ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE
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2024
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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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DOI
PubMed
高影响因子
Current Computer-Aided Drug Design
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2023
·Vol. 21
·期 1
·50-66
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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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DOI
高影响因子
MOLECULAR REPRODUCTION AND DEVELOPMENT
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2015
·Vol. 82
·期 4
·305-314
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IF 2.527
Wei-Rong Yang,Yong Wang,Yi Wang,Jiao-Jiao Zhang,Jia-Hua Zhang,Cheng Lu,Xian-Zhong Wang
SUMMARY Mammalian target of rapamycin (mTOR) is known to be involved in mammalian cell proliferation, while S-phase kinase-associated protein 2 (SKP2) plays a vital role in the cell cycle. Within the testis, estrogen also plays an important role in Sertoli cell proliferation, although it is not clear how. The present study asked if mTOR is involved in 17β-estradiol-dependent Sertoli cell proliferation. We specifically assessed if extracellular signal-regulated kinase 1/2 (ERK1/2) and/or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) exert convergent effects toward the activation of mTOR signaling, and if this signaling regulates the expression of SKP2 through retinoblastoma (RB) and early mitotic inhibitor 1 (EMI1) protein and on CCNE1 and CCND1 mRNA levels. Treatment with 17β-estradiol for 15–90 min activated mTOR, with mTOR phosphorylation peaking after 30 min. U0126 (5 μM), a specific inhibitor of (MEK1/2), and 10-DEBC (2 μM), a selective inhibitor of AKT, both significantly reduced 17β-estradiol-induced phosphorylation of mTOR. Rapamycin suppressed 17β-estradiol-induced Sertoli cell proliferation, appearing to act by reducing the abundance of SKP2 , CCND1 , and CCNE1 mRNA as well as RB and EMI1 protein. These data indicated that 17β-estradiol enhances Sertoli cell proliferation via mTOR activation, which involves both ERK1/2 and PI3K/AKT signaling. Activated mTOR subsequently increases SKP2 mRNA and protein expression by enhancing the expression of CCND1 and CCNE1 , and inhibits SKP2 protein degradation by increasing EMI1 abundance. Mol. Reprod. Dev. 82: 305–314, 2015. © 2015 Wiley Periodicals, Inc .
研究领域:
生殖生物学
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细胞信号传导
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内分泌学
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DOI
PubMed
高影响因子
Food & Function
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2025
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IF 5.4
Qi Gu,Litao Wang,Mingyue Xu,Wan-Mei Zhou,Guosheng Liu,Haiting Tian,Thomas Efferth,Chenlu Wang,Yujie Fu
Phloretin is a natural dihydrochalcone with a variety of biological activities. Its potential in modulating lipid metabolism in vitro and in vivo with HepG2 and C. elegans was investigated in this study. Phloretin significantly diminished lipid accumulation and ROS levels, mitigated the degree of lipid peroxidation, and ameliorated mitochondrial dysfunction in HepG2 cells. The expression levels of lipid synthesis genes (SREBP and FASN) were downregulated, while PI3K-AKT related genes (AKT, FOXO, MTOR) were upregulated. Furthermore, phloretin significantly alleviated the detrimental effects of lipid accumulation on growth indices and locomotor ability in C. elegans. It also reduced lipofuscin, ROS level as well as glucose and triglyceride contents, significantly affected amino acid and lipid metabolism pathways based on metabolomics profiles and analysis. Gene expression levels of sbp-1, mdt-15, fat-5, fat-6, and fat-7 were markedly down-regulated following treatment with phloretin, while daf-16, age-1 and skn-1were significantly up-regulated. Tests with mutant C. elegans strains of daf-16, age-1, sbp-1 and nhr-49 further confirmed that the phloretin-induced decrease in lipid accumulation was attributed to the inhibition of lipid biosynthesis pathway by IIS and sbp-1/SREBP. Our study indicated that phloretin exerted hypolipidemic effects in vitro and in vivo, providing a basic foundation for considering phloretin as a phytochemical candidate for regulating lipid metabolism and preventing hyperlipidemia.
研究领域:
代谢生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
HEREDITAS
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2025
·
IF 2.5
Qing Zhang,Song He,Zhonghao Ji,Xiwen Zhang,Bao Yuan,Ruirui Liu,Yimin Yang,Yu Ding
Skin cutaneous melanoma (SKCM) arises from melanocytes and is an aggressive form of skin cancer. If left untreated, most melanomas will metastasize, posing a major health risk. GADD45B, a member of the GADD45 family, is known to be involved in DNA damage repair; however, its specific role in SKCM remains largely unclear. In this study, we comprehensively investigated the function of GADD45B in SKCM. By integrating 26 SKCM-related datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), cBioPortal for Cancer Genomics (cBioPortal), Gene Expression Omnibus (GEO), and other databases, we conducted functional enrichment, immune infiltration, and single-cell analyses using R. Additionally, transcriptome sequencing of 30 human SKCM cell lines, phenotype characterization of 29 SKCM lines in vitro, and macrophage polarization analysis were performed. We found that GADD45B expression was significantly downregulated in SKCM patients compared to normal controls ( p < 0.001), and higher GADD45B levels correlated with better prognosis ( p < 0.05). GADD45B also showed high diagnostic accuracy, with an area under the curve (AUC) of 0.986. GO and KEGG analyses revealed a strong association between GADD45B and immune-related pathways. Gene Set Variation Analysis (GSVA) and single-cell sequencing suggested that GADD45B may serve as a novel immune checkpoint, predominantly expressed in macrophages and promoting M1 polarization. In vitro, overexpression of GADD45B significantly inhibited SKCM cell proliferation, potentially via suppression of the PI3K/Akt signaling pathway, and also reduced chemotherapy resistance. Furthermore, in vivo experiments using a xenograft mouse model demonstrated that GADD45B overexpression significantly suppressed tumor growth. Mice injected with GADD45B-overexpressing tumor cells exhibited smaller tumor volumes from day 15 onwards compared to controls, with markedly reduced tumor volume and weight at the endpoint. These results underscore the potential of GADD45B as an effective tumor suppressor in SKCM. In conclusion, our findings highlight GADD45B as a key regulator in SKCM progression, capable of restraining tumor cell proliferation and enhancing apoptosis. GADD45B holds promise as a novel diagnostic and prognostic biomarker and a potential target for SKCM immunotherapy.
研究领域:
肿瘤学
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生物信息学
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免疫学
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DOI
PubMed
高影响因子
LIFE SCIENCES
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2025
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IF 5.1
Fangdi Wang,Li Hu,Xingyue Zeng,Wenbin You,Huijun Li,Bing Liu,Xiaohan Zhang
AKT is a pivotal kinase involved in diverse cellular processes, including tumorigenesis and glycogen metabolism. Ubiquitination modification of AKT has been reported as a critical cellular event that regulates its kinase activity and membrane translocation; however, the molecular mechanisms involved in AKT ubiquitination remain elusive. Here, we employed loss-of-function approaches and mutants of PDK1 with altered phosphorylation and modified nucleocytoplasmic shuttling behaviors to identify the functional roles of PDK1 on the ubiquitination of AKT. Our findings reveal that the nuclear entry of PDK1 in an importin7-dependent manner is required for insulin-induced TRAF6-mediated ubiquitination of AKT, which has been previously shown to occur in the nucleus. Moreover, the phosphorylation of PDK1 at S241 and the PI3K-mediated phosphorylation of PDK1 at S396 both regulate AKT ubiquitination by controlling nuclear entry of PDK1. These results provide new insights into the control of AKT signaling and suggest potential avenues for developing targeted AKT-modulating therapeutics.
研究领域:
分子生物学
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细胞信号传导
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生物化学
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内分泌学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
ChemistryOpen
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2024
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IF 2.5
Wei Gao,Xiaoju Hua,Shengliang Liao,Zhikai Xiahou,Haikuan Yang,Lifang Hu,Yunyang Chi
Graphical Compound 3h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells.The results show that 3h induces cell-cycle arrest in the S phase. Additionally, 3h exerts a strong pro-apoptotic effect. Specifically, compound 3h reduces the phosphorylation of PI3K, AKT, and ERK, thereby inhibiting both the MAPK/ERK and PI3K/AKT signaling pathways. 2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N -arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC 50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell-cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real-time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti-apoptotic protein BCL2 was inhibited in a dose-dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h . Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti-cancer drug in the future.
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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DOI
PubMed
高影响因子
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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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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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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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Songtao Zheng,Yefei He,Xiaoying Cui,Xinran Xu,Ruonan Tang,Shuhui Liu,Wenkai Xie,Wenhui Yu,Xiaowen Jiang
Melatonin (MT), a neurohormone secreted by the mammalian pineal gland, has been demonstrated to exert hepatoprotective effects. In this study, we employed exogenous MT intervention in both in vivo and in vitro models of chronic liver injury induced by D-galactose (D-gal) in mice to investigate the specific mechanisms underlying its hepatoprotective action, aiming to provide a reference for the prevention of liver injury by MT. Preliminary network toxicology and network pharmacology analyses revealed that D-gal possesses potential hepatotoxicity, whereas MT exerts hepatoprotective effects through modulating oxidative damage and inflammation. Further analysis indicated that the targets of MT and D-gal are highly enriched in the PI3K/AKT signaling pathway. We therefore examined the PI3K/AKT pathway and downstream proteins associated with NLRP3 inflammasome activation. Our results demonstrated that exogenous MT improves hepatic physiological function and alleviates liver injury by activating the PI3K/AKT signaling pathway, which in turn inhibits NLRP3 inflammasome activation. Download: Download high-res image (273KB) Download: Download full-size image
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DOI
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
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2026
·Vol. 48
·期 5
·510
·
IF 4.1
Guliziremu Ainiwaer,Xiaoxuan Zhang,Mukatansi Tayier,Xin Luo
Background: The development of Slow Transit Constipation (STC) is associated with intestinal barrier damage.Coreopsis tinctoriaNutt. (CT) is effective in treating STC, but the mechanisms are unclear.Methods: We investigated three CT extracts—traditional aqueous extract, and an aqueous extract from supercritical fluid extraction, with or without lipophilic components—on intestinal transit in a loperamide-induced STC rat model. The potential therapeutic targets of CT for STC were initially predicted using an integrated approach of network pharmacology and molecular docking. The therapeutic effect of CT was evaluated in a STC rat model by assessing defecation parameters (fecal count, water content, intestinal transit), colon histology (H&E and AB-PAS staining), inflammatory markers (ELISA), and target protein expression (Western blotting and immunohistochemistry). In parallel, an LPS-induced IEC-6 cell injury model was used to investigate intestinal barrier protection, analyzing cell viability (CCK-8), apoptosis (flow cytometry and Western blotting), migration (scratch assay), and protein expression (Western blotting).Results: Docking and enrichment analysis highlighted hub targets (TNF, AKT1, Caspase3, STAT3, and BCL-2) and the PI3K/AKT pathway. In vivo, CT treatment improved defecation function, reduced colonic damage, and decreased markers of inflammation and apoptosis in STC rats. It also up-regulated ZO-1 and Occludin, lowered serum markers of intestinal permeability D-lactate (D-LA) and Diamine oxidase (DAO), and restored intestinal barrier function. Furthermore, CT reduced Caspase3 expression and increased the expression of proteins such as BCL-2, PI3K, and P-AKT/AKT. These findings were further supported by in vitro experiments.Conclusions: CT improves STC and its associated intestinal barrier damage by activating the PI3K/AKT pathway and suppressing inflammation and apoptosis, among which the aqueous extract from supercritical fluid extraction combined with the lipophilic fraction exhibits the best efficacy.
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2026
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IF 5.4
ZeYue Xu,ZhuangYin Qu,Xia Wu
Hyperglycemia can lead to excessive production of reactive oxygen species (ROS), contributing to diabetes and its complications, such as diabetic cardiomyopathy (DCM). This study aims to elucidate the protective mechanisms of Curcumin (CUR) against hyperglycemia-induced cardiomyocyte injury. We constructed a high-glucose (HG) model using primary cardiomyocytes and determined the optimal concentration of CUR by assessing cell viability with the CCK-8 assay. Enzyme-linked assays were used to measure the activities of HO-1, T-SOD, and GSH-Px, investigating the antioxidant effects of the Nrf2 signaling pathway. Flow cytometry was employed to measure apoptosis and mitochondrial membrane potential (ΔΨm). Mitochondria were isolated from cardiomyocytes to examine cytosolic and mitochondrial cytochrome c (cytc) expression. Western blotting was used to analyze the expression levels of Nrf2, PI3K, AKT, Keap1, HO-1, Bcl-2, and Bax proteins. Our findings suggest that CUR enhanced the viability and antioxidant enzyme activity of primary cardiomyocytes under HG conditions, stabilized ΔΨm, reduced ROS production, and decreased apoptosis. Moreover, CUR alleviated HG-induced cardiomyocyte damage by upregulating Nrf2, PI3K, AKT, HO-1, and Bcl-2 expression, while downregulating Bax. These findings demonstrate that the protective effect of CUR against diabetic cardiac injury may be mediated through activation of the Nrf2 and PI3K/AKT signaling pathways and upregulation of antioxidant enzyme expression, aiming to provide a theoretical foundation for further research into the therapeutic application of CUR in DCM.
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高影响因子
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