A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation
(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and i...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/11/1678 |
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| author | Md. Rezaul Karim Md. Niaj Morshed Safia Iqbal Shahnawaz Mohammad Ramya Mathiyalagan Deok Chun Yang Yeon Ju Kim Joon Hyun Song Dong Uk Yang |
| author_facet | Md. Rezaul Karim Md. Niaj Morshed Safia Iqbal Shahnawaz Mohammad Ramya Mathiyalagan Deok Chun Yang Yeon Ju Kim Joon Hyun Song Dong Uk Yang |
| author_sort | Md. Rezaul Karim |
| collection | DOAJ |
| description | (1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species and 114 metabolites from the gutMgene database. Further, we used different online-based database platforms to predict 1890 gene targets associated with metabolites. Moreover, DisGeNET, OMIM, and Genecard databases were used to consider 13,104 disease-related gene targets. We used a Venn diagram and various protein−protein interactions (PPIs), KEGG pathways, and GO analyses for the functional analysis of gene targets. Moreover, the subnetwork of protein−protein interactions (through string and cytoscape platforms) was used to select the top 20% of gene targets through degree centrality, betweenness centrality, and closeness centrality. To screen the possible candidate compounds, we performed an analysis of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of metabolites and then found the best binding affinity using molecular docking simulation. (3) Results: Finally, we found the key gene targets that interact with suitable compounds and function against kidney cancer and inflammation, such as MTOR (with glycocholic acid), PIK3CA (with 11-methoxycurvularin, glycocholic acid, and isoquercitrin), IL6 (with isoquercitrin), PTGS2 (with isoquercitrin), and IGF1R (with 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, isoquercitrin), showed a lower binding affinity. (4) Conclusions: This study provides evidence to support the positive effects of SCFA-producing microbial metabolites that function against kidney cancer and inflammation and makes integrative research proposals that may be used to guide future studies. |
| first_indexed | 2024-03-09T16:59:05Z |
| format | Article |
| id | doaj.art-e74e06ad7deb4c79961a4cf0ee3a3bb7 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T16:59:05Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e74e06ad7deb4c79961a4cf0ee3a3bb72023-11-24T14:32:15ZengMDPI AGBiomolecules2218-273X2023-11-011311167810.3390/biom13111678A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and InflammationMd. Rezaul Karim0Md. Niaj Morshed1Safia Iqbal2Shahnawaz Mohammad3Ramya Mathiyalagan4Deok Chun Yang5Yeon Ju Kim6Joon Hyun Song7Dong Uk Yang8Department of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaDepartment of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaDepartment of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaGraduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaGraduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaDepartment of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaGraduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of KoreaDepartment of Veterinary International Medicine, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDepartment of Biopharmaceutical Biotechnology, College of Life Science, Kyung Hee University, Yongin-si 17104, Republic of Korea(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species and 114 metabolites from the gutMgene database. Further, we used different online-based database platforms to predict 1890 gene targets associated with metabolites. Moreover, DisGeNET, OMIM, and Genecard databases were used to consider 13,104 disease-related gene targets. We used a Venn diagram and various protein−protein interactions (PPIs), KEGG pathways, and GO analyses for the functional analysis of gene targets. Moreover, the subnetwork of protein−protein interactions (through string and cytoscape platforms) was used to select the top 20% of gene targets through degree centrality, betweenness centrality, and closeness centrality. To screen the possible candidate compounds, we performed an analysis of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of metabolites and then found the best binding affinity using molecular docking simulation. (3) Results: Finally, we found the key gene targets that interact with suitable compounds and function against kidney cancer and inflammation, such as MTOR (with glycocholic acid), PIK3CA (with 11-methoxycurvularin, glycocholic acid, and isoquercitrin), IL6 (with isoquercitrin), PTGS2 (with isoquercitrin), and IGF1R (with 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, isoquercitrin), showed a lower binding affinity. (4) Conclusions: This study provides evidence to support the positive effects of SCFA-producing microbial metabolites that function against kidney cancer and inflammation and makes integrative research proposals that may be used to guide future studies.https://www.mdpi.com/2218-273X/13/11/1678network pharmacologygut microbial metabolitesSCFA-producing microbeskidney cancerkidney inflammationmolecular docking |
| spellingShingle | Md. Rezaul Karim Md. Niaj Morshed Safia Iqbal Shahnawaz Mohammad Ramya Mathiyalagan Deok Chun Yang Yeon Ju Kim Joon Hyun Song Dong Uk Yang A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation Biomolecules network pharmacology gut microbial metabolites SCFA-producing microbes kidney cancer kidney inflammation molecular docking |
| title | A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation |
| title_full | A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation |
| title_fullStr | A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation |
| title_full_unstemmed | A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation |
| title_short | A Network Pharmacology and Molecular-Docking-Based Approach to Identify the Probable Targets of Short-Chain Fatty-Acid-Producing Microbial Metabolites against Kidney Cancer and Inflammation |
| title_sort | network pharmacology and molecular docking based approach to identify the probable targets of short chain fatty acid producing microbial metabolites against kidney cancer and inflammation |
| topic | network pharmacology gut microbial metabolites SCFA-producing microbes kidney cancer kidney inflammation molecular docking |
| url | https://www.mdpi.com/2218-273X/13/11/1678 |
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