Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis
Osteoporosis is the most common metabolic disease of skeleton with reduced bone density and weaker bone. Qianggu Capsule as a traditional chinese medicine has been widely used to treat osteoporosis. The potential pharmacological mechanism of its active ingredient Gusuibu is not well understood. The...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1011561/full |
| _version_ | 1811266023959035904 |
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| author | Ann Yehong Huang Zhencheng Xiong Kuankuan Liu Yanan Chang Li Shu Guolan Gao Chi Zhang Chi Zhang Chi Zhang |
| author_facet | Ann Yehong Huang Zhencheng Xiong Kuankuan Liu Yanan Chang Li Shu Guolan Gao Chi Zhang Chi Zhang Chi Zhang |
| author_sort | Ann Yehong Huang |
| collection | DOAJ |
| description | Osteoporosis is the most common metabolic disease of skeleton with reduced bone density and weaker bone. Qianggu Capsule as a traditional chinese medicine has been widely used to treat osteoporosis. The potential pharmacological mechanism of its active ingredient Gusuibu is not well understood. The purpose of this work is to analyze the anti-osteoporosis function of Gusuibu based on network pharmacology, and further explore the potential mechanism of Qianggu Capsule. The active compounds and their corresponding targets of Gusuibu were obtained from TCMSP, TCMID, and BATMAN-TCM databases. Potential therapeutic targets for osteoporosis were obtained through DisGeNET, TTD, GeneCards, MalaCards, CTD, and OMIM databases. The overlapping targets of Gusuibu and osteoporosis were obtained. GO and KEGG pathway enrichment analysis were performed. The “Gusuibu-active compounds-target genes-osteoporosis” network and protein-protein interaction (PPI) network were constructed, and the top hub genes were screened by using the plug-in CytoHubba. Molecular docking was used to verify the binding activity of hub genes and key compounds. We identified 21 active compounds and 140 potential therapeutic targets that may be related to Gusuibu and 10 hub genes (AKT1, IL6, JUN, TNF, MAPK3, VEGFA, EGFR, MAPK1, CASP3, PTGS2). Molecular docking analysis demonstrated that four key active small molecules in Gusuibu (including Luteolin, Naringenin, Kaempferol, and Beta-sitosterol) have excellent binding affinity to the target proteins encoded by the top 10 hub genes. Our new findings indicated that one key active compound kaempferol activated the expression of osteoblast specific transcription factor OSX through JNK kinase pathway. |
| first_indexed | 2024-04-12T20:34:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T20:34:31Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-16e90749490744e3b5aba65f4a359e042022-12-22T03:17:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.10115611011561Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosisAnn Yehong Huang0Zhencheng Xiong1Kuankuan Liu2Yanan Chang3Li Shu4Guolan Gao5Chi Zhang6Chi Zhang7Chi Zhang8Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, United StatesCentral Laboratory, Peking University International Hospital, Beijing, ChinaCentral Laboratory, Peking University International Hospital, Beijing, ChinaCentral Laboratory, Peking University International Hospital, Beijing, ChinaCentral Laboratory, Peking University International Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking University International Hospital, Beijing, ChinaCentral Laboratory, Peking University International Hospital, Beijing, ChinaDepartment of Orthopedics, Peking University International Hospital, Beijing, ChinaBiomedical Engineering Department, Peking University, Beijing, ChinaOsteoporosis is the most common metabolic disease of skeleton with reduced bone density and weaker bone. Qianggu Capsule as a traditional chinese medicine has been widely used to treat osteoporosis. The potential pharmacological mechanism of its active ingredient Gusuibu is not well understood. The purpose of this work is to analyze the anti-osteoporosis function of Gusuibu based on network pharmacology, and further explore the potential mechanism of Qianggu Capsule. The active compounds and their corresponding targets of Gusuibu were obtained from TCMSP, TCMID, and BATMAN-TCM databases. Potential therapeutic targets for osteoporosis were obtained through DisGeNET, TTD, GeneCards, MalaCards, CTD, and OMIM databases. The overlapping targets of Gusuibu and osteoporosis were obtained. GO and KEGG pathway enrichment analysis were performed. The “Gusuibu-active compounds-target genes-osteoporosis” network and protein-protein interaction (PPI) network were constructed, and the top hub genes were screened by using the plug-in CytoHubba. Molecular docking was used to verify the binding activity of hub genes and key compounds. We identified 21 active compounds and 140 potential therapeutic targets that may be related to Gusuibu and 10 hub genes (AKT1, IL6, JUN, TNF, MAPK3, VEGFA, EGFR, MAPK1, CASP3, PTGS2). Molecular docking analysis demonstrated that four key active small molecules in Gusuibu (including Luteolin, Naringenin, Kaempferol, and Beta-sitosterol) have excellent binding affinity to the target proteins encoded by the top 10 hub genes. Our new findings indicated that one key active compound kaempferol activated the expression of osteoblast specific transcription factor OSX through JNK kinase pathway.https://www.frontiersin.org/articles/10.3389/fphar.2022.1011561/fullkaempferolosteoporosisqianggu capsulegusuibuOSXnetwork pharmacology |
| spellingShingle | Ann Yehong Huang Zhencheng Xiong Kuankuan Liu Yanan Chang Li Shu Guolan Gao Chi Zhang Chi Zhang Chi Zhang Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis Frontiers in Pharmacology kaempferol osteoporosis qianggu capsule gusuibu OSX network pharmacology |
| title | Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis |
| title_full | Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis |
| title_fullStr | Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis |
| title_full_unstemmed | Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis |
| title_short | Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis |
| title_sort | identification of kaempferol as an osx upregulator by network pharmacology based analysis of qianggu capsule for osteoporosis |
| topic | kaempferol osteoporosis qianggu capsule gusuibu OSX network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1011561/full |
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