[Mechanism study on treating psoriasis of blood-heat type with Tuhuaidan Siwu Decoction based on metabolomics and p38 MAPK/NF-κB signaling pathway].

This study aims to investigate the effects of Tuhuaidan Siwu Decoction on serum metabolomics and p38 mitogen-activated protein kinase(p38 MAPK)/nuclear factor kappa B(NF-κB) signaling pathway in propranolol-induced mouse model of psoriasis with syndrome, and to investigate its mechanism of action. Forty KM mice were randomly divided into a blank group, a model group, a positive group, and a treatment group, with 10 mice in each group. The psoriasis model was induced by 5% propranolol hydrochloride, and the blood heat syndrome model was established by intragastric administration of Zingiberis Rhizoma and Glycyrrhizae Radix et Rhizoma decoction combined with ultraviolet lamp irradiation. After 7 days of modeling, the treatment group and the positive group were given corresponding drug interventions, while the blank group and the model group were given normal saline, for 14 consecutive days. The skin lesions of mice were recorded and scored using the psoriasis area and severity index(PASI). Spleen index was detected. Pathological changes of skin lesion tissues were observed by hematoxylin-eosin(HE) staining and scored by Baker scores. The expression of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, and IL-17 in mouse serum was detected by enzyme-linked immunosorbent assay(ELISA). The expression of p38 MAPK, p-p38 MAPK, inhibitor of nuclear factor kappa B alpha(IκBα), NF-κB p65, and p-NF-κB p65 was detected by Western blot. Serum metabolomics analysis of mice was performed to screen differential metabolites and psoriasis-related metabolic pathways. The results showed that compared with the blank group, the model group showed significantly increased PASI score and spleen index, manifestations of parakeratosis or hyperkeratosis, acanthosis, inflammatory cell infiltration in skin histopathology, a significantly increased Baker score, significantly increased expression levels of TNF-α, IL-1β, IL-6, and IL-17, significantly up-regulated phosphorylation levels of p38 MAPK and NF-κB p65, and a significantly down-regulated IκBα level. Compared with the model group, the positive group and the treatment group exhibited significantly decreased PASI scores and spleen indices, improved skin pathological changes, significantly decreased Baker scores, significantly decreased expression levels of TNF-α, IL-1β, IL-6, and IL-17, significantly down-regulated phosphorylation levels of p38 MAPK and NF-κB p65, and significantly up-regulated IκBα levels. Serum metabolomics showed that there were 42 differential metabolites between the blank group and the model group, with 21 of them up-regulated and 21 down-regulated, which were related to metabolic pathways such as glycerophospholipid metabolism, arachidonic acid metabolism, citrate cycle(TCA cycle), and valine, leucine, and isoleucine degradation. There were 38 differential metabolites between the model group and the treatment group, with 15 of them up-regulated and 23 down-regulated, which were mainly related to metabolic pathways such as glycerophospholipid metabolism, valine, leucine, and isoleucine degradation, biosynthesis of ubiquinone and other terpenoid-quinones, and biosynthesis of pantothenate and CoA. Among them, the common metabolic pathways included glycerophospholipid metabolism, valine, leucine, and isoleucine degradation, etc. In conclusion, Tuhuaidan Siwu Decoction may treat psoriasis by regulating the expression of TNF-α, IL-1β, IL-6, and IL-17 and glycerophospholipid metabolism through the p38 MAPK/NF-κB signaling pathway.