JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Dong-mei Li,Fu-cui Zhu,Jie Wei,Jia-xiu Xie,Jun-hui He,Dong-mei Wei,Yi Li,Ke-dao Lai,Li-min Liu,Qi-biao Su,Gui-ning Wei,Bin Wang,Yan-cheng Liu
Ethnopharmacological relevance Polyrhachis vicina Roger ( P. vicina ), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis , hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia . Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. Aim of the study The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. Methods To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology , molecular docking, qRT-PCR, western blotting , CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. Results Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. Conclusion According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.
研究领域:
药理学
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肿瘤学
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传统中药
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2023
·Vol. 20
·期 4
·480-492
·
IF 2.1
Li Xuejing,Wang Ying,Zhou Xiang,Wang Hui,Xu Jiang
Background: Increasing evidence shows that electroacupuncture pretreatment (EP) plays a crucial role in cerebral ischemia-reperfusion (I/R) injury, and cerebral I/R injury is the most serious complication of ischemic stroke treatment. The role of miR-155-5p in cerebral I/R injury has
been studied, but the regulation of EP on miR-155-5p has not been reported.Methods: The middle cerebral artery occlusion (MCAO) mice were used to investigate the role of EP in cerebral I/R injury. Longa and modified neurological severity scores (mNSS) were used to evaluate neurological
impairment. HE staining and TUNEL staining were used to evaluate brain injury. The expressions of miR-155-5p, Yin Yang 1 (YY1) and p53 were detected by qRT-PCR. The expressions of related proteins were detected by western blot. The binding of YY1 to miR- 155-5p was verified by dual-luciferase
reporter assay and chromatin immunoprecipitation (ChIP) assay. Mice brain microvascular endothelial cells (BMECs) were isolated and cultured for in vitro experiments. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to verify the role of YY1, p53 and miR-155-5p in cerebral I/R injury
in vitro.Results: MCAO modeling induced brain injury, apoptosis, and increased levels of miR-155-5p, YY1, and p53. EP markedly alleviated brain injury and reduced levels of miR-155-5p, p53, and YY1. miR-155 agomir markedly increased the expression of miR-155-5p and p53. miR-155 antagomir
decreased the levels of miR-155-5p and p53. Dual-luciferase reporter and ChIP assay verified that YY1 regulated miR-155-5p expression. YY1 shNRA greatly decreased miR-155-5p and p53. Inhibition of p53 decreased miR-155-5p expression. Both miR-155-5p inhibitor and YY1 shRNA promoted proliferation,
inhibited apoptosis, and decreased levels of ICAM-1 and Eselectin of OGD/R-treated BMECs. Inhibition of p53 strengthened the effect of miR-155-5p inhibitor and YY1 shNRA on BMECs.Conclusion: Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury by regulating the
YY1/p53/miR-155-5p axis.
研究领域:
神经科学
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分子生物学
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针灸
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脑血管疾病
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DOI
PubMed
高影响因子
Metallomics
·
2024
·
IF 2.9
Zhang Yan,Hua Xia,Han Xiaohu,Fang Xue,Li Peng,Zhai Jingbo,Xie Lin,Lv Yanming,Lai Yonghao,Meng Chengcheng,Zhang Yi,Liu Shiwei,Chen Zeliang
Bacterial biofilms are associated with antibiotic resistance and account for approximately 80% of all bacterial infections. In this study, we explored novel nanomaterials for combating bacteria and their biofilms. Artemisinin nano-copper (ANC) was synthesised using a green synthesis strategy, and its shape, size, structure, elemental composition, chemical valence, zeta potential, and conductivity were characterised using transmission electron microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, zeta potential, and dynamic light scattering (DLS). The results showed that ANC was successfully synthesised utilizing a liquid-phase chemical reduction method using chitosan as a modified protectant and l-ascorbic acid as a green reducing agent. The stability of ANC was evaluated using DLS. The results showed that the particle size of the ANC at different concentrations was comparable to that of the original solution after 7 days of storage, and there was no significant change in PDI (P > 0.05). The antibacterial effects of ANC on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were determined by Disk diffusion and broth dilution methods. The results demonstrated that ANC inhibited and killed E. coli and S. aureus. The effect of ANC on bacterial biofilms was investigated using Crystal Violet staining, scanning electron microscopy, laser confocal microscope, and quantitative PCR. The results showed that ANC treatment was able to destroy bacterial biofilms and downregulate biofilm- and virulence-related genes in E. coli (HlyA, gyrA, and F17) and S. aureus (cna, PVL, ClfA, and femB). Green-synthesised ANC possesses excellent anti-biofilm properties and is expected to exhibit antibacterial and anti-biofilm properties.
研究领域:
纳米技术
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微生物学
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生物医学工程
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材料科学
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药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Yunxia,Wu Xiaoxiao,Li Ruoqi,Sui Mengru,Li Guoyin,Fan Shuhua,Yang Mingsheng,Liu Qiuping,Liu Xiaomeng,Wu Changjing,Li Lili
Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyHC1 and MyHC2a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.
研究领域:
药理学
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肌肉生物学
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代谢疾病
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分子生物学
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细胞生物学
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动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Cao Xu,Zhang Ningyi,Chen Hening,Wang Wei,Liang Yijun,Zhang Jiaxin,Liu Ruijia,Li Shuo,Yao Yuhao,Jin Qian,Guo Ziwei,Chen Yue,Gong Yuanyuan,Li Xiaoke,Zao Xiaobin,Ye Yong’an
The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.
研究领域:
药理学
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病毒学
·
分子生物学
·
网络药理学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Hanghai Zhou,Qing Liu,Lijia Jiang,Qi Shen,Chunlei Chen,Chunfang Zhang,Jiangwu Tang
Oil pollution in intertidal zones is an important environmental issue that has serious adverse effects on coastal ecosystems . This study investigated the efficacy of a bacterial consortium constructed from petroleum degraders and biosurfactant producers in the bioremediation of oil-polluted sediment. Inoculation of the constructed consortium significantly enhanced the removal of C 8 –C 40 n -alkanes (80.2 ± 2.8% removal efficiency) and aromatic compounds (34.4 ± 10.8% removal efficiency) within 10 weeks. The consortium played dual functions of petroleum degradation and biosurfactant production, greatly improving microbial growth and metabolic activities. Real-time quantitative polymerase chain reaction (PCR) showed that the consortium markedly increased the proportions of indigenous alkane-degrading populations (up to 3.88-times higher than that of the control treatment). Microbial community analysis demonstrated that the exogenous consortium activated the degradation functions of indigenous microflora and promoted synergistic cooperation among microorganisms . Our findings indicated that supplementation of a bacterial consortium of petroleum degraders and biosurfactant producers is a promising bioremediation strategy for oil-polluted sediments.
研究领域:
环境科学
·
微生物学
·
生物技术
·
生态学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Shuai Chen,Jie Jin,Ziqing Xu,Huawei Han,Lan Wu,Zhiwei Li
Background Catalpol , a major active component of the Chinese herb Rehmannia glutinosa , possesses various pharmacological benefits, including anti-inflammatory, antidiabetic , and antitumor properties. Recent studies have reported that catalpol can attenuate bone loss and enhance bone formation. Nevertheless, the molecular mechanisms underlying its effects on osteoporosis pathogenesis remain unclear. Purpose We investigated whether catalpol had a protective effect against postmenopausal osteoporosis (PMOP) and explored its exact mechanism of action. Methods Seventy-two rats were randomly divided into six groups: sham, model, low-dose catalpol (5 mg/kg/day), medium-dose catalpol (10 mg/kg/day), high-dose catalpol (20 mg/kg/day), and positive control (alendronate, 2.5 mg/kg). In this experiment, a ovariectomy was performed to establish a female rat model of PMOP. After 12 weeks of gavage, micro-computed tomography (micro-CT) and histochemical staining were performed to evaluate bone mass, bone microstructure and histological parameters. Furthermore, RAW 264.7 cells were induced by RANKL to form mature osteoclasts to investigate the effect of catalpol on osteoclast differentiation and apoptosis in vitro . Additionally, the osteoclast apoptosis-related proteins of Sirt6 , ERα, FasL , NFATc1, cleaved-caspase 8, cleaved-caspase 3, and Bax were assessed using western blotting . The expressions of NFATc1, Ctsk, Oscar , and Trap were quantified using RT-qPCR. The apoptotic rate of the osteoclasts was determined using flow cytometry. Sirt6 knockdown was performed using siRNA gene silencing in experiments to investigate its role in catalpol-mediated osteoclast apoptosis. The deacetylation of ERα in osteoclasts was tested via co-immunoprecipitation. Results Catalpol (10 and 20 mg/kg) and alendronate (2.5 mg/kg) could significantly improve bone mineral density (BMD) and microstructure and decrease osteoclast density in ovariectomized (OVX) rats. In addition, catalpol (10 and 20 mg/kg) upregulated the expression of Sirt6, ERα, FasL, cleaved-caspase 8, cleaved-caspase 3, Bax, and downregulated the expression of NFATc1, Ctsk, Oscar, Trap both in vivo and in vitro . Catalpol also promoted ERα deacetylation and stabilized ERα protein to enhance the expression of FasL. In addition, Sirt6 knockdown by siRNA prevented ERα deacetylation and eliminated catalpol-mediated osteoclast apoptosis. Conclusions The present study demonstrated that catalpol prevents estrogen deficiency-induced osteoporosis by promoting osteoclast apoptosis via the Sirt6-ERα-FasL axis. These findings revealed a novel molecular mechanism underpinning the impact of catalpol in the progression of osteoporosis and provided novel insights into the treatment of osteoporosis.
研究领域:
药理学
·
骨骼生物学
·
分子生物学
·
内分泌学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Chen-Ri Su,Shi-Song Yu,Jia-Meng Zhao,Jing Yang,Lin-Yi Dong,Xian-Hua Wang
Exploiting high-performance magnetic beads for specific enrichment of ribonucleic acid (RNA) has important significance in the biomedical research field. Herein, a simple strategy was proposed for fabricating boronate-decorated polyethyleneimine-grafted magnetic agarose beads (BPMAB), which can selectively isolate cis -diol-containing substances through boronate affinity. The size of the basic magnetic agarose beads was controlled through the emulsification of the water-in-oil emulsion with a high-speed shear machine, which enhanced the specific surface area of BPMAB. Subsequently, to modify more boronic acid ligands, branched PEI with excellent hydrophilicity and numerous reaction sites was grafted. 2,4-Difluoro-3-formylphenyl boronic acid (2,4-DFPBA) was covalently immobilized for selectively capturing cis -diol-containing substances under physiological condition (pH 7.4). The BPMAB with a diameter range from 1.86 μm to 11.60 μm possessed clearly spherical structure, and excellent magnetic responsiveness and suspension ability in aqueous solution. β-Nicotinamide adenine dinucleotide (β-NAD), a short-chain cis -diol carrying agent, was selected as a target molecule for evaluating the adsorption property of BPMAB and the maximum adsorption capacity of BPMAB for β-NAD could reach 205.11 mg g −1 . In addition, the BPMAB as adsorbent was used to selectively enrich RNA from mammalian cells. The maximum adsorption capacity of BPMAB for RNA was 140.50 mg g −1 . Under optimized conditions, the BPMAB-based MSPE successfully enriched the high-quality total RNA with 28S to 18S ribosomal RNA ratios ranging from 2.06 to 2.16. According to the PCR analysis of GADPH gene, the extracted total RNA was successfully reverse transcribed into cDNA. Therefore, we believe that the BPMAB-based MSPE could be applicable for the specific enrichment of RNA from complex biological systems.
研究领域:
生物医学工程
·
分子生物学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·Vol. 29
·期 4
·1000-1011
·
IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
·
细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Meng Luan,Bijun Zhang,Yifan Wei,Fanghua Liu,Yuhong Zhao,Yalian Yu,Qijun Wu
Enhanced drug resistance poses a significant challenge in treating ovarian cancer (OC). Phenylethyl isothiocyanate (PEITC) is involved in drug resistance in OC, but the mechanism remains unclear. In this study, we investigated the molecular regulatory mechanism of carboplatin sensitivity in OC associated with PEITC, MAF BZIP Transcription Factor F (MAFF), and Zinc finger proteins (ZNF) 711. The carboplatin sensitivity was significantly increased in OC cells after PEITC treatment. Knockdown of MAFF significantly enhanced the carboplatin sensitivity of OC cells, promoted apoptosis, inhibited colony-forming efficiency in vitro , and suppressed tumor growth in vivo . The binding site of MAFF to the ZNF711 promoter was predicted, and the knockdown of MAFF significantly increased the ZNF711 expression. Results of the dual luciferase assay and ChIP-PCR confirmed the binding of MAFF to the ZNF711 promoter. Immunofluorescence and CoIP results demonstrated the colocalization and the binding of MAFF and its interacting protein, BZIP Transcription Factor ATF-like 3 (BATF3). Similarly, we confirmed the binding of BATF3 to the ZNF711 promoter. Knockdown of BATF3 alone and simultaneous knockdown of BATF3 and MAFF showed similar regulatory effects on ZNF711 transcription and apoptosis. These suggested that the binding of MAFF to BATF3 inhibited ZNF711 transcription and reduced carboplatin sensitivity in OC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2020
·
IF 4.268
Xiaotian Qi,Jing Liu,Xiaoyu Li,Mengyue Fan,Nana Huang,Rong Sun
Background Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical, cancer chemotherapy induced neutropenia (CCIN) infection and infection-related mortality is high for lack of functionally mature neutrophils . Generating functional neutrophils is new therapeutic approaches to reduce CCIN-associated infection and mortality. Saikosaponin a (SSA) is one of the major bioactive components of Radix Bupleuri (RB) and exerts immunoregulatory effects. Purpose The present study aims to investigate the efficacy and mechanism of SSA in CCIN therapy. Methods SSA was applied both in vitro and in vivo to assess the efficacy of CCIN therapy. The differentiation of neutrophils was measured by Nitroblue tetrazolium (NBT) reduction assay and Giemsa staining assay. The neutrophil differentiation related real-time transcription factors were detected by quantitative PCR (RT-qPCR) and Western Blot . Bacteria killing assay was used to assess the ability of fighting infection. Network pharmacology was employed to explore the mechanism network, and the predicted pathways were validated by Western Blot. Results We found that SSA contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo . Network pharmacology prediction showed 55 pathways were predicted involved in SSA against CCIN. Further validation showed that CBL-ERK1/2 pathway was activated by SSA, which could upregulate PU.1 and CEBPβ expression leading to neutrophil differentiation. Conclusions Our findings suggest a natural regimen SSA regenerates microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2 pathway, providing a rationale for future therapeutic approaches.
研究领域:
药理学
·
肿瘤学
·
免疫学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Jin-hua Fan,Min-min Xu,Li-ming Zhou,Zheng-wei Gui,Lu Huang,Xue-gang Li,Xiao-li Ye
Background and purpose Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear. Method Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets. Results In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes ( CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 , and MMP9 ). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target. Conclusions In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer.
研究领域:
药理学
·
肿瘤学
·
系统生物学
·
中药学
✓ 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）