Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease
<b>Background/Objectives:</b> Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. <i>C...
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2025-01-01
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| author | Mingzhang Lin Linghua Piao Zhendong Zhao Li Liao Dayong Wang Haiwen Zhang Xiande Liu |
| author_facet | Mingzhang Lin Linghua Piao Zhendong Zhao Li Liao Dayong Wang Haiwen Zhang Xiande Liu |
| author_sort | Mingzhang Lin |
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| description | <b>Background/Objectives:</b> Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. <i>Cajanus cajan</i> (L.) <i>Millsp.</i>, traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. <b>Methods:</b> In this study, the major compounds from <i>Cajanus cajan</i> leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (<i>w</i>/<i>v</i>) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-α, IL-1β, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). <b>Results:</b> We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (<i>Erysipelatoclostridium</i> and <i>Staphylococcus</i>) and beneficial bacteria (<i>Odoribacter</i>, unidentified <i>Oscillospiraceae</i>, <i>Lachnoclostridium</i>, and <i>Oscillibacter</i>) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. <b>Conclusions:</b> The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier’s structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-ff108b71d4c14eab8956cec4938eed8d2025-01-24T13:45:16ZengMDPI AGPharmaceuticals1424-82472025-01-011816710.3390/ph18010067Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel DiseaseMingzhang Lin0Linghua Piao1Zhendong Zhao2Li Liao3Dayong Wang4Haiwen Zhang5Xiande Liu6School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, No. 58 Renmin Avenue, Haikou 570228, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Science, Hainan Medical University, Haikou 570228, ChinaAnalytical & Testing Center, Center for Advanced Studies in Precision Instruments, Hainan University, Haikou 570228, ChinaSchool of Tropical Agriculture and Forestry, Hainan University, No. 58 Renmin Avenue, Haikou 570228, ChinaSchool of Pharmaceutical Science, Hainan University, Haikou 570228, ChinaSchool of Tropical Agriculture and Forestry, Hainan University, No. 58 Renmin Avenue, Haikou 570228, ChinaSchool of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of One Health, Hainan University, No. 58 Renmin Avenue, Haikou 570228, China<b>Background/Objectives:</b> Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. <i>Cajanus cajan</i> (L.) <i>Millsp.</i>, traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. <b>Methods:</b> In this study, the major compounds from <i>Cajanus cajan</i> leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (<i>w</i>/<i>v</i>) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-α, IL-1β, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). <b>Results:</b> We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (<i>Erysipelatoclostridium</i> and <i>Staphylococcus</i>) and beneficial bacteria (<i>Odoribacter</i>, unidentified <i>Oscillospiraceae</i>, <i>Lachnoclostridium</i>, and <i>Oscillibacter</i>) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. <b>Conclusions:</b> The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier’s structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses.https://www.mdpi.com/1424-8247/18/1/67IBD<i>Cajanus cajan</i> leaf extractinflammatory immune responsegut microbiota |
| spellingShingle | Mingzhang Lin Linghua Piao Zhendong Zhao Li Liao Dayong Wang Haiwen Zhang Xiande Liu Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease Pharmaceuticals IBD <i>Cajanus cajan</i> leaf extract inflammatory immune response gut microbiota |
| title | Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease |
| title_full | Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease |
| title_fullStr | Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease |
| title_full_unstemmed | Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease |
| title_short | Therapeutic Potential of <i>Cajanus cajan</i> (L.) <i>Millsp</i>. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease |
| title_sort | therapeutic potential of i cajanus cajan i l i millsp i leaf extract in modulating gut microbiota and immune response for the treatment of inflammatory bowel disease |
| topic | IBD <i>Cajanus cajan</i> leaf extract inflammatory immune response gut microbiota |
| url | https://www.mdpi.com/1424-8247/18/1/67 |
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