Search PubMedSearch

SEARCH · Search PubMed

Results for “Kaempferol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Hydroxycinnamoyl: coenzyme A transferase involved in the biosynthesis of kaempferol-3-(p-coumaroyl triglucoside) in Pisum sativum.

The major flavonoids of Pisum are derivatives of kaempferol and quercetin, including both triglucosides and acylated triglucosides in which the acyl group is p-coumaric acid. Although hydroxycinnamic acid esters of flavonoids are common pigments in many plants, neither the enzymes nor the precursors involved in their biosynthesis have been demonstrated. We report here that crude enzyme preparations extracted from peas catalyze the transfer of the p-coumaroyl moiety of p-coumaroyl:Coenzyme A to kaempferol-3-triglucoside forming kaempferol-3-(p-coumaroyl triglucoside) as the acylated product. The reaction product has been vigorously shown to be identical to the naturally occurring kaempferol-3-(p-coumaroyl triglucoside) in both chromatographic and chemical properties. The enzymatic formation of the acylated derivative occurred only minimally when incubated with the cofactors required for carboxyl group activation (ligase) and maximally when incubated with p-coumaroyl : Coenzyme A as the acyl donor.

Acyltransferases

Mutagenicity of quercetin and kaempferol on cultured mammalian cells.

Mutagenic activity of quercetin and kaempferol on V79 Chinese hamster cells was investigated. Quercetin was proved to have mutagenicity not only by metabolic activation system using rat liver microsomes, but also by direct application method. Kaempferol was mutagenic by metabolic activation system, but its activity by direct method seemed very low. These data suggest that the tested flavonoids seem to be metabolized for exerting their mutagenic activity and V79 cells themselves have an enzymic activation system which metabolizes at a very slow rate but in a cumulative way.

Animals

[Isolation and identification of flavon(ol)-O-glycosides in caraway (Carum carvi L.), fennel (Foeniculum vulgare Mill.), anise (Pimpinella anisum L.), and coriander (Coriandrum sativum L.), and of flavon-C-glycosides in anise. I. Phenolics of spices (author's transl)].

The flavonoid constituents of various spices were separated by means of chromatography on cellulose colums, and the following compounds were obtained crystalline: Quercetin 3-glucuronide from caraway, fennel, anise, and coriander; isoquercitrin from caraway and fennel; rutin from fennel and anise; quercetin 3-O-caffeylglucoside and kaempferol 3-glucoside from caraway; quercetin 3-arabinoside from fennel, and luteolin 7-glucoside, isoorientin and isovitexin from anise. Other constitutents which were however not obtained crystalline, but which could be identified by the usual procedures were kaempferol 3-glucuronide and kaempferol 3-arabinoside in fennel, apigenin 7-glucoside and a luteolin glycoside in anise, and isoquercitrin and rutin in coriander. The glycosides contained in the fruit of the four spices also occur in the leaves. Leaves of caraway and fennel in addition contain isorhammetin glycosides in low concentration.

Condiments

Proteomic regulation of anti-proliferative and anti-migratory activity by potent phytochemicals from Pistacia integerrima J.L. Steward Ex Brandis via PI3K, AKT1, and KRAS for Lung Cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of mortality worldwide and remains a major therapeutic challenge due to high metastasis, drug resistance and limited treatments. Pistacia integerrima J.L. Steward Ex Brandis (PI) consists of flavonoids, steroids, terpenoids and phenolic compounds reported for pharmacological activities. The efficacy of potent bioactives from P. integerrima may be ascertained employing cytotoxic, antiproliferative, anti-migratory, and anti-metastatic evaluations in A549 NSCLC cells with proteomic profiling, molecular docking, and dynamics simulation study. METHODS AND RESULTS: PI EtAc produced significant dose-dependent cytotoxicity in A549 cells (100&#xa0;&#xb5;g/mL, p&#x2009;<&#x2009;0.0001 in the MTT assay. There was a pronounced decrease in colony formation after treatment with EtAc, with 18.41% (p&#x2009;<&#x2009;0.002), and markedly. Furthermore. PI EtAC markedly inhibited cell migration emphasized by wound healing and Transwell migration (p&#x2009;<&#x2009;0.01) assays, indicating reduced metastatic migratory potential. Proteomic analysis demonstrated significant downregulation of Endoglin (CD105), KLK5 and MMP-2, indicating suppression of angiogenic and metastatic signalling pathways in the Human XL Oncology protein array. The interaction of major PI phytochemicals with key NSCLC-associated targets was recorded in Molecular docking, revealing favourable binding affinities of kaempferol, &#x3b2;- sitosterol, luteolin, and quercetin towards several oncogenic targets, including AKT1(-&#x2009;7.6&#xa0;kcal/mol), PI3K(-&#x2009;9.4&#xa0;kcal/mol), KRAS (-&#x2009;8.5&#xa0;kcal/mol) and MMP9 (-&#x2009;8.1&#xa0;kcal/mol). Molecular dynamics simulation confirmed the structural stability of the kaempferol -AKT1 complex throughout the 100 ns simulation. CONCLUSION: Pistacia integerrima bioactives exhibited significant anti-proliferative, anti-migratory, and anti-metastatic activities in vitro, which may provide scientific rationale identifying newer promising candidates for NSCLC.

Humans

Comparative mutagenesis of plant flavonoids in microbial systems.

The plant flavonoids quercetin (3,5,7,3',4'-pentahydroxyflavone), morin (3,5,7,2',4'-pentahydroxyflavone), kaempferol (3,5,7,4'-tetrahydroxyflavone), chrysin (5,7-dihydroxyflavone), fisetin (3,7,3',4'-tetrahydroxyflavone), myricetin (3,5,7,3',4',5'-hexahydroxyflavone), myricitrin (myricetin-3-rhamnoside), hesperetin (3',5,7-trihydroxy-4'-methoxyflavanone), quercitrin (quercetin-3-L-rhamnoside), rutin (quercetin-3-rhamnosylglucoside or quercetin-3-rutinoside), and hesperidin (hesperetin-7-rutinoside) have been assayed for mutagenicity in the Salmonella/microsomal activation system. Quercetin, morin, kaempferol, fisetin, myricetin, quercitrin and rutin were mutagenic in the histidine reversion system with the frameshift strain TA98. The flavonols quercetin and myricetin are mutagenic without metabolic activation, although more effective when a rat liver microsomal preparation (S-9) is included; all others require metabolic activation. Flavonoids are common constituents of higher plants, with extensive medical uses. In addition to pure compounds, we have examined crude extracts of tobacco (snuff) and extracts from commonly available nutritional supplements containing rutin. Mutagenic activity can be detected and is correlated with the flavonoid content.

Animals

Mutagenicity of plant flavonols in the Salmonella/mammalian microsome test: activation of flavonol glycosides by mixed glycosidases from rat cecal bacteria and other sources.

Over 70 naturally occurring and synthetic flavonoids were screened for mutagenicity with 5 tester strains in the Salmonella/mammalian microsome assay: TA1535, TA100, TA1537, TA1538 and TA98. Frameshift mutagenicity was confined to the flavonols (flavon-3-ols) in strain TA98, TA1537 and TA100. The two most mutagenic falvonols, namely, quercetin (3,3',4',5,7-pentahydroxyflavone) and kaempferol (3,4',5,7-tetrahydroxyflavone), exhibiting 12 and 7 revertants/nmol in TA98 respectively, are also the most common flavonols occurring in plants. Other flavonols exhibited less activity (revertants/nmol): galangin (2.0), rhamnetin (0.45), kaempferide (0.24), fisetin (0.14), myricetin (0.12), robinetin (0.06) and morin (0.05). All of these flavonols apparently exhibited significant activation by Aroclor 1254 induced rat-liver microsome preparations (S9). However, subsequent study revealed that only those flavonols either lacking or possessing one B ring hydroxyl group had an absolute requirement for microsomal activation. Alternatively, quercetin with two B-ring OH groups is not activated by microsomal enzymes, but by soluble (S100) enzymes from liver which are apparently constitutive and not subject to the usual chemical induction. 3 flavonol glycosides, namely, quercetrin (quercetin-3-O-rhamnoside), rutin (quercetin-3-O-rutinoside) and robinin (kaempferol-3-O-galactosido-rhamnoside-7-O-rhamnoside), were found to be nonmutagenic. They could, however, be activated by a variety of mixed glycosidases incorporated in the usual pour plate procedure. The most effective enzyme mixtures were obtained from rat cecal bacteria and from the snail Helix pomatia.

Animals

Mutagens in Japanese pickle identified as flavonoids.

A kind of Japanese pickel was mutagenic to TA100 and TA98 with S9 mix. Its activity was one sixth that of the Chinese pickle from Linhsien County (China), reported previously. Mutagens in this Japanese pickle were isolated; the main component was identified as kaempferol, and a minor component as isorhamnetin. Flavonoids are ubiquitous and the principles identified, kaempferol and isorhamnetin, do not seem to be specific to the pickle vegetable, implying that the mutagenic substances responsible for the high incidence of human cancer in China remain to be identified.

Drug Evaluation, Preclinical

Sphingobium yanoikuyae 41R9 Enhances Nitrogen Uptake by Modulating Transporter Genes and Root Development in Rapeseed.

Plant growth-promoting rhizobacteria (PGPR) are widely recognized for enhancing the absorption of mineral nutrients by crops. While Sphingobium species have been reported as PGPRs, their capacity to improve nitrogen use efficiency (NUE) and the underlying regulatory mechanisms are not yet fully understood. Here, a strain 41R9, isolated from the rhizosphere of N-deficient rapeseed, was found to significantly enhance the growth performance of rapeseed under both low and normal N conditions. Genomic analysis revealed that strain 41R9 was closely related to Sphingobium yanoikuyae. 15N isotope tracer experiments confirmed that inoculation with strain 41R9 significantly boosted N uptake and translocation in rapeseed roots. Transcriptome profiling demonstrated that strain 41R9 directly upregulated N transporter genes (NRT2.5&#xa0;and SLAH1/3), facilitating efficient N acquisition. Furthermore, strain 41R9 maintained jasmonic acid (JA) homoeostasis via JAZ-mediated negative feedback, balancing defense responses and root development, thereby improving the plant's N acquisition capacity in the roots. Metabolomic and in vitro assays further demonstrated that strain 41R9 displayed strong chemotaxis towards kaempferol, a N-deficiency-induced root exudate, suggesting kaempferol might as a chemical effector for S. yanoikuyae recruitment. These findings advance our understanding of PGPR-driven mechanisms in enhancing crop NUE and highlight the potential of harnessing PGPRs for sustainable agriculture.

Plant Roots

Effects and mechanisms of Stauntonia brachyanthera Hand.-Mazz against Alzheimer's disease through network pharmacology and experimental validation.

Stauntonia brachyanthera Hand.-Mazz. (SB), a traditional medicinal plant of the Dong ethnic group with nutraceutical applications, exhibits broad-spectrum pharmacological activity. However, the therapeutic effects and mechanisms of SB on Alzheimer's disease (AD) remain unclear. This study aims to investigate the neuroprotective potential and underlying mechanisms of SB against AD. We utilized network pharmacology and molecular docking to predict the active components, targets, and pathways of SB associated with AD treatment. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were further used to identify potential therapeutic targets and underlying mechanisms of SB in relation to AD. Then, the neuroprotective effects, neuronal differentiation-promoting activity and potential mechanism of key active components of SB on the main therapeutic targets were verified by in vitro experiments. The network pharmacological prediction results showed that the treatment of AD with SB was closely related to MAPK and PI3K/Akt pathways. Further experiments showed that the SB active component kaempferol (KMF) alleviated A&#x3b2;1-42-induced injury and promoted neuronal differentiation. Additionally, we found that KMF-mediated promotion of neuronal differentiation in N2a cells was dependent on the PI3K/Akt and MAPK pathways. In this study, we employed a combined computational-experimental approach to elucidate the neuroprotective mechanisms of SB against Alzheimer's disease. We further validated KMF as a key active component of SB that alleviates A&#x3b2;1-42-induced injury and promotes neuronal differentiation through the PI3K/Akt and MAPK pathways.

Alzheimer's disease

In silico identification of DNMT1 inhibitors from the PlantCyc database through computational approach to assess the anti-cancer potential of nutraceutical compounds in breast cancer.

Breast cancer accounts for a disproportionate share of global cancer-related deaths, with 670,000 fatalities and 2.3 million new diagnoses recorded in women during 2022 alone. Existing treatment modalities carry considerable toxicity burdens, and resistance to available agents remains an unresolved clinical problem. DNA methyltransferase 1 (DNMT1), the enzyme chiefly responsible for maintaining genome-wide methylation patterns during DNA replication, has been mapped out as a high-value target in breast cancer because its dysregulation silences tumour suppressor genes through promoter hypermethylation. The present work involves hierarchical in silico workflow to screen 4549 plant-derived compounds from the PlantCyc database (v16.0.3) against the human DNMT1 catalytic domain (PDB ID: 4WXX). Ten top-scoring compounds were taken forward for molecular docking via AutoDock Vina; Quercetin and Kaempferol both recorded the highest binding affinities at -9.5&#x202f;kcal/mol, Wogonin (-9.3&#x202f;kcal/mol) and Xanthohumol (-8.1&#x202f;kcal/mol) also emerged as strong binders. Pharmacokinetic evaluation using ADMET-AI confirmed that all 10 compounds met Lipinski's rule of five, with human intestinal absorption values at or above 0.98. Wogonin and Xanthohumol were selected for a 100 ns all-atom molecular dynamics (MD) simulation in GROMACS due to their well-rounded ADMET profiles and limited existing data on their specific interactions with DNMT1 in breast cancer. Across all measured trajectory metrics, backbone RMSD, residue fluctuation, radius of gyration, solvent-accessible surface area, and intermolecular hydrogen bond count, Wogonin formed a more stable, compact complex. These findings suggest that Wogonin and Xanthohumol are non-toxic nutraceutical candidates suitable for DNMT1 targeted epigenetic therapy, with computational foundation strong enough to facilitate future in vitro and in vivo validation work.

Humans

Chemical constituents of Echites hirsuta (Apocynaceae).

A phytochemical investigation of an ethanolic extract of the whole plant of Echites hirsuta (Apocynaceae) resulted in the isolation and identification of the flavonoids naringenin, aromadendrin (dihydrokaempferol), and kaempferol; the coumarin fraxetin; the triterpene ursolic acid; and the sterol glycoside sitosteryl glucoside.

Chromatography, Gel

[Flavonol glycosides of leaves and fruits of dill (Anethum graveolens L.). II. Phenolics of spices (author's transl)].

From the leaves of dill (Anethum graveolens L.) ten flavonol glycosides have been isolated by means of polyamide, paper and thin-layer chromatography and could be identified by the usual procedures. The two major flavonoids, quercetin 3-O-beta-D-glucuronide and isorhamnetin 3-O-beta-D-glucuronide, were obtained crystalline. The minor components were found to be the 3-glucosides, 3-galactosides and 3-rhamnoglucosides of quercetin and isorhamnetin. Two other 3-glycosides of quercetin and isorhamnetin occur with the component sugars galactose, xylose, and arabinose. Besides these there are probably other two flavonoids present in trace amounts. In addition, the fruits of dill contain kaempferol 3-glucuronide as main component thought this component is completely absent in leaves.--This is probably the first time that isorhamnetin 3-O-beta-D-glucuronide has been obtained crystalline from a plant.

Chromatography, Thin Layer

Multi-omics identification of therapeutic targets of compound sappan decoction in hepatocellular carcinoma.

BACKGROUND: Compound sappan decoction (CSD) is a multi-herbal traditional Chinese medicine formulation with clinical relevance in hepatocellular carcinoma (HCC). However, its therapeutic mechanisms remain unclear. METHODS: Bioactive compounds of CSD were identified and standardized using pharmacological and chemical databases. Potential targets were predicted via multiple target inference platforms. HCC-related genes were curated from comprehensive disease databases. Summary-data-based Mendelian randomization (SMR) was conducted to infer causal relationships between compound targets and HCC risk using large-scale quantitative trait loci (QTL) datasets and HCC genome-wide association study data. Colocalization analysis, protein-protein interaction (PPI) network construction, and GO/KEGG enrichment were performed on SMR-identified targets. Molecular docking evaluated binding affinities of representative compounds to prioritized targets. RESULTS: A total of 784 overlapping genes between predicted CSD targets and HCC-related genes were subjected to SMR analysis. Among these, 22 targets were significantly associated with HCC risk based on transcriptomic or proteomic QTLs and showed colocalization evidence. Notably, four targets (ADRB2, APOE, SYK, and PGF) were supported by both replication in an independent cohort and strong colocalization. These 22 targets were enriched in apoptosis, PI3K-Akt signaling, redox metabolism, and detoxification pathways. PPI analysis revealed central hubs including MMP9, BCL2, CASP1, and MCL1. Molecular docking demonstrated strong binding of APOE to quercetin, PGF to luteolin-7-olate, and SYK to kaempferol. CONCLUSIONS: CSD may exert therapeutic effects on HCC through modulation of genetically validated targets involved in tumor progression, inflammation, and metabolic reprogramming, supporting its potential clinical utility as an adjunctive treatment strategy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12672-026-04740-8.

Caesalpinia

Mutagenicity of plant flavonoids: structural requirements for mutagenic activity in Salmonella typhimurium.

40 compounds structurally related to the plant flavonol quercetin were tested for mutagenic activity in Salmonella typhimurium strain TA98. 10 flavonols, quercetin, myricetin, rhamnetin, galangin, kaempferol, tamarixetin, morin, 3'-O-methylquercetin, 7,4'-di-O-methylquercetin and 5,7-di-O-methyl-quercetin, exhibited unequivocal mutagenic activity. 4 compounds, quercetin, myricetin, rhamnetin and 5,7-di-O-methylquercetin, were active without metabolic activation, although metabolic activation markedly enhanced their activity. All 4 have free hydroxyl groups at the 3' and 4' positions of the B ring. The other active compounds required an in vitro rat-liver metabolizing system for significant activity. Structural features which appear essential for mutagenic activity in this strain are a basic flavanoid ring structure with (1) a free hydroxyl group at the 3 position, (2) a double bond at the 2, 3 position, (3) a keto group at the 4 position, and (4) a structure which permits the proton of the 3-hydroxyl group to tautomerise to a 3-keto compound. The data are consistent with the requirement for a B ring structure that permits oxidation to quininoid intermediates. Free hydroxyl groups in the B ring are not essential for activity if a rat-liver metabolic activating system is employed. Data from 12 compounds which differ only at the essential sites described above indicate that the structural requirements for mutagenicity in strain TA100 are the same as those for activity in strain TA98. Based on the above structural requirements, a metabolic pathway for flavonol activation to DNA-reactive species is proposed.

Animals

Discussion on the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation technology.

To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and &#x3b2;-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97&#x2009;&#xb1;&#x2009;1.41&#x2009;kcal/mol and -21.15&#x2009;&#xb1;&#x2009;3.17&#x2009;kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.

Network Pharmacology

Integrated data mining and network pharmacology to explore the prescription patterns from a senior TCM oncologist's clinical practice in treating chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) is a common and refractory adverse effect of chemotherapy lacking specific therapeutic strategies currently. Traditional Chinese medicine (TCM) has shown empirical efficacy in clinical HFS management. This study integrated data mining and network pharmacology to systematically elucidate the medication principles and molecular mechanisms underlying Professor Gang Xie's prescriptions for HFS. All medical records from Professor Xie's specialist clinic (January 2020 to March 2025) were retrospectively collected and standardized in Excel. Prescriptions were analyzed through frequency statistics, association and clustering. Active ingredients of core herb pairs and their disease-related targets were identified using TCMSP, HERB, GeneCards, PharmGKB and GEO databases. Protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Molecular docking validated interactions between key bioactive compounds and targets. This study involved 217 prescriptions containing 150 herbs. Core herb combinations comprised Radix Astragali (Huangqi), Poria (Fuling), and Radix Pseudostellariae (Taizishen), predominantly classified as spleen-tonifying agents with warm properties, targeting lung, spleen, and stomach meridians. Network analysis identified 67 bioactive compounds and 899 disease targets. Quercetin, kaempferol, acacetin and luteolin were identified the key ingredients. The core targets (TP53, STAT3, PIK3CA, HSP90AA1, AKT1, CTNNB1, PI3KR1, MAPK1) were enriched in MAPK and PI3K-Akt signaling pathways. Molecular docking confirmed strong binding affinity between key compounds and targets. Professor Xie's therapeutic strategy for HFS emphasizes "spleen fortification, phlegm elimination, and stasis resolution." The core herb combination likely exerts anti-HFS effects via modulation of MAPK and PI3K-Akt pathways, providing a pharmacological basis for TCM-driven HFS management.

Network Pharmacology

UDP-glucose: glucosyltransferase activity involved in the biosynthesis of flavonol triglucosides in Pisum sativum L. seedlings.

From young, light-grown seedlings of Pisum sativum L. an enzyme activity catalyzing the glucosylation of kaempferol and quercetin in the 3-position to form the 3-0-triglucoside derivative has been demonstrated. The reaction proceeds from the aglycone via the mono- and diglucoside intermediates. The triglucoside can be produced from any of the less substituted derivatives with uridine diphosphate-D-glucose (UDPG) as the glucosyl donor. Young leaf tissues had much higher levels of glucosyltransferase activity than the petioles and internodes. This is the first report of the synthesis of flavonol-3-0-triglucosides in vitro.

Flavonoids

Integrating network pharmacology and experimental validation to uncover the synergistic effects of Huangqi ()-Ezhu () with 5-fluorouracil in colorectal cancer models.

OBJECTIVE: To evaluate the effects of Huangqi (Radix Astragali Mongolici)-Ezhu (Rhizoma Curcumae Phaeocaulis) (HQEZ) on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ, especially in combination with 5-Fluorouracil (5-FU). METHODS: The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro. The network pharmacological assay was used to investigate potential mechanisms of HQEZ. Potential target genes were selected by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction network (PPI) and molecular docking. Within key targets, potential targets related to drug sensitivity, especially the sensitivity to 5-FU, were evaluated in HCT116 in vitro by immunofluorescence, quantitative real-time polymerase chain reaction (qPCR) and Western-blot. Then, changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer (COAD) patients from the Cancer Genome Atlas Program (TCGA) database. RESULTS: HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro. By network pharmacological analysis, key targets, such as protein kinase B (AKT1), epidermal growth factor receptor (EGFR), adenosine triphosphate (ATP) binding cassette subfamily B member 1 (ABCB1, also named multidrug resistance protein 1, MDR1), ATP binding cassette subfamily G member 2 (ABCG2), thymidylate synthetase (TYMS, also named TS), prostaglandin-endoperoxide synthase 2 (PTGS2), matrix metallopeptidase 2 (MMP2), MMP9, toll like receptor 4 (TLR4), TLR9 and dihydropyrimidine dehydrogenase (DPYD), were identified. Additionally, 4 potential core active ingredients (Folate, Curcumin, quercetin and kaempferol) were identified to be important for the treatment of colorectal cancer with HQEZ. In key targets, chemoresistance related targets were validated to be affected by HQEZ. Furthermore, 5-FU sensitivity related targets, including MDR1, TS, EGFR, ribonucleotide reductase catalytic subunit M1, Breast and Ovarian Cancer Susceptibility Protein 1 (BRCA1) and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo. Finally, these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database. CONCLUSION: HQEZ has synergistic effects on the anti-tumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro. The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU. The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.

Humans