Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review.

The interleukin (IL)-17 axis is involved in many inflammatory and autoimmune diseases. Secukinumab, an IL-17 inhibitor, has been approved for psoriasis treatment. There are accumulating cases of lupus erythematosus induced by IL-17 inhibition. Lupus nephritis after IL-17 inhibition has not been reported. We report the case of a 57-year-old man who developed membranous lupus nephritis after secukinumab treatment for psoriasis. Anti-SSA and PM-Scl antibodies were positive. dsDNA, anti-Smith, and anti-histone antibodies were negative, and serum complement was low. Secukinumab was discontinued, while tacrolimus was initiated, subsequently switched to cyclosporin, belimumab, glucocorticosteroid, and hydroxychloroquine with a good response. The relationship between lupus erythematosus and IL-17 inhibition requires further research.

Real-world outcomes and drug survival of brodalumab: results from the German Psoriasis Registry PsoBest.

Brodalumab, a human monoclonal antibody that targets interleukin-17 receptor A (IL-17RA), is approved in the US and EU for treatment of adults with moderate-to-severe plaque psoriasis. Although brodalumab has demonstrated efficacy and safety vs placebo in clinical trials of patients with psoriasis and psoriatic arthritis (PsA), real-world evidence is needed to evaluate long-term effectiveness and safety of brodalumab in routine care. This interim analysis of the German Psoriasis Registry PsoBest examined patient profiles, treatment outcomes, and drug survival of first-time use of brodalumab for 12 months in adult patients with moderate-to-severe plaque-type psoriasis (with and without PsA) (data cutoff: June 30, 2021). Clinician and patient-reported outcomes of the total cohort (n = 227; PsA, n = 38) indicated a rapid response to brodalumab treatment within the first 3 months, which was maintained up to 12 months. The overall one-year drug survival rate was 76.2%, the mean time to discontinuation was 8.3 months. Reasons for discontinuation were mainly loss/lack of effectiveness, followed by adverse events, contraindication and skin clearance. In sum, brodalumab demonstrated rapid and sustained effectiveness and was well-tolerated over 12 months in German patients with moderate-to-severe psoriasis and PsA in a real-world setting.

Structural elucidation and anti-psoriasis activity of a novel polysaccharide from Saussurea Costus.

PSCP, a novel water-soluble polysaccharide, was extracted from the root of Saussurea costus and subsequently purified using DEAE-52 cellulose and Sephadax G-50 columns. The elucidation of its structure involved various techniques including HPGPC, FT-IR, HPLC-ELSD, GC-MS, NMR, AFM, and SEM. The results show that PSCP was a homogeneous heteropoly saccharide having molecular weight of 4131 Da and mainly composed of 1-α-D-Glcp-(-2-ß-D-Fruf-1-)23-2-ß-D-Fruf. The anti-psoriasis activity of PSCP was evaluated in imiquimod-induced psoriasis in Balb/C mice. This study revealed that treatment with PSCP resulted in a significant improvement in the pathological morphology of the skin and a reduction in the PASI score. Analysis of liver RNA-Seq data indicated that the MAPK signaling pathway may play a crucial role in the ability of PSCP to ameliorate psoriasis. PSCP was found to effectively inhibit the phosphorylation of JNK, ERK, and p38, as well as down-regulate the expression of the transcription factor AP-1 (c-fos and c-jun) in the nucleus, thereby reducing the expression of inflammatory factors. These findings suggest that PSCP holds promise as a novel therapeutic approach for the treatment of psoriasis.

NJK14047 inhibition of p38 MAPK ameliorates inflammatory immune diseases by suppressing T cell differentiation.

p38 MAPK has been implicated in the pathogenesis of rheumatoid arthritis and psoriasis. To assess the therapeutic efficacy of the p38 MAPK inhibitor NJK14047 in the treatment of rheumatoid arthritis and psoriasis, we developed mouse models of collagen-induced rheumatoid arthritis (CIA) and imiquimod-induced psoriasis (IIP). NJK14047 was found to suppress arthritis development and psoriasis symptoms and also suppressed histopathological changes induced by CIA and IIP. Furthermore, we established that CIA and IIP evoked increases in the mRNA expression levels of Th1/Th17 inflammatory cytokines in the joints and skin, which was again suppressed by NJK14047. NJK14047 reversed the enlargement of spleens induced by CIA and IIP as well as increases in the levels of inflammatory cytokine in spleens following induction by CIA and IIP. In human SW982 synovial cells, NJK14047 was found to suppress lipopolysaccharide-induced increases in the mRNA expression of proinflammatory cytokines. NJK14047 inhibition of p38 MAPK suppressed the differentiation of naïve T cells to Th17 and Th1 cells. Our findings in this study provide convincing evidence indicating the therapeutic efficacy of the p38 MAPK inhibitor NJK14047 against CIA and IIP, which we speculate could be associated with the suppression on T-cell differentiation.

Topical Delivery of microRNA-125b by Framework Nucleic Acids for Psoriasis Treatment.

Purpose: Psoriasis is a chronic and recurrent inflammatory dermatitis characterized by T cell imbalance and abnormal keratinocyte proliferation. MicroRNAs (miRNAs) hold promise as therapeutic agents for this disease; however, their clinical application is hindered by poor stability and limited skin penetration. This study demonstrates the utilization of Framework Nucleic Acid (FNA) for the topical delivery of miRNAs in psoriasis treatment. Methods: By utilizing miRNA-125b as the model drug, FNA-miR-125b was synthesized via self-assembly. The successful synthesis and stability of FNA-miR-125b in bovine fetal serum (FBS) were verified through gel electrophoresis. Subsequently, flow cytometry was employed to investigate the cell internalization on HaCaT cells, while qPCR determined the effects of FNA-miR-125b on cellular functions. Additionally, the skin penetration ability of FNA-miR-125b was assessed. Finally, a topical administration study involving FNA-miR-125b cream on imiquimod (IMQ)-induced psoriasis mice was conducted to evaluate its therapeutic efficacy. Results: The FNA-miR-125b exhibited excellent stability, efficient cellular internalization, and potent inhibition of keratinocyte proliferation. In the psoriasis mouse model, FNA-miR-125b effectively penetrated the skin tissue, resulting in reduced epidermal thickness and PASI score, as well as decreased levels of inflammatory cytokines.

Perspectives on Psoriasiform Adverse Events from Immune Checkpoint Inhibitors: Lessons Learned from Our Practice.

Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. Literature Review: We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. Conclusions: As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.

Tick cysteine protease inhibitors suppress immune responses in mannan-induced psoriasis-like inflammation.

Protease inhibitors regulate various biological processes and prevent host tissue/organ damage. Specific inhibition/regulation of proteases is clinically valuable for treating several diseases. Psoriasis affects the skin in the limbs and scalp of the body, and the contribution of cysteine and serine proteases to the development of skin inflammation is well documented. Cysteine protease inhibitors from ticks have high specificity, selectivity, and affinity to their target proteases and are efficient immunomodulators. However, their potential therapeutic effect on psoriasis pathogenesis remains to be determined. Therefore, we tested four tick cystatins (Sialostatin L, Sialostatin L2, Iristatin, and Mialostatin) in the recently developed, innate immunity-dependent mannan-induced psoriasis model. We explored the effects of protease inhibitors on clinical symptoms and histological features. In addition, the number and percentage of immune cells (dendritic cells, neutrophils, macrophages, and γδT cells) by flow cytometry, immunofluorescence/immunohistochemistry and, the expression of pro-inflammatory cytokines (TNF-a, IL-6, IL-22, IL-23, and IL-17 family) by qPCR were analyzed using skin, spleen, and lymph node samples. Tick protease inhibitors have significantly decreased psoriasis symptoms and disease manifestations but had differential effects on inflammatory responses and immune cell populations, suggesting different modes of action of these inhibitors on psoriasis-like inflammation. Thus, our study demonstrates, for the first time, the usefulness of tick-derived protease inhibitors for treating skin inflammation in patients.

A therapeutic strategy of parthenolide in improving imiquimod-induced psoriasis-like skin inflammation targeting IL-36/NETs through skin transdermal therapeutic system.

BACKGROUND: Psoriasis is an inflammatory skin disease that occurs repeatedly over time. The natural product of sesquiterpene lactones, Parthenolide (Par), is isolated from Tanacetum parthenium L. (feverfew) which has significant effects on anti-inflammatory. The therapeutic effect of the medication itself is crucial, but different routes of administration of the same drug can also produce different effects. PURPOSE: The aim of our research sought to investigate the ameliorating effects of Par in psoriasis-like skin inflammation and its related mechanism of action. RESULTS: In the IMQ-induced model, intragastric administration of Par reduced the Psoriasis Area and Severity Index (PASI) score, improved skin erythema, scaling, and other symptoms. And Par decreased the expression of Ki67, keratin14, keratin16 and keratin17, and increased the expression of keratin1. Par could reduce IL-36 protein expressions, meanwhile the expression of Il1b, Cxcl1 and Cxcl2 mRNA were also decreased. Par regulated the expression levels of F4/80, MPO and NE. However, skin transdermal administration of Par was more effective. Similarly, Par attenuated IL-36γ, IL-1ß and caspase-1 activated by Poly(I:C) in in vitro and ex vivo. In addition, Par also reduced NE, PR3, and Cathepsin G levels in explant skin tissues. CONCLUSION: Par ameliorated psoriasis-like skin inflammation in both in vivo and in vitro, especially after treatment with transdermal drug delivery, possibly by inhibiting neutrophil extracellular traps and thus by interfering IL-36 signaling pathway. It indicated that Par provides a new research strategy for the treatment of psoriasis-like skin inflammation and is expected to be a promising drug.

Discontinuation of Fumaric Acid Esters is Affected by Depressive Symptomatology: A Retrospective Analysis.

Fumaric acid esters (FAEs) remain a widespread therapy option for moderate-to-severe psoriasis. However, drug survival of FAEs is limited by adverse events (AEs) or inadequate treatment response. Depressive disturbances are highly prevalent in psoriasis patients and are hypothesized to be associated with the reporting of AEs and therapy discontinuation. This study's aim was to analyze whether psoriasis patients with comorbid depressive symptomatology are more likely to discontinue treatment with FAEs due to AEs and/or inadequate treatment response. Data were retrospectively extracted from the records of patients starting therapy with FAEs in the Department of Dermatology, University Hospital Essen, Germany between 2017 and 2022, covering the first 52 weeks of treatment. Psoriasis severity and depressive symptomatology, as well as AEs and therapy discontinuation, were analyzed. Psoriasis patients (N = 95, 47.37% female) with depressive symptomatology (42.11%) were more likely to discontinue therapy due to patient-reported AEs, while the total number of reported AEs was not associated with depression. The results support the hypothesis that among psoriasis patients with depressive symptoms, the associated introspection and somatization may result in increased sensitivity for AEs and thus in quicker therapy discontinuation. In these patients, the occurrence of nocebo effects should be minimized, e.g. by special communication techniques.

Analysis of Nanoparticles' Effects on Drug-Induced Psoriasis.

Psoriasis, an auto-inflammatory disorder, has major manifestations in the skin but can affect other organs. Currently, this condition has no cure, and the treatments include anti-inflammatory medications. Nanoparticles are widely used for drug delivery and have found successful applications in therapy for cancer and infectious diseases. Nanoparticles can also be used to deliver anti-inflammatory drugs to sites of inflammation. Moreover, some nanotechnology platforms possess intrinsic anti-inflammatory properties and may benefit the therapy of inflammation-driven disorders. Herein, we present a protocol to study nanotechnology concepts' anti-inflammatory properties in a chemically-induced psoriasis model.

Anti-Psoriatic Activity of Black, Green and White Tea Extracts from Southeastern China.

Psoriasis is a common chronic inflammatory disease, but most of its current treatments come with a high risk of side effects. As one of the world's top three beverages, tea has a traditional history of being used as a treatment for skin conditions due to its high safety profile, anti-inflammatory and other properties. In this study, we investigated the anti-psoriasis effects of ethanol extracts of black tea, green tea and white tea from southeastern China. The compositions of the tea extracts (TEs) were first determined by UPLC-Q-Exactive-Orbitrap MS and then genetic analysis, antibacterial, anti-inflammatory, and immunocompetence assays were performed. Imiquimod was used to establish a mouse model of psoriasis-like dermatitis and treating with the extracts to examine their efficacy. A total of 88 chemical components, mainly phenols and organic acids, were identified from the TEs. These TEs ameliorated skin damage and they all reduced the expression of cytokines IL-17 and TNF-α. By analyzing the genes, TEs may affect the inflammatory signaling pathway by regulating the metabolic changes. In addition, TEs can significantly scavenge ROS, NO, and inhibit cellular inflammation. In conclusion, this study examined the inhibitory effects of three TEs on psoriasis and their potential as nutritional supplements for the treatment of skin inflammation.

Comparison between super-responders and non-super-responders in psoriasis under adalimumab treatment: a real-life cohort study on the effectiveness and drug survival over one-year.

BACKGROUND: Data on the characteristics and treatment outcomes of super-responders and non-super-responders in psoriasis under adalimumab treatment are limited. METHODS: A retrospective analysis from psoriatic patients treated with adalimumab was compared to characterize super-responders vs non-super-responders' groups, identify factors associated with super response, and assess treatment outcomes after switching. RESULTS: 15 out of 70 (21.4%) patients were categorized as super-responder. The proportion of patients achieving a PASI 100 response was significantly higher in super-responders than non-super-responders at weeks 12, 24, and 52. Female sex and Charlson Co-morbidity Index were significantly associated with super-responders. A high level of high-density lipoprotein was independently associated with PASI 90 response at weeks 24 and 52. Additionally, nearly 35%-43% of non-super-responders switching to interleukin-17A (IL-17A) inhibitors may achieve a PASI 100 response at week 12. In contrast, all super-responders switching to IL-17A inhibitors achieved a PASI 100 response at week 4. CONCLUSIONS: Super-responders treated with adalimumab have a higher rate of being female and fewer comorbidities. And super-responders have better PASI responses than non-super-responders, whether the patients were treated with adalimumab or switched to IL-17A inhibitors.

Yinxieling decoction ameliorates psoriasis by regulating the differentiation and functions of Langerhans cells via the TGF-ß1/PU.1/IL-23 signal axis.

Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)-induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin-draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin-draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor-ß (TGFß) messenger RNA (mRNA) and interleukin-23 (IL-23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFß/PU.1/IL-23 signal axis.

Secoemestrin C Ameliorates Psoriasis-like Skin Inflammation in Mice by Suppressing the TNF-α/NF-κB Signaling Pathway.

OBJECTIVE: Secoemestrin C (SC), an epitetrathiodioxopiperazine isolated from Aspergillus nidulans, has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis. However, the effect of SC on regulating the inflammation and its underlying mechanisms in the pathogenesis of psoriasis remain unclear. This study aimed to evaluate the effects of SC on inflammatory dermatosis both in vitro and in vivo. METHODS: In vitro, HaCaT cells were induced with tumor necrosis factor-alpha (TNF-α, 10 ng/mL) to establish an inflammatory injury model, and the expression of nuclear transcription factor-κB (NF-κB) pathway components was measured using qRT-PCR and Western blotting. An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like skin inflammation was used to evaluate the effectiveness of SC in alleviating psoriasis. RESULTS: SC significantly blocked the activation of NF-κB signaling in TNF-α-stimulated HaCaT cells. In addition, systemic and local administration of SC improved psoriatic dermatitis in the IMQ-induced mouse model. SC reduced skin scale and significantly inhibited the secretion of inflammatory factors in skin lesions. CONCLUSION: The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.

Protective effect and regulatory mechanism of salidroside on skin inflammation induced by imiquimod in psoriasis mice.

Salidroside (SAL) is a glucoside of tyrosol commonly existing in the roots of Rhodiola rosea. This study unveils the protective effect of SAL on skin inflammation in imiquimod (IMQ)-induced psoriasis. The mouse model of psoriasis was established by local application of IMQ, and SAL efficacy was evaluated through PASI scoring, H&E staining, and skin tissue pathology observation. The HaCaT cell model was established by interferon (IFN)-γ induction, followed by MTT assay detection of cell viability, detection of ROS, SOD, MDA, and CAT levels in skin tissues and cells using reagent kits, ELISA detection of inflammatory factors (TNF-α, IL-6, IL-1ß), and qRT-PCR detection of psoriasis-related genes (S100a9, Cxcl1, Cxcl2) as well as miR-369-3p and SMAD2 expressions. The binding relationship between miR-369-3p and SMAD2 was validated using dual-luciferase reporter assay. SAL treatment reduced PASI scores and alleviated psoriasis symptoms of IMQ-induced mice, and also augmented the viability and subsided the oxidative stress and inflammation of IFN-γ-treated HaCaT cells. SAL treatment restrained miR-369-3p expression but elevated SMAD2 expression. Mechanistically, miR-369-3p targeted SMAD2 expression. miR-369-3p overexpression or SMAD2 inhibition partially offset the alleviating effect of SAL on psoriasis skin inflammation. In conclusion, SAL alleviates skin inflammation in IMQ-induced psoriasis mice via the miR-369-3p/SMAD2 axis.

Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway.

BACKGROUND: Psoriasis, a common chronic inflammatory skin condition, impacts around 2%-3% of the global population. Theacrine is recognized for its potential anti-inflammatory and antioxidant properties. However, the role of theacrine in psoriasis remains unclear. PURPOSES: To investigate the effects of theacrine on psoriasis and explore the underlying signaling pathways. METHODS: For imiquimod (IMQ)-induced Psoriasis-like mice, the psoriatic inflammation was monitored using Psoriasis Area and Severity Index (PASI). The skin damage was observed using Hematoxylin and Eosin staining. The KI67 and CD4 in skin tissues were assessed using Immunohistochemistry analysis. Western blots were performed to evaluate the expression of Keratin 1 (KRT1), KRT6, LC3, P62, Beclin1, T-bet, GATA3, RAR-related orphan receptor (ROR)-γt, Sirtuin-3 (SIRT3), Forkhead Box O3a (FOXO3a) and Parkin. Additionally, LC3B expression was analyzed using an immunofluorescent assay, while flow cytometry was performed to analyze the percentage of Th17, Th1, and Th2 positive cells in skin-draining lymph node. RESULTS: Theacrine improved skin condition by reducing hyperkeratosis and acanthosis, lowering PASI scores, and decreasing KI67-positive cells. Theacrine also modulated keratin expression, elevating KRT1 while reducing KRT6 levels. Theacrine enhanced autophagy indicated by an increased LC3-II/LC3-I ratio and Beclin1, while reduced P62 levels. Additionally, Theacrine reduced CD4-positive cells and suppressed Th17 and Th1 cell activation. Theacrine activated the FOXO3a/Parkin pathway by upregulating SIRT3 expression, and down-regulation of SIRT3 counteracted theacrine's effects in psoriasis-like mice. CONCLUSION: Theacrine inhibits skin damage, promotes autophagy, and mediates inflammation in IMQ-induced psoriasis mice via upregulating SIRT3 to activate FOXO3a/Parkin pathway, positioning theacrine as a candidate for psoriasis treatment.

Pioglitazone attenuate level of myeloperoxidases and nitic oxide in psoriatic lesion: a proof-of-concept study in a imiquimod induced psoriasis model in rat.

OBJECTIVES: Psoriasis is a persistent autoimmune inflammatory condition that is primarily affecting the skin. Pioglitazone (PGZ), a peroxisome proliferator activated receptor gamma (PPARγ) agonist, has been reported to have anti-inflammatory effects. However, the role of PGZ in psoriatic disease remains unclear. In this study, we aimed to repurpose the use of the PGZ for the treatment of psoriasis. METHODS: To investigate its efficacy, we employed an imiquimod (IMQ)-induced rat model. Wistar rats are randomly allocated to four different groups. Group, I served as a negative control, Group II IMQ control, Group III was treated with pioglitazone hydrogel and Group IV received standard drug betamethasone cream. PASI score was monitored on every alternative day and on day 7 animals were sacrificed and histopathology of skin was performed. Level of nitric oxide (NO) and myeloperoxidase (MPO) was also performed using established methods. RESULTS: The results of the experiment revealed that treatment with PGZ significantly (p<0.05) reduced redness, scaling, and skin thickening, surpassing the effectiveness of standard drugs. Our result also indicates that PGZ significantly (p<0.05) inhibits the release of both MPO and NO from the psoriatic lesions. CONCLUSIONS: PGZ effectively reduces the severity of psoriasis possibly by inhibiting the accumulation of neutrophil at the psoriatic area which indirectly regulates the release of NO in the affected area. Our study showed we can repurpose the PGZ for the management of psoriasis.

Anti-psoriasis molecular targets and active components discovery of Optimized Yinxieling Formula via affinity-purified strategy.

Psoriasis, a prevalent inherited skin condition, involves an inflammatory response as a key pathogenic mechanism. The Optimized Yinxieling Formula (OYF), rooted in traditional Chinese medicine, is extensively utilized in clinical settings to treat psoriasis. Although previous studies have demonstrated OYF's significant anti-inflammatory effects in psoriasis, its potential molecular targets and active components remain unexplored. This study aimed to unveil the anti-psoriasis molecular targets and active components of OYF. Our findings indicated that OYF extract markedly reduced the production of several inflammatory mediators, including IL-23, nitric oxide, TNF-α, and IL-1ß, in LPS-induced RAW264.7 cells. We synthesized OYF extract-crosslinked beads to isolate pharmacological targets from RAW264.7 lysates using an affinity purification strategy, known as Target Fishing. The enriched target proteins were subsequently identified via LC-MS/MS, followed by bioinformatics analysis to map the psoriasis-associated pathway-gene network. We identified a total of 76 potential target proteins, which were highly associated with mRNA transcription mechanisms. In particular, pathway-gene network analysis revealed that the IL-23 inflammatory pathway was involved in the anti-psoriasis effect of OYF extract. We further utilized a target protein-based affinity capture strategy, combined with LC-MS and SPR analysis, to globally screen OYF's active components, focusing on the mRNA transcription regulator, fused in sarcoma (FUS). This process led to the identification of umbelliferone, vanillic acid, protocatechuic acid, gentisic acid, and echinacoside as key compounds targeting FUS to inhibit IL-23 expression. Additionally, we formulated a compound cocktail (CpdC), which significantly reduced psoriasis area and severity index (PASI) scores and the expressions of IL-23 and Ki67 in an imiquimod (IMQ)-induced psoriasis mouse model. Collectively, our study elucidates the primary molecular targets and active components of OYF, offering novel insights for psoriasis treatment.