Elucidating the Effects of Curcumin against Influenza Using In Silico and In Vitro Approaches

The influenza virus is a constantly evolving pathogen that challenges medical and public health systems. Traditionally, curcumin has been used to treat airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate common targets of curcumin and influenza infection and underlying mechanisms, we employed network pharmacology and molecular docking approaches and confirmed results using in vitro experiments. Biological targets of curcumin and influenza were collected, and potential targets were identified by constructing compound–disease target (C-D) and protein–protein interaction (PPI) networks. The ligand–target interaction was determined using the molecular docking method, and in vitro antiviral experiments and target confirmation were conducted to evaluate curcumin’s effects on influenza. Our network and pathway analyses implicated the four targets of AKT1, RELA, MAPK1, and TP53 that could be involved in the inhibitory effects of curcumin on influenza. The binding energy calculations of each ligand–target interaction in the molecular docking showed that curcumin bound to AKT1 with the highest affinity among the four targets. In vitro experiments, in which influenza virus-infected MDCK cells were pre-, co-, or post-treated with curcumin, confirmed curcumin’s prophylactic and therapeutic effects. Influenza virus induction increased the level of mRNA expression of AKT in MDCK cells, and the level was attenuated by curcumin treatment. Collectively, our findings identified potential targets of curcumin against influenza and suggest curcumin as a potential therapy for influenza infection.

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Network pharmacology, molecular docking, and experimental study for the mechanisms of Qishen Yiqi Pills against Cardiovascular Diseases

10.21203/rs.3.rs-889464/v1 ◽

2021 ◽

Author(s):

Jie-wen Zhao ◽

Hai-dong Liu ◽

Ming-yin Man ◽

Lv-ya Wang ◽

Ning Li ◽

...

Keyword(s):

Molecular Docking ◽

Cardiovascular Diseases ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Network Pharmacology ◽

Literature Mining ◽

Therapeutic Effects ◽

Active Components

Abstract Background Qishen Yiqi Pills (QSYQP) is a traditional Chinese compound recipe. However, our understanding of its mechanism has been hindered due to the complexity of its components and targets. In this work, the network pharmacology-based approaches were used to explore QSYQP’s pharmacological mechanism on treating cardiovascular diseases (CVD). Results From ETCM and TCM MESH databases we collected QSYQP’s 333 active components and their 674 putative targets. We constructed the sub-network influence by CVD genes and found that 40% QSYQP targets appeared in 20 modules, in which QSYQP’s targets and CVD genes co-existed as hub nodes in the sub-network. Functional enrichment analysis suggested that the 42 key targets were mainly expressed in platelets, blood vessels, cardiomyocytes, and other tissues. The main signaling pathways regulated and controlled by the key targets were inflammation, immunity, blood coagulation and energy metabolism. Network and pathway analysis identified 7 key targets, which were regulated by 7 compounds of QSYQP. 26 of the 42 important targets, including the 7 key targets were verified by literature mining. Twelve pairs of interactions between key targets and QSYQP’s compounds were validated by molecular docking. Further validation experiments suggested that QSYQP suppressed H/R induced apoptosis and cytoskeleton disruption of cardiomyocytes. Western blotting showed that the expression of cardiovascular diseases-related genes including ACTC1, FoxO1 and DIAPH1 was significantly decreased by establishing the hypoxia-reoxygenation model in vitro, while the protein expression of experimental group was significantly increased by adding QSYQP or its ingredients. Conclusion These results indicated the correlation of QSYQP treatment to the therapeutic effects of CVD. At the molecular level, this study revealed the multicomponent and multitargeting mechanisms of QSYQP in the regulation and treatment of cardiovascular diseases, potentially providing a reference for the further utilization of QSYQP.

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Exploring the effect of Polyphyllin I on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210816141436 ◽

2021 ◽

Vol 24 ◽

Author(s):

Shuxian Yu ◽

Wenhui Gao ◽

Puhua Zeng ◽

Chenglong Chen ◽

Zhuo Liu ◽

...

Keyword(s):

Molecular Docking ◽

Liver Cancer ◽

Mechanism Of Action ◽

Active Ingredient ◽

Vehicle Group ◽

Network Pharmacology ◽

Dependent Manner ◽

In Vitro Experiments ◽

Concentration Dependent Manner

Aim and Objective: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. Materials and Methods: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. Results: Bioinformatics analysis found that PPI had totally 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 μmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). Conclusion: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

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Network Pharmacology Analysis of the Therapeutic Mechanisms Underlying Beimu-Gualou Formula Activity against Bronchiectasis with In Silico Molecular Docking Validation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/3656272 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Xin Shen ◽

Hong Li ◽

Wen-Jun Zou ◽

Jian-Ming Wu ◽

Long Wang ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Cellular Response ◽

Inflammatory Responses ◽

Interaction Network ◽

Mechanisms Of Action ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Target Interaction ◽

In Silico Molecular Docking

Background. The classical Chinese herbal prescription Beimu-Gualou formula (BMGLF) has been diffusely applied to the treatment of respiratory diseases, including bronchiectasis. Although concerning bronchiectasis the effects and mechanisms of action of the BMGLF constituents have been partially elucidated, it remains to be determined how the formula in its entirety exerts therapeutic effects. Methods. In this study, the multitarget mechanisms of BMGLF against bronchiectasis were predicted with network pharmacology analysis. Using prepared data, a drug-target interaction network was established and subsequently the core therapeutic targets of BMGLF were identified. Furthermore, the biological function and pathway enrichment of potential targets were analyzed to evaluate the therapeutic effects and pivotal signaling pathways of BMGLF. Finally, virtual molecular docking was performed to assess the affinities of compounds for the candidate targets. Results. The therapeutic action of BMGLF against bronchiectasis involves 18 core target proteins, including the aforementioned candidates (i.e., ALB, ICAM1, IL10, and MAPK1), which are assumed to be related to biological processes such as drug response, cellular response to lipopolysaccharide, immune response, and positive regulation of NF-κB activity in bronchiectasis. Among the top 20 signaling pathways identified, mechanisms of action appear to be primarily related to Chagas disease, allograft rejection, hepatitis B, and inflammatory bowel disease. Conclusion. In summary, using a network pharmacology approach, we initially predicted the complex regulatory profile of BMGLF against bronchiectasis in which multilink suppression of immune/inflammatory responses plays an essential role. These results may provide a basis for novel pharmacotherapeutic approaches for bronchiectasis.

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Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Danyu Gukang Pills for Application to Osteonecrosis of the Femoral Head Disease

10.21203/rs.3.rs-143355/v1 ◽

2021 ◽

Author(s):

Yongchang Guo ◽

Dapeng Zhang ◽

Yuju Cao ◽

Xiaoyan Feng ◽

Caihong Shen ◽

...

Keyword(s):

Molecular Docking ◽

Femoral Head ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

In Vitro Experiments ◽

Active Components

Abstract Ethnopharmacological relevanceOsteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide, which may lead to disability in patients without effective treatment. A newly developed formula of Chinese medicine, Danyu Gukang Pills (DGP), was recognized to be effective for ONFH. Nevertheless, its molecular mechanisms remain to be clarified. MethodsNetwork pharmacology was adopted to detect the mechanism of DGP on ONFH. The compounds of DGP were collected from the online databases, and active components were selected based on their OB and DL index. The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. The compounds-targets and targets-pathways network were constructed in an R and Cytosacpe software. The mechanism was further investigated via molecular docking. Finally, in-vitro experiments were validated in the BMSCs. ResultsA total of 2305 compounds in DGP were gained, among which, 370 were selected as active components for which conforming to criteria. Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. ConclusionThe current study firstly researched the molecular mechanism of DGP on ONFH based on network pharmacology. The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway.

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A Network Pharmacology Approach for Exploring the Mechanisms of Panax notoginseng Saponins in Ischaemic Stroke

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5582782 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Cong Wang ◽

Hao Chen ◽

Shi-tang Ma ◽

Bin-bin Mao ◽

Yu Chen ◽

...

Keyword(s):

Molecular Docking ◽

Ischaemic Stroke ◽

Panax Notoginseng ◽

Docking Studies ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Panax Notoginseng Saponins ◽

Ginsenoside Re ◽

Molecular Docking Studies ◽

Ppi Networks

Background. Panax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology. Methods. PNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins. Results. A total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments. Conclusions. The ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS.

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A Systematic Study of the Mechanism of Acacetin Against Sepsis Based on Network Pharmacology and Experimental Validation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.683645 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuanshuo Ouyang ◽

Yi Rong ◽

Yanming Wang ◽

Yanli Guo ◽

Liya Shan ◽

...

Keyword(s):

Molecular Docking ◽

Gap Junctions ◽

Active Sites ◽

Experimental Validation ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Protective Effects ◽

M1 Polarization ◽

Highly Involved

Sepsis is a dysregulated systemic response to infection, and no effective treatment options are available. Acacetin is a natural flavonoid found in various plants, including Sparganii rhizoma, Sargentodoxa cuneata and Patrinia scabiosifolia. Studies have revealed that acacetin potentially exerts anti-inflammatory and antioxidative effects on sepsis. In this study, we investigated the potential protective effect of acacetin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation and molecular docking. First, we found that acacetin significantly suppressed pathological damage and pro-inflammatory cytokine expression in mice with LPS-induced fulminant hepatic failure and acute lung injury, and in vitro experiments further confirmed that acacetin attenuated LPS-induced M1 polarization. Then, network pharmacology screening revealed EGFR, PTGS2, SRC and ESR1 as the top four overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 20 enriched biological processes and signalling pathways associated with the therapeutic effects of acacetin on sepsis. Further network pharmacological analysis indicated that gap junctions may be highly involved in the protective effects of acacetin on sepsis. Finally, molecular docking verified that acacetin bound to the active sites of the four targets predicted by network pharmacology, and in vitro experiments further confirmed that acacetin significantly inhibited the upregulation of p-src induced by LPS and attenuated LPS-induced M1 polarization through gap junctions. Taken together, our results indicate that acacetin may protect against sepsis via a mechanism involving multiple targets and pathways and that gap junctions may be highly involved in this process.

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Prediction of Rhizoma Drynariae Targets in the Treatment of Osteoarthritis Based on Network Pharmacology and Experimental Verification

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5233462 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Guang-yao Chen ◽

Xiao-yu Liu ◽

Jia-qi Chen ◽

Xin-bo Yu ◽

Jing Luo ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Critical Role ◽

Network Pharmacology ◽

Inflammatory Factor ◽

In Vitro Experiments ◽

Ppi Network ◽

Rhizoma Drynariae

Rhizoma Drynariae has been widely used for the treatment of osteoarthritis (OA), but its potential targets and molecular mechanisms remain to be further explored. Targets of Rhizoma Drynariae and OA were predicted by relevant databases, and a protein-protein interaction (PPI) network was constructed to identify key targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to obtain related pathways and then select significant pathways associated with OA. The OA chondrocyte model was established by inflammatory factor-induced SW1353 chondrocytes, and molecular docking was conducted to verify the above theoretical prediction. The results showed that a total of 86 Rhizoma Drynariae-OA interaction targets were identified, among which IL-6 and AKT1 were the key targets in the PPI network. Luteolin was the most critical component of Rhizoma Drynariae. KEGG results indicated that the effects of Rhizoma Drynariae on OA are associated with the PI3K/AKT, TNF, IL-17, apoptosis, and HIF-1 signaling pathway. The PI3K/AKT pathway can activate the downstream NF-κB pathway and further regulate the transcription and expression of downstream IL-6, IL-17, HIF-1α, Bax, and TNF, suggesting that the PI3K/AKT/NF-κB pathway is the critical pathway in the treatment of OA with Rhizoma Drynariae. Active components of Rhizoma Drynariae and key proteins of the PI3K/AKT/NF-κB signaling pathway were subjected to molecular docking, whose results showed that luteolin and IKK-α played a critical role. In vitro experiments indicated that both aqueous extracts of Rhizoma Drynariae (AERD) and luteolin inhibited the expression of IL-6 and HIF-1α and suppressed the activation of PI3K/AKT/NF-κB, IL-17, and TNF pathways. The measurement of mitochondrial membrane potential (Δψm) indicated that AERD and luteolin can decrease the LPS-induced early apoptotic cells. Luteolin had a more prominent inhibitory effect than AERD in the abovementioned in vitro experiments. In conclusion, the therapeutic mechanism of Rhizoma Drynariae against OA may be closely related to the inhibition of the PI3K/AKT/NF-κB pathway and downstream pathways, and luteolin plays a vital role in the treatment.

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Anti-influenza Sesquiterpene from the Roots of Reynoutria japonica

Natural Product Communications ◽

10.1177/1934578x1400900308 ◽

2014 ◽

Vol 9 (3) ◽

pp. 1934578X1400900 ◽

Cited By ~ 1

Author(s):

Nguyen Xuan Nhiem ◽

Phan Van Kiem ◽

Chau Van Minh ◽

Nguyen Thi Hoai ◽

Ho Viet Duc ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Mdck Cells ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Therapeutic Index ◽

Reynoutria Japonica ◽

Influenza Activity ◽

Oseltamivir Phosphate

One new flavonol glycoside, 4′- O-methylmyricitrin 3′- O-β-D-glucopyranoside (1), one new sesquiterpene, reynoudiol (11), as well as the 12 known compounds (2–10, 12–14) quercetin 3- O-methyl ether (2), quercitrin (3), isorhamnetin 3- α-L-rhamnopyranoside (4), tamarixetin 3- α-L-rhamnopyranoside (5), myricitrin (6), 4′- O-methylmyricitrin (7), isorhamnetin 3- O-β-D-xylopyranosyl (1→2)- O-β-D-glucopyranoside (8), isorhamnetin 3- O-β-D-apiofuranosyl-(1→2)- O-β-D-glucopyranoside (9), (+)-catechin (10), 7-drimene-3,11,12-triol (12), clovane-2 β,9 α-diol (13), and α-cadinol (14), were isolated from the methanol extract of Reynoutria japonica roots. Based on in vitro screening of the anti-influenza activity of the isolated compounds, reynoudiol showed significantly higher activity than that of oseltamivir phosphate at the same concentration, and did not induce any detectable cytopathic effect in MDCK cells. The CC50 of reynoudiol was above 50 μM and could inhibit influenza virus infection with an IC50 of 0.29 ± 0.01 μM. The therapeutic index (TI) of reynoudiol against influenza infection was 172.4, and thus, this compound can be potentially used to treat oseltamivir-resistant influenza virus infection.

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Network Pharmacology Prediction and Molecular Docking-Based Strategy to Discover the Potential Pharmacological Mechanism of Wen-yu-jin Against Pulmonary Fibrosis in Mouse Model

10.21203/rs.3.rs-923117/v1 ◽

2021 ◽

Author(s):

lu wang ◽

Wenxiang Zhu ◽

Rui Sun ◽

Jing Liu ◽

Qihong Ma ◽

...

Keyword(s):

Molecular Docking ◽

Pulmonary Fibrosis ◽

Signaling Pathway ◽

Lung Fibrosis ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Network Pharmacology ◽

In Vitro Experiments

Abstract Background Pulmonary fibrosis (PF) is a devastating lung disease. The two drugs approved by the FDA, pirfenidone and nintedanib, can only delay the progression of the disease but cannot cure the disease. These drugs also present adverse effects. Wen-yu-jin (WYJ) obtained from steamed roots of Curcuma wenyujin showed a variety of pharmacological activities. In this study we investigated whether WYJ present anti-lung fibrosis effects. Methods Ultra-high pressure liquid chromatography combined with linear ion trap-orbital tandem mass spectrometry (UHPLC-LTQ-orbital trap) was used to identify chemical composition of WYJ. PF-related and WYJ-related targets were obtained from public databases. Network pharmacological was performed to acquire potential targets and major signaling pathways. The binding activity of composition with core targets was predicted by molecular docking. Based on the predicted results, the anti-lung fibrosis effect of WYJ was verified in vivo and in vitro experiments. Results 23 major compositions of WYJ were identified based on UHPLC-LTQ-Orbitrap. According to the results of network pharmacology, MAPK signaling pathway might play an important role in WYJ against lung fibrosis and STAT3 also could be the potential therapeutic targets. Molecular docking results indicated that most of the compositions have good binding activities with core targets. In vivo and in vitro experiments showed that WYJ alleviated process of fibrosis by inhibiting MAPK signaling pathway and the levels of phosphorylated STAT3 (p-STAT3). Conclusion According to the results of network pharmacology and molecular docking, in vivo and in vitro experiments further verified potential targets and molecular mechanism of WYJ against lung fibrosis. Our study provided a novel approach to explain the pharmacological basis of other herbs.

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Systematic Elucidation of the Mechanism of Action of Curcumin Against Colorectal Cancer via Network Pharmacology Approach

10.21203/rs.3.rs-535607/v1 ◽

2021 ◽

Author(s):

Xinyue Han ◽

Yimin Xu ◽

Xiaoqiang Liu ◽

Yuan Li ◽

Cui Guo ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Docking ◽

Signaling Pathways ◽

Signaling Pathway ◽

Mechanism Of Action ◽

Experimental Verification ◽

Enrichment Analysis ◽

Network Pharmacology ◽

In Vitro Experiments

Abstract Background: Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated.Aim: To investigate the mechanism of action of curcumin in the treatment of CRC via network pharmacology, molecular docking and experimental verification.Methods: The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking and in vitro experiments.Results: A total of 30 potential targets of curcumin for CRC treatment were collectedThe core targets included AKT1, EGFR and STAT3 were identified. GO function enrichment analysis showed 140 items, and KEGG pathway enrichment analysis showed 61 signaling pathways, that were related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway and PI3K-Akt signali-ng pathway. In vitro experimental verification showed that curcumin could promote the apoptosis of CRC cells, and the key proteins of these signaling pathways were differentially expressed.Conclusion: This study explored the targets and pathways of curcumin in the treatment of colorectal cancer. In vitro experiments showed that curcumin has a therapeutic effect against CRC by inhibiting PI3K-Akt signaling pathway. Our results will lay a foundation for subsequent clinical research and drug development.

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