Chinese Journal of Pharmacology and Toxicology

Current Issue

  • Select all
    |
    Contents
  • Contents
    Contents
    2025, 39(11): 0.
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    • ORIGINAL ARTICLES
  • ORIGINAL ARTICLES
    Liuwei Dihuang-active fraction combination and its active component glycoside improve memory reconsolidation impairment by regulating brain O-GlcNAc modification
    YANG Hexi, WANG Chenran, XIA Mengting, WANG Jianhui, ZHOU Wenxia
    2025, 39(11): 801. https://doi.org/10.3867/j.issn.1000-3002.2025.08542
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    OBJECTIVE  To investigate the effects of Liuwei Dihuang-active fraction combination (LW-AFC) and its active component glycoside (LWD-b) on memory reconsolidation and their relationship with O-linked β-N-acetylglucosamine (O-GlcNAc) modification. METHODS  ① Six-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were divided into three groups:SAMP8 group, SAMP8+LW-AFC group and SAMP8+LWD-b group. Senescence-accelerated mouse resistant 1 (SAMR1) mice served as the control group. The SAMP8+LW-AFC group and SAMP8+LWD-b group were given LW-AFC 1.6 g·kg-1 and LWD-b 0.216 g·kg-1 ig for 60 days, respectively, while the SAMR1 group and SAMP8 group were ig given the same volume of deionized water. ② Male C57BL/6J mice were divided into four groups: control group, exogenous corticosterone (CORT) group, CORT+LW-AFC group, and CORT+LW-AFC+6-diazo-5-oxo-L-norleucine (DON) group. The CORT group was given CORT 25 mg·kg-1 sc for 15 consecutive days; CORT+LW-AFC group was given LW-AFC ig for 30 consecutive days, and CORT at 25 mg·kg-1 sc continuously from the 15th day; CORT+LW-AFC+DON group was given LW-AFC ig for 30 consecutive days, and CORT at 25 mg·kg-1 sc and DON at 600 μg·kg-1 ip continuously from the 15th day. The control group was given an equal volume of deionized water ig per day. ③ C57BL/6J mice were divided into the control group, CORT group, CORT+LWD-b group, and CORT+LWD-b+DON group. The drug was administered at the same time and in the same order as in ② except that LW-AFC 1.6 g·kg-1 was replaced by LWD-b 0.216 g·kg-1. In three experiments, the modified novel object recognition test (retrieval-enhancement paradigm) and conditional fear test (retrieval-extinction paradigm) were used to evaluate memory reconsolidation. ELISA and Western blotting were performed to detect hippocampus O-GlcNAc levels. Pearson correlation analysis was used to explore the correlations between memory reconsolidation performance (preference index of the novel object and freezing time after retrieval) and O-GlcNAc levels. RESULTS  ① Compared with the SAMR1 group, the SAMP8 group showed a significantly decreased preference index for the novel object, prolonged freezing time, and reduced hippocampal O-GlcNAc levels. Compared with the SAMP8 group, SAMP8+LW-AFC and SAMP8+LWD-b groups showed a significantly increased preference index for the novel object, decreased freezing time, and elevated hippocampal O-GlcNAc levels. Pearson analysis revealed a positive correlation between the novel object preference index and O-GlcNAc levels, and significantly negative correlations between context/cue freezing time and O-GIcNAc levels. ② Compared with the control group, the CORT group showed a significantly decreased preference index for the novel object, prolonged freezing time, and reduced hippocampal O-GlcNAc levels. Compared with the CORT group, the CORT+LW-AFC group showed a significantly increased preference index for the novel object, decreased freezing time, and elevated hippocampal O-GlcNAc levels. Compared with the CORT+LW-AFC group, the CORT+LW-AFC+DON group showed a significantly decreased preference index for the novel object, prolonged freezing time, and reduced hippocampal O-GlcNAc levels. Pearson analysis revealed a positive correlation between the novel object preference index and O-GlcNAc levels, but a significantly negative correlation between context/cue freezing time and O-GIcNAc levels. ③ Compared with the control group, the CORT group showed a significantly decreased preference index for the novel object, prolonged freezing time, and reduced hippocampal O-GlcNAc levels. Compared with the CORT group, the CORT+LWD-b group showed a significantly increased preference index for the novel object, decreased freezing time, and elevated hippocampal O-GlcNAc levels. Compared with the CORT+LWD-b group, the CORT+LWD-b+DON group showed a significantly decreased preference index for the novel object, prolonged freezing time, and reduced hippocampal O-GlcNAc levels. Pearson analysis revealed a positive correlation between the novel object preference index and O-GlcNAc levels, but a significantly negative correlations between context/cue freezing time and O-GIcNAc levels. CONCLUSION  LW-AFC and LWD-b can significantly ameliorate memory reconsolidation impairment induced by aging and stress in mice, and the mechanism may be associated with upregulation of O-GlcNAc modification levels in the hippocampus of mice.
  • ORIGINAL ARTICLES
    Ameliorative effect and mechanisms of Sini powder against fear and anxiety behaviors in post-traumatic stress disorder mice
    WANG Yajing, ZHANG Xue, YUAN Zengqiang, CHEN Jianxin, LI Shuoshuo
    2025, 39(11): 813. https://doi.org/10.3867/j.issn.1000-3002.2025.08628
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    OBJECTIVE  To investigate the effects of Sini powder (a traditional Chinese medicine formula) on the behavior of post-traumatic stress disorder (PTSD) model mice and explore the potential mechanism of Sini powder against PTSD. METHODS  Male C57BL/6 mice were randomly assigned to the normal control group, model group, model+paroxetine 2.43 mg·kg-1 group, and the model+Sini powder (2.184 and 10.92 g·kg-1) groups. Except the normal control group, mice in these groups were subjected to the foot shock (inescapable electric foot shocks administered for 2 consecutive days, at an intensity of 1 mA, lasting 10 s, with a 10 s interval, and 15 shocks per day) to establish a PTSD model. Twenty-four hours prior to modeling, mice in the drug treatment groups were intragastrically administered corresponding doses of their respective drugs, while the normal control group and model group received an equal volume of saline via intragastric administration, once daily for 30 consecutive days. At different time points after modeling, the effects of the drugs on PTSD-like behaviors were analyzed using the contextual fear conditioning test (on days 7, 14 and 48 post-modeling), open field test (on day 40 post-modeling), elevated plus maze test (on days 9 and 39 post-modeling), and sucrose preference test (on day 37 post-modeling). Upon completion of behavioral tests (day 48 post-modeling), brain tissues were collected from mice in the normal control, model, and model+Sinisan (10.92 g·kg-1) groups. Immunofluorescence staining was used to observe the number of microglia in the murine hippocampal region. Real-time quantitative PCR (RT-qPCR) was adopted to detect the mRNA expression levels of interleukin-4 (IL-4), IL-6, IL-1β, tumor necrosis factor-α (TNF-α), arginase-1 (Arg1) and macrophage mannose receptor (CD206 ) in order to investigate the mechanism of action of the drug. RESULTS  Compared with the normal control group, the model group showed a significant increase in the percentage of freezing time, and a significant decrease in the percentage of entries and time spent in the central area of the open field, as well as the percentage of entries and time spent in the open arms of the elevated plus maze, suggesting the success of modeling. Compared with the model group, both the model+paroxetine group and the model+Sini powder group showed a significant decrease in the percentage of freezing time, and a significant increase in the percentage of entries and time spent in the central area of the open field, and in the percentage of entries and time spent in the open arms of the elevated plus maze. Compared with the normal control group, the model group showed a significant increase in the number of microglia in the hippocampal region, and a significant upregulation of IL-6 mRNA expression. Compared with the model group, the model+Sini powder 10.92 g·kg-1 group exhibited a significantly smaller number of microglia in the hippocampal region, and the expression levels of the inflammatory factors IL-6 and TNF-α were significantly decreased. CONCLUSION  Sini powder may improve fear and anxiety-like behaviors in PTSD model mice by regulating microglial activation and neuroinflammation.
  • ORIGINAL ARTICLES
    Effects of echinacoside on monocrotaline-induced pulmonary arterial hypertension model rats by regulating CaM and TRPC1/4/6 protein
    ZHAO Yuefu, WANG Jinyu, XIA Qingqing, SUN Haotian, LEI Gaoxiang, ZHAO Enqi, BI Hongtao, GAI Xiangyun
    2025, 39(11): 821. https://doi.org/10.3867/j.issn.1000-3002.2025.08285
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    OBJECTIVE To investigate the effect and mechanism of echinacoside (ECH) on monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. METHODS  ① In vivo, SD rats were randomly divided into the normal control group, PAH group, model+ECH 15 mg·kg-1 group, model+ECH 30 mg·kg-1 group and model+aspirin 8 mg·kg-1 group. On the first day, a PAH rat model was established via intraperitoneal injection of 40 mg·kg-1 of monocrotaline. The normal control group was given the same volume of normal saline by intraperitoneal injection. The treatment started on the second day after modeling, once a day, for 28 d. The mean pulmonary artery pressure (mPAP) was measured via right cardiac catheterization and the degree of right ventricular hypertrophy was measured by weighing. Pulmonary artery remodeling was observed using HE staining. The protein expression levels of calmodulin (CaM), transient receptor potential channel 1 (TRPC1), TRPC4, and TRPC6 were detected by Western blotting. ② In vitro, pulmonary artery smooth muscle cells (PASMCs) of rats were randomly divided into the cell control group, noradrenaline (NE) group, NE+ECH 400 μmol·L-1 group and NE+ECH 450 μmol·L-1 group. Each group was pre-incubated with the corresponding concentration of ECH for 20 min, 
    followed by the addition of 1 μmol·L-1 NE, and then cultured for 24 h. The protein expression levels of CaM, TRPC1, TRPC4, and TRPC6 were detected by Western blotting. RESULTS  ① In vivo, compared with the normal control group, the right cardiac hypertrophy index and mPAP of the PAH group were significantly increased, the pulmonary vascular wall was thickened, and the expressions of CaM, TRPC1, TRPC4 and TRPC6 proteins were significantly increased. After ECH 30 mg·kg-1 treatment of monocrotaline-induced PAH rats, the right cardiac hypertrophy index and mPAP were significantly decreased, and the expressions of CaM, TRPC1, TRPC4 and TRPC6 proteins were significantly down-regulated. The pulmonary artery remodeling in PAH rats treated with ECH 15 and ECH 30 mg·kg-1 was improved. ② In vitro, compared with cell control group, the expressions of CaM, TRPC1, TRPC4 and TRPC6 in PASMCs of the NE group were upregulated. Compared with the NE group, the expressions of CaM, TRPC1, TRPC4 and TRPC6 in PASMCs were significantly decreased. CONCLUSION  ECH may inhibit the expressions of CaM, TRPC1, TRPC4 and TRPC6 proteins, thus improving pulmonary vascular contraction and pulmonary artery remodeling, and  alleviating PAH.
  • ORIGINAL ARTICLES
    Mailuoning inhibits hepatocellular carcinoma growth by improving tumor microenvironments in Hepa1-6 tumor-bearing mice
    ZHOU Siyan, WU Zeqi, KE Chuang, LU Bin, HUANG Zhenlin, JI Lili
    2025, 39(11): 829. https://doi.org/10.3867/j.issn.1000-3002.2025.08459
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    OBJECTIVE  To explore the inhibitory effect of Mailuoning (MLN) on ectopic hepatocellular carcinoma (HCC) growth and the potential mechanism. METHODS  ① C57BL/6J male mice were inoculated with Hepa1-6 cells (1×106) in the axilla to establish ectopic HCC models and randomly divided into 4 groups: model group, model+MLN 5 g·kg-1 group, model+MLN 15 g·kg-1 group and model+sorafenib (SRF) 30 mg·kg-1 group. The drug administration groups were intragastrically given corresponding doses of drugs for 14 consecutive days, and body mass and tumor volume were monitored every 2 days during this period. At the end of the animal experiment, mice were sacrificed and tumors were harvested. The anti-tumor effect of MLN was evaluated via tumor illustration, tumor mass and tumor size. Bioinformatic analyses were conducted to identify key biological processes in hepatocellular carcinoma. Sirius red staining was used to assess collage fiber content in tumors of mice. Quantitative real-time polymerase chain reaction (RT-qPCR) test was performed to detect mRNA expressions of extracellular matrix components including collagen typeⅠalpha 1 chain (Col1a1), Col3a1 and fibronectin, epithelial-mesenchymal transition markers like E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA) and vimentin, and immune checkpoint-related molecules such as programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1) and B7 homologue 3 (B7-H3). Protein levels of E-cadherin, α-SMA, and PD-L1 were subsequently detected by Western blotting. ② HepG2 cells were incubated with the vehicle, β-ecdysone, harpagide, harpagoside, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, luteoloside, macranthoidin B and dipsacoside B (10 μmol·L-1) for 24 h, respectively. After incubation, the expression of Col1a1 mRNA was measured to assess the impact of MLN active ingredients on COL1A1 production. Further more, HepG2 cells were incubated with the vehicle, β-ecdysone, chlorogenic acid, luteoloside or macranthoidin B (10 μmol·L-1) for 24 h before the COL1A1 protein level was assessed. RESULTS  ① Bioinformatic analysis results showed that extracellular matrix and fibroblast proliferation related genes were notably changed in HCC patients. Compared with the model group, the mass and volume of tumors were significantly reduced in the model+MLN 15 g·kg-1 group, so was the positive area of sirius red staining in tumor tissues. In the model+MLN 15 g·kg-1 group, the mRNA expression of E-cadherin was upregulated while those of Col1a1, Col3a1, fibronectin, N-cadherin, α-SMA, vimentin, PD-L1 and B7-H3 were downregulated compared to the model group. Western blotting results revealed that the E-cadherin protein level in HCC tissues in the model+MLN 15 g·kg-1 group increased while the protein levels of α-SMA and PD-L1 in HCC tissues in both the model+MLN 5 g·kg-1 and model+MLN 15 g·kg-1 group decreased compared to the model group. ② MLN active ingredients-β-ecdysone, chlorogenic acid, luteoloside, macranthoidin B-were effective at decreasing the mRNA and protein expressions of Col1a1 in HepG2 cells  compared with the control group. CONCLUSIN  MLN can ameliorate ectopic HCC growth by inhibiting epithelial-mesenchymal transition, decreasing extracellular matrix deposition, reducing immune checkpoint-related molecule PD-L1 expressions and improving immune microenvironments.
  • ORIGINAL ARTICLES
    Celastrol inhibits lipid droplet accumulation and modulates lipid metabolism in triple-negative breast cancer cells
    MA Ninghui, XU Ziyi, YE Yuhao, XIONG Yang
    2025, 39(11): 839. https://doi.org/10.3867/j.issn.1000-3002.2025.08255
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    OBJECTIVE  To investigate the effect of celastrol (Cel) on lipid droplet accumulation in triple-negative breast cancer cells promoted by adipocytes in the tumor microenvironment. METHODS 3T3-L1 preadipocytes were differentiated into mature adipocytes using an adipogenic induction kit, with lipid droplet distribution assessed by Oil Red O staining. Adipocytes-derived conditioned medium (Adi-CM) was collected 2 days post-differentiation. 4T1 cells were divided into control and Adi-CM groups (25%, 50% and 75%) and cultured for 48 h. Cell viability was measured by CCK-8 assay, and lipid droplet accumulation was quantified via Oil Red O staining to determine the optimal Adi-CM concentration. For Cel treatment, 4T1 cells exposed to 75% Adi-CM were assigned to control and Cel groups (0.2, 0.4, 0.8, 1.6, 3.2 and 6.4 μmol·L-1), with viability assessed after 48 h to establish Cel dosing. Subsequent experiments involved control, Adi-CM (75%), and Adi-CM-Cel (0.8 μmol·L-1) groups. Lipid droplets were extracted using a lipid droplet isolation kit, and lipid composition was analyzed by high-resolution liquid chromatography-mass spectrometry. RESULTS  Twenty days into differentiation, 3T3-L1 preadipocytes exhibited abundant intracellular lipid droplets as confirmed by Oil Red O staining, and Adi-CM was collected 2 days post-maturation. Compared to the control group, 4T1 cells treated with 75% Adi-CM demonstrated a significant increase in viability and maximal lipid droplet accumulation. Cel at concentrations below 0.8 μmol·L-1 maintained 4T1 cell viability above 70% while dose-dependently suppressing lipid droplet accumulation. Lipidomic profiling revealed 22 differentially expressed lipid species between the 75% Adi-CM group and control group, which were predominantly upregulated. Cel treatment did not alter lipid species diversity but reduced their abundance, with notable inhibition of phosphatidylethanolamine expression levels. CONCLUSION  Cel inhibits tumor cell proliferation by suppressing Adi-CM-induced lipid droplet accumulation and modulating lipid contents in 4T1 cells.
  • ORIGINAL ARTICLES
    Establishment and evaluation of a mouse model of thirst induced by hypertonic sodium chloride solution
    DENG Qingmei, ZHENG Aiping, CHEN Qiu, LU Guanyi, ZHUANG Xiaomei
    2025, 39(11): 847. https://doi.org/10.3867/j.issn.1000-3002.2025.08352
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    OBJECTIVE  To determine the optimal induction concentration from among different concentrations of hypertonic saline in order to establish a mouse model of thirst and conduct a multi-dimensional evaluation. METHODS  Male C57BL/6J mice were randomly divided into the control group (NaCl 0.15 mol·L-1) and hypertonic saline treatment groups (NaCl 1 and 2 mol·L-1). Each group was intraperitoneally administered with the corresponding solution at a dose of 5 μL·g-1. Ten minutes after administration, plasma osmolality was measured via the freezing point osmometry, water intake was measured using the weighing method, and water intake behavior was recorded by a lickometer. Real-time dynamic changes in calcium signals of excitatory neurons in the subfornical organ (SFO) were 
    detected using fiber photometry, and the area under the curve (AUC) was used as the indicator to quantify the excitability of neurons. RESULTS  Compared with the control group, plasma osmolality of mice in the treatment groups increased significantly in a dose-dependent manner. In the 2 mol·L-1 treatment group, water intake of mice increased significantly, and parameters of water intake behavior (licks per burst, licking rate, number of bursts and burst size) all increased significantly, so did the AUC of the calcium signals of excitatory neurons in the SFO at 400 s after injection, in contrast, these indicators only trended upward in the 1 mol·L-1 treatment group, with no statistical significance. CONCLUSION  Treatment with NaCl at 2 mol·L-1 (5 μL·g-1, ip) can help establish a mouse model of thirst, in which water intake is increased, drinking behavior enhanced, plasma osmolarity elevated, and SFO excitatory neuron activity is enhanced.
    • REVIEWS
  • REVIEWS
    Recent advances in macrophage-organoid co-culture 
    WANG Jiru, TAN Yingxia, LOU Zhangrong, WU Chengjun
    2025, 39(11): 854. https://doi.org/10.3867/j.issn.1000-3002.2025.08532
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Macrophages are critical effector cells involved in maintaining tissue homeostasis, mediating immune responses, and regulating inflammatory reactions. Organoids, serving as three-dimensional (3D) in vitro models mimicking tissue structure and function, are widely employed for disease modeling and drug screening. However, organoids typically lack immune system components such as macrophages and therefore cannot fully recapitulate the complex immune microenvironment present in vivo. Co-culturing macrophages with organoids to develop physiologically relevant in vitro models has emerged as a current research focus, enhancing the depth of human disease modeling. This review summarizes recent advances in co-culture studies utilizing macrophages derived from human acute monocytic leukemia THP-1 cells, induced pluripotent stem cells (iPSCs), and other cellular sources, discussing their potential applications in reconstructing immune microenvironments, elucidating disease mechanisms, and facilitating personalized therapeutic strategies.
  • REVIEWS
    Research progress in the regulatory role of translocase of the outer mitochondrial membrane 20 in tumor development
    LI Wenyao, WANG Qianqian, CHEN Shuang
    2025, 39(11): 863. https://doi.org/10.3867/j.issn.1000-3002.2025.08321
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Mitochondrial dysfunction is a key driving force behind the occurrence and development of cancers, and the proper transport of proteins plays a central role in maintaining mitochondrial homeostasis. As a key translocation receptor in the mitochondrial outer membrane, translocase of outer mitochondrial membrane 20 (Tom20) is abnormally overexpressed in a wide range of cancer cells, and is closely related to their proliferation, invasion, drug resistance, and evasion of apoptosis. This review   summarizes research progress in the roles of Tom20 in cancers, including hepatocellular carcinoma, lung cancer, colorectal cancer, and esophageal cancer, focusing on the effect of Tom20 on the survival and death of cancer cells by regulating apoptosis, pyroptosis, and autophagy. Studies have shown that Tom20 may not only promote tumor development but also act as a key factor inducing cell death under specific conditions, demonstrating a ”double-edged sword” characteristic. In the future, targeted regulation based on Tom20 is expected to create new strategies for cancer treatment. But further in-depth research into its mechanisms of action and differences among tumor types is still needed to achieve precise and safe clinical application.
  • REVIEWS
    Research progress of cholesterol analogs in lipid nanoparticles optimization
    XU Yi, WANG Hongbo, SONG Xiang, WANG Shengqi
    2025, 39(11): 871. https://doi.org/10.3867/j.issn.1000-3002.2025.08480
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Lipid nanoparticle (LNP) are currently the most widely used nucleic acid delivery vectors in clinical practice. As a key component of LNP, cholesterol contributes to the structural integrity of LNP by modulating the fluidity of bilayer membrane of lipids. However, conventional LNP are inadequate in delivery efficiency and tissue targeting, which hinders their applications in extrahepatic delivery. Therefore, the optimization of LNP, especially for cholesterol replacement, remains a priority in delivery system research. Cholesterol analogs have unique structures, and are promising substitutes due to their ability to preserve LNP stability enhance delivery efficiency and improve targeting specificity. Some analogs may even deliver therapeutic effects. This review summarizes recent advances in the design of LNP naturally occurring cholesterol analogs, such as phytosterols and saponins, as well as synthetic ones. This study is expected to provide insights into research in this field.