Therapeutic Effects and Mechanisms of Fufang Longdan Mixture on Metabolic Syndrome with Psoriasis via miR-29a-5p/IGF-1R Axis

Guangyun LUO^1,2Xiangyi KONG²Fang WANG³Zhiming WANG²Zhuo ZHANG²Huan CUI²Yiwen ZHANG²Wen HUANG²Xuesong YANG^2*Jianzhou YE^1,2*

• ¹Nanjing University of Chinese Medicine, Nanjing, China
• ²Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China
• ³First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China

The 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.Objective: This 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.Methods: UPLC-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.Results: Chemical 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.Our 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.