Fufang Shengdi mixture alleviates psoriasis-like skin inflammation via promoting Annexin-A proteins expression

Traditional Chinese medicine believes that "blood fever" is an important cause of psoriasis. Fufang Shengdi mixture (FFSD), based on the Hongban Decoction, is composed of Rehmannia glutinosa (Gaertn.) DC., Raw gypsum (Chinese: Sheng Shi Gao), and Lonicera japonica Thunb (Caprifoliaceae). FFSD has effects on nourishing Yin, clearing heat, connecting collaterals, and cooling blood. In modern medical explanation, FFSD has the effects of anti-inflammatory and immunosuppression. Our study proved that FFSD can suppress immunity and ameliorate the symptoms of imiquimod-induced psoriasis in mice.This study evaluated the efficacy and possible mechanism of FFSD in psoriasis mice.First, the main components of FFSD were analyzed using high-performance liquid chromatography-tandem high-resolution mass spectrometry (HPLC-HRMS). An imiquimod (IMQ)-induced psoriasis mouse model was used to evaluate the efficacy of FFSD orally. Psoriasis area and severity index (PASI) scores were recorded throughout the course of the mice to reflect the severity of psoriasis. Hematoxylin-eosin staining was used to observe the pathological changes in skin lesions. Enzyme-linked immunosorbent assay (ELISA) was performed to test the level of IFN-γ and TNF-α in plasma. To further investigate the immunopharmacological effect of FFSD, we used chicken ovalbumin (OVA) to induce immunoreaction in mice. ELISA was used to detect the levels of anti-OVA antibody, IFN-γ and TNF-α in mice. Flow cytometry was performed to quantify the ratio of cell types in peripheral blood mononuclear cells (PBMCs) to evaluate the effect of FFSD on immunosuppression. Proteomics and bioinformatics analyzes were performed to find the regulation pathway of the immunosuppressive effect of FFSD. Finally, quantitative PCR (qPCR) and immunohistochemistry were used to measure the upregulation of Annexin-A proteins (ANXAs) in the skin lesion tissue of IMQ-induced mouse.On the basis of knowing the composition of FFSD, we first proved the efficacy of FFSD in alleviating IMQ-induced psoriasis in mice. Second, we further clarified the pharmacological effect of FFSD on immunosuppression via OVA-induced mice. Subsequently, it was found that the significant up-regulation of ANXAs was caused by FFSD through proteomics analysis, and the finding was proved in the IMQ-induced psoriasis mouse model.This study elucidates the immunosuppressive pharmacological effect of FFSD on improving psoriasis through up-regulating ANXAs.