Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis
Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). Howeve...
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| creator | Ge, Xinyu Ma, Zhaochen Wei, Wenjing Deng, Huaijue Tang, Shuhui Han, Yefeng Li, Yifan He, Xiaofang Li, Mingxiao Lin, Na Li, Houkai Zhang, Yanqiong Sheng, Lili |
| description | Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated.
This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.
Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.
Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.
Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and |
| doi_str_mv | 10.1016/j.jep.2024.119176 |
| format | Article |
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This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.
Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.
Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.
Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.
[Display omitted]
•Quanduzhong capsule (QDZ) effectively attenuates spontaneous hypertension combined with knee osteoarthritis in rats.•QDZ treatment regulates the expression of immune response and vascular function related proteins.•Metabolomics analysis reveals the reversed effect of QDZ in amino acid and organic acid metabolism.•Comprehensive analysis uncovers close interaction between functional proteins and metabolites after QDZ intervention.</description><identifier>ISSN: 0378-8741</identifier><identifier>ISSN: 1872-7573</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2024.119176</identifier><identifier>PMID: 39617089</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; blood proteins ; blood serum ; Disease Models, Animal ; Drugs, Chinese Herbal - pharmacology ; Drugs, Chinese Herbal - therapeutic use ; endocytosis ; endothelins ; Eucommia ulmoides ; gene expression regulation ; hypertension ; Hypertension - drug therapy ; inflammation ; interleukin-1beta ; isoleucine ; Knee osteoarthritis ; leucine ; macrophage colony-stimulating factor ; Male ; metabolites ; Metabolomics ; musculoskeletal system ; norepinephrine ; Oriental traditional medicine ; osteoarthritis ; Osteoarthritis, Knee - drug therapy ; Osteoarthritis, Knee - metabolism ; protein synthesis ; Proteomics ; Quanduzhong capsule ; Rats ; Rats, Inbred SHR ; Rats, Sprague-Dawley ; Spontaneous hypertension ; synaptic vesicles ; therapeutics ; tricarboxylic acid cycle ; tumor necrosis factor-alpha ; valine</subject><ispartof>Journal of ethnopharmacology, 2025-01, Vol.340, p.119176, Article 119176</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c268t-37f46e61c988a31580cb2029fa3b525732a744483c98406f5a97b345d596f81f3</cites><orcidid>0000-0002-1142-6512</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378874124014752$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39617089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ge, Xinyu</creatorcontrib><creatorcontrib>Ma, Zhaochen</creatorcontrib><creatorcontrib>Wei, Wenjing</creatorcontrib><creatorcontrib>Deng, Huaijue</creatorcontrib><creatorcontrib>Tang, Shuhui</creatorcontrib><creatorcontrib>Han, Yefeng</creatorcontrib><creatorcontrib>Li, Yifan</creatorcontrib><creatorcontrib>He, Xiaofang</creatorcontrib><creatorcontrib>Li, Mingxiao</creatorcontrib><creatorcontrib>Lin, Na</creatorcontrib><creatorcontrib>Li, Houkai</creatorcontrib><creatorcontrib>Zhang, Yanqiong</creatorcontrib><creatorcontrib>Sheng, Lili</creatorcontrib><title>Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated.
This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.
Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.
Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.
Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.
[Display omitted]
•Quanduzhong capsule (QDZ) effectively attenuates spontaneous hypertension combined with knee osteoarthritis in rats.•QDZ treatment regulates the expression of immune response and vascular function related proteins.•Metabolomics analysis reveals the reversed effect of QDZ in amino acid and organic acid metabolism.•Comprehensive analysis uncovers close interaction between functional proteins and metabolites after QDZ intervention.</description><subject>Animals</subject><subject>blood proteins</subject><subject>blood serum</subject><subject>Disease Models, Animal</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Drugs, Chinese Herbal - therapeutic use</subject><subject>endocytosis</subject><subject>endothelins</subject><subject>Eucommia ulmoides</subject><subject>gene expression regulation</subject><subject>hypertension</subject><subject>Hypertension - drug therapy</subject><subject>inflammation</subject><subject>interleukin-1beta</subject><subject>isoleucine</subject><subject>Knee osteoarthritis</subject><subject>leucine</subject><subject>macrophage colony-stimulating factor</subject><subject>Male</subject><subject>metabolites</subject><subject>Metabolomics</subject><subject>musculoskeletal system</subject><subject>norepinephrine</subject><subject>Oriental traditional medicine</subject><subject>osteoarthritis</subject><subject>Osteoarthritis, Knee - drug therapy</subject><subject>Osteoarthritis, Knee - metabolism</subject><subject>protein synthesis</subject><subject>Proteomics</subject><subject>Quanduzhong capsule</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Sprague-Dawley</subject><subject>Spontaneous hypertension</subject><subject>synaptic vesicles</subject><subject>therapeutics</subject><subject>tricarboxylic acid cycle</subject><subject>tumor necrosis factor-alpha</subject><subject>valine</subject><issn>0378-8741</issn><issn>1872-7573</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUGL1TAUhYMoznP0B7iRLN30mTRpkuJKBp0ZGBBB1yFNb6d5tklN0pHnj_I3mmefLsXV5cJ3zz2cg9BLSvaUUPHmsD_Asq9JzfeUtlSKR2hHlawr2Uj2GO0Ik6pSktML9CylAyFEUk6eogvWCiqJanfo563PcB9Nhh4vMWQIs7PY-B7PkE0XpvNupmNyCUd4ADMlnEfAS6F9dmY6bdEssOaCzmBH412acRjwp7UorT_G4O-xNUtaJ8DO4_Iu4e8ujzgtwWfjIawJj8cFYpFMLvjfDr56ABxS8WRiHqPLLj1HT4byH16c5yX68uH956ub6u7j9e3Vu7vK1kLlismBCxDUtkoZRhtFbFdiagfDuqYu4dRGcs4VKwAnYmhMKzvGm75pxaDowC7R6023ZPJthZT17JKFadq86qLJ60bVrfoPlJekGeeioHRDbQwpRRj0Et1s4lFTok-N6oMujepTo3prtNy8Osuv3Qz934s_FRbg7QZAyePBQdTJOvAWehfBZt0H9w_5X0crtXg</recordid><startdate>20250131</startdate><enddate>20250131</enddate><creator>Ge, Xinyu</creator><creator>Ma, Zhaochen</creator><creator>Wei, Wenjing</creator><creator>Deng, Huaijue</creator><creator>Tang, Shuhui</creator><creator>Han, Yefeng</creator><creator>Li, Yifan</creator><creator>He, Xiaofang</creator><creator>Li, Mingxiao</creator><creator>Lin, Na</creator><creator>Li, Houkai</creator><creator>Zhang, Yanqiong</creator><creator>Sheng, Lili</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-1142-6512</orcidid></search><sort><creationdate>20250131</creationdate><title>Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis</title><author>Ge, Xinyu ; Ma, Zhaochen ; Wei, Wenjing ; Deng, Huaijue ; Tang, Shuhui ; Han, Yefeng ; Li, Yifan ; He, Xiaofang ; Li, Mingxiao ; Lin, Na ; Li, Houkai ; Zhang, Yanqiong ; Sheng, Lili</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c268t-37f46e61c988a31580cb2029fa3b525732a744483c98406f5a97b345d596f81f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Animals</topic><topic>blood proteins</topic><topic>blood serum</topic><topic>Disease Models, Animal</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Drugs, Chinese Herbal - therapeutic use</topic><topic>endocytosis</topic><topic>endothelins</topic><topic>Eucommia ulmoides</topic><topic>gene expression regulation</topic><topic>hypertension</topic><topic>Hypertension - drug therapy</topic><topic>inflammation</topic><topic>interleukin-1beta</topic><topic>isoleucine</topic><topic>Knee osteoarthritis</topic><topic>leucine</topic><topic>macrophage colony-stimulating factor</topic><topic>Male</topic><topic>metabolites</topic><topic>Metabolomics</topic><topic>musculoskeletal system</topic><topic>norepinephrine</topic><topic>Oriental traditional medicine</topic><topic>osteoarthritis</topic><topic>Osteoarthritis, Knee - drug therapy</topic><topic>Osteoarthritis, Knee - metabolism</topic><topic>protein synthesis</topic><topic>Proteomics</topic><topic>Quanduzhong capsule</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Sprague-Dawley</topic><topic>Spontaneous hypertension</topic><topic>synaptic vesicles</topic><topic>therapeutics</topic><topic>tricarboxylic acid cycle</topic><topic>tumor necrosis factor-alpha</topic><topic>valine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ge, Xinyu</creatorcontrib><creatorcontrib>Ma, Zhaochen</creatorcontrib><creatorcontrib>Wei, Wenjing</creatorcontrib><creatorcontrib>Deng, Huaijue</creatorcontrib><creatorcontrib>Tang, Shuhui</creatorcontrib><creatorcontrib>Han, Yefeng</creatorcontrib><creatorcontrib>Li, Yifan</creatorcontrib><creatorcontrib>He, Xiaofang</creatorcontrib><creatorcontrib>Li, Mingxiao</creatorcontrib><creatorcontrib>Lin, Na</creatorcontrib><creatorcontrib>Li, Houkai</creatorcontrib><creatorcontrib>Zhang, Yanqiong</creatorcontrib><creatorcontrib>Sheng, Lili</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ge, Xinyu</au><au>Ma, Zhaochen</au><au>Wei, Wenjing</au><au>Deng, Huaijue</au><au>Tang, Shuhui</au><au>Han, Yefeng</au><au>Li, Yifan</au><au>He, Xiaofang</au><au>Li, Mingxiao</au><au>Lin, Na</au><au>Li, Houkai</au><au>Zhang, Yanqiong</au><au>Sheng, Lili</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2025-01-31</date><risdate>2025</risdate><volume>340</volume><spage>119176</spage><pages>119176-</pages><artnum>119176</artnum><issn>0378-8741</issn><issn>1872-7573</issn><eissn>1872-7573</eissn><abstract>Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated.
This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.
Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.
Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.
Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.
[Display omitted]
•Quanduzhong capsule (QDZ) effectively attenuates spontaneous hypertension combined with knee osteoarthritis in rats.•QDZ treatment regulates the expression of immune response and vascular function related proteins.•Metabolomics analysis reveals the reversed effect of QDZ in amino acid and organic acid metabolism.•Comprehensive analysis uncovers close interaction between functional proteins and metabolites after QDZ intervention.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>39617089</pmid><doi>10.1016/j.jep.2024.119176</doi><orcidid>https://orcid.org/0000-0002-1142-6512</orcidid></addata></record> |
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| subjects | Animals blood proteins blood serum Disease Models, Animal Drugs, Chinese Herbal - pharmacology Drugs, Chinese Herbal - therapeutic use endocytosis endothelins Eucommia ulmoides gene expression regulation hypertension Hypertension - drug therapy inflammation interleukin-1beta isoleucine Knee osteoarthritis leucine macrophage colony-stimulating factor Male metabolites Metabolomics musculoskeletal system norepinephrine Oriental traditional medicine osteoarthritis Osteoarthritis, Knee - drug therapy Osteoarthritis, Knee - metabolism protein synthesis Proteomics Quanduzhong capsule Rats Rats, Inbred SHR Rats, Sprague-Dawley Spontaneous hypertension synaptic vesicles therapeutics tricarboxylic acid cycle tumor necrosis factor-alpha valine |
| title | Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis |
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