题目人参皂苷-Rg5通过PI3K/AKT/mTOR信号通路与伊马替尼抗慢性粒细胞白血病K562细胞的协同作用.目的探讨人参皂苷-Rg5与伊马替尼在抗慢性粒细胞白血病K562细胞中的协同作用及其机制。.方法采用CCK-8法检测不同浓度的人参皂苷-Rg5和伊马替尼对K562细胞增殖的抑制作用；根据人参皂苷-Rg5和伊马替尼的IC₅₀调整浓度共同作用于K562细胞，并使用在线软件Synergy finder分析两药的协同作用；采用流式细胞术分析单独或联合用药对K562细胞凋亡和细胞周期分布的影响；采用Western blot检测单独或联合用药后K562细胞PI3K/AKT/mTOR信号通路相关蛋白及凋亡相关蛋白的表达。.结果人参皂苷-Rg5和伊马替尼均可以剂量依赖性的方式抑制K562细胞的增殖(r =-0.991，r =-0.942)。Synergy finder分析结果显示，人参皂苷-Rg5和伊马替尼对K562细胞具有协同作用，ZIP评分>10。人参皂苷-Rg5和伊马替尼单药处理后的K562细胞凋亡率分别为11.96%和8.13%，联合用药后K562细胞的凋亡率为21.35%，联合处理组的细胞凋亡率高于单药组（ P <0.05）。两药联合处理后K562细胞G₀/G₁期比例较单药组明显增加（ P <0.05）。两药联合处理后K562细胞中p-PI3K、p-AKT、p-mTOR蛋白表达显著降低，下调BCL-2的表达，上调BAX的表达，导致Bcl-2/BAX比值下降，而非磷酸化的PI3K、AKT和mTOR蛋白表达未见显著变化。.结论人参皂苷-Rg5通过调控PI3K/AKT/mTOR通路与伊马替尼抗白血病K562细胞具有协同作用，为慢性粒细胞白血病患者提供更多的治疗选择。.

2024-10-01·Journal of Ethnopharmacology

Study on the anti-skin aging effect and mechanism of Sijunzi Tang based on network pharmacology and experimental validation

Article

作者: Zhang, Xingjiang ; Zhou, Chengyue ; Ke, Hui ; Liang, Shuang ; Hu, Yunwei ; Huang, Qing ; Wu, Jianxin

ETHNOPHARMACOLOGICAL RELEVANCESi Jun Zi Tang (SJZT) is a famous traditional Chinese medicine formula composing of 4 herbal medicines (Ginseng Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma) with tonifying spleen and anti-aging effects. It is also known that SJZT can be used to tone, nourish the skin and accelerate wound healing. However, due to the complexity of the formulation, the anti-aging especially anti-skin aging mechanisms as well as the key components of SJZT have not been fully investigated. Therefore, further in vitro and in vivo experimental studies are particularly needed to investigate the anti-skin ageing efficacy of SJZT.AIM OF THE STUDYThe purpose of this article was to explore the therapeutic effect and possible pharmacological mechanism of SJZT in the treatment of skin aging by topical application using network pharmacology and to validate the findings using in vitro and in vivo tests.MATERIALS AND METHODSNetwork pharmacology method was applied to predict the underlying biological function and mechanism involved in the anti-skin aging effect of SJZT. Molecular docking was used to preliminarily predict the active components of SJZT-Skin Aging. UPLC QTOF MS/MS was carried out to analyze the chemical compounds. Finally, to confirm the anti-skin aging effort of SJZT, a mouse skin-aging model and UVB-induced EpiSCs (epidermal stem cells) senescence model were established.RESULTSPPI network analysis and KEGG studies indicated that TP53, CDKN2A, TNF, IL6, and IL1B might be parts of the core targets associated with EpiSCs senescence. Furthermore, molecular docking suggested the top active components, glycyrrhizin, ginsenoside Rg5, ginsenoside Rh2, liquiritin, polyporenic acid C and atractylenolide II showed strong affinity to the key proteins involved in cellular senescence signaling. UPLC QTOF MS/MS analysis of SJZT confirmed the presence of these key components. In-vivo experiments revealed that SJZT could improve UVB-induced skin thickening, increase the number of collagen fibers, strengthen the structure of elastin fibers, and decrease the expression of MDA, as well as increase the expression of CAT and T-SOD in the skin tissue of mouse. And, in-vitro experiments indicated that SJZT could reduce ROS generation and oxidative stress, increase mitochondrial membrane potential, and upregulate the expression of stem cell markers. Moreover, SJZT could suppress the expression of p53, p-p53 and p21, downregulated p38 phosphorylation. Furthermore, the anti-cellular senescence effect of SJZT on EpiSCs disappeared after treatment with the p38 inhibitor adesmapimod. Taken all together, the regulation of senescence signaling in EpiSCs is an important mechanism of SJZT in combating skin aging.CONCLUSIONThe research results indicate that SJZT has anti-skin aging effects on UVB-induced skin-aging model, possibly by mediating p38/p53 signaling pathway. These findings strongly demonstrate the great potential of SJZT as an active composite for anti-skin aging and cosmeceutical applications.

2024-07-01·Phytomedicine

Shenqi Yizhi prescription prevents AβO-induced memory impairment in mice by regulating the contractility of brain pericytes

Article

作者: Wang, Jingji ; Cheng, Ping ; Zhu, Guoqi ; Wang, Xuncui ; Zhao, Panpan

BACKGROUNDCerebral microcirculation disturbance manifested by decrease of cerebral blood flow (CBF) is one of early features of Alzheimer's disease (AD). Shenqi Yizhi prescription (SQYZ) is widely used in the treatment of AD. However, the effect of SQYZ on the early feature of AD is not clarified.PURPOSETo explore the effect and mechanism of SQYZ on AD-like behavior from the perspective of early pathological features of AD.METHODSThe fingerprint of SQYZ was established by ultra-high-performance liquid chromatograph. The improvement effect of SQYZ on Aβ_1-42 Oligomer (AβO)-induced AD-like behavior of mice was evaluated by behavioral test. The changes of CBF were detected by laser doppler meter and laser speckle imaging. The pathological changes of the hippocampus were observed by HE staining and transmission electron microscope. The expressions of intercellular communication molecules were detected by western blotting or immunofluorescence staining. The content of platelet-derived growth factor-BB (PDGF-BB) was detected by ELISA. Finally, the core components of SQYZ were docked with platelet-derived growth factor receptor beta (PDGFRβ) using AutoDock Vina software.RESULTSThe similarity of the components in SQYZ extracted from different batches of medicinal materials was higher than 0.9. SQYZ administration could improve AβO-induced memory impairment and CBF reduction. Compared with the sham group, the number of neurons in the hippocampi of AβO group was significantly reduced, and the microvessels were shrunken and deformed. By contrary, SQYZ administration mitigated those pathological changes. Compared with the sham mice, the expressions of CD31, N-cadherin, PDGFRβ, glial fibrillary acidic protein, phosphorylation of focal adhesion kinase, integrin β1, and integrin α5 in the hippocampi of AβO mice were significantly increased. However, SQYZ administration significantly reduced AβO-induced expression of those proteins. Interestingly, the effect of PDGFRβ inhibitor, sunitinib demonstrated a consistent modulating effect as SQYZ. Finally, the brain-entering components of SQYZ, including ginsenoside Rg5, coptisine, cryptotanshinone, dihydrotanshinone IIA, stigmasterol, and tanshinone IIA had high binding force with PDGFRβ, implicating PDGFRβ as a potential target for SQYZ.CONCLUSIONSOur data indicate that SQYZ improves CBF in AβO-triggered AD-like mice through inhibiting brain pericyte contractility, indicating the treatment potential of SQYZ for AD at the early stage.

项与 Ginsenoside Rg5 相关的新闻（医药）

2024-01-26

·PRNewswire

Three Journal of Pharmaceutical Analysis Studies Explore the Use of Traditional Chinese Medicine for Various Diseases

XI'AN, China, Jan. 26, 2024 /PRNewswire/ -- Despite demonstrating significant clinical efficacy against various diseases, the widespread use of Traditional Chinese Medicine (TCM) is still limited. This is mainly due to the complexity in their formulation and lack of sufficient pharmacological and safety-related data. To address this gap, a new issue of the Journal of Pharmaceutical Analysis presents three independent studies which assessed the potency of TCM-based compounds for various human diseases, along with their molecular mechanisms of action. Continue Reading Latest research unveils the potential of Traditional Chinese Medicine compounds for the treatment of human diseases The accumulation of excess fat in the liver leads to non-alcoholic fatty liver disease (NAFLD). Oridonin (ORI), a TCM derived from the Chinese herb Rabdosia rubescens, exhibits anti-inflammatory effects. An article available online on 21 August 2023 and published in Volume 13, Issue 11 of the journal in November 2023, now reveals that ORI regulates lipid homeostasis in the liver by maintaining the balance between triglyceride (TG) and phosphatidylethanolamine (PE), through modulation of adipose triglyceride lipase (ATGL) and ethanolamine phosphotransferase 1 (EPT1) expression via the liver X receptor alpha (LXRα) signaling pathway. "When the TG-PE lipid balance is disturbed, the seesaw tilts towards TG, increasing the risk of NAFLD. Restoring lipid homeostasis using compounds like oridonin can alleviate lipid accumulation and liver cytotoxicity," explains Professor Lan Tang. Tumor heterogeneity compromises the efficacy of radiotherapy for treating lung cancer. Radiosensitizers help prime tumor cells and improve their response to radiation. Now, in an article available online on 7 June 2023 and published in Volume 13, Issue 11 of the journal in November 2023, researchers found that ginsenoside Rg5 induced cell-cycle arrest and enhanced radiation-induced cell death. Ginsenoside Rg5 interacts with heat shock protein alpha (HSP90α) with high affinity and reduces the binding between HSP90 and cell division cycle 37 (CDC37), promoting HSP90-CDC37 client protein degradation. "Ginsenoside Rg5 can be potentially developed into a new drug for improving the sensitivity of lung cancer and other types of tumors to radiation therapy," the authors explain. Diabetic retinopathy (DR) is characterized by the activation of oxidative stress pathways in response to high glucose. In a study available online on 12 May 2023 and published in Volume 13, Issue 11 of the journal in November 2023, researchers synthesized a polymeric drug complex by combining a natural flavonoid antioxidant known as dihydromyricetin (DMY) with iron (Fe) ions in nano-coordinated polymer particles (NCPs). Fe-DMY NCPs can alleviate glucose-induced oxidative damage and reverse the pathological features of DR by decreasing the expression of key proteins involved in microvascular dysfunction. Fe-DMY NCPs could also inhibit the activation of Poldip2-Nox4-H2O2 signaling pathway and down-regulate important vascular function indicators such as VCAM-1, HIF-1α, and VEGF. Explaining its applications, the authors say, "We report for the first time the synthesis and validation of ultra-small Fe-DMY NCPs. Fe-DMY complexes bear the potential to alleviate the impact of DR on vision, thus improving the quality of life of affected individuals." These studies provide a scientific basis for the development of TCM-based compounds into effective targeted therapies for various diseases. Reference Titles of original papers: Oridonin restores hepatic lipid homeostasis in an LXRa-ATGL/EPT1 axis-dependent manner Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy Journal name: Journal of Pharmaceutical Analysis DOI: Media contact Mengjie Wang [email protected] Xi'an, China +86-(0)29-88960092 SOURCE Journal of Pharmaceutical Analysis

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适应症	最高研发状态	国家/地区	公司	日期
单纯疱疹病毒性脑炎	临床前	韩国	Korea Institute of Oriental Medicine	2024-07-01
胶质母细胞瘤	临床前	中国	中国医科大学附属第一医院	2024-07-01
心脏病	临床前	中国	四川省肿瘤医院（四川省第二人民医院四川省癌症防治中心）	2024-05-24
非酒精性脂肪性肝炎	临床前	中国	Northwest University (China)	2024-02-01