Abstract
Pithecellobium clypearia Benth. (accepted name: Archidendron clypearia (Jack) I.C.Nielsen; Mimosaceae), a popular traditional Chinese medicine, has a significant anti-inflammatory effect. The crude water extract of the aerial part of P. clypearia has been clinically applied to treat upper respiratory tract infections, acute gastroenteritis, laryngitis, and pharyngitis. However, the therapeutic mechanism of ethanol fraction of water extract (ESW) of P. clypearia to treat psoriasis should be complemented. The aim of our research was to clarify the protective effects of ESW from P. clypearia against psoriasis-like skin inflammation induced by imiquimod (IMQ) in mice with efficacy indexes and target tissue (spleen and serum) metabolomics. The ingredient of ESW was analyzed by ultrahigh-performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) method. The imiquimod-induced psoriatic mouse model was employed to investigate the effect of ESW against psoriasis, where the treatment method was implemented for 6 days both topically (Gel at 5%) and orally (at 2.4 g/kg p.o.). Traditional pharmacodynamic indicators (phenotypic characteristics, psoriasis area and severity index (PASI) score, H&E staining, immunohistochemical staining, the thickness of epidermis, body weight change, and spleen index) were conducted to appraise the efficacy of ESW. Furthermore, a gas chromatography-mass spectrometer (GC-MS) coupled with multivariate analysis was integrated and applied to obtain serum and spleen metabolic profiles for clarifying metabolic regulatory mechanisms of ESW. The current study illustrated that ESW is composed mainly of gallic acid, ethyl gallate, quercitin, 7-O-galloyltricetiflavan, quercetin, and myricetin by UHPLC-MS/MS analysis. ESW could distinctly improve IMQ-induced psoriasis in mouse through reducing PASI score, alleviating tissue damage, restoring spleen index, and inhibiting proliferating cell nuclear antigen (PCNA) expression in psoriasis-like skin tissue. From the metabolomics study, 23 markers with significant changes are involved in eight main pathways in spleen and serum samples, including linoleic acid metabolism and glycine, serine, and threonine metabolism. The current study showed that ESW had obvious antipsoriasis effects on IMQ-induced psoriasis in mice, which might be attributed to regulating the dysfunction of differential biomarkers and related pathways. In summary, ESW of P. clypearia showed a favourable therapeutic effect on IMQ-induced psoriasis, and metabolomics provided insights into the mechanisms of ESW to the treatment of psoriasis.
Highlights
Psoriasis is a chronic inflammatory and immune-mediated skin disease
Oral administration of 2.4 g/kg ethanol fraction of water extract (ESW) for six consecutive days for effective treatment of psoriasis was visualized by apparent characteristics and histology
In view of highthroughput and high-resolution metabolomics analysis method of GC/MSD united with cluster analysis and metabolic pathway analysis, it was discovered that ESW could ameliorate psoriatic lesions by acting on 17 different biomarkers in spleen samples which regulated 21 metabolic pathways and six diverse variances in serum samples which regulated 11 metabolic pathways
Summary
Psoriasis is a chronic inflammatory and immune-mediated skin disease. Inverse psoriasis, guttate psoriasis, and pustular psoriasis are typical clinical classification (Rendon and Schäkel, 2019). It presents clinically as sharp erythema, scaly patches, and thickening that may spread to all parts of the body (Parmar et al, 2017). Various factors were related to the pathogenesis of psoriasis, including genetic factors, the immune system, and environmental conditions. Some inflammatory cytokines including tumor necrosis factor-α (TNFα), interleukin- (IL-) 23, and IL-17 derived from T cells and dendritic cells, macrophages, and keratinocytes play a key role in the pathogenesis of psoriasis (Kamiya et al, 2019). There are some systemic drugs with substantial clinical experience (i.e., acitretin, methotrexate, and cyclosporine), the well-known adverse effects of those drugs, teratogen, hepatotoxicity, and nephrotoxicity, are still inevitable (Kim et al, 2017)
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