in treating two types of breast cancer. Then, in vitro, cultured MCF-7 cells and BT-474 cells were divided into control group, PI3K inhibitor + control group, Jolkinolide B group and PI3K inhibitor + Jolkinolide B group. The CCK-8 assay, Flow cytometric analysis and Transwell cell migration assay was used to detect the cell proliferation, apoptosis, and migration in each group, respectively. ELISA was used to measure the content of Akt and phosphorylated Akt (p-Akt) in cell lysis buffer. Results Compared to luminal A breast cancer, Jolkinolide B had more targets, proliferation, migration processes and KEGG pathways when treating luminal B subtype breast cancer. Jolkinolide B significantly prolonged the survival time of luminal B subtype breast cancer patients. Compared to the control group, the cell proliferation absorbance value (A value) and migration number of the two kinds of breast cancer cells in the Jolkinolide B group were decreased ( P < 0.01, n = 6), and the number of apoptotic cells was increased ( P < 0.01, n = 6). Compared to the Jolkinolide B group, the A value and migration number of the two types of breast cancer cells were significantly decreased in the PI3K inhibitor + Jolkinolide B group ( P < 0.01, n = 6), and the number of apoptotic cells was significantly increased ( P < 0.01, n = 6). In addition, compared to MCF-7 cells, the A value and migration number of BT-474 cells stimulated with Jolkinolide B were significantly decreased ( P < 0.01, n = 6), and the number of apoptotic cells was significantly increased ( P < 0.01, n = 6). Akt and p-Akt protein levels in the two breast cancer cell lines in the Jolkinolide B group were all decreased ( P < 0.01, n = 6), especially in BT-474 cells stimulated by Jolkinolide B. Conclusion Jolkinolide B regulates the luminal A and luminal B subtypes of breast cancer through PI3K-Akt, EGFR and other pathways. Jolkinolide B has more significant therapeutic effect on luminal B subtype breast cancer. In vitro, experiments verified that Jolkinolide B significantly inhibited the proliferation and migration activity of BT-474 breast cancer cells by downregulating the PI3K-Akt pathway.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2017
·
IF 2.981
Zhongcheng Ke,Gang Wang,Lei Yang,Huihui Qiu,Hao Wu,Mei Du,Juan Chen,Jie Song,Xiaobin Jia,Liang Feng
Ethnopharmacological relevance Radix paeoniae rubra , also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis . It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown. This study was conducted to explore the protective and curative effects of CS-TG against isoproterenol (ISO)-induced myocardial ischemic injury in rats and investigate the underlying myocardial protective mechanisms. Materials and methods A rat model of ISO-induced myocardial ischemia was established to evaluate the protective effect of CS-TG in ameliorating heart injury. Myocardial ischemia was induced by administering ISO (40 mg/kg/d) subcutaneously for 2 days. Serum was collected and analyzed for the levels of different cardiac biomarkers, and heart tissues were isolated and prepared for ATP analysis, glycogen content determination, histopathology assay, and ultrastructure observation. The regulatory effects of CS-TG on myocardial apoptosis in rats were studied by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of cleaved caspase-3, Bax, and Bcl-2 were detected by western blotting . Furthermore, in vitro experiments were conducted to examine whether the CS-TG's cardioprotective effects were linked to the inhibition of apoptosis via activation of the phosphoinositide-3-kinase/serine-threonine kinase AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Results CS-TG (300 mg/kg/d) significantly decreased serum levels of creatine kinase and lactate dehydrogenase in ISO-induced myocardial ischemic rats. Analysis of ATP and glycogen contents, myocardial ultrastructure, and pathological examination showed that CS-TG (300 mg/kg/d) significantly improved energy metabolism and alleviated myocardial injury in vivo. In addition, the expression of p-AKT and p-mTOR in rats subjected to CS-TG significantly elevated, while the levels of caspase-3 and Bax/Bcl-2 dramatically reduced. Moreover, treatment with LY294002 , a PI3K inhibitor, abrogated CS-TG (200 μg/mL) induced down-regulation of cleaved caspase-3, Bax/Bcl-2 in the serum. Conclusions CS-TG protects the heart from ISO-induced myocardial ischemia, potentially by improving cardiac energy metabolism and inhibiting cardiomyocyte apoptosis via activation of the PI3K/AKT/mTOR signaling pathway. Thus, CS -TG might be a potential therapeutic candidate for the prevention and treatment of myocardial ischemia.
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Heliyon
·
2024
·
IF 3.4
Chunhua Liu,Yu He,Kun Zhou,Hong Wang,Meng Zhou,Jia Sun,Yuan Lu,Yong Huang,Yonglin Wang,Ting Liu,Yongjun Li
Background Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed "Mixture") containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2118
·
IF 4.9
Xiyue Wang,Miaoyunhuan Wang,Yuqing Dong,Shuqing Yu,Shanshan Zhang,Pinghua Sun,Lu Wang,Jibin Liu,Houwen Lin,Xinhui Pan,Xiaobin Li
Chenopodium albumL., as a folkloric herb, is traditionally used to treat poisonous insect bites, vitiligo, and other ailments. However, its impact on thrombosis remains unknown. In this study, we discovered that the ethanol extract ofC. albumexhibited a remarkable antithrombotic effect using a zebrafish thrombosis model for the first time. Activity evaluation showed that fraction CA-C could improve thrombus aggregation in the caudal vein, increase blood return in the heart, and alleviate the slowing of blood flow compared with those in the model group. Then, analysis by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass (UPLC-Q-TOF-MS) identified 58 constituents of CA-C, with most of them belonging to flavonoids, alkaloids, and steroidal saponin components. Moreover, using a comprehensive strategy of network pharmacological analysis, transcriptomic assay, and RT-qPCR validation, we found that CA-C could mediate the TLR’s signaling pathway and its downstream MAPKs and PI3K/AKT signaling pathways to exert an antithrombotic effect. This study broadens the clinical application of plantC. albumand provides new insight into the chemical profile, pharmacodynamics, and potential mechanisms of CA-C as candidate agents for treating thrombosis.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shaojie Zhang,Renjie Gao,Baocong Ding,Junhao Li,Tanggan Wang,Jiaheng Chen,Chong Li,Yukun Jiao,Lijun Song
Combining selenium nanoparticles (SeNPs) with bioactive polysaccharides is one of the effective ways to overcome the shortcomings of SeNPs and polysaccharide and obtain novel antitumor drug candidates. In this study, a heteropolysaccharide (MTP70) with moderate antihepatoma activity was isolated from the stems of Marsdenia tenacissima (Roxb.) Wight et Arn. To further improve the antihepatoma activity of MTP70 and the application of SeNPs, a novel stable nanoparticle (MTP-SeNP) was designed and fabricated. MTP-SeNPs (Se content of 8.25 %) were characterized as monodisperse spherical nanoparticles (50 nm) with MTP70 wrapped on the surface of the SeNPs by the formation of C O⋯Se bonds and possessed high stability and good dispersion in water for almost a month. In addition, MTP-SeNPs showed higher inhibitory effect compared with MTP70. MTP-SeNPs could effectively inhibit the proliferation, invasion, and metastasis of HePG2 cells by inducing apoptosis and arresting the cell cycle at the S phase, which were closely related to the activation of the Bax/Bcl-2/Caspases and p-21/Akt/Cyclin A2 signaling pathways. Our results provide a theoretical basis for further development and application of M. tenacissima polysaccharide, and show that MTP-SeNPs could be explored as a promising anti-hepatoma agent in the pharmaceutical and biomedical industries.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Jue Liu,Yue-Xuan Liu,Yu-Song Song,Chen-Kai Liu,Fei-Xue Yu,Gao Liu,Tian-Rui Xu,Jun Sang
Ethnopharmacological relevance Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz., known as “Chonglou” in traditional Chinese medicine, is clinically used in cancer therapy, with saponins identified as the key antitumor constituents. However, the therapeutic potential and mechanisms of the total saponins from P. polyphylla var. yunnanensis (PPT) against bladder cancer, particularly their ability to overcome chemoresistance, remain unexplored. Aim of the study This study aimed to investigate PPT's anti-bladder cancer effects and mechanisms, with a focus on its potential to overcome cisplatin resistance. Materials and methods We established a UPLC-DAD method for saponin profiling and developed an eco-friendly extraction protocol using hydroxypropyl- β -cyclodextrin-assisted extraction combined with macroporous resin purification to prepare PPT. Anti-cancer efficacy was assessed in bladder cancer cell lines, mouse/zebrafish xenograft models, and cisplatin-resistant models. Mechanistic investigations integrated network pharmacology, metabolomics, molecular docking, and experimental validations (siRNA silencing, western blotting, flow cytometry, molecular dynamics simulations, cellular thermal shift assay, and surface plasmon resonance). Results The hydroxypropyl- β -cyclodextrin-based extraction system enhanced PPT purity by 15-fold, with the purified fraction showing dose-dependent anti-bladder cancer activity in vitro and in vivo . Mechanistically, PPT exerted anti-proliferative, pro-apoptotic, anti-lipogenic, and chemosensitizing effects by inhibiting the growth factor receptor binding protein 2 (GRB2)-mediated Akt-SREBP1 signaling axis. Notably, polyphyllin VII, a key constituent of PPT, was identified as a novel GRB2 inhibitor, potently suppressing bladder cancer progression and overcoming cisplatin resistance. Conclusion This study demonstrates that targeting the GRB2-Akt-SREBP1 signaling axis is a promising strategy for bladder cancer therapy, further establishing PPT as a multicomponent phytomedicine and PPVII as a novel GRB2 inhibitor with high translational potential.
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危险品化学品经营许可证（带存储）