Objective To analyze the clinical characteristics of patients with generalized pus-tular psoriasis,we aimed to provide stronger theoretical support for the health management of GPP patients.Methods A retrospective analysis was conducted on the data of 150 patients with gener-alized pustular psoriasis(GPP)who visited the Dermatology Hospital,Southern Medical Universi-ty from July 2017 to July 2023.The patients were grouped according to age of onset,gender,and whether GPP was accompanied by psoriasis vulgaris(PV).The analysis aimed to explore the differences in clinical characteristics among different groups of GPP patients,including the season of onset and triggers,recurrence frequency,comorbidities,and treatment outcomes.Results A total of 150 patients with generalized pustular psoriasis(GPP),with a mean onset age of 32.83±21.65 years,were included in the analysis.The mean age of onset was significantly lower in pa-tients with GPP alone than in those with both GPP and psoriasis vulgaris(PV)(28.30±19.27 vs.40.87±23.43 years,t=-3.51,P＜0.05).The proportion of patients who were overweight was significantly higher in those with an onset age of ≥18 years(39.4％)compared to those with an onset age of＜18 years(17.4％)(x2=7.04,P＜0.05).The mean waist circumference of all adult male and female patients met the criteria for abdominal obesity.GPP had a predilection for onset in spring and summer.The probability of onset in spring and summer was significantly higher in patients with GPP alone(70.3％)than in those with GPP and PV(50.0％)(x2=5.45,P＜0.05).Improper treatment was identified as the primary triggering factor for GPP.The proportion of patients with improper treatment as a triggering factor was significantly higher in the GPP+PV group than in the GPP alone group(71.7％vs.5.2％,x2=74.22,P＜0.001).Re-garding triggering factors for relapse,improper treatment was the most common in patients with an onset age of＞18 years(39.5％),while upper respiratory tract infections were predominant in patients with an onset age of ≤18 years(40.0％).In female patients,some relapses were associ-ated with special physiological states such as pregnancy and menstruation.The recurrence rate was significantly higher in patients with an onset age of≤18 years than in those＞18 years(91.3％vs.71.7％,x2=7.39,P＜0.05).Females had a significantly higher probability of experiencing 3 to 4 relapses within a year than males(x2=4.20,P＜0.05).Patients with GPP alone were more prone to recurrence,with significantly higher probabilities of experiencing 1 to 2 relapses and 1 to 4 relapses within one year compared to the GPP+PV group(all P＜0.05).Males had a sig-nificantly higher probability of nail involvement and moderate fever than females(both P＜0.05)but a significantly lower probability of high fever(x2=3.90,P＜0.05).The probability of joint involvement was significantly higher in the GPP+PV group than in the GPP alone group(x 2=7.55,P＜0.05).Furthermore,hypertension was more commonly associated with GPP+PV than with GPP alone(x2=5.79,P＜0.05).Acitretin was the most commonly used drug.Patients re-ceiving combination therapy with immunosuppressants had the longest hospital stay(12.57±5.47 days),while those treated with biological agents alone had the shortest hospital stay(5.61±2.33 days)(P＜0.05).Conclusions Factors such as gender,age,and comorbidity with PV signifi-cantly impact the clinical presentation and treatment response of GPP.Early identification of trig-gering factors,precise subgroup-based interventions,and monitoring of biomarkers are crucial strategies to improve the clinical outcomes of GPP patients.

BACKGROUND:Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS:This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20 weeks of vunakizumab discontinuation. RESULTS:There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR] = 0.922, p = 0.024) and treatment interruption (OR = 0.550, p = 0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR = 0.972, p = 0.049) and treatment interruption (OR = 0.257, p < 0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS:PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20 weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Obesity is considered a significant global health issue. The gut microbiota plays a crucial role in preventing obesity. Sargassum fusiforme and its fucoidan extract have lipid-lowering effects, but their mechanisms are not yet fully understood. This study investigates the mechanisms by exploring changes in gut microbiota composition, gene expression, and metabolites in mice fed a high-fat diet after intervention with Sargassum fusiforme (SF) and Sargassum fusiforme fucoidan (SFF) through integration of 16S rRNA sequencing, transcriptomics, and non-targeted metabolomics. Our results demonstrate that Sargassum fusiforme can ameliorate high-fat diet-induced obesity by decreasing the abundance of specific Firmicutes phylum bacteria, reducing the levels of glycochenodeoxycholic acid, glycoursodeoxycholic acid, glycohyodeoxycholic acid, and glycodeoxycholic acid, and regulating the expression of the Elovl3, Gm3734, Per2, and Tnnc1 genes. This offers a new perspective for hypercholesterolemia treatment strategies.

The lack of a validated Chinese version of the Recap of Atopic Eczema questionnaire (RECAP) questionnaire limits its applicability. This prospective study, conducted at a Chinese tertiary hospital between April and November 2024, aimed to evaluate measurement properties of the Chinese RECAP. Participants completed RECAP and reference instruments at baseline, 1–3 days, and 4–6 weeks. Construct validity was evaluated through hypothesis testing, while reliability was assessed using standard error of measurement (SEMagreement) and intraclass correlation coefficient (ICCagreement). Interpretability of both single and change scores was examined using anchor-based methods. In total, 153 adults with atopic dermatitis (AD) (mean age 28.4 years, 51.0% male) were included, with approximately half having moderate-to-severe disease. Of the predefined hypotheses, 57.1% (single score) and 71.4% (change score) were confirmed. The SEMagreement was 1.99, and the ICCagreement was 0.96. Final RECAP bandings were established, with a binary cutoff of ≥ 11 defining uncontrolled AD. The Smallest Detectable Change was 5.5. while the Minimally Important Change was 3.5 using the receiver operating characteristics (ROC) method and 0.6 after adjustment via predictive modelling. Our finding confirmed that the Chinese RECAP is a valid, reliable, and responsive tool for evaluating eczema control. An improvement of ≥ 6 represents a real and clinically meaningful change.

Soyasaponin Bb has various health-promoting bioactivities. However, the bioavailability of soyasaponin Bb is not fully understood. This study aimed to explore the absorption and metabolism of soyasaponin Bb by using both in vivo and in vitro methods. Soyasaponin Bb (100 mg/kg) was orally administrated in Sprague–Dawley (SD) rats, and the content of soyasaponin Bb and soyasapogenol B in plasma, urine and feces were determined by HPLC–MS/MS. The Caco-2 intestinal epithelial cell model was established by culturing on Transwell plates and assessing through cell morphology, transepithelial electrical resistance, alkaline phosphatase activity, and phenol red flux. Then, the apical (AP) to basolateral (BL) transport or uptake of soyasaponin Bb in the model were determined. In SD rats, soyasaponin Bb reached a maximum of 19.8 ng/mL in plasma and showed two material peaks. The cumulative excretion of soyasaponin Bb at 168 h was (0.0022 ± 0.0006)

Background::Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited.Methods::This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed.Results::Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]–3rd quartile [Q3]: 11–44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P = 0.021) and transitioning to plaque psoriasis ( P = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1–Q3: 2–41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1–Q3: 13.0–23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. Conclusions::The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.

Psoriasis is a chronic, recurrent inflammatory skin disease that significantly impacts patients' quality of life. With the advancement of patient-centered care, shared decision-making (SDM) has gradually been introduced into psoriasis management. SDM enables healthcare professionals and patients to collaboratively formulate individualized treatment plans through mutual communication and respect. It has been widely applied in chronic dermatological conditions abroad and has been shown to improve patient satisfaction, adherence, and quality of life. Patient decision aids (PDAs), a core component of SDM, have been proven to enhance patient understanding, reduce decisional conflict, and promote active involvement in treatment decisions. This article reviews the theoretical foundation, practical application, and effectiveness of SDM and PDAs in the management of psoriasis, drawing on international experiences. It also discusses key challenges and strategies for localization in China, including clinician training, PDA development, digital integration, and policy support. Establishing standardized SDM procedures and localized PDA systems may foster a more efficient, precise, and patient-centered chronic disease management model for psoriasis.

Background Acrodermatitis continua of Hallopeau (ACH) is a rare pustular psoriasis variant predominantly affects the distal phalanges of the fingers and toes. However, data on aggravating factors and treatment outcomes is limited.Objective This study aims to analyze the aggravating factors and treatment outcomes of ACH in a three-tertiary-hospital in South China.Methods We analyzed ACH patients from Dermatology Hospital of Southern Medical University, considering patient and disease characteristics along with treatment experiences.Results We identified 96 ACH patients. Various predisposing events were identified, including lifestyle factors, vaccination, stress, trauma, menstruation and drug exposure. A total of 293 systemic treatment courses were analyzed. 54.3% of patients received at least one biologic therapy, while 45.7% were treated with nonbiologic treatments. Acitretin was the most common therapy (20.5%). However, the effectiveness of systemic treatments was low (excellent response rate: 26.3%). Among non-biologic treatments, Acitretin showed a significant response in 30.0% (18/60) of cases, followed by cyclosporin (20.0%, 2/10). Among biologics, spesolimab had the best response rate at 75.0% (n = 3), followed by ixekizumab (44.4%, 8/18). Small molecule drugs did not yeild satisfactory outcomes in ACH treatment.Conclusion Identifying triggers and aggravating factors is crucial for effective ACH treatment. We suggest that biologics may be a useful first-line treatment option for clinicians managing ACH.

A 51-year-old female with red plaques and scales for 20 years, aggravated with pustules for more than 10 days.Physical examination: scattered red patches, silver-white scales, thin film, Auspitz sign (+) can be seen on the head and face.The trunk and limbs were scattered in large erythema and erythema, on which were dense pustules of the size of chestnut. The central color of local pustules was brown, presenting target-shaped lesions, and some pustules fused into pus lake.Vulvar mucosa scattered in pustules, erosion surface.Nail clipping thimble changes, deck thickening changes.Histopathology: Hyperkeratosis, fusion keratosis, thinning or disappearance of granular layer, epidermal psoriatic hyperplasia, munro and Kogoj microabscess, dermal papilloma, vascular dilatation, perivascular lymphocyte infiltration.Diagnosis: pustular psoriasis.

Objective: Psoriasis is a chronic inflammatory systemic disease that severely impacts patients’ quality of life (QoL) and psychological health. While biologics have been shown to be effective in treating psoriatic lesions, thus improving QoL, real-life data regarding such effects remain scant. We administered a repeated cross-sectional survey to assess the effects of 8 weeks of biologics treatment on the QoL and mental health status of patients with moderate-to-severe plaque psoriasis. Methods: From March to May 2022, patients with moderate-to-severe plaque psoriasis were enrolled and treated with biologics in the outpatient clinic at the Dermatology Hospital of Southern Medical University. Assessments were performed before treatment and after 4 and 8 weeks of treatment with biologics. Psoriasis severity, QoL, and mental health status were evaluated using the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), 36-Item Short-form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). A multivariate generalized estimating equations (GEE) analysis was used to account for repeated measures and to determine the effects of treatment duration and type of biological agent on relevant indicators. Results: Among the 78 enrolled patients, the ranges of pretreatment scores were 4.6 to 46.8 for the PASI, 1 to 30 for the DLQI, 31.5 to 100.0 for the physical component score (PCS) of the SF-36, 16.6 to 100.0 for the mental component score (MCS) of the SF-36, 0 to 15 for the HADS-A, and 0 to 17 for the HADS-D. After 8 weeks of biologics treatment, 98.7% (77/78) of patients had obtained PASI 75. All assessed scores changed over time (GEE, P < 0.001). Moreover, there were group-by-time interaction effects for the DLQI score (GEE, P = 0.023) and PCS (GEE, P = 0.029). The HADS-A and HADS-D scores were both decreased at week 8 compared with pretreatment values. Correlation analyses revealed that higher DLQI scores were associated with lower levels of QoL and higher levels of anxiety or depression. Conclusion: Biologics are not only effective in the treatment of skin lesions but also exert beneficial effects upon the QoL and mental health of patients with psoriasis as determined in the short-term assessments conducted in this study.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Mutations in the tumor suppressor M receptor (OSMR) gene are associated with primary localized cutaneous amyloidosis (PLCA). Recently, we confirmed that OSMR loss-of-function mutations enhance epidermal keratinocyte differentiation via inactivation of the STAT5/KLF7 signaling. However, no disease model was available for PLCA. Accordingly, we generated an OSMR c.1538G > A mutant human embryonic stem cell line (SMUDHe010-A-82) using CRISPR/Cas9-mediated homologous recombination. The cell line preserves normal karyotype, pluripotency and the ability to differentiate into all three germ layers. Moreover, the cell line can be used to prepare human skin organoid, which may provide a disease model for PLCA.

Dear Editor, Primary localized cutaneous amyloidosis (PLCA) is a skin-limited disorder characterized by deposition of amyloid material in the superficial dermis.According to clinical characteristics,PLCA is divided into lichen,macular,and nodular amyloidosis.PLCA is found worldwide but has a higher incidence in South America and Southeast Asia,such as in Brazil and China (Chang et al.,2014;Tey et al.,2016).

The mechanisms of soyasaponin A1 (SS-A1) on antagonizing inflammation via regulating the lipid raft-mediated toll-like receptor 4 (TLR4) signaling are not completely understood. In this study, SS-A1 inhibited palmitic acid (PA)-induced recruitments of TLR4 and its adaptor molecules into lipid rafts in Raw264.7 macrophage cell line by using ultracentrifugation and confocal microscopy. SS-A1 also suppressed the PA-caused dimerization of TLR4 with and its adaptor molecules by applying immunoprecipitation and fluorescence resonance energy transfer. Meanwhile, SS-A1 modified the formation, clustering, and size of lipid rafts and decreased cholesterol in lipid rafts. Cholesterol replenishment abrogated SS-A1’s inhibition on the lipid rafts recruitment and dimerization of TLR4 and its adaptor molecules and its anti-inflammatory activity. Additionally, SS-A1 inhibited the mature sterol regulatory element-binding protein 2 and increases ATP-binding cassette transporter A1. Collectively, SS-A1 inhibits the lipid raft recruitment and dimerization of TLR4 and its adaptor molecules by maintaining cholesterol homeostasis in PA-stimulated inflammatory Raw264.7 macrophage cell line.

Abstract Background Psoriasis is a chronic immune‐mediated skin disorder. Systemic inflammation plays an important role in the pathogenesis of psoriasis. Methods A total of 477 patients with psoriasis vulgaris (PsV, n = 347), generalized pustular psoriasis (GPP, n = 37), erythrodermic psoriasis (PsE, n = 45), arthritic psoriasis (PsA, n = 25) and mixed psoriasis (n = 23), and 954 healthy control subjects were included in the study. Demographic, clinical, and laboratory information were collected and compared between subgroups. Results Compared with the healthy control group, patients with psoriasis had higher total white blood cell (WBC), neutrophil, platelet counts, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), but lower hemoglobin (Hb) levels, lymphocyte and red blood cell (RBC) counts. NLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups, with GPP group being the highest. PLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups. There was no significant correlation between the psoriasis area severity index (PASI) score and either the NLR or PLR in the PsV group. Conclusions Elevated NLR and PLR were associated with psoriasis and differed between subtypes, suggesting that they could be used as markers of systemic inflammation in psoriasis patients.

SCOPE:Nonalcoholic steatohepatitis (NASH) is a chronic progressive disease with complex pathogenesis of which the bile acids (BAs) and gut microbiota are involved. Soyasaponins (SS) exhibits many health-promoting effects including hepatoprotection, but its prevention against NASH is unclear. This study aims to investigate the preventive bioactivities of SS monomer (SS-A2 ) against NASH and further clarify its mechanism by targeting the BAs and gut microbiota.METHODS AND RESULTS:The methionine and choline deficient (MCD) diet-fed male C57BL/6 mice were intervened with obeticholic acid or SS-A2 for 16 weeks. Hepatic pathology is assessed by hematoxylin-eosin and Masson's trichrome staining. BAs in serum, liver, and colon are measured by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS). Gut microbiota in caecum are determined by 16S rDNA amplicon sequencing. In the MCD diet-induced NASH mice, SS-A2 significantly reduces hepatic steatosis, lobular inflammation, ballooning, nonalcoholic fatty liver disease activity score (NAS) scores, and fibrosis, decreases Erysipelotrichaceae (Faecalibaculum) and Lactobacillaceae (Lactobacillus) and increases Desulfovibrionaceae (Desulfovibrio). Moreover, SS-A2 reduces serum BAs accumulation and promotes fecal BAs excretion. SS-A2 changes the BAs profiles in both liver and serum and specifically increases the taurohyodeoxycholic acid (THDCA) level. Faecalibaculum is negatively correlated with serum THDCA.CONCLUSION:SS-A2 alleviates steatohepatitis possibly through regulating BAs and gut microbiota in the MCD diet-induced NASH mice.

Background: Oncostatin M (OSM), an interleukin-6 (IL-6) family proinflammatory cytokine, plays a critical role in inflammatory skin diseases, but its mechanism of action is not well understood. Objective: To demonstrate the mechanism of OSM induced pyropotosis in normal human epidermal keratinocytes (NHEKs) and immortalized human keratinocytes (HaCaT cells). Methods: NHEKs and HaCaT cells were treated with OSM. Knockout of OSM receptor (OSMR) with CRISPR/ Cas9 system, knockdown of GSDME with small interfering RNA and primary keratinocytes from Osmr-/- and Gsdme-/- mice were used to study the effect of OSMR and GSDME. After treatment of OSM, NHEKs and HaCaT cells were irradiated with UVB. The mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and RNA sequencing, protein level was detected by Western Blotting, Elisa and immunofluorescence. Cell death was examined by lactate dehydrogenase (LDH) releasing. Results: Here we found that OSM induced pyropotosis in NHEKs and HaCaT cells, but knockout of OSMR abolished pyropotosis. RNA sequencing revealed an upregulation of several key genes involved in NLRP3 inflammasome activation following OSM treatment, among which NLRP3, GSDME, and IL-1 beta were confirmed by qRT-PCR and Western Blotting. Knockdown of GSDME alleviated OSM-induced pyropotosis. Pretreatment of OSM boosted UVB-induced pyroptosis and inflammation in NHEKs and HaCaT cells, and this priming function was lost in keratinocytes of Osmr-/- and Gsdme-/- mice. Similar results were obtained in a 3-dimensional culture of human epidermis. Conclusion: OSM functions as a priming cytokine to enhance UVB-induced inflammation in keratinocytes, providing insight into the pathogenesis of inflammatory skin diseases. (C) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Secukinumab, a full human immunoglobulin G1κ monoclonal antibody that targets interleukin-17A, has demonstrated remarkable efficacy and appreciable tolerance in patients with moderate-to-severe psoriasis. However, data on its real-life performance, particularly on drug survival in China are limited. To investigate the efficacy, safety, and drug survival of secukinumab in Chinese patients with psoriasis, we conducted a monocentric retrospective study of 66 patients with moderate-to-severe psoriasis to followed-up for 52 weeks. At week 12, 86.4%, 57.6%, and 10.6% of the patients attained 75% improvement in psoriasis area and severity Index (PASI) score from baseline (PASI 75), PASI 90, and PASI 100 responses, respectively. The quality of life of patients markedly improved. The overall survival rate was 74.2%. Adverse events occurred in 30 patients (45.5%). The results revealed favorable efficacy, safety, and tolerability of secukinumab in the treatment of patients with psoriasis and provided data on drug survival in real-life clinical setting in China for the first time.

Atherosclerosis is a chronic inflammatory disease causing coronary heart attacks and strokes. Soyasaponins (SS), the phytochemicals naturally existing in soybeans and their products, have been shown to reduce hypercholesterolemia and inflammation, which are intimately related to the genesis and development of atherosclerosis. However, the anti-atherosclerotic functionality of soyasaponins remains unknown. The aim of this study was to investigate the effects of the supplementation of two types of soyasaponin monomers (A1 and A2) on atherosclerotic plaque formation, serum lipid profiles, and inflammation in ApoE gene knockout (ApoE-/-) mice. Sixty 5-week-old ApoE-/- male mice were fed with a high-fat diet (HFD) and intervened by SSA1 and SSA2 (10 and 20 μmol per kg BW, respectively) or simvastatin (10 μmol per kg BW) for 24 weeks. The atherosclerotic lesions in the aorta, aortic root, and innominate artery, lipid profile and inflammatory markers in serum, and TLR4/MyD88/NF-κB signaling in arterial tissues were determined. SSA1 and SSA2 decreased the plaque ratio in the aortic root and innominate artery but not in the entire aorta. In serum, SSA1 reduced TG, TC, and LDL-C but increased HDL-C; SSA2 decreased TC, TG, and LDL-C but did not affect HDL-C. Meanwhile, SSA1 increased TG, SSA2 increased TC, and both of them increased bile acids in the feces. SSA1 and SSA2 lowered TNF-α, MCP-1, and hs-crp in serum. Furthermore, SSA1 and SSA2 reduced the TLR4 and MyD88 expressions in the aorta and innominate artery and inhibited NF-κB p65 and IκBα phosphorylation in the aorta. These results suggest that SSA1 and SSA2 exert anti-atherosclerotic functionalities by decreasing hypercholesterolemia and inflammation in HFD-fed ApoE-/- mice.

Abstract Background Previous studies indicate that soyasaponins may reduce inflammation via modulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling. However, its underlying mechanisms are still not fully understood. Methods Lipopolysaccharide (LPS)-challenged inflamed male ICR mice were intervened by intragastrical administration with 10 and 20 μmol/kg·BW of soyasaponin A1, A2 or I for 8 weeks. The serum inflammatory markers were determined by commercial kits and the expression of molecules in TLR4/MyD88 signaling pathway in liver by real-time PCR and western blotting. The recruitments of TLR4 and MyD88 into lipid rafts of live tissue lysates were detected by sucrose gradient ultracentrifugation and western blotting. LPS-stimulated RAW264.7 macrophages were treated with 10, 20 and 40 μmol/L of soyasaponin A1, A2 or I for 2 h. MyD88-overexpressed HEK293T cells were treated with 20 and 40 μmol/L of soyasaponins (A1, A2 or I) or 20 μmol/L of ST2825 (a MyD88 inhibitor) for 6 h. The expression of molecules in TLR4/MyD88 signaling pathway were determined by western blotting. Data were analyzed by using one way analysis of variance or t-test by SPSS 20.0 statistical software. Results Soyasaponins A1, A2 or I significantly reduced the levels of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and nitric oxide (NO) in serum (p < 0.05), and decreased the mRNA levels of TNFα, IL-6, IL-1β, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (p < 0.05), the protein levels of myeloid differentiation protein 2 (MD-2), TLR4, MyD88, toll-interleukin1 receptor domain containing adaptor protein (TIRAP), phosphorylated interleukin-1 receptor-associated kinase 4 (p-IRAK-4), phosphorylated interleukin-1 receptor-associated kinase 1 (p-IRAK-1) and TNF receptor associated factor 6 (TRAF6) (p < 0.05), and the recruitments of TLR4 and MyD88 into lipid rafts in liver (p < 0.05). In LPS-stimulated macrophages, soyasaponins A2 or I significantly decreased MyD88 (p < 0.05), soyasaponins A1, A2 or I reduced p-IRAK-4 and p-IRAK-1 (p < 0.05), and soyasaponin I decreased TRAF6 (p < 0.05). In MyD88-overexpressed HEK293T cells, soyasaponins (A1, A2 or I) and ST2825 significantly decreased MyD88 and TRAF6 (p < 0.05). Conclusion Soyasaponins can reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts. This study provides novel understanding about the anti-inflammatory mechanism of soyasaponins.