Heliyon
·
2023
·Vol. 9
·期 7
·e17393
·
IF 4
Kang Kai,Jiang Han-bing,Cheng Bing-lin,Zhang Shu-jun
Gastric cancer (GC) is a deadly malignant tumor with a high fatality rate and limited curative options. A growing body of research suggests that network pharmacology can replace traditional methods for determining the precise mechanism of action of medicinal substances in conditions such as cancer. The goal of this study was to clarify the biological mechanism of chelerythrine (CHE) and develop a prediction target for CHE against GC using network pharmacology. First, the genes related to GC were identified from the databases Genecards, Disgenet, Online Mendelian Inheritance in Man, Therapeutic Target Database, and Drugbank, and the targets of CHE were obtained from the SwissTargetPrediction database. Fifty linked targets were identified as anti -GC targets of CHE. Functional enrichment and pathway analyses revealed important biological mechanisms mediated by these targets. The core target PIK3CA of CHE anti -GC was obtained using the protein-protein interaction network, CytoHubba plug-in, and Human Protein Atlas. Molecular docking studies revealed that CHE has a strong affinity for PIK3CA (-10.5 kcal/mol). In addition, we used MTT, colony formation, wound-healing, Transwell®, and flow cytometry experiments to confirm that CHE inhibited the proliferation and migration of GC cells and induced cell cycle arrest and apoptosis. Finally, western blotting results showed that CHE downregulated the expression of the PIK3CA protein and inhibited the activation of the PI3K/AKT signaling pathway. Therefore, we concluded that CHE inhibited GC cell proliferation and migration and induced cell cycle arrest and apoptosis by targeting the PIK3CA protein to inhibit the PI3K/AKT pathway activity.
研究领域:
药理学
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肿瘤学
·
分子生物学
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DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2022
·
IF 4.345
Songjiang Wu,Yanying Yang,Feiping Li,Lifu Huang,Zihua Han,Guanfu Wang,Hongyuan Yu,Haiping Li
Introduction Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time.Methods In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis.Results Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE.Conclusion Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Yizhong Shen,Chunlei Zhu,Yaping Wang,Jingjing Xu,Ruyu Xue,Fuyun Ji,Yiwei Wu,Zeyu Wu,Wencheng Zhang,Zhi Zheng,Yingwang Ye
Chelerythrine (CHE), a benzophenanthridine alkaloid , is usually used as a nutritional and functional additive in variety of health foods . However, it should be paid enough attention because of its potential toxicity to human health. In this work, the binding mechanism of CHE with bovine serum albumin (BSA) was systematically investigated with spectroscopic approaches. The results showed that the mixture of BSA with CHE could spontaneously cause the formation of BSA-CHE complex through electrostatic interaction under simulative physiological conditions (0.01 mol L −1 Tris-HCl, 0.015 mol L −1 NaCl, pH = 7.4). Site marker competitive displacement experiments exhibited that CHE was primarily bound to the hydrophobic pocket of the site II (subdomain IIIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, conformation, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of CHE in vivo and guide human to take it safely and reasonably.
研究领域:
生物化学
·
毒理学
·
药理学
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DOI
高影响因子
VIROLOGY
·
2025
·
IF 2.4
Yao Yao,Rui Jing,Xiang Liu,Li Kang,Pinghuang Liu
Feline infectious peritonitis (FIP), a fatal disease in cats caused by feline infectious peritonitis virus (FIPV), has limited treatment options and lacks effective vaccines. Cepharanthine (CEP), a natural isoquinoline alkaloid, possesses many medicinal properties, including antiviral activities. However, the role of CEP in management of FIPV infection remains poorly understood. Here, we identified that CEP had a potent ability to inhibit FIPV infection in vitro . CEP significantly inhibited FIPV infection when administered at different times, with co-treatment showing the most significant inhibitory effect. Time-of-addition assays demonstrated that CEP exerted antiviral activity during the post-entry stages of the FIPV infection. We also verified that CEP inhibited FIPV infection not through affecting type I interferon expression, and it could decrease pro-inflammatory factors expression induced by FIPV infection. The combination of CEP and GS-441524 exhibited synergistic antiviral effects against FIPV infection. Our findings highlight the therapeutic potential of CEP for treatment of FIP.
研究领域:
兽医学
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病毒学
·
药理学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Hongyao Li,Xinyu Gao,Zidan Luo,Subhan Mahmood,Enming Liu,Shun Yao
A ZrC@DES nanofluid system based on different deep eutectic solvents (DESs) and Zirconium carbide (ZrC) nanoparticles was synthesized for green extraction of cepharanthine (CEP) for the first time. The basic properties of DESs were explored and the prepared nanofluid system was characterized with a series of ways. As the key performance, the photothermal conversion performance of the latter was investigated in details as well as its stability. On the basis of above results, a novel extraction method for CEP under near-infrared light radiation was established, and the effects of various factors on its extraction yield were systematically studied under optimized conditions. The final yield of CEP reached 7.2978 mg/g, which was approximately four times higher than that of traditional heating method with ethanol. The Fick’s model could be well applied to fit the kinetic data; CEP was recovered and the components of nanofluid system were reused through the developed post-treatment procedures. Finally, the friendliness and low risk were proved by Zebrafish experiment. The whole study aimed to provide new reference for the extraction of natural bioactive products through energy conversion.
研究领域:
药学
·
纳米技术
·
植物化学
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产品关联
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Jiqiang Hu,Nannan Tu,Cuiying Lin,Yuzhe Fan,Zhijian Xu,Jianbiao Yao,Su Zeng,Bingxian Yang,Lianli Sun
Stephania tetrandra is a medicinal plant that contains four main types of benzylisoquinoline alkaloids (BIAs): mono-BIAs, bis-BIAs, aporphine-type BIAs (APT-BIA), and tetrahydroprotoberberines (THBs). S. tetrandra is particularly rich in the bis-BIAs, tetrandrine and fangchinoline, which are critical quality markers and major components of the traditional Chinese medicine “Fangji”. However, changes in their BIA profiles and associated metabolic regulatory networks over time remain unclear. In this study, metabolomics and transcriptomics were integrated to investigate the dynamic accumulation patterns and underlying mechanisms of these alkaloids across three developmental stages: Autumnal Equinox (AuEq), Winter Solstice (WinSo), and Vernal Equinox (VeEq). Quantification revealed that both alkaloids reached their highest concentrations at VeEq, with tetrandrine levels more than doubling from WinSo. Untargeted metabolomics identified 61 differentially accumulated BIAs, displaying stage-specific accumulation patterns. Hierarchical clustering grouped these BIAs into four structural categories, predominantly enriched at VeEq. Transcriptome profiling showed significant upregulation of genes involved in isoquinoline alkaloid biosynthesis during VeEq, especially key enzymes such as TyrAT, TYDC, 4HPPDC, and NCS. Co-expression and protein interaction network analyses further identified abscisic acid (ABA) signaling pathways as major hormonal regulators. Notably, ABA levels and exogenous ABA application confirmed its pivotal role in promoting bis-BIA biosynthesis, acting in concert with reactive oxygen species (ROS) to fine-tune alkaloid production. Collectively, this study establishes a hormone–ROS–BIA regulatory framework that explains seasonal fluctuations in alkaloid content and provides new entry points for improving the medicinal quality and cultivation strategies of S. tetrandra .
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Yang-yang Lu,Yuan-yuan Fang,Sha-sha Wang,Jing Guo,Jia-lin Song,Liang Zhu,Zhong-kun Lin,Rui Wang,Si-yi Zhang,Wen-sheng Qiu,Wei-wei Qi
Background Gastric cancer is among the common solid tumors. Chemotherapy resistance is the most common issue in gastric cancer treatment. Inhibiting intracellular autophagy may be a feasible method for overcoming chemotherapy resistance. Cepharanthine (CEP), a natural small molecule extracted from the stephania cephalantha Hayata plant, has been demonstrated to significantly inhibit cancer growth and can regulate autophagy. Although CEP can significantly inhibit cancer growth, it remains unclear whether CEP can regulate autophagy in gastric cancer. This study aimed to investigate whether CEP can enhance the sensitivity of gastric cancer to chemotherapy and elucidate its molecular mechanism. Methods Three gastric cancer cell lines (AGS, SGC7901, and MFC) and one normal gastric mucosal epithelial cell line (GES-1) were used for in vitro experiments. The characterization of autophagy in gastric cancer cells included the detection of autophagy markers and autophagy flux through immunofluorescence staining and Western blotting, as well as the assessment of lysosomal function using fluorescence staining (LysoTracker Red DND-99, Acridine Orange staining) and Western blotting. The cytotoxicity of CEP, autophagy inhibitors (chloroquine [CQ] and 3-methyladenine [3MA]), and chemotherapy drugs (doxorubicin [DOX] and cisplatin [CIS]) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell colony formation, and fluorescence staining techniques (H2DCFDA, Dihydroethidium, and JC-1 staining). The interaction between CEP and autophagy inhibitors was tested in a 615 mice model, and changes in the gut microbiota were determined through accurate 16S absolute quantification sequencing. The signaling pathway and autophagy regulatory target TRIB3-FOXO3-FOXM1 were confirmed through molecular docking, RNA sequencing, bioinformatic analysis, transfection techniques, and Western blotting. Results CEP blocked autophagic flux in gastric cancer cells without affecting lysosomal function. As a novel autophagy inhibitor, CEP could combine with conventional autophagy inhibitors (CQ and 3MA) to block intracellular autophagy, thereby inhibiting gastric cancer growth. During this process, changes in the gut microbiota were observed, including low-level changes in Odoribacterium, Erysipelatoclostridium , and ParaPrevotella and high-level changes in Ileibacterium, Enterorhabdus , and Bifidobacterium . Additionally, CEP synergistically inhibited the growth of gastric cancer when combined with chemotherapy drugs. Mechanistically, the TRIB3-FOXO3-FOXM1 signaling axis was found to be involved in the inhibition of gastric cancer by CEP combined with autophagy inhibitors and chemotherapy drugs, thereby mediating cell apoptosis. Conclusion This study links the TRIB3-FOXO3-FOXM1 axis with chemotherapy efficacy. Our findings demonstrated that CEP inhibits autophagy by modulating the FOXO3-FOXM1 axis. When combined with chemotherapy drugs (DOX and CIS), CEP, as an autophagy inhibitor, can limit TRIB3 protein expression, thereby regulating the FOXO3-FOXM1 axis and enhancing its ability to prevent gastric cancer growth. These findings may contribute to improving the prognosis of patients with gastric cancer. Furthermore, these results enrich the fundamental understanding of how autophagy inhibition can enhance clinical cancer treatment efficacy and provide insights into the potential mechanisms by which CEP functions as an anti-tumor drug, thereby exploring its value for clinical application.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 7
·期 3
·1028-1042
·
IF 5.831
Fulei Liu,Xiaoxian Huang,Lingfei Han,Mangmang Sang,Lejian Hu,Bowen Liu,Bingjing Duan,Pan Jiang,Xin Wang,Zhou Qiao,Congyu Ma,Wenyuan Liu,Jun Liu,Feng Feng,Wei Qu
Gambogic acid (GA) is a natural antitumor drug candidate with advantages of broad-spectrum activity, low toxicity and multiple mechanisms. Its clinical application is hindered, however, by low aqueous solubility, instability and poor pharmacokinetic properties. In this research, core–shell hybrid nanoparticles have been developed to improve the druggability of GA. The nanoparticles are composed of a benzylamidated poly(γ-glutamic acid) (BzPGA) derivative as a core material and an amphiphilic hyaluronic acid derivative grafted with all-trans retinoic acid (HA-C6-ATRA) as a shell material. Through π–π stacking interactions, GA is encapsulated into BzPGA to form the “core” of the hybrid nanoparticle and the “shell” is formed by HA-C6-ATRA with a π–π stacking mediated “molecular fence”. The nanovehicle, with sub 100 nm size, provides almost 100% encapsulation efficiency, a good protective effect and a sustained release profile for GA. A series of evaluations suggest that the core–shell nanoparticles provide a stable aqueous injection formulation (I), improved stability (II), prolonged circulation time and conferred tumor targeting properties (III) for GA. As a result, the anti-tumor activity of GA is significantly enhanced without causing higher toxicity, indicating that the designed nanoplatform dramatically improves the druggability of GA. This study may also provide inspiration for drug development research.
研究领域:
药学
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纳米技术
·
药物递送系统
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
BRIEFINGS IN BIOINFORMATICS
·
2021
·Vol. 22
·期 2
·1378-1386
·
IF 11.622
Li Shasha,Liu Wenli,Chen Yangzhen,Wang Liqin,An Wenlin,An Xiaoping,Song Lihua,Tong Yigang,Fan Huahao,Lu Chenyang
Antiviral therapies targeting the pandemic coronavirus disease 2019 (COVID-19) are urgently required. We studied an already-approved botanical drug cepharanthine (CEP) in a cell culture model of GX_P2V, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related virus. RNA-sequencing results showed the virus perturbed the expression of multiple genes including those associated with cellular stress responses such as endoplasmic reticulum (ER) stress and heat shock factor 1 (HSF1)-mediated heat shock response, of which heat shock response-related genes and pathways were at the core. CEP was potent to reverse most dysregulated genes and pathways in infected cells including ER stress/unfolded protein response and HSF1-mediated heat shock response. Additionally, single-cell transcriptomes also confirmed that genes of cellular stress responses and autophagy pathways were enriched in several peripheral blood mononuclear cells populations from COVID-19 patients. In summary, this study uncovered the transcriptome of a SARS-CoV-2-related coronavirus infection model and anti-viral activities of CEP, providing evidence for CEP as a promising therapeutic option for SARS-CoV-2 infection.
研究领域:
病毒学
·
分子生物学
·
药理学
·
转录组学
·
传染病学
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DOI
PubMed
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-15
·
IF 7
Lu Yang-yang,Zhu Chun-yang,Ding Yi-xin,Wang Bing,Zhao Shu-fen,Lv Jing,Chen Shu-ming,Wang Sha-sha,Wang Yan,Wang Rui,Qiu Wen-sheng,Qi Wei-wei
Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata , is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2021
·
IF 7.991
Lulu Cai,Lina Dong,Xuan Sha,Shuai Zhang,Siwen Liu,Xiaoxi Song,Mingming Zhao,Qi Wang,Kai Xu,Jingjing Li
Traditional photothermal therapy (PTT) usually requires hyperthermia (greater than50 °C) to mediate effective tumor ablation, which could inevitably induce heating damage to the adjacent normal tissues. Therefore, to achieve effective tumor killing at relatively low temperature is crucial to improve the application of PTT. MoS 2 , as an attractive photothermal agents, have attracted much attention in biomedical applications. But the separation of exfoliation and functionalization of MoS 2 nanosheets (NSs) partly complicates the preparation process of MoS 2 NSs-based theranostic nanomaterials. Herein, we formulated a facile one-pot approach for the exfoliation and in situ functionalization of single-layer MoS 2 nanosheets by using bovine serum albumin template gadolinium oxide (BSA-Gd 2 O 3 ) nanoparticles as the exfoliating agent and magnetic resonance imaging (MRI) T 1 contrast agent. On this basis, hyaluronic acid (HA) was further conjugated to target cancer cells with overexpression of CD44, and then gambogic acid (GA), a natural heat shock protein 90 inhibitor and antitumor drug was loaded, which could reduce the thermo-resistance of tumor cells and achieve effective PTT at a mild temperature (43–45 °C). In this research, both in vitro and in vivo experiments have confirmed that the GA/MoS 2 /BSA-Gd 2 O 3 -HA nanocomposite possesses good biocompatibility and is promising for the application in MRI-guided combined low-temperature PTT and chemotherapy.
研究领域:
纳米技术
·
生物医学工程
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癌症治疗
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材料科学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Minjun Yao,Caihua Zhang,Lingzhi Ni,Xiaoxiao Ji,Jianqiao Hong,Yazhou Chen,Jie Wang,Congsun Li,Jiyan Lin,Tingting Lu,Yihao Sheng,Menghao Sun,Mingmin Shi,Chenhe Zhou,Xunzi Cai
Osteoarthritis is a worldwide joint disease caused by abnormal chondrocytic metabolism. However, traditional therapeutic methods aimed at anti-inflammation for early-stage disease are palliative. In the present study, we demonstrated that cepharanthine (CEP), extracted from the plant Stephania cepharantha , exerted protective medicinal efficacy on osteoarthritis for the first time. In our in vitro study, CEP suppressed the elevated expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and inducible nitric oxide synthase (iNOS) stimulated by IL-1β or TNF-α by inhibiting the activation of MAPK and NF-κB signaling pathways, and upregulated the protein expression of aggrecan, collagen II, and Sox9. Also, CEP could reverse the reduced level of cellular autophagy in IL-1β or TNF-α–induced chondrocytes, indicating that the protective effect of CEP on osteoarthritis was achieved by restoring MAPK/NF-κB-mediated autophagy. Furthermore, in a murine OA model, CEP mitigated cartilage degradation and prevented osteoarthritis in the CEP-treated groups versus the OA group. Hence, our results revealed the therapeutic prospect of CEP for anti-osteoarthritic treatment.
研究领域:
药理学
·
风湿病学
·
细胞生物学
·
分子生物学
✓ 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）