Qinzhuliangxue mixture ameliorates psoriasis by restraining apoptosis in psoriasis via downregulating the MDA-5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.

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.

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.

Anti-psoriasis effect of 18ß-glycyrrhetinic acid by breaking CCL20/CCR6 axis through its vital active group targeting GUSB/ATF2 signaling.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Current research suggests that the long-term persistence and recurrence of psoriasis are closely related to the feedback loop formed between keratinocytes and immune cells, especially in Th 17 or DC cells expressing CCR6. CCL20 is the ligand of CCR6. Therefore, drugs that block the expression of CCL20 or CCR6 may have a certain therapeutic effect on psoriasis. Glycyrrhetinic acid (GA) is the main active ingredient of the plant drug licorice and is often used to treat autoimmune diseases, including psoriasis. However, its mechanism of action is still unclear. METHODS: Psoriasis like skin lesion model was established by continuously applying imiquimod on the back skin of normal mice and CCR6-/- mice for 7 days. The therapeutic and preventive effects of glycyrrhetinic acid (GA) on the model were observed and compared. The severity of skin injury is estimated through clinical PASI scores and histopathological examination. qRT-PCR and multiple cytoline assay were explored to detect the expression levels of cytokines in animal dorsal skin lesions and keratinocyte line HaCaT cells, respectively. The dermis and epidermis of the mouse back were separated for the detection of CCL20 expression. Transcription factor assay was applied to screen, and luciferase activity assay to validate transcription factors regulated by GA. Technology of surface plasmon laser resonance with LC-MS (SPR-MS), molecular docking, and enzyme activity assay were used to identified the target proteins for GA. Finally, we synthesized different derivatives of 18beta-GA and compared their effects, as well as glycyrrhetinic acid (GL), on the skin lesion of imiquimod-induced mice to evaluate the active groups of 18beta-GA. RESULTS: 18ß-glycyrrhetinic acid (GA) improved IMQ-induced psoriatic lesions, and could specifically reduce the chemokine CCL20 level of the epidermis in lesion area, especially in therapeutic administration manner. The process was mainly regulated by transcription factor ATF2 in the keratinocytes. In addition, GUSB was identified as the primary target of 18ßGA. Our findings indicated that the subject on molecular target research of glycyrrhizin should be glycyrrhetinic acid (GA) instead of glycyrrhizic acid (GL), because GL showed little activity in vitro or in vivo. Apart from that, α, ß, -unsaturated carbonyl in C11/12 positions was crucial or unchangeable to its activity of 18ßGA, while proper modification of C3 or C30 position of 18ßGA may vastly increase its activity. CONCLUSION: Our research indicates that 18ßGA exerted its anti-psoriasis effect mainly by suppressing ATF2 and downstream molecule CCL20 predominately through α, ß, -unsaturated carbonyl at C11/12 position binding to GUSB in the keratinocytes, and then broke the feedback loop between keratinocytes and CCR6-expressing immune cells. GA has more advantages than GL in the external treatment of psoriasis. A highlight of this study is to investigate the influence of special active groups on the pharmacological action of a natural product, inspired by the molecular docking result.

Rutaecarpine ameliorates imiquimod-induced psoriasis-like dermatitis in mice associated with alterations in the gut microbiota.

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.

Anti-psoriatic characteristics of ROCEN (topical Arthrocen) in comparison with Cyclosporine A in a murine model.

Topical ROCEN (Roc), liposomal arthrocen hydrogel, is a robust anti-inflammatory formulation which has been developed for skin diseases such as eczema. Therefore, we aimed to evaluate the efficacy of Roc 2% on the healing of imiquimod (Imiq)-induced psoriasis in a mouse model. Psoriasis was induced by applying Imiq topically to the mice's back skin once daily for five consecutive days. Moreover, a group of animal experiments was treated with Cyclosporine A (CsA), as a standard drug, for comparison with Roc treated group. The efficacy of Roc on skin lesions was evaluated by employing Psoriasis Area and Severity Index (PASI) scores. Subsequently, the skin samples were assessed using Baker's scoring system and Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis. The observational and histopathological results indicated that topical application of Roc significantly reduced the PASI and Baker's scores in the plaque-type psoriasis model. Moreover, biochemical assessments showed that Roc suppressed significantly the increase of IL-17, IL-23, and TNF-α cytokines gene expression in the lesion site of psoriatic animals. In conclusion topical Roc 2% could significantly alleviate major pathological aspects of Imiq-induced psoriasis through inflammation inhibition which was comparable to the CsA drug. The beneficial outcomes of Roc application in the psoriasis model suggest its potential usage in complementary medicine.

Evaluating the efficacy and mechanisms of Hua-Zhuo-Ning-Fu-Decoction on psoriasis using integrated bioinformatics analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Hua Zhuo Ning Fu Decoction (HZD) is an empirical prescription from traditional Chinese medicine that shows excellent clinical results for psoriasis patients. Uncertainty lingered over HZD's potential anti-psoriasis mechanisms. AIM OF THE STUDY: The study's objective is to investigate the pharmacological processes and therapeutic effects of HZD on psoriasis. MATERIALS AND METHODS: In the initial phase of the study, an investigation was conducted to assess the effects of HZD on psoriasis-afflicted mice using an imiquimod (IMQ)-induced murine model. The experimental mice were randomly allocated to different groups, including the IMQ-induced model group, the control group, the HZD therapy groups with varying dosage levels (low, medium, and high), and Dexamethasone (DEX, the positive control medicine) group. Bioinformatics analysis and molecular docking were subsequently employed to identify the primary components and molecular targets associated with the therapeutic action of HZD in the context of psoriasis. Additionally, to find the impacts on metabolite regulation, plasma metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used. It's interesting to note that the combined mechanisms from metabolomics were examined in tandem with the targets. In vivo tests were the last step in validating the potential mechanism. Throughout the trial, the following data were recorded: body weight, psoriasis area and severity index (PASI). The molecular targets connected to HZD's anti-psoriasis activities were revealed using histological examination, western blot (WB), and ELISA investigation. RESULTS: In mice induced with IMQ, HZD shown good anti-psoriasis effects in terms of PASI score and epidermal acanthosis. 95 HZD targets and 77 bioactive chemicals connected to psoriasis were found by bioinformatics research; of these, 7 key targets (EPHX2, PLA2G2A, TBXAS1, MAOA, ALDH1A3, ADH1A, and ADH1B) were linked to the mechanisms of HZD, the combination degree of which was finally expressed by the score of docking. In addition, HZD regulated nine metabolites. In line with this, HZD modified three metabolic pathways. Additionally, a combined examination of 7 key targets and 9 metabolites suggested that the metabolism of arachidonic acid might be the key metabolic route, which was identified by ELISA analysis. The in vivo investigation shown that HZD could control cytokines associated to inflammation (IL-10, TGF-ß, IL-17A, and IL-23), as well as important antioxidant system markers (ROS, GSH, and MDA). Moreover, HZD controlled iron levels and the expression of ferroptosis-related proteins (ACSL4 and GPX4), suggesting that ferroptosis played a crucial role in this process. CONCLUSIONS: Our findings demonstrated the whole mechanism and anti-psoriasis effectiveness of HZD, which will promote its clinical application and aid in the investigation of new bioactive components of HZD against psoriasis.

Cang-ai volatile oil ameliorates imiquimod-induced psoriatic skin lesions by suppressing the ILC3s.

ETHNOPHARMACOLOGICAL RELEVANCE: Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine with potent antibacterial and immune regulatory properties. While CAVO has been used to treat upper respiratory tract infections, depression, otomycosis, and bacterial infections in the skin, its effect on psoriasis is unknown. AIM OF THE STUDY: This study explores the effect and mechanism of CAVO in psoriasis intervention. MATERIAL AND METHODS: The effect of CAVO on the expression of IL-6 and IL-1ß was assessed in TNF-α-induced HaCaT cells using enzyme-linked immunosorbent assay (ELISA). Mice were given imiquimod (IMQ) and administered orally with different CAVO doses (0.03 and 0.06 g/kg) for 5 days. The levels of inflammatory cytokines related to group-3 innate lymphoid cells (ILC3s) in the skin were assessed using hematoxylin and eosin (H&E) staining, ELISA, and western blotting (WB). The frequency of ILC3s in mice splenocytes and skin cells was evaluated using flow cytometry. RESULTS: The results demonstrated that CAVO decreased the expression of IL-6 and IL-1ß in TNF-α- induced HaCaT cells. CAVO significantly reduced the severity of psoriatic symptoms in IMQ-induced mice. The expression of inflammatory cytokines in the skin, such as IL-1ß, IL-6, IL-8, IL-22, IL-23, and IL-17 A were decreased, whereas IL-10 levels were increased. The mRNA expressions of TNF-α, IL-23 A, IL-23 R, IL-22, IL-17 A, and RORγt were down-regulated in skin tissues. CAVO also decreased the levels of NF-κB, STAT3, and JAK2 proteins. CONCLUSIONS: CAVO potentially inhibits ILC3s activation to relieve IMQ-induced psoriasis in mice. These effects might be attributed to inhibiting the activation of NF-κB, STAT3, and JAK2 signaling pathways.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS: TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Oral administration of punicalagin attenuates imiquimod-induced psoriasis by reducing ROS generation and inflammation via MAPK/ERK and NF-κB signaling pathways.

Psoriasis, an immune-mediated chronic inflammatory skin disease, imposes a huge mental and physical burden on patients and severely affects their quality of life. Punicalagin (PU), the most abundant ellagitannin in pomegranates, has become a research hotspot owing to its diverse biological activities. However, its effects on psoriasis remain unclear. We explored the impact and molecular mechanism of PU on M5-stimulated keratinocyte cell lines and imiquimod (IMQ)-induced psoriasis-like skin inflammation in BABL/c mice using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), hematoxylin and eosin (H&E) stain, immunohistochemistry, and immunofluorescent. Administration of PU-enriched pomegranate extract at dosages of 150 and 250 mg/kg/day markedly attenuated psoriatic severity, abrogated splenomegaly, and reduced IMQ-induced abnormal epidermal proliferation, CD4+ T-cell infiltration, and inflammatory factor expression. Moreover, PU could decrease expression levels of pro-inflammatory cytokines, such as IL-1ß, IL-1α, IL-6, IL-8, TNF-α, IL-17A, IL-22, IL-23A, and reactive oxygen species (ROS), followed by keratinocyte proliferation inhibition in the M5-stimulated cell line model of inflammation through inhibition of mitogen-activated protein kinases/extracellular regulated protein kinases (MAPK/ERK) and nuclear factor kappaB (NF-κB) signaling pathways. Our results indicate that PU may serve as a promising nutritional intervention for psoriasis by ameliorating cellular oxidative stress and inflammation.

Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway.

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.

Immunoadjuvant-Modified Rhodobacter sphaeroides Potentiate Cancer Photothermal Immunotherapy.

Photothermal immunotherapy has become a promising strategy for tumor treatment. However, the intrinsic drawbacks like light instability, poor immunoadjuvant effect, and poor accumulation of conventional inorganic or organic photothermal agents limit their further applications. Based on the superior carrying capacity and active tumor targeting property of living bacteria, an immunoadjuvant-intensified and engineered tumor-targeting bacterium was constructed to achieve effective photothermal immunotherapy. Specifically, immunoadjuvant imiquimod (R837)-loaded thermosensitive liposomes (R837@TSL) were covalently decorated onto Rhodobacter sphaeroides (R.S) to obtain nanoimmunoadjuvant-armed bacteria (R.S-R837@TSL). The intrinsic photothermal property of R.S combined R837@TSL to achieve in situ near-infrared (NIR) laser-controlled release of R837. Meanwhile, tumor immunogenic cell death (ICD) caused by photothermal effect of R.S-R837@TSL, synergizes with released immunoadjuvants to promote maturation of dendritic cells (DCs), which enhance cytotoxic T lymphocytes (CTLs) infiltration for further tumor eradication. The photosynthetic bacteria armed with immunoadjuvant-loaded liposomes provide a strategy for immunoadjuvant-enhanced cancer photothermal immunotherapy.

The therapeutic efficacy and mechanism action of Si Cao formula in the treatment of psoriasis: A pilot clinical investigation and animal validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammation and relapsing disease that affected approximately 100 million individuals worldwide. In previous clinical study, it was observed that the topical application of Si Cao Formula (SCF) ameliorated psoriasis skin lesions and reduced the recurrence rate of patients over a period of three months. However, the precise mechanism remains unclear. AIM OF THE STUDY: The objective of this study was to assess the effectiveness and safety of SCF in patients diagnosed with psoriasis and explore the molecular mechanisms that contribute to SCF's therapeutic efficacy in psoriasis treatment. MATERIALS AND METHODS: A randomized, controlled, and pilot clinical study was performed. This study assessed 30 individuals diagnosed with mild to moderate plaque psoriasis. 15 of them underwent local SCF treatment, the others received calcipotriol intervention. The outcome measure focused on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and recurrence rate. In addition, IMQ-induced psoriasis-like mice model were used to assess the impact of SCF on ameliorating epidermal hyperplasia, suppressing angiogenesis, and modulating immune response. Furthermore, we performed bioinformatics analysis on transcriptome data obtained from skin lesions of mice model. This analysis allowed us to identify the targets and signaling pathways associated with the action of SCF. Subsequently, we conducted experimental validation to confirm the core targets. RESULTS: Our clinical pilot study demonstrated that SCF could ameliorate skin lesions in psoriasis patients with comparable efficacy of calcipotriol in drop of PASI and DLQI scores. SCF exhibited a significantly reduced recurrence rate within 12 weeks (33.3%). Liquid Chromatography Mass Spectrometry (LC-MS) identified 41 active constituents of SCF (26 cations and 15 anions). Animal experiments showed SCF ameliorates the skin lesions of IMQ-induced psoriasis like mice model and suppresses epidermal hyperkeratosis and angiogenesis. There were 845 up-regulated and 764 down-regulated DEGs between IMQ and IMQ + SCF groups. GO analysis revealed that DEGs were linked to keratinization, keratinocyte differentiation, organic acid transport epidermal cell differentiation, and carboxylic acid transport interferon-gamma production. KEGG pathway analysis showed that SCF may play a vital part through IL-17 and JAK/STAT signaling pathway. In addition, SCF could reduce the number of positive cells expressing PCNA, CD31, pSTAT3, CD3, and F4/80 within the epidermis of psoriatic lesions, as well as the expression of Il-17a and Stat3 in IMQ-induced psoriasis mice. CONCLUSIONS: Our research suggests that SCF serves as a reliable and efficient local approach for preventing and treating psoriasis. The discovery of plausible molecular mechanisms and therapeutic targets associated with SCF may support its broad implementation in clinical settings.

Intelligent Nanoplatform Integrating Macrophage and Cancer Cell Membrane for Synergistic Chemodynamic/Immunotherapy/Photothermal Therapy of Breast Cancer.

Cell membrane-coated nanoplatforms for drug delivery have garnered significant attention due to their inherent cellular properties, such as immune evasion and homing abilities, making them a subject of widespread interest. The coating of mixed membranes from different cell types onto the surface of nanoparticles offers a way to harness natural cell functions, enhancing biocompatibility and improving therapeutic efficacy. In this study, we merged membranes from murine-derived 4T1 breast cancer cells with RAW264.7 (RAW) membranes, creating a hybrid biomimetic coating referred to as TRM. Subsequently, we fabricated hybrid TRM-coated Fe3O4 nanoparticles loaded with indocyanine green (ICG) and imiquimod (R837) for combination therapy in breast cancer. Comprehensive characterization of the RIFe@TRM nanoplatform revealed the inherent properties of both cell types. Compared to bare Fe3O4 nanoparticles, RIFe@TRM nanoparticles exhibited remarkable cell-specific self-recognition for 4T1 cells in vitro, leading to significantly prolonged circulation life span and enhanced in vivo targeting capabilities. Furthermore, the biomimetic RIFe@TRM nanoplatform induced tumor necrosis through the Fenton reaction and photothermal effects, while R837 facilitated enhanced uptake of tumor-associated antigens, further activating CD8+ cytotoxic T cells to strengthen antitumor immunotherapy. Hence, RIFe@TRM nanoplatform demonstrated outstanding synergy in chemodynamic/immunotherapy/photothermal therapies, displaying significant inhibition of breast tumor growth. In summary, this study presents a promising biomimetic nanoplatform for effective treatment of breast cancer.

Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9.

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION: Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

Nutraceutical combination ameliorates imiquimod-induced psoriasis in mice.

Psoriasis is a chronic inflammatory skin disease that affects both localized and systemic regions of the body. This condition is characterized by the hyperproliferation of keratinocytes, resulting in skin thickening, scaling, and erythema. The severity of psoriasis depends on the extent of skin involvement, the location of the infection, and the symptoms that the person exhibits. While no cure exists, conventional therapies such as topical and systemic drugs are generally used to manage the exacerbation of symptoms. However, chronic use and overdose can lead to other severe adverse effects. Therefore, scientists and researchers are exploring potential nutraceuticals that can be considered as an alternative source of management for psoriasis. Current research aims to use different combinations of natural compounds like cannabidiol, myo-inositol, eicosapentaenoic acid, and krill oil to study the effect of these compounds in the prevention and treatment of psoriasis in the imiquimod (IMQ)-induced psoriatic mice model. The Psoriasis Area Severity Index (PASI) scoring system is used to analyze skin thickness, scales, and erythema. The results indicate that the krill oil combined with the cannabidiol and myo-inositol shows better results than other nutraceutical combinations. In the future, the natural products of krill oil can be combined with cannabidiol and myo-inositol to create an improved alternative to existing steroidal and nonsteroidal anti-inflammatory drugs for psoriasis treatment.

Characterization and active component identification of Premna herbacea roxb. root extract reveals anti-inflammatory effect and amelioration of imiquimod induced psoriasis via modulation of macrophage inflammatory response.

BACKGROUND: 1-2.88% of human populations are affected by psoriasis, one type of chronic inflammatory skin disease. Skin thickenings, erythema, scaling in skin are the most important symptoms of psoriasis. There are renewed interests amongst scientists in studying anti-inflammatory property of the plant extracts due to lower side effects and cost effectiveness. There are few reports suggesting anti-inflammatory activity of Premna herbacea roxb. but lacks systematic evaluation of these properties. METHODS: We, initially tested the anti-inflammatory activity of crude root methanolic extract in vitro, where it significantly reduced LPS generated ROS in splenic macrophages. We further tested the TLC and HPLC fraction in order to find active ingredient in Premna herbacea roxb. root extract that ameliorated the chronic inflammation of skin and performed GC-MS and LC-MS studies to identify active component. Upon finding significant anti-inflammatory effect of the crude root extract in vitro, We studied the efficacy of the Premna herbacea roxb. root extract in Imiquimod induced psoriasis like skin inflammation in male BALB/C mice that closely resembles human psoriasis. Immunophenotyping, Cytokine productions were observed by flow cytometry, status of gene expression was done by Real time PCR and nuclear co-localization was studied by confocal microscopy. RESULTS: We observed progressive increase in signs and symptoms of the disease in imiquimod treated diseased animals but the Premna herbacea roxb. Root Methanolic Extract (PHRME) reduced the thickening of the skin, redness and scaling in these animals. In our study, along with progression of the disease, the production of macrophages increases and with the application of PHRME, the percentage of macrophages have reduced. CONCLUSION: As per the previous Indigenous traditional knowledge regarding use of Premna herbacea roxb. against inflammatory disorder and lack of detail mechanistic study of the crude root extract prompted us to elucidate the efficacy of the root extract in vitro and in vivo psoriatic mice model. For the first time we have identified three putative bioactive active components (5­hydroxy-7-methoxyflavanone, 3-Hydroxy-7,8,2',3'-tetramethoxyflavone, 2,4',6'-trimethoxy chalcone) from Premna herbacea root methanolic extract (PHRME) and we suggest PHRME and purified active fractions influence NFκB and COX2 signaling pathway to suppress inflammatory conditions. All of the purified components show strong binding efficiency in our molecular docking analysis. Our study also suggests that Premna herbacea roxb. root extract may be explored as cost effective alternative for established treatment regimen as our study also indicates low side effect of the extract against pre-clinical psoriatic model.

[Current Management of Basal Cell Carcinoma]. / Aktuelles Management des Basalzellkarzinoms.

For the management of basal cell carcinoma, the primary performance of a risk stratification, which is decisive for the further diagnostic and therapeutic steps, is becoming increasingly important.Various non-invasive methods are available to confirm the clinical diagnosis. Histological confirmation of the diagnosis is recommended in unclear cases. In poorly displaced lesions, preoperative cross-sectional imaging of the tumor area should be performed to exclude osseous infiltration.The gold standard in treatment remains surgery, which should be performed by means of micrographically controlled surgery if possible. In addition, there are other therapeutic methods such as radiotherapy or a number of topical therapy options (photodynamic therapy, cryotherapy or application of 5-fluorouracil or imiquimod), which can be used in certain cases. Also for advanced or metastatic basal cell carcinoma, effective drugs are available in the form of the hedgehog inhibitors, for which there is now several years of application experience with regard to efficacy and handling of adverse events. With the PD-1 inhibitor cemiplimab, a further therapeutic option for non-operable or metastatic tumors has been available since June 2021.The most important preventive measure is consistent textile or chemical UV protection in already affected individuals. In addition, nicotinamide and celecoxib can be used orally for prevention. For follow-up, the current S2k guideline recommends regular self-monitoring and standardized medical check-ups.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.