JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yuling Tong,Ruilin Wang,Xia Liu,Miao Tian,Yanling Wang,Yanfei Cui,Wenjun Zou,Yanling Zhao
Ethnopharmacological relevance Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases . Aim of this study The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG . Materials and methods The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot . Results The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. Conclusion ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
研究领域:
药理学
·
民族药理学
·
胃肠病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2024
·Vol. 14
·期 10
·1226
·
IF 4.8
Wenjuan Quan,Taoli Sun,Bo Hu,Quanye Luo,Yancheng Zhong,Wen Chen,Qinhui Tuo
Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and foam cell formation in the arterial wall. Promoting macrophage autophagy has emerged as a promising therapeutic strategy against atherosclerosis. Dipsacoside B (DB) is an oleanane-type pentacyclic triterpenoid saponin extracted from Lonicerae flos with potential anti-atherosclerotic properties. In this study, we investigated the effects of DB on atherosclerosis progression in ApoE −/− mice fed a high-fat diet and explored the underlying mechanisms in oxidized low-density lipoprotein (ox-LDL)-induced foam cells. DB treatment significantly reduced atherosclerotic lesion size, improved plaque stability, and regulated lipid metabolism without impairing liver and kidney function in ApoE −/− mice. In vitro studies revealed that DB dose-dependently inhibited ox-LDL internalization and intracellular lipid accumulation in RAW264.7 macrophages. Mechanistically, DB induced autophagy, as evidenced by increased autophagosome formation and upregulated expression of autophagy markers LC3-II and p62 both in vivo and in vitro. Inhibition of autophagy by chloroquine abolished the antiatherosclerotic and pro-autophagic effects of DB. Furthermore, DB treatment increased LC3-II and p62 mRNA levels, suggesting transcriptional regulation of autophagy. Collectively, our findings demonstrate that DB exerts anti-atherosclerotic effects by inhibiting foam cell formation via autophagy induction, providing new insights into the pharmacological actions of DB and its potential as a therapeutic agent against atherosclerosis.
研究领域:
心血管疾病
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Genes
·
2025
·Vol. 16
·期 9
·1037
·
IF 2.8
Zhiyu Wu,Menghuan Xiao,Zelin Gong,Benjie Wang,Wenxin Zhao,Yiyuan Guo,Lu Yang
Objectives: The objectives of this study are to investigate the therapeutic targets and mechanisms of proanthocyanidins in alleviating fluoride-induced liver injury through network pharmacology and animal experimental validation and to explore the medicinal value of grape seed proanthocyanidins.Methods: Potential targets of proanthocyanidins were predicted using databases such as PubChem, SwissTargetPrediction, and GeneCards, and disease-related targets of fluoride-induced liver injury were retrieved to identify common targets between proanthocyanidins and fluoride-induced liver injury. The STRING database was utilized to construct a protein–protein interaction network, and key targets were analyzed for network topology using Cytoscape software. GO and KEGG enrichment analyses were performed on core target genes to explore the potential molecular mechanisms by which proanthocyanidins alleviate fluoride-induced liver injury. The Genes-miRNA interaction network was generated using Networkanalyst, and the molecular docking results between active components and key targets were validated using the CB-Dock2 visualization tool. In the academic context, a rat model of chronic fluoride poisoning was successfully established by means of intragastric administration of sodium fluoride. The protein expression levels of p-mTOR, p-p70s6, p62, LC3-II, and PARP1 in rat liver tissues were detected via Western blot analysis.Results: Network pharmacological analysis successfully identified 96 key genes, through which proanthocyanidins mitigate fluoride-induced liver injury. KEGG enrichment analysis predicted that proanthocyanidins mainly exert their therapeutic effects through the mTOR signaling pathway. The molecular docking results further demonstrated strong binding affinities between proanthocyanidins and key targets, including mTOR and PARP1. The in vivo experimental results indicate that, compared with the control group, the protein expression levels of p-mTOR, p-p70s6k, and p62 in the liver tissues of rats exposed to sodium fluoride significantly increase. Conversely, the protein expression levels of LC3-II and PARP1 significantly decrease (p< 0.05). The outcome of liver intervention with proanthocyanidins is exactly the opposite.Conclusions: Proanthocyanidins can effectively alleviate fluoride-induced liver injury, potentially by regulating the mTOR signaling pathway, autophagy, and apoptosis mechanisms. This study provides valuable insights into the protective effects of proanthocyanidins against fluoride-induced hepatic damage and offers a theoretical basis for further research in this field.
研究领域:
药理学
·
毒理学
·
分子生物学
·
生物信息学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 28
·期 4
·1-13
·
IF 3.4
Qi Nie,Wenqing Chen,Tianmei Zhang,Shangrong Ye,Zhongyu Ren,Peng Zhang,Jian Wen
In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non‑invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)‑loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI‑H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK‑8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH‑DA fluorescent probe and a C11‑BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy‑ and iron death‑related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy‑related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)‑II/I in NCI‑H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX‑induced the upregulation of Beclin 1, LC3‑II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX‑induced downregulation of p62 protein in NCI‑H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.
研究领域:
纳米技术
·
癌症治疗
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 10
·4582-4590
·
IF 5.396
Xue-Yan Dai,Yi Zhao,Jing Ge,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Jin-Long Li
Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.
研究领域:
毒理学
·
药理学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-13
·
IF 10.2
Zhang Yue,Pan Deng,Ning Zhenqiang,Huang Fang,Wei Yiting,Zhang Mingming,Zhang Yuanjian,Wang Li-xin,Shen Yanfei
Tumor cell-released LC3 + extracellular vesicles (LC3 + EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3 + EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3 + EVs levels with high sensitivity to identify LC3 + EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3 + EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3 + EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3 + EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.
研究领域:
癌症生物学
·
生物医学工程
·
电化学
·
生物标志物研究
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Chen Ping,Zhang Xueer,Fang Qiaomiao,Zhao Zhongxiang,Lin Chaozhan,Zhou Yuan,Liu Fangle,Zhu Chenchen,Wu Aizhi
Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca 2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention. Graphical abstract
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Ping Guan,Zhaoxu Meng,Xinran Liu,Jiaxiang Mu,Zichun Gao,Xinrong Yu,He Lian
The complex, invasive, and metastatic nature of malignant tumors make the current treatment of patients challenging in advanced stages. The present study proposes a multi-effect synergistic biomimetic mineralization nanosystem ( [email protected] 4 ) to regulate tumor cell metabolism and relevant biological behaviors through glycolysis-oxidative stress-autophagy process. Bovine serum albumin complexed with lonidamine served as a template to induce the formation of iron phosphate mineralization in situ . After intratumoral administration, the released lonidamine inhibited hexokinase II and down-regulated the level of glycolysis, cutting off the energy and biosynthesis supply source for tumor growth. Ferric ions dissociated from biomineralization in acidic microenvironment converted reduced glutathione to oxidized glutathione, elevated oxidative stress and induced ferroptosis through chemokinetic reactions. The dissociated phosphate ions function as an autophagy inhibitor to block the protective autophagy cased by energy deprivation for efficacy enhancement. The up-regulation of Nrf2 and LC3 proteins, the down-regulation of HK2 and GPX4 proteins, and the increase of ROS level in tumors all confirmed this conclusion. Notably, the nanosystem also down-regulated the release of inflammatory factors (IL-6, IL-8) and metastasis-related proteins (N-Cadherine, Vimentin) simultaneously, effectively preventing distant lung metastasis of tumor. In summary, this biomineralization-based nanosystem exhibited powerful antitumor effects both in vitro and in vivo and provides a new perspective for addressing the dilemma of malignant tumor treatment.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
PeerJ
·
2018
·
IF 2.118
Yu Lei,Chengkun Wang,Quan Jiang,Xiaoyi Sun,Yongzhong Du,Yaofeng Zhu,Yingmei Lu
The toxicity of engineered nanoparticles remains a concern. The knowledge of biohazards associated with particular nanoparticles is crucial to make this cutting-edge technology more beneficial and safe. Here, we evaluated the toxicity of Ga 2 O 3 nanoparticles (NPs), which are frequently used to enhance the performance of metal catalysts in a variety of catalytic reactions. The potential inflammatory signaling associated with the toxicity of HA/β-Ga 2 O 3 :Cr 3+ NPs in primary cortical neurons was examined. We observed a dose-dependent decrease in cell viability and an increase in apoptosis in neurons following various concentrations (0, 1, 5, 25, 50, 100 µg/ml) of HA/β-Ga 2 O 3 :Cr 3+ NPs treatment. Consistently, constitutively active forms of calcineurin (48 kDa) were significantly elevated in cultured primary cortical neurons, which was consistent with calpain activation indicated by the breakdown products of spectrin. Moreover, HA/β-Ga 2 O 3 :Cr 3+ NPs result in the elevation of LC3-II formation, SQSTM/p62, and Cathepsin B, whereas phosphorylation of CaMKII (Thr286) and Synapsin I (Ser603) were downregulated in the same context. Taken together, these results demonstrate for the first time that calpain activation and a disturbance of autophagy signaling are evoked by exposure to HA/β-Ga 2 O 3 :Cr 3+ NPs, which may contribute to neuronal injury in vitro .
研究领域:
纳米技术
·
神经科学
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Huanyan Wu,Linlin Qu,Xue Bai,Chenhui Zhu,Yuan Liu,Zhiguang Duan,Hongyan Liu,Rongzhan Fu,Daidi Fan
Hepatocellular carcinoma (HCC) is the third most lethal cancer in the world. Recent studies have shown that suppression of autophagy plays an important role in the development of HCC. Ginsenoside Rk1 is a protopanaxadiol saponin isolated from ginseng and has a significant anti-tumor effect, but its role and mechanism in HCC are still unclear. In this study, a mouse liver cancer model induced by diethylnitrosamine and carbon tetrachloride (DEN + CCl 4 ) was employed to investigate the inhibitory effect of Rk1 on HCC. The results demonstrate that ginsenoside Rk1 effectively inhibits liver injury, liver fibrosis, and cirrhosis during HCC progression. Transcriptome data analysis of mouse liver tissue reveals that ginsenoside Rk1 significantly regulates the AMPK/mTOR signaling pathway, autophagy pathway, and apoptosis pathway. Subsequent studies show that ginsenoside Rk1 induces AMPK protein activation, upregulates the expression of autophagy marker LC3-II protein to promote autophagy, and then downregulates the expression of Bcl2 protein to trigger a caspase cascade reaction, activating AMPK/mTOR-induced toxic autophagy to promote cells death. Importantly, co-treatment of ginsenoside Rk1 with autophagy inhibitors can inhibit apoptosis of HCC cells, once again demonstrating the ability of ginsenoside Rk1 to promote autophagy-dependent apoptosis. In conclusion, our study demonstrates that ginsenoside Rk1 inhibits the development of primary HCC by activating toxic autophagy to promote apoptosis through the AMPK/mTOR pathway. These findings confirm that ginsenoside Rk1 is a promising new strategy for the treatment of HCC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 16
·2657-2666
·
IF 5.047
Maowen Chen,Yan Hu,Yanhua Hou,Menghuan Li,Maohua Chen,Caiyun Mu,Bailong Tao,Wei Zhu,Zhong Luo,Kaiyong Cai
Autophagy is associated with the proliferation and differentiation of mesenchymal stem cells (MSCs). In this study, we investigated the biological impact of silica-based nanobiomateiral-induced autophagy on the differentiation of MSCs, in which the nanoparticulate cues include solid silica nanoparticles (SSN), mesoporous silica nanoparticles (MSN) and biodegradable mesoporous silica nanoparticles (DMSN). The treatment with SSN significantly up-regulated the LC3-II expression via ERK1/2 and AKT/mTOR signaling pathways compared to DMSN and MSN, leading to a higher autophagic activity in MSCs. The enhanced protein adsorption of DMSN and MSN could prevent the direct interaction between cells and nanoparticles, which consequently reduces the autophagic stimulation of MSCs. It should be noted that MSCs exhibited increased differentiation potential when the autophagic activity was enhanced by the treatment with different nanoparticles. In comparison, no difference in the cell differentiation potential was found when an autophagy inhibitor (chloroquine, CQ) was incorporated in all groups. The study may contribute to the development of silica-based nanobiomaterials in the future.
研究领域:
纳米生物技术
·
干细胞生物学
·
材料科学
·
细胞与分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2017
·
IF 2.936
En-Xia Wang,Bo-Yang Zou,Lei Shi,Lin-Ying Du,Yan-Yan Zhu,Ya-Meng Jiang,Xiao-Dong Ma,Xiao-Hui Kang,Chang-Yuan Wang,Yu-Hong Zhen,Li-Dan Sun
Aims To investigate the antitumor effects of 7- O -geranylquercetin (GQ), a novel O -alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. Main methods Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay. Cell cycle and reactive oxygen species (ROS) level were detected using flow cytometry. Key findings GQ inhibited viability of A549 and NCI-H1975 cells in a dose- and time-dependent manner without apparent cytotoxicity to normal human lung fibroblast cells. GQ down-regulated the expression of apoptosis-related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation of ROS, and ROS inhibitor N -acetylcysteine could reverse GQ-induced autophagy and apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to apoptosis. Significance Our findings highlight that GQ is a promising anticancer agent for the treatment of lung cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）