Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis
BackgroundThe occurrence of comorbid metabolic syndrome and psoriasis (MS-P) is owing to the complex interplay between metabolic dysregulation and inflammatory responses. However, current treatments have shown limited efficacy in improving the symptoms of both conditions simultaneously.ObjectiveThis...
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Frontiers Media S.A.
2025-05-01
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| author | Guangyun Luo Guangyun Luo Xiangyi Kong Fang Wang Zhiming Wang Zhuo Zhang Huan Cui Yiwen Zhang Wen Huang Xuesong Yang Jianzhou Ye Jianzhou Ye |
| author_facet | Guangyun Luo Guangyun Luo Xiangyi Kong Fang Wang Zhiming Wang Zhuo Zhang Huan Cui Yiwen Zhang Wen Huang Xuesong Yang Jianzhou Ye Jianzhou Ye |
| author_sort | Guangyun Luo |
| collection | DOAJ |
| description | BackgroundThe occurrence of comorbid metabolic syndrome and psoriasis (MS-P) is owing to the complex interplay between metabolic dysregulation and inflammatory responses. However, current treatments have shown limited efficacy in improving the symptoms of both conditions simultaneously.ObjectiveThis study aimed to investigate the therapeutic efficacy of Fufang Longdan Mixture (FLM) in treating MS-P comorbidity, elucidate its mechanism through the miR-29a-5p/IGF-1R axis and evaluate treatment responses between APOE−/− and C57BL/6 mice.MethodsUPLC-Q-exactive-MS/MS analysis was used to characterise FLM’s chemical composition. Metabolic syndrome was induced in APOE−/− and C57BL/6 mice using a high-fat, high-sugar diet, while psoriasis-like lesions were induced in the mice via the administration of imiquimod. The mice were randomised into control, model, Yinxieling (8 g/kg/d) and FLM (0.5 mL/d) groups. We assessed the treatment efficacy through metabolic parameters, hematoxylin and eosin (H&E) staining and inflammatory cytokine profiling. The direct targeting of IGF-1R by miR-29a-5p was verified via dual-luciferase reporter assays. We analysed the expression patterns and interactions of miR-29a-5p/IGF-1R using RT-qPCR, Western blotting and fluorescence in situ hybridisation.ResultsChemical analysis identified 2,665 compounds in FLM, which were predominantly shikimates and phenylpropanoids (32%), alkaloids (20%) and terpenoids (13%). FLM significantly improved metabolic parameters in MS-P mice, including fasting glucose levels, insulin resistance indices and lipid profiles (p < 0.05), with more pronounced effects observed in the C57BL/6 mice (p < 0.05). FLM demonstrated superior metabolic regulatory effects compared with Yinxieling (p < 0.05). The treatment significantly reduced Psoriasis Area and Severity Index (PASI) scores and inhibited epidermal hyperplasia (p < 0.05). Furthermore, FLM suppressed the pro-inflammatory cytokines, such as GM-CSF, IFN-γ, IL-9 and IL-17, while elevating the anti-inflammatory IL-10 levels (p < 0.05). Dual-luciferase assays confirmed that IGF-1R is a direct target of miR-29a-5p. Mechanistic studies revealed that FLM upregulated miR-29a-5p expression while downregulating IGF-1R (p < 0.05), with evident co-localisation in lesional tissues.ConclusionOur findings demonstrate that FLM effectively ameliorates MS-P comorbidity through modulation of the miR-29a-5p/IGF-1R axis, showing significant therapeutic efficacy across different genetic backgrounds. |
| format | Article |
| id | doaj-art-951069a9f864404d9d8554d911f9b130 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-951069a9f864404d9d8554d911f9b1302025-08-20T02:28:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15853691585369Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axisGuangyun Luo0Guangyun Luo1Xiangyi Kong2Fang Wang3Zhiming Wang4Zhuo Zhang5Huan Cui6Yiwen Zhang7Wen Huang8Xuesong Yang9Jianzhou Ye10Jianzhou Ye11The First Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaDepartment of Dermatology, First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaThe First Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaCollege of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaBackgroundThe occurrence of comorbid metabolic syndrome and psoriasis (MS-P) is owing to the complex interplay between metabolic dysregulation and inflammatory responses. However, current treatments have shown limited efficacy in improving the symptoms of both conditions simultaneously.ObjectiveThis study aimed to investigate the therapeutic efficacy of Fufang Longdan Mixture (FLM) in treating MS-P comorbidity, elucidate its mechanism through the miR-29a-5p/IGF-1R axis and evaluate treatment responses between APOE−/− and C57BL/6 mice.MethodsUPLC-Q-exactive-MS/MS analysis was used to characterise FLM’s chemical composition. Metabolic syndrome was induced in APOE−/− and C57BL/6 mice using a high-fat, high-sugar diet, while psoriasis-like lesions were induced in the mice via the administration of imiquimod. The mice were randomised into control, model, Yinxieling (8 g/kg/d) and FLM (0.5 mL/d) groups. We assessed the treatment efficacy through metabolic parameters, hematoxylin and eosin (H&E) staining and inflammatory cytokine profiling. The direct targeting of IGF-1R by miR-29a-5p was verified via dual-luciferase reporter assays. We analysed the expression patterns and interactions of miR-29a-5p/IGF-1R using RT-qPCR, Western blotting and fluorescence in situ hybridisation.ResultsChemical analysis identified 2,665 compounds in FLM, which were predominantly shikimates and phenylpropanoids (32%), alkaloids (20%) and terpenoids (13%). FLM significantly improved metabolic parameters in MS-P mice, including fasting glucose levels, insulin resistance indices and lipid profiles (p < 0.05), with more pronounced effects observed in the C57BL/6 mice (p < 0.05). FLM demonstrated superior metabolic regulatory effects compared with Yinxieling (p < 0.05). The treatment significantly reduced Psoriasis Area and Severity Index (PASI) scores and inhibited epidermal hyperplasia (p < 0.05). Furthermore, FLM suppressed the pro-inflammatory cytokines, such as GM-CSF, IFN-γ, IL-9 and IL-17, while elevating the anti-inflammatory IL-10 levels (p < 0.05). Dual-luciferase assays confirmed that IGF-1R is a direct target of miR-29a-5p. Mechanistic studies revealed that FLM upregulated miR-29a-5p expression while downregulating IGF-1R (p < 0.05), with evident co-localisation in lesional tissues.ConclusionOur findings demonstrate that FLM effectively ameliorates MS-P comorbidity through modulation of the miR-29a-5p/IGF-1R axis, showing significant therapeutic efficacy across different genetic backgrounds.https://www.frontiersin.org/articles/10.3389/fphar.2025.1585369/fullmetabolic syndrome-psoriasis comorbidityFufang Longdan mixtureMiR-29a-5pIGF-1Rtraditional Chinese medicine |
| spellingShingle | Guangyun Luo Guangyun Luo Xiangyi Kong Fang Wang Zhiming Wang Zhuo Zhang Huan Cui Yiwen Zhang Wen Huang Xuesong Yang Jianzhou Ye Jianzhou Ye Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis Frontiers in Pharmacology metabolic syndrome-psoriasis comorbidity Fufang Longdan mixture MiR-29a-5p IGF-1R traditional Chinese medicine |
| title | Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis |
| title_full | Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis |
| title_fullStr | Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis |
| title_full_unstemmed | Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis |
| title_short | Therapeutic effects and mechanisms of Fufang Longdan mixture on metabolic syndrome with psoriasis via miR-29a-5p/IGF-1R axis |
| title_sort | therapeutic effects and mechanisms of fufang longdan mixture on metabolic syndrome with psoriasis via mir 29a 5p igf 1r axis |
| topic | metabolic syndrome-psoriasis comorbidity Fufang Longdan mixture MiR-29a-5p IGF-1R traditional Chinese medicine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1585369/full |
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