Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking
Ren-Shen-Bai-Du Powder (RSBDP) is currently used for inflammatory bowel disease (IBD) therapy in China. However, its potential mechanism against IBD remains unknown. In this study, we initially identified potential targets of RSBDP against IBD through network pharmacology analysis and molecular dock...
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MDPI AG
2022-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/9/1038 |
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| author | Ni Jin Yao Liu Peiyu Xiong Yiyi Zhang Jingwen Mo Xiushen Huang Yi Zhou |
| author_facet | Ni Jin Yao Liu Peiyu Xiong Yiyi Zhang Jingwen Mo Xiushen Huang Yi Zhou |
| author_sort | Ni Jin |
| collection | DOAJ |
| description | Ren-Shen-Bai-Du Powder (RSBDP) is currently used for inflammatory bowel disease (IBD) therapy in China. However, its potential mechanism against IBD remains unknown. In this study, we initially identified potential targets of RSBDP against IBD through network pharmacology analysis and molecular docking. Afterwards, the DSS-induced colitis mice model was employed to assess the effects of RSBDP. The results of network pharmacology indicated that a total of 39 main active ingredients in RSBDP generated 309 pairs of drug-ingredient and ingredient-target correspondences through 115 highly relevant targets of IBD. The primary ingredients (quercetin, kaempferol, luteolin, naringenin, and sitosterol) exerted functions through multiple targets that include CYP1B1, CA4/7, and ESR1/2, etc. GO functional enrichment analysis revealed that the targets related to IBD were significantly enriched in the oxidation-reduction process, protein binding, and cytosol. Per the KEGG pathway analysis, pathways in cancer, adherens junction, and nitrogen metabolism were pivotal in the RSBDP’s treatment of IBD. Additionally, molecular docking demonstrated that a set of active ingredients and their targets displayed good bonding capabilities (e.g., kaempferol and AhR with combined energy < 5 kcal/mol). For the animal experiment, oral RSBDP promoted weight recovery, reduced intestinal inflammation, and decreased serum IL-1, IL-6, and IL-8 concentrations in the DSS + RSBDP group. Meanwhile, oral RSBDP significantly up-regulated the mRNA levels of <i>CA7</i>, <i>CPY1B1</i>, and <i>PTPN11</i>; in particular, the expression level of <i>CYP1B1</i> in the DSS + RSBDP group was up-regulated by as high as 9-fold compared to the DSS group. Western blot results indicated that the protein levels of AKR1C1, PI3K, AKT, p-AKT, and Bcl-2 were significantly down-regulated, and Bax was significantly up-regulated in the DSS + RSBDP group. Compared to the DSS and control groups, the Bax/Bcl-2 value in the DSS + RSBDP group increased 4-fold and 8-fold, respectively, which suggested that oral RSBDP promotes apoptosis of intestinal epithelial cells. In short, this study established quercetin, kaempferol, luteolin, naringenin, and sitosterol as the primary key active ingredients of RSBDP that exert synergistic therapeutic effects against IBD through modulating the AhR/CYP1B1 and AKR1C1/PI3K/AKT pathways. |
| first_indexed | 2024-03-09T22:52:01Z |
| format | Article |
| id | doaj.art-1ce5f31759884ce283e1f9a5e0b02902 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:52:01Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-1ce5f31759884ce283e1f9a5e0b029022023-11-23T18:17:27ZengMDPI AGPharmaceuticals1424-82472022-08-01159103810.3390/ph15091038Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular DockingNi Jin0Yao Liu1Peiyu Xiong2Yiyi Zhang3Jingwen Mo4Xiushen Huang5Yi Zhou6School of Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, ChinaSchool of Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaRen-Shen-Bai-Du Powder (RSBDP) is currently used for inflammatory bowel disease (IBD) therapy in China. However, its potential mechanism against IBD remains unknown. In this study, we initially identified potential targets of RSBDP against IBD through network pharmacology analysis and molecular docking. Afterwards, the DSS-induced colitis mice model was employed to assess the effects of RSBDP. The results of network pharmacology indicated that a total of 39 main active ingredients in RSBDP generated 309 pairs of drug-ingredient and ingredient-target correspondences through 115 highly relevant targets of IBD. The primary ingredients (quercetin, kaempferol, luteolin, naringenin, and sitosterol) exerted functions through multiple targets that include CYP1B1, CA4/7, and ESR1/2, etc. GO functional enrichment analysis revealed that the targets related to IBD were significantly enriched in the oxidation-reduction process, protein binding, and cytosol. Per the KEGG pathway analysis, pathways in cancer, adherens junction, and nitrogen metabolism were pivotal in the RSBDP’s treatment of IBD. Additionally, molecular docking demonstrated that a set of active ingredients and their targets displayed good bonding capabilities (e.g., kaempferol and AhR with combined energy < 5 kcal/mol). For the animal experiment, oral RSBDP promoted weight recovery, reduced intestinal inflammation, and decreased serum IL-1, IL-6, and IL-8 concentrations in the DSS + RSBDP group. Meanwhile, oral RSBDP significantly up-regulated the mRNA levels of <i>CA7</i>, <i>CPY1B1</i>, and <i>PTPN11</i>; in particular, the expression level of <i>CYP1B1</i> in the DSS + RSBDP group was up-regulated by as high as 9-fold compared to the DSS group. Western blot results indicated that the protein levels of AKR1C1, PI3K, AKT, p-AKT, and Bcl-2 were significantly down-regulated, and Bax was significantly up-regulated in the DSS + RSBDP group. Compared to the DSS and control groups, the Bax/Bcl-2 value in the DSS + RSBDP group increased 4-fold and 8-fold, respectively, which suggested that oral RSBDP promotes apoptosis of intestinal epithelial cells. In short, this study established quercetin, kaempferol, luteolin, naringenin, and sitosterol as the primary key active ingredients of RSBDP that exert synergistic therapeutic effects against IBD through modulating the AhR/CYP1B1 and AKR1C1/PI3K/AKT pathways.https://www.mdpi.com/1424-8247/15/9/1038Ren-Shen-Bai-Du Powder (RSBDP)inflammatory bowel diseasenetwork pharmacologymolecular dockingunderlying mechanism |
| spellingShingle | Ni Jin Yao Liu Peiyu Xiong Yiyi Zhang Jingwen Mo Xiushen Huang Yi Zhou Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking Pharmaceuticals Ren-Shen-Bai-Du Powder (RSBDP) inflammatory bowel disease network pharmacology molecular docking underlying mechanism |
| title | Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking |
| title_full | Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking |
| title_fullStr | Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking |
| title_full_unstemmed | Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking |
| title_short | Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking |
| title_sort | exploring the underlying mechanism of ren shen bai du powder for treating inflammatory bowel disease based on network pharmacology and molecular docking |
| topic | Ren-Shen-Bai-Du Powder (RSBDP) inflammatory bowel disease network pharmacology molecular docking underlying mechanism |
| url | https://www.mdpi.com/1424-8247/15/9/1038 |
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