Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex
Abstract Background Inflammation is a critical protective response in the body, essential for combating infections and healing injuries. However, chronic inflammation can be harmful and significantly contribute to the development and progression of chronic diseases, with macrophage-mediated response...
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BMC
2025-01-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01083-y |
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| author | Hyunseong Kim Jin Young Hong Wan-Jin Jeon Hyun Kim Changhwan Yeo Junseon Lee Yoon Jae Lee In-Hyuk Ha |
| author_facet | Hyunseong Kim Jin Young Hong Wan-Jin Jeon Hyun Kim Changhwan Yeo Junseon Lee Yoon Jae Lee In-Hyuk Ha |
| author_sort | Hyunseong Kim |
| collection | DOAJ |
| description | Abstract Background Inflammation is a critical protective response in the body, essential for combating infections and healing injuries. However, chronic inflammation can be harmful and significantly contribute to the development and progression of chronic diseases, with macrophage-mediated responses being central to these processes. This study presents “SBR-Pel,” a new therapeutic blend of Shinbaro tab (SBR), a traditional herbal formula, and pelubiprofen (Pel), a non-steroidal anti-inflammatory drug, and investigated their combined anti-inflammatory effects to create a treatment that both improves efficacy and reduces side effects. Methods To this end, we performed both in vitro and in vivo analyses, utilizing a mouse model of inflammation. Viability and cytotoxicity assays, immunohistochemistry, enzyme-linked immunosorbent assays, real-time polymerase chain reaction assays, nociception assays, writhing tests, and blood biochemical analyses were performed. Results In vitro, SBR-Pel synergistically reduced the production of nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines. SBR-Pel also significantly attenuated paw edema in vivo in a Complete Freund’s adjuvant-induced inflammation model in adult mice. Furthermore, immunohistochemical analyses showed that treatment with SBR-Pel reduced both the infiltration of CD68+ macrophages and the expression of pro-inflammatory cytokines in inflamed tissues. Additionally, compared with individual treatment alone, SBR-Pel enhanced the expression of anti-inflammatory cytokines CD206, TGF-β, and IL-10, indicating a synergistic effect. Our research demonstrates that SBR-Pel effectively diminishes inflammatory pain by reducing macrophage infiltration and pro-inflammatory cytokine secretion. Additionally, while 1.5 mg/kg of Pel alone increases levels of liver and kidney toxicity markers, such as aspartate aminotransferase, alanine aminotransferase, and creatinine, combining it with SBR at a reduced dosage of 0.5 mg/kg maintains these markers at normal levels. Conclusions This combined effect highlights SBR-Pel’s potential as an effective treatment for inflammatory diseases driven by heightened macrophage activity, while also minimizing side effects by reducing the Pel dosage. |
| format | Article |
| id | doaj-art-436f9c43ef834a32872bd6b82382460e |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-436f9c43ef834a32872bd6b82382460e2025-01-26T12:38:37ZengBMCMolecular Medicine1528-36582025-01-0131111610.1186/s10020-025-01083-ySynergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complexHyunseong Kim0Jin Young Hong1Wan-Jin Jeon2Hyun Kim3Changhwan Yeo4Junseon Lee5Yoon Jae Lee6In-Hyuk Ha7Jaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationJaseng Spine and Joint Research Institute, Jaseng Medical FoundationAbstract Background Inflammation is a critical protective response in the body, essential for combating infections and healing injuries. However, chronic inflammation can be harmful and significantly contribute to the development and progression of chronic diseases, with macrophage-mediated responses being central to these processes. This study presents “SBR-Pel,” a new therapeutic blend of Shinbaro tab (SBR), a traditional herbal formula, and pelubiprofen (Pel), a non-steroidal anti-inflammatory drug, and investigated their combined anti-inflammatory effects to create a treatment that both improves efficacy and reduces side effects. Methods To this end, we performed both in vitro and in vivo analyses, utilizing a mouse model of inflammation. Viability and cytotoxicity assays, immunohistochemistry, enzyme-linked immunosorbent assays, real-time polymerase chain reaction assays, nociception assays, writhing tests, and blood biochemical analyses were performed. Results In vitro, SBR-Pel synergistically reduced the production of nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines. SBR-Pel also significantly attenuated paw edema in vivo in a Complete Freund’s adjuvant-induced inflammation model in adult mice. Furthermore, immunohistochemical analyses showed that treatment with SBR-Pel reduced both the infiltration of CD68+ macrophages and the expression of pro-inflammatory cytokines in inflamed tissues. Additionally, compared with individual treatment alone, SBR-Pel enhanced the expression of anti-inflammatory cytokines CD206, TGF-β, and IL-10, indicating a synergistic effect. Our research demonstrates that SBR-Pel effectively diminishes inflammatory pain by reducing macrophage infiltration and pro-inflammatory cytokine secretion. Additionally, while 1.5 mg/kg of Pel alone increases levels of liver and kidney toxicity markers, such as aspartate aminotransferase, alanine aminotransferase, and creatinine, combining it with SBR at a reduced dosage of 0.5 mg/kg maintains these markers at normal levels. Conclusions This combined effect highlights SBR-Pel’s potential as an effective treatment for inflammatory diseases driven by heightened macrophage activity, while also minimizing side effects by reducing the Pel dosage.https://doi.org/10.1186/s10020-025-01083-yComplete freund’s adjuvantInflammationMacrophagesPainPelubiprofenShinbaro |
| spellingShingle | Hyunseong Kim Jin Young Hong Wan-Jin Jeon Hyun Kim Changhwan Yeo Junseon Lee Yoon Jae Lee In-Hyuk Ha Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex Molecular Medicine Complete freund’s adjuvant Inflammation Macrophages Pain Pelubiprofen Shinbaro |
| title | Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex |
| title_full | Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex |
| title_fullStr | Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex |
| title_full_unstemmed | Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex |
| title_short | Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex |
| title_sort | synergistic attenuation of complete freund s adjuvant induced inflammation in mice using shinbaro pelubiprofen a novel therapeutic complex |
| topic | Complete freund’s adjuvant Inflammation Macrophages Pain Pelubiprofen Shinbaro |
| url | https://doi.org/10.1186/s10020-025-01083-y |
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