curcumin and Psoriasis

To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases.. Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software.. A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet 's disease (BD) involves one RCT, Crohn 's disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ' s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs.. Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.

Topics: Arteritis; Arthritis, Rheumatoid; Colitis, Ulcerative; Crohn Disease; Curcuma; Curcumin; Humans; Lichen Planus, Oral; Lupus Erythematosus, Systemic; Plant Extracts; Psoriasis; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing

Curcuma and its derivatives are associated with anti-inflammatory and antioxidant activities in the skin. They exhibit beneficial effects in wound healing and prevention of chronic ultraviolet B damage and may prevent facial redness such as rosacea and flushing. This review aims to provide an up-to-date and rigorous synthesis of studies that demonstrated the clinical efficacy of curcuminoids in the skin. We evaluated studies published in the MEDLINE-PubMed/PMC (National Library of Medicine) databases, and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this review. This search included papers published in the past 10 years in controlled clinical trials, double-blind and randomized controlled studies, and case studies. The search resulted in 12 studies published in the past 10 years. Curcuma species (Curcuma longa and Curcuma aeruginosa) and curcumin were found to produce various dermatological effects, including influencing antioxidant and anti-inflammatory processes in the production of hyaluronan, increasing skin moisture, and reducing axillary hair growth. Curcuma was also found to reduce thickness, erythema, pruritus, burning and pain in psoriasis lesions and to improve radiodermatitis lesions. Our review results show that Curcuma species may play a role in skin health management and may exhibit various dermatological effects, thus it could be a new therapeutic arsenal for dermatology professionals. Nevertheless, more clinical trials should be conducted with humans to establish the optimum delivery method and dosages for different dermatological conditions.

Topics: Anti-Inflammatory Agents; Antioxidants; Curcuma; Curcumin; Double-Blind Method; Female; Humans; Hyaluronic Acid; Male; Plant Extracts; Psoriasis; Radiodermatitis; Randomized Controlled Trials as Topic; Rosacea; Skin; Treatment Outcome; Wound Healing

The microbiome is an important contributor to a variety of fundamental aspects of human health, including host metabolism, infection, and the immune response. Gut dysbiosis has been identified as a contributor to the errant immune response in a variety of immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriatic disease (psoriasis and psoriatic arthritis). Given this, probiotics and prebiotics have been investigated as therapeutic options in these disease states. In our review, we highlight the current evidence on prebiotics and probiotics as well as other supplements (such as fish oils, vitamin D, and curcumin) as therapies for IBD. Recommendations, however, regarding the specific use of such supplements in IBD have been lacking, particularly from professional societies, often due to study limitations related to small sample sizes and design heterogeneity. Hence, we additionally examine the literature on the use of prebiotics, probiotics, and other supplements in related IMIDs, namely RA and psoriasis/psoriatic arthritis, as these diseases share many approved therapeutic options with IBD. Based on these combined findings, we offer additional evidence that may help guide clinicians in their treatment of patients with IBD (and other IMIDs) and provide recommendations on potential next steps in therapeutic research in this area.

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Curcumin; Dietary Supplements; Female; Fish Oils; Humans; Inflammatory Bowel Diseases; Male; Prebiotics; Probiotics; Psoriasis; Vitamin D

Topics: Animals; Autoimmune Diseases; Curcumin; Humans; Hypersensitivity; Inflammatory Bowel Diseases; Neoplasms; Organ Transplantation; Psoriasis; T-Lymphocytes, Helper-Inducer

Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis. Several immune modulatory oligonucleotides and small molecular weight compounds, including IMO-3100, IMO-8400, and CPG-52364, that block the interaction between endosomal TLRs and their ligands are under clinical investigation for their effectiveness in the treatment of psoriasis. In addition, several chemical compounds, including AS-2444697, PF-05387252, PF-05388169, PF-06650833, ML120B, and PHA-408, can inhibit TLR signaling. Although these compounds have demonstrated anti-inflammatory activity in animal models, their therapeutic potential for the treatment of psoriasis has not yet been tested. Recent studies demonstrated that natural compounds derived from plants, fungi, and bacteria, including mustard seed,

Topics: Aminoquinolines; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cytokines; Dermatitis; Endosomes; Humans; Imiquimod; Indazoles; Isonicotinic Acids; Mice; Psoriasis; Resveratrol; Signal Transduction; Skin; Stilbenes; Toll-Like Receptor 7; Toll-Like Receptor 8; Toll-Like Receptor 9; Toll-Like Receptors

Curcumin, or diferuloylmethane, is a crystalline compound which gives the East Asian spice turmeric its bright yellow color. The medicinal properties of this spice have been referenced in numerous countries and cultures throughout the world. Today, there is growing scientific evidence suggesting curcumin's utility in the treatment of chronic pain, inflammatory dermatoses, acceleration of wound closure, skin infections, as well as cosmetic ailments such as dyspigmentation. In addition, curcumin may have a protective role against various pollutants and cytotoxic agents, indicating that it may be beneficial in a mitigational or prophylaxis role. Although turmeric has been used for thousands of years in alternative medicine, curcumin has yet to emerge as a component of our mainstream dermatologic therapeutic armamentarium. Interestingly, curcumin provides an ideal alternative to current therapies because of its relative safety profile even at high doses. Although the advantageous properties of curcumin in medicine are well established, its therapeutic potential thus far has been limited because of its poor oral bioavailablity. Topical administration of curcumin can directly deliver it to the affected tissue making it useful in treating skin-related disorders. However, limitations still exist such as the cosmetically unpleasing bright yellow-orange color, its poor solubility, and its poor stability at a high pH. Here the current literature detailing the potential and current use of curcumin in dermatology is reviewed.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Curcuma; Curcumin; Humans; Lichen Planus; Melanoma; Psoriasis; Scleroderma, Diffuse; Skin Diseases; Skin Neoplasms

Curcumin has long been expected to be a therapeutic or preventive agent for several major human diseases because of its antioxidative, anti-inflammatory, and anticancerous effects. In phase I clinical studies, curcumin with doses up to 3600-8000 mg daily for 4 months did not result in discernible toxicities except mild nausea and diarrhea. The pharmacokinetic studies of curcumin indicated in general a low bioavailability of curcumin following oral application. Nevertheless, the pharmacologically active concentration of curcumin could be achieved in colorectal tissue in patients taking curcumin orally and might also be achievable in tissues such as skin and oral mucosa, which are directly exposed to the drugs applied locally or topically. The effect of curcumin was studied in patients with rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers. Although the preliminary results did support the efficacy of curcumin in these diseases, the data to date are all preliminary and not conclusive. It is imperative that well-designed clinical trials, supported by better formulations of curcumin or novel routes of administration, be conducted in the near future.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Biological Availability; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Curcumin; Dose-Response Relationship, Drug; Drug Administration Schedule; Forecasting; Humans; Inflammatory Bowel Diseases; Neoplasm Metastasis; Precancerous Conditions; Psoriasis; Tissue Distribution

In this study, nanoparticles of curcumin were developed and orally administered to moderate-to-severe psoriasis (Psoriasis Area Severity Index values, PASI > 10) patients, in a placebo controlled, double blind, randomised clinical trial to evaluate the effectiveness.. Diverse binary systems of curcumin and hydrophilic polymers were investigated to optimise solubility and stability in terms of curcumin residual content and size of the crystals. Nanocrystals of curcumin stabilised with PVP (1 : 0.5, w/w), were characterised using X-ray diffraction, differential scanning calorimetry, TEM analyses and stability studies. The formulation was evaluated with a parallel artificial membrane permeability assay to predict the passive intestinal absorption. The first group of patients was treated orally with acitretin (0.4 mg/kg per day) plus nanocurcumin (3 g/day), the second group with acitretin, for 12 weeks.. Curcumin nanoparticles were homogeneous and stable systems. Curcumin permeability was significantly enhanced when compared with aqueous saturated solution of curcumin. The reduction in PASI was significantly higher in patients treated with curcumin (P < 0.0001) and cholesterol serum levels remained unchanged in patients treated with acitretin plus nanocurcumin.. Curcumin nanoparticles represent an effective adjuvant therapy in moderate-to-severe psoriasis patients treated with oral acitretin, improving their lipid serum profile.

Topics: Acitretin; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cholesterol; Curcumin; Double-Blind Method; Drug Stability; Drug Synergism; Female; Humans; Keratolytic Agents; Male; Membranes, Artificial; Middle Aged; Nanoparticles; Permeability; Psoriasis; Severity of Illness Index; Surface Properties; Young Adult

Psoriasis is an autoimmune and recurrent chronic inflammatory skin disorder with a strong genetic basis. The characteristic features are hyperproliferation of keratinocytes, leading to redness, thickening, and scaling of the epidermis followed by itching and the appearance of lesions, which in most cases can affect the patients both medically and psychologically. The scalp is one of the most common sites for psoriasis. This condition is predominantly managed with steroids, which are associated with various side effects. Turmeric (Curcuma longa L.), a spice commonly used throughout the world, has been shown to exhibit anti-inflammatory, antimicrobial, antioxidant, and antineoplastic properties. It has been reported to exhibit inhibitory activity on potassium channels in T cells and plays a key role in psoriasis.. We were prompted to investigate the turmeric tonic as an immune modulation and anti-inflammatory therapy on scalp psoriasis.. Forty patients with mild-to-moderate scalp psoriasis who fulfilled the inclusion criteria were randomly allocated into two groups. The case group received turmeric tonic twice a day for 9 weeks, whereas the other group received a placebo applied in the same manner. Patients were evaluated at the following points: baseline, weeks 3, 6, and 9. The dermatology life quality index (DLQI) questionnaire and PASI (psoriasis area & severity index) scores, as well as medical photos before, during and after treatment were also evaluated. The probable adverse effects were also recorded and reported.. Compared to the placebo, turmeric tonic significantly reduced the erythema, scaling and induration of lesions (PASI score), and also improved the patients' quality of life (P value < .05).. The clinical effects of turmeric tonic on scalp psoriasis were satisfactory overall. This formulation could be considered as a treatment for scalp psoriasis.

Topics: Adult; Curcuma; Double-Blind Method; Female; Humans; Immunologic Factors; Male; Middle Aged; Photography; Plant Extracts; Psoriasis; Quality of Life; Scalp Dermatoses; Severity of Illness Index

Topics: Adult; Combined Modality Therapy; Curcuma; Humans; Phototherapy; Pilot Projects; Plant Extracts; Psoriasis; Treatment Outcome

Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22.

Topics: Adult; Anti-Inflammatory Agents; Curcumin; Female; Humans; Interleukin-22; Interleukins; Male; Middle Aged; Psoriasis

There is a need for safe, inexpensive, and effective psoriasis therapies. Many anecdotal accounts of patients' successful treatment with the alternative medicine curcumin exist.. We sought to determine the safety and efficacy of oral curcumin in patients with psoriasis.. We conducted a phase II, open-label, Simon's two-stage trial of 4.5 g/d of oral curcuminoid C3 complex in patients with plaque psoriasis. End points included improvement in Physicians Global Assessment score, Psoriasis Area and Severity Index score, and safety end points throughout the study.. The intention-to-treat analysis response rate was 16.7% (95% confidence interval: 2%, 48%) and both responders achieved a Psoriasis Area and Severity Index 75 score. There were no study-related adverse events that necessitated participant withdrawal.. Small sample size and lack of placebo group are limitations.. The response rate was low and possibly caused by a placebo effect or the natural history of psoriasis. Large placebo-controlled studies are necessary before recommending oral curcumin as a psoriasis treatment.

Topics: Administration, Oral; Adult; Curcumin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Psoriasis

Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calmodulin-dependent signalling pathways, including those involved in cell migration and cell proliferation, while coupling these pathways to glycogenolysis and ATP-dependent phosphorylation, thus ensuring continuing energy supply for these activities.. Our laboratory recently reported correlation of elevated PhK activity with psoriatic activity. This study further evaluates the significance of drug-induced suppression of PhK activity on psoriatic activity.. PhK activity was assayed in four groups, each with 10 patients: (i) active untreated psoriasis; (ii) resolving psoriasis treated by calcipotriol (Dovonex(R), Bristol Myers Squibb, Princeton, NJ, U.S.A. ), a vitamin D3 analogue and an indirect inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriatic subjects.. PhK activity in units mg-1 protein was highest in active untreated psoriasis (1204 +/- 804.3; mean +/- SD), lower in the calcipotriol-treated group (550.7 +/- 192. 9), lower in curcumin-treated group (207.2 +/- 97.6), and lowest in normal skin (105.4 +/- 44.6). One-way analysis of variance performed on log-transformed PhK activity measure showed significant differences among the four groups, F3,36 = 48.79, P < 0.0001. Decreased PhK activity in curcumin-and calcipotriol-treated psoriasis was associated with corresponding decreases in keratinocyte transferrin receptor (TRR) expression, severity of parakeratosis and density of epidermal CD8+ T cells.. Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity.

Topics: Adult; Aged; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Calcitriol; CD8-Positive T-Lymphocytes; Cell Division; Curcumin; Dermatologic Agents; Enzyme Inhibitors; HLA-DR Antigens; Humans; Keratinocytes; Ki-67 Antigen; Male; Middle Aged; Parakeratosis; Phosphorylase Kinase; Psoriasis; Receptors, Transferrin

The aim is to achieve the targeting function of Aptamer 21-2 (Apt) by modifying glycyrrhizic acid (GA) to obtain Apt-GA and by delivering it through mesoporous silica in μm-size (μmS). Moreover, it is planned to induce synergistic effects of the novel amorphous preparation of Apt-GA with curcumin (Cur) in the treatment of psoriasis. UV/vis spectrophotometric analysis and Fourier transform infrared spectroscopy were performed to demonstrate the linkage of Apt and GA. The replacement of GA with Apt-GA in GA-Cur-μmS did not make a difference in the amorphous state, but showed superior fluorescence of Cur in the inflamed dermis similar to psoriatic induced by imiquimod. Consequently, compared to GA-Cur-μmS and Apt, Apt-GA-Cur-μmS exhibited less pronounced psoriatic characteristics in vivo, including Psoriasis Area and Severity Index, histological image, immunohistochemistry and immuno-fluorescence labeling neutrophils. The enzyme-linked immunosorbent assay showed a similar phenomenon that less IL-17A was observed after treatment with Apt-GA-Cur-μmS than with GA-Cur-μmS or Apt. Our finding suggests that this novel Apt delivery system achieved the Apt targeting function in the dermis by taking advantage of GA and μmS, and exhibited synergistic anti-psoriatic effect by co-delivering curcumin.

Topics: Curcumin; Glycyrrhizic Acid; Humans; Imiquimod; Psoriasis; Silicon Dioxide

Psoriasis is a recurrent, life-threatening anti-inflammatory condition that affects nearly 1-3% of the global population. It is an autoimmune illness distinguished by hyperplasia of skin cells or fast skin cell development, resulting in abnormally irritating scales and skin patches. Curcumin, as a selective phosphorylase kinase inhibitor, actively suppresses inflammation and keratinocyte proliferation in psoriasis. However, limited solubility in water and poor skin permeability poses a significant hurdle in curcumin's topical effectiveness in psoriasis. The present study focuses on enhancing the solubility and skin permeability of curcumin for better transdermal application. Curcumin-loaded invasomes were formulated, and a factorial design was applied to study the effect of the type of terpenes and their concentrations on the properties of prepared invasomes. A topical gel was formulated using the optimised invasomal formulation which was further evaluated for anti-psoriatic potential in BALB/c mice. The optimised formulation showed 85.84 ± 0.56% entrapment efficiency and a vesicle size of 302.33 ± 1.53 nm. The invasomal gel of the optimised formulation showed a permeation flux of 3 times greater than the plain gel. In vivo studies demonstrated that the invasomal gel of curcumin promoted faster and earlier recovery in psoriatic mice than conventional curcumin gel.

Topics: Administration, Cutaneous; Animals; Curcumin; Mice; Psoriasis; Skin; Solubility

Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects.. The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model.. Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis.. Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (. Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Cytokines; Disease Models, Animal; Imiquimod; Interleukin-12 Subunit p40; Interleukin-17; Psoriasis; Rats; Skin; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Ustekinumab

The aim of this study was to explore the function of glycyrrhizic acid (GA) in an anti-psoriatic dermal delivery, whereby GA is originally designed as the matrix agent, with curcumin (Cur) as the active agent and silica as the drug carrier. Formulations with different GA proportions were prepared and named W-GA (without GA), L-GA (13% w/w GA) and H-GA (26% w/w GA). The results showed that GA had no significant effect on the physical characteristics, such as particle size and amorphous state, as exhibited by scanning electron microscopy and x-ray diffractograms, respectively. Compared with W-GA and L-GA, H-GA resulted in 10% less photodegradation of Cur after storage for one month, 0.45 μg more penetrated Cur in the epidermis, 2-fold higher viscosity, fewer signals of imiquimod-induced psoriasiform skin lesions and less histological morphological changes. The findings showed that H-GA significantly inhibited expression of interleukin 17 A in the dermis, and interleukin IL-23 in the epidermis, compared with Cur raw drug powder (RDP), whereas L-GA had no significant effect on the expression. These results indicated that a high GA proportion results in superior anti-psoriatic efficacy. Therefore, Cur-loaded silicas with approximately 26% GA are recommended as the superior formulation for the treatment of psoriasis.

Topics: Curcumin; Drug Carriers; Gels; Glycyrrhizic Acid; Humans; Nanoparticles; Particle Size; Psoriasis; Silicon Dioxide

Preclinical safety and proof of concept studies for a topical ointment comprising of concentrated tetrahydrocurcumin loaded lipidic nanoparticles (THC-LNs) and tacrolimus ointment (TTO) is proposed in the present investigation. The skin irritation potential and acute dermal toxicity were performed in rats in compliance with the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404 and 410) while the cytotoxic potential was performed in HaCaT cells. Finally, in vivo evaluation was performed in Imiquimod mice model of psoriasis. In primary skin irritation assessment, TTO formulation, marketed formulation (Tacroz® Forte), THC-LNs, and blank LNs were topically applied on intact skin sites in rats while another group served as a negative control group for 72 h. TTO did not induce any adverse reactions. Repeated 28 days dermal toxicity followed by biochemical and histopathological assessment showed negligible alternations and skin lesions. THC-LNs revealed negligible cytotoxic potential in HaCaT cells. TTO showed significantly high anti-psoriatic activity in comparison to marketed ointment. This was also confirmed via histopathological evaluation. Based on these findings, it can be ascertained that TTO showed minimal toxicity and has ample potential for further clinical analysis. The above studies affirm the potential of TTO as an alternative for psoriasis.

Topics: Animals; Curcumin; Mice; Mice, Inbred BALB C; Nanoparticles; Ointments; Psoriasis; Rats; Tacrolimus

As a chronic skin disease, psoriasis is a relatively common disease among various types of skin diseases. Because this disease is often distributed throughout the patient's body and is prone to develop, it is difficult to guarantee the quality of life and physical and mental health of patients with this disease. The purpose of this article is to investigate whether curcumin can effectively inhibit the NLRP3 inflammatory body and thereby reduce the inflammation in the mouse psoriasis model. Through the use of the curcumin gel prepared and the mouse psoriasis model, the percutaneous administration was used to investigate the mechanism and mechanism of curcumin's effect on reducing inflammation in the mouse psoriasis model. In addition, in order to better explore the curative effect of curcumin on psoriasis, related experiments were conducted by setting up a control group and an experimental group. The results show that curcumin has a good inhibitory effect on NLRP3 inflammatory bodies. Curcumin can not only reduce the NLRP3 expression and inhibit the inflammation caused by IL-22 and IL-18 but also reduce the damage of psoriasis. 22 Induced phosphorylation of STAT3 almost completely inhibits phosphorylation in normal cells. Among them, curcumin inhibited IL-22-induced phosphorylation of STAT3 up to 95.6%, and inhibited IL-22 and IL-18 by about 47%.

Topics: Animals; Curcumin; Disease Models, Animal; Inflammation; Interleukin-18; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Psoriasis; Quality of Life

Psoriasis seriously harms physical and mental health of patients. Hyaluronic acid (HA)-based topical formulation can increase drug concentration in psoriatic skin via CD44-assisted targeting. Herein, we developed a supramolecular medicine composed of curcumin-loaded HA-cucurbit[7]uril (HA-CB[7]@Cur), which could efficiently sequester polyamines (PAs) via host-guest interactions of CB[7] and PAs to suppress RNA-PAs immunocomplex formation. Meanwhile, anti-psoriasis drug Cur could be released from HA-CB[7]@Cur by PAs. With phenotypical disease evaluation, psoriasis area measurements and severity index scoring, and histological characterizations, we demonstrate topical administration of Carbopol gel formulation of HA-CB[7]@Cur on psoriasis-like skin in mice exhibited an enhanced anti-psoriasis activity, in comparison with gel of free Cur or HA-CB[7]. Cytokine expression analysis in psoriatic skin also supported the observed therapeutic outcomes. We provide a novel and effective supramolecular strategy to realize cooperative anti-psoriasis via controlled release of curcumin and PAs sequestration, which can be potentially expanded to treat other PA-involved skin inflammatory diseases.

Topics: Animals; Curcumin; Drug Carriers; Hyaluronic Acid; Mice; Polyamines; Psoriasis

This work investigates the synergistic potential of the nanostructured lipid carrier (NLC) gel of Ibrutinib with Curcumin as a repurposing strategy to treat psoriasis. In the present work, various components such as liquid lipid, solid lipid, and surfactant were selected and optimized based on the solubility of each drug, size, and polydispersity index. The optimized NLC consists of Capryol PGMC as liquid lipid, Glyceryl Mono Stearate as solid lipid, and Pluronics-F-127 as a surfactant. The prepared NLCs have a particle size of 95.12 ± 3.39 nm with PDI of 0.285 ± 0.009, exhibiting high entrapment efficiency (86.04 ± 2.86% for IBR and 87.25 ± 2.14% for CUR) with spherical geometry. CI value of 0.283 suggests synergism. Carbopol 940 was used as a gelling agent and has shown improved flux compared to plain drug gel. Anti-psoriatic studies in BALB/c mice indicated negligible skin irritation and improved histopathological features of psoriasis. Moreover, a reduced amount of inflammatory markers (TNF-alpha, IL-6, IL-22, and IL-23), and psoriasis severity score was observed with prepared gel than the IMQ group. The study suggested integrated benefits of repurposing Ibrutinib with Curcumin as NLC topical gel and it could possibly reduce remission of Psoriasis like inflammation and merit additional investigation.

Topics: Animals; Curcumin; Drug Carriers; Drug Repositioning; Excipients; Gels; Lipids; Mice; Mice, Inbred BALB C; Nanostructures; Particle Size; Protein Kinase Inhibitors; Psoriasis; Surface-Active Agents

Topics: Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cell Line; Curcumin; Drug Carriers; Drug Liberation; Epichlorohydrin; Humans; Psoriasis; Solubility

Curcumin, resveratrol, and thymoquinone are the potential natural bio-actives reported with good anti-psoriatic activity. However, poor aqueous solubility and limited skin permeation of these natural bio-actives hinder their effective delivery and potential therapeutic outcome. In this regard, current research work focuses on the design and optimization of nanoemulsion (NE) gel formulation for the concurrent delivery of these three drugs. The NE system is consisting of oleic acid as oil phase, Tween 20 as surfactant, and PEG 200 as co-surfactant. The optimized formulation exhibited the droplet size 76.20 ± 1.67 nm, PDI of 0.12 ± 0.05, RI of 1.403 ± 0.007, and viscosity of 137.9 ± 4.07 mp. Carbopol 940 (0.5% w/v) was used as the gelling agent to prepare the NE gel which exhibited a good texture profile. The optimized formulation exhibited a higher % of growth inhibition on A-431 cells and demonstrated good anti-angiogenic activity in the HET-CAM test. Finally, in vivo studies in Balb/c mice model showed improved anti-psoriatic conditions which indicated that the triple natural bio-actives combination in nanoemulgel formulation is effective in the management of psoriasis.

Topics: Animals; Benzoquinones; Curcumin; Emulsions; Mice; Nanoparticles; Particle Size; Psoriasis; Resveratrol

Psoriasis is one of the most influential and fastest-growing inflammatory diseases of the skin. Curcumin (CRC) is an effective antipsoriatic drug that is often carried by nanoparticles or liposomes mainly administered via the skin. However, the therapeutic effectiveness and bioavailability of this drug are restricted due to the functions of the skin barrier to liposomes. Herein, we proposed a peptide-modified curcumin-loaded liposome (CRC-TD-Lip) to expedite the transdermal delivery of curcumin and enhance the inhibition of psoriasis. CRC-TD-Lip was prepared and dispersed uniformly with high stability and high curcumin encapsulation efficiency. We confirmed the improved intracellular uptake of CRC-TD-Lip, the increased inhibitory effect of CRC-TD-Lip on HaCaT cells, and the heightened transdermal ability of CRC-TD-Lip. Then, the enhanced antipsoriatic ability of CRC-TD-Lip was evaluated in vivo using an imiquimod-induced psoriasis mouse model. The results indicated that the developed CRC-TD-Lip can effectively improve the delivery of curcumin across the skin and enhance the antipsoriasis efficiency. This work can provide a strategy for enhancing the transdermal delivery efficiency of drugs for various skin diseases.

Topics: Administration, Cutaneous; Animals; Curcumin; Liposomes; Mice; Nanoparticles; Peptides; Psoriasis; Skin

Combined therapy with anti-inflammatory drugs is preferred for the topical treatment of psoriasis, but the codelivery of drugs is restricted due to the lack of a suitable delivery system. Ethosomes with excellenttransdermal propertiesare perfect as carriers for hyperplastic skin. Therefore, glycyrrhetinic acid-D-α-tocopherol acid polyethylene glycol succinate (GA-TPGS) was synthesized, which prevented the inflammation and lipid peroxidation damage, thus effectively stabilizing the psoriasis. Then GA-TPGS was surface-modified on the curcumin (Cur) loaded ethosomes to construct curcumin-loaded GA-TPGS-modified multifunctional ethosomes (Cur@GA-TPGS-ES), exerting synergistic treatment for psoriasis. Using an interleukin-6-induced cell model, we found that Cur@GA-TPGS-ES displayed desirable suppression of inflammation response and oxidative stress damage. Compared with the ethanol solution, the percutaneous penetration rates of Cur and GA in Cur@GA-TPGS-ES were superior. In vivo microdialysis revealed similar results, suggesting an increase of transcutaneous absorption in Cur@GA-TPGS-ES. Fluorescence staining revealed that the cellular uptake and skin distribution were distinctly enhanced with the delivery by Cur@GA-TPGS-ES. After topical administration to imiquimod-induced psoriatic mice, the Cur@GA-TPGS-ES group showed powerful treatment from inflammatory infiltration inhibition of Cur, glucocorticoid-like effects of GA and anti-lipid peroxidation of TPGS. Overall, GA-TPGS mediated ethosomes possess more advantageous transdermal properties and synergistic antipsoriatic efficacy.

Topics: Administration, Cutaneous; Animals; Curcumin; Drug Carriers; Glycyrrhetinic Acid; Mice; Psoriasis; Vitamin E

Recent advances have revealed that progranulin (PGRN) is related to the aetiology of psoriasis. Moreover, curcumin, a compound derived from turmeric, has been proposed as a potential therapeutic approach in psoriasis-like dermatitis, but it is still unclear whether curcumin affects the development of psoriasis-like skin lesions under PGRN-deficient conditions. Therefore, in this study, we developed a mouse model of psoriatic skin lesions using topical application of imiquimod (IMQ) in both wild type and PGRN-knockout mice to test this possibility. We observed that PGRN deficiency not only increased proinflammatory cytokine IL-17A levels and aggravated psoriasis-like damaged appearance and epidermal thickening but also directly mediated changes in keratinocyte proliferation (Krt 14, cyclinD1 and c-Myc) and differentiation (Krt 10 and Filaggrin) associated gene expression following IMQ challenge, compared to those in the control group. Furthermore, curcumin treatment (50 mg/kg and 200 mg/kg, intragastrically) for 21 consecutive days suppressed the IMQ exposure-induced increase in PGRN expression. Importantly, curcumin treatment significantly alleviated the PGRN deficiency-induced exacerbation of psoriatic appearance, histological features and keratinocyte proliferation after IMQ exposure. In summary, these results demonstrate the direct regulation of PGRN in keratinocyte proliferation and differentiation in psoriatic lesions and demonstrate the protective effect of curcumin on PGRN deficiency-induced psoriatic skin lesion exacerbation.

Topics: Animals; Cell Proliferation; Curcumin; Disease Models, Animal; Humans; Imiquimod; Interleukin-17; Keratinocytes; Male; Mice; Mice, Knockout; Progranulins; Psoriasis

This study was to develop a combination of zedoary turmeric oil (ZTO) and tretinoin (TRE)-loaded liposomal gel as a topical drug delivery system. We used a combination of single-factor experiment and orthogonal experiment to systematically optimize encapsulation process of the compound liposomes. The optimized liposome vesicles were incorporated into Carbopol gel matrix and studied by continuous

Topics: Animals; Curcuma; Gels; Liposomes; Mice; Particle Size; Psoriasis; Tretinoin

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and expression of pro-inflammatory cytokines in the epidermis. New biological drugs were developed for the systemic treatment of moderate to severe psoriasis. However, products for the topical treatment of mild psoriasis are still required. Here, we examined the effect of natural compounds on psoriasis-like keratinocytes in vitro and ex vivo. Psoriasis-like keratinocytes were generated by treating human primary keratinocytes with the psoriasis-associated cytokines IL-17A, TNF-α and IL-22. Initially, 10 botanical extracts from Ayurvedic Medicine, Traditional Chinese Medicine, Northern American traditional medicine and Occidental Monastic Medicine were investigated using BrdU assays and IL-6 and IL-8 ELISAs.

Topics: Cell Line; Cell Proliferation; Curcuma; Cytokines; Gene Expression Regulation; Humans; Humulus; Hypericum; Keratinocytes; Models, Biological; Plant Extracts; Plants, Medicinal; Psoriasis

smartPearls technology is one appropriate method to produce anti-psoriatic curcumin (Cur) topical delivery system. To prevent the sedimentation of loaded silica and release changing over the storage, which are disadvantages of smartPearls production, extra glycyrrhizic acid (GA) was added in classical smartPearls ingredients (active and porous material) to get an improved smartPearls production (Cur-GA-silica). The capacity of Cur-GA-silica to remain the gelation state after mixing with water was superior compared to that of the solid cluster without GA and that of the physical mixture of Cur, GA and silica. The Cur-GA-silica practically contained Cur with 1.68% ± 0.12% and showed significant difference with Cur raw drug powder in kinetic solubilities (4.55 ± 0.78 µg/mL vs 0 in 5 min; 3.26 ± 0.17 µg/mL vs 0 in 4 h) which was traceable to the amorphous state of Cur-GA-silica detected by X-ray diffractometer. With the amorphous Cur, two times as much penetrated Cur in Cur-GA-silica as in Cur raw drug powder was achieved on the imiquimod-induced psoriasis-like mice model. The anti-psoriatic efficacy of Cur-GA-silica was confirmed by Psoriasis Area and Severity Index (PASI) evaluation, histological evaluation and decreased IL-17A in the imiquimod-induced psoriasiform mouse skin analyzed by enzyme-linked immunosorbent assay. In conclusion, with the addition of GA, a stable amorphous curcumin topical vehicle fabricated by smartPearls technology without extra dermal matrix is available and facilitates penetration efficacy and anti-psoriatic capacity in imiquimod-induced psoriasiform mice.

Topics: Administration, Cutaneous; Animals; Curcumin; Drug Carriers; Excipients; Female; Gels; Glycyrrhizic Acid; Mice; Mice, Inbred C57BL; Particle Size; Psoriasis; Silicon Dioxide; Solubility; Technology, Pharmaceutical

Curcumin exhibits anti-inflammatory properties and has been used for centuries in traditional medicine and as dietary supplement. Data from clinical trials has strengthened the notion that curcumin may exert an anti-inflammatory and immunosuppressive role in patients with psoriatic disease, but its mode of action has remained elusive. We hypothesized that curcumin could inhibit interferon (IFN)-γ and interleukin (IL)-17 production in peripheral blood mononuclear cells from patients with psoriasis and psoriatic arthritis (PsA). To this end, we assessed the in vitro effect of curcumin on IFN-γ production by cluster differentiation (CD)4(+), CD8(+) T cells, natural killer (NK) and NKT cells and on IL-17 production by CD4(+) T cells from 34 patients with psoriatic disease (22 with psoriasis and 12 with PsA); 15 normal subjects were included as healthy controls. We also assessed the effect of curcumin on signal transducer and activator of transcription (STAT)3 activation. Curcumin significantly decreased, in a dose dependent manner, IFNγ-production by CD4(+) and CD8(+) T cells, and NK and NKT cells in patients with psoriatic disease and healthy controls. It also decreased IL-17 production by CD4(+) T cells (Th17). At the molecular level, curcumin increased STAT3 serine 727 phosphorylation intensity and p-STAT3(+) CD4(+) T cells in patients with PsA and psoriasis. In conclusion, curcumin in vitro inhibits pro-inflammatory IFN-γ and IL-17 production in psoriatic disease, and this may strengthen its role as a dietary immunosuppressant in patients with this disease.

Topics: Adult; Aged; Anti-Inflammatory Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Curcumin; Diet; Female; Humans; Immunosuppressive Agents; Inflammation; Interferon-gamma; Interleukin-17; Killer Cells, Natural; Male; Middle Aged; Psoriasis; STAT3 Transcription Factor

Combination of curcumin with anti-inflammatory drug like caffeine shows augmented antipsoriatic action compared to curcumin alone and reduce the time taken for treatment of Psoriasis.. The objective of the present study was to develop nanosponge (NS) based topical gel of curcumin (CUR) and caffeine (CFN) combination that acts as a potential system for the treatment of psoriasis.. NS composed of dimethyl carbonate (DMC) as crosslinker and beta-cyclodextrin (β-CD) as polymer were prepared by hot melt method and incorporated in topical gels. Factorial design (3. The physical and chemical characteristics exhibited by the prepared NS and gels (F1-F9) were found to be optimal. The optimization resulted in achieving formulation N10 with 69.72% in vitro drug release and 12,329.78cp viscosity. Histopathology studies revealed that prepared nanogel has promising anti-psoriatic activity. The results concluded that CUR and CFN combination has reduced the time required for showing anti-psoriatic activity to 10 days when compared to CUR alone that took around 20 days. Moreover, the nanogel has depicted sustained drug release till 12 h.. From the experimental findings it has been concluded that CUR and CFN combination significantly augmented the anti-psoriatic efficacy with respect to individual components and also reduced the time required for onset of effect. Thus, the proposed nanogel would be an imperative drug delivery system for more effective anti-psoriatic therapy. Graphical abstract.

Topics: Administration, Topical; Animals; beta-Cyclodextrins; Caffeine; Curcumin; Delayed-Action Preparations; Disease Models, Animal; Drug Combinations; Drug Compounding; Female; Formates; Imiquimod; Male; Mice; Nanostructures; Particle Size; Psoriasis

The current investigation aimed to improve the topical efficacy of imiquimod in combination with curcumin using the nanoemulsion-based delivery system through a combinatorial approach. Co-delivery of curcumin acts as an adjuvant therapeutic and to minimize the adverse skin reactions that are frequently associated with the topical therapy of imiquimod for the treatment of cutaneous infections and basal cell carcinomas. The low-energy emulsification method was used for the nano-encapsulation of imiquimod and curcumin in the nanodroplet oil phase, which was stabilized using Tween 20 in an aqueous dispersion system. The weak base property of imiquimod helped to increase its solubility in oleic acid compared with ethyl oleate, which indicates that fatty acids should be preferred as the oil phase for the design of imiquimod-loaded topical nanoemulsion compared with fatty acid esters. The phase diagram method was used to optimize the percentage composition of the nanoemulsion formulation. The mean droplet size of the optimized nanoemulsion was 76.93 nm, with a polydispersity index (PdI) value of 0.121 and zeta potential value of -20.5 mV. The optimized imiquimod-loaded nanoemulsion was uniformly dispersed in carbopol 934 hydrogel to develop into a nanoemulgel delivery system. The imiquimod nanoemulgel exhibited significant improvement (p<0.05) in skin permeability and deposition profile after topical application. The in vivo effectiveness of the combination of imiquimod and curcumin nanoemulgel was compared to the imiquimod nanoemulgel and imiquimod gel formulation through topical application for ten days in BALB/c mice. The combination of curcumin with imiquimod in the nanoemulgel system prevented the appearance of psoriasis-like symptoms compared with the imiquimod nanoemulgel and imiquimod gel formulation entirely. Further, the imiquimod nanoemulgel as a mono-preparation slowed and reduced the psoriasis-like skin reaction when compared with the conventional imiquimod gel, and that was contributed to by the control release property of the nano-encapsulation approach.

Topics: Administration, Topical; Animals; Curcumin; Disease Models, Animal; Drug Combinations; Drug Compounding; Emulsions; Imiquimod; Male; Mice; Mice, Inbred BALB C; Nanogels; Oleic Acid; Particle Size; Permeability; Polyethylene Glycols; Polyethyleneimine; Polysorbates; Psoriasis; Rats

Curcumin (CUR) has shown remarkable efficacy in the treatment of skin diseases, but its effective transdermal delivery is still a major challenge and stimulates interest in the design of novel systems for CUR dispersion, preservation, and delivery facilitation to the deeper layers of the skin. The present work aimed to investigate the potential of a nanohydrogel, formed by a micellar choline-calix[4]arene amphiphile (CALIX) and CUR, in the treatment of skin diseases through an imiquimod (IMQ)-induced psoriasis model. Psoriasis plaques are associated with aberrant keratinization, abnormal distribution of tight junctions (TJs) proteins, and enhanced expression of inflammatory markers. The nanohydrogel restored the normal distribution of TJs proteins ZO1 and occludin and reduced the expression of TNF-α and inducible nitric oxide synthetase (iNOS) compared to the untreated IMQ group. The novelty lies in the calix[4]arene-based nanohydrogel as a potential new soft material for the topical skin delivery of CUR. The nanohydrogel, due to its physicochemical and mechanical properties, enhances the drug water-solubility, preserves CUR from rapid degradation, and eases the local skin administration and penetration.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calixarenes; Choline; Curcumin; Disease Models, Animal; Drug Carriers; Hydrogels; Male; Mice; Mice, Inbred BALB C; Phenols; Psoriasis

Curcuma was the dried rhizomes of Curcuma kwangsiensis S.G. Lee et C.F. Liang (Chinese name: e zhu), have been used in China for thousands of years. There are some reports have shown that curcumin, the major component of curcuma, has a good curative effect on psoriasis, but the mechanism is still unknown, so the present study was designed to investigate the effect of curcuma's extraction on psoriasis-like mouse, and to explore the mechanisms of therapy. First, we observed that curcuma's extractions effect on mitosis of mouse vaginal epithelial cells; then making psoriasis like model and measuring the score of skin damage on days 7 and 14; finally, we observed the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) in propranolol induced psoriasis like rats. Curcuma's extraction prohibited the mitosis of mouse vaginal epithelial cells; curcuma's extractions have a significantly efficacy and dose dependent inhibition on imiquimod induced psoriasis like rats; and the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) was decreasing in the curcuma's extraction treated groups compared with normal groups. Our research proved that curcuma's extractions have a significantly efficacy on psoriasis like rats, thus, curcuma's extractions can be a potential novel treatment for psoriasis. Furthermore, the expression of immune factors was decreasing after treatment with curcuma's extraction suggest us cytokines has strong relation with the mechanism of therapy for psoriasis. Our results contribute towards validation of curcuma in the treatment of psoriasis and other joint disorders.

Topics: Animals; Curcuma; Dermatologic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial Cells; Female; Guinea Pigs; Imiquimod; Keratins; Male; Mice; Mitosis; Plant Extracts; Proliferating Cell Nuclear Antigen; Propranolol; Psoriasis; Rhizome; Skin; Time Factors; Toll-Like Receptors; Vagina

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Drug Carriers; Gels; Hyaluronan Receptors; Hyaluronic Acid; Mice; Nanoparticles; Psoriasis; Treatment Outcome

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of the epidermal cells and is clinically presented as thick, bright red to pink plaques with a silvery scale. Photodynamic therapy (PDT) using visible light has become of increasing interest in the treatment of inflammatory skin diseases. In this study, we demonstrate that a combination of curcumin-loaded chitosan/alginate nanoparticles (Cur-CS/Alg NPs) and blue light emitting diodes (LED) light irradiation effectively suppressed the hyperproliferation of tumor necrosis factor-alpha (TNF-α)-induced cultured human kerlatinocyte (HaCaT) cells. The Cur-CS/Alg NPs were fabricated by emulsification of curcumin in aqueous sodium alginate solution and ionotropic gelation with calcium chloride and chitosan using an optimized formulation derived from a Box-Behnken design. The fabricated Cur-CS/Alg NPs were characterized for their particle size, zeta potential, encapsulation efficiency, and loading capacity. The surrogate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, to measure the relative number of viable cells, showed that the CS/Alg NPs were nontoxic to normal HaCaT cells, while 0.05 µg/mL and 0.1 µg/mL of free curcumin and Cur-CS/Alg NPs inhibited the hyperproliferation of HaCaT cells induced by TNF-α. However, the Cur-CS/Alg NPs demonstrated a stronger effect than the free curcumin, especially when combined with blue light irradiation (10 J/cm²) from an LED-based illumination device. Therefore, the Cur-CS/Alg NPs with blue LED light could be potentially developed into an effective PDT system for the treatment of psoriasis.

Topics: Alginates; Cell Line, Transformed; Cell Proliferation; Chitosan; Curcumin; Drug Delivery Systems; Humans; Keratinocytes; Light; Nanoparticles; Psoriasis; Tumor Necrosis Factor-alpha

Psoriasis is a chronic autoimmune disease mediated by dysregulated immune responses in dendritic cells (DC) and T cells. The stress-response enzyme heme oxygenase-1 (HO-1) has been described as protective in animal models of psoriasis, however, implementation of HO-1-based therapies is hindered by the lack of clinically-suitable HO-1 inducers. The plant-derived polyphenols, carnosol and curcumin, have been identified as candidate HO-1 inducers however there has been little investigation into their effects on human immune cells. We demonstrate that treatment of human DC with these polyphenols limits DC maturation, reduces pro-inflammatory cytokine production, and prevents induction of allospecific T cell responses, in a manner partially dependent on carbon monoxide (CO). We also characterised their effects in ex-vivo psoriasis PBMC and report that curcumin, but not carnosol, strongly reduces T cell proliferation and cytokine poly-functionality, with reduced expression of psoriatic cytokines IFNγ, IL-17, GM-CSF and IL-22. This study therefore supports reports highlighting the therapeutic potential of curcumin in psoriasis by providing insight into its immunological effects on healthy human DC and psoriasis PBMC. We also demonstrate, for the first time, the anti-inflammatory effects of carnosol in human immune cells.

Topics: Abietanes; Anti-Inflammatory Agents, Non-Steroidal; Carbon Monoxide; Cell Differentiation; Cell Proliferation; Curcumin; Dendritic Cells; Enzyme Activation; Gene Expression Regulation, Enzymologic; Heme Oxygenase-1; Humans; Inflammation; Leukocytes, Mononuclear; Lymphocyte Activation; Psoriasis; T-Lymphocytes

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Curcumin; Dermatitis; Drug Carriers; Imiquimod; Lipids; Male; Mice; Nanofibers; Psoriasis

As an immune-mediated skin disease, psoriasis encounters therapeutic challenges on topical drug development due to the unclear mechanism, and complicated morphological and physiological changes in the skin.. In this study, imiquimod-induced psoriatic mouse skin (IMQ-psoriatic skin) was chosen as the in vitro pathological model to explore the penetration behaviors of drugs and nanoparticles (NPs).. Compared with normal skin, significantly higher penetration and skin accumulation were observed in IMQ-psoriatic skin for all the three model drugs. When poorly water-soluble curcumin was formulated as NPs that were subsequently loaded in gel, the drug's penetration and accumulation in both normal and IMQ-psoriatic skins were significantly improved, in comparison with that of the curcumin suspension. Interestingly, the NPs' size effect, in terms of their penetration and accumulation behaviors, was more pronounced for IMQ-psoriatic skin. Furthermore, by taking three sized FluoSpheres. In conclusion, the alternation of the IMQ-psoriatic skin structure will lead to the enhanced penetration of drug and NPs, and should be considered in topical drug formulation and further clinical practice for psoriasis therapy.

Topics: Adjuvants, Immunologic; Aminoquinolines; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Female; Imiquimod; Mice; Mice, Inbred C57BL; Nanoparticles; Psoriasis; Skin

Psoriasis is an immune-mediated skin disorder, which is triggered by the aberrant activation of dendritic cells in skin. This activation is followed by the complex interaction between the immune cells in the skin and keratinocyte in the epidermis. To improve the conditions of poor aqueous solubility and chemical stability, overcome skin barriers, and enhance in vivo anti-psoriatic activity, curcumin (Cur) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were fabricated and administered by topical route to treat imiquimod (IMQ)-induced psoriasis-like mouse model. Spherical Cur-NPs with the mean particle sizes of 50nm and 150nm, respectively, were fabricated using a multi-inlet vortex mixer system, with both exhibiting significantly stronger anti-proliferation effect than Cur solution on HaCaT cells in vitro. Psoriatic skin was utilized in the in vitro skin penetration studies, and the results demonstrated that more drugs penetrated through or accumulated in the skin when administered as the Cur-NPs-loaded hydrogel compared to the drug suspension loaded hydrogel. To compare the nanosizing effect of these Cur-NPs, the mice with IMQ-induced psoriasis-like skin disease were treated with blank gel, Cur gel, 50nm sized NPs gel, 150nm sized NPs gel or tracrolimus cream (positive control), respectively. The results indicated that Cur-NPs hydrogel has a superior performance to Cur hydrogel on the IMQ-induced psoriasis-like mouse model in terms of morphological evaluation, biomarkers at mRNA, and protein levels. In conclusion, encapsulation of Cur into PLGA NPs, particularly for NPs of 50nm, could facilitate lipophilic Cur's dispersion, sustained-release, accumulation, and penetration across the skin and into the blood circulation, which significantly improves anti-psoriasis activity in mice.

Topics: Administration, Topical; Animals; Anti-Infective Agents, Local; Apoptosis; Cell Line; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Drug Liberation; Drug Stability; Female; Humans; Hydrogels; Lactic Acid; Mice, Inbred C57BL; Nanoparticles; Particle Size; Permeability; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Psoriasis; Skin; Skin Absorption; Solubility; Spleen; Surface Properties

Psoriasis is considered to be a systemic disease of immune dysfunction. It is still unclear what triggers the inflammatory cascade associated with psoriasis but recent evidences suggest the vital role of IL-23/IL-17A cytokine axis in etiology of psoriasis. Several studies have been conducted in psoriatic-like animal models but ethical issues and complexity surrounding it halts the screening of new anti-psoriatic drug candidates. Hence, in this study, we developed a new in-vitro model for psoriasis using imiquimod (IMQ) induced differentiated HaCaT cells which could be used for screening of new anti-psoriatic drug candidates. The differentiated HaCaT cells were treated with IMQ (100μM) to induce psoriatic like inflammation and its effect was investigated using a natural anti-psoriatic compound, curcumin. The proliferation of psoriatic-like cells was inhibited by curcumin at 25 and 50µM concentrations. The psoriatic-like cells decreased in number with increase in apoptotic and dead cells upon curcumin treatment. Curcumin inhibited the proliferation of IMQ-induced differentiated HaCaT cells (Psoriatic-like cells) by down-regulation of pro-inflammatory cytokines, interleukin-17, tumor necrosis factor-α, interferon-γ, and interleukin-6. Apart from this, curcumin significantly enhanced the skin-barrier function by up-regulation of involucrin (iNV) and filaggrin (FLG), the regulators of epidermal skin barrier. The IMQ-induced differentiated HaCaT in vitro model recapitulated some aspects of the psoriasis pathogenesis similar to murine model. Henceforth, we conclude that this model may be used for rapid screening of anti-psoriatic drug candidates and warrant further mechanistic studies.

Topics: Aminoquinolines; Biomarkers; Cell Differentiation; Cell Line; Cell Proliferation; Cell Survival; Curcumin; Cytokines; Drug Evaluation, Preclinical; Filaggrin Proteins; Humans; Imiquimod; Keratinocytes; Molecular Docking Simulation; Protein Conformation; Psoriasis; Skin

A poor percutaneous penetration capability for most topical anti-inflammatory drugs is one of the main causes compromising their therapeutic effects on psoriatic skin. Even though curcumin has shown a remarkable efficacy in the treatment of psoriasis, its effective penetration through the stratum corneum is still a major challenge during transdermal delivery. The aim of our study was to design skin-permeating nanoparticles (NPs) to facilitate delivery of curcumin to the deeper layers of the skin. A novel amphiphilic polymer, RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL) was synthesized and self-assembled into polymeric nanoparticles. The nanoparticles of VES-g-ε-PLL exhibiting an ultra-small hydrodynamic diameter (24.4nm) and a positive Zeta potential (19.6mV) provided a strong skin-penetrating ability in vivo. Moreover, curcumin could effectively be encapsulated in the polymeric nanoparticles with a drug loading capacity of 3.49% and an encapsulating efficiency of 78.45%. In order to prolong the retention time of the ultra-small curcumin-loaded nanoparticles (CUR-NPs) in the skin, silk fibroin was used as a hydrogel-based matrix to further facilitate topical delivery of the model drug. In vitro studies showed that CUR-NPs incorporated in silk fibroin hydrogel (CUR-NPs-gel) exhibited a slower release profile of curcumin than the plain CUR-gel, without compromising the skin penetration ability of CUR-NPs. In vivo studies on miquimod-induced psoriatic mice showed that CUR-NPs-gel exhibited a higher therapeutic effect than CUR-NPs as the former demonstrated a more powerful skin-permeating capability and a more effective anti-keratinization process. CUR-NPs-gel was therefore able to inhibit the expression of inflammatory cytokines (TNF-α, NF-κB and IL-6) to a greater extent. In conclusion, the permeable nanoparticle-gel system may be a potential carrier for the topical delivery of lipophilic anti-psoriatic drugs.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Drug Delivery Systems; Fibroins; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Male; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Nanoparticles; Particle Size; Polymers; Psoriasis; Silk; Skin

Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis.

Topics: Animals; Curcumin; Disease Models, Animal; Kidney; Kv1.3 Potassium Channel; Mice; Mice, Transgenic; Psoriasis

Psoriasis is an autoimmune skin disorder characterized by hyper proliferation and poor differentiation of keratinocytes. It significantly affects patient's quality of life. This study reports the anti-psoriatic efficacy of tacrolimus and curcumin loaded liposphere gel formulation. Poor solubility, poor skin penetration and erratic absorption are some problems associated with the topical delivery of these drugs. To overcome these problems, lipospheres containing combination of tacrolimus and curcumin was prepared with a particle size of nearly 50nm and incorporated into a gel for topical application. Liposphere gel showed slow release of both the drugs and shear thinning behaviour that is desirable property of topical formulation. Further, dermal distribution study using dye loaded formulation suggested penetration of dye into skin layers. The therapeutic efficacy of tacrolimus and curcumin loaded liposphere gel was assessed on imiquimod induced psoriatic plaque model, and the level of expression of psoriatic biochemical markers was evaluated using enzyme-linked immunosorbent assay. Results indicated improvement in the phenotypic and histopathological features of psoriatic skin treated with tacrolimus and curcumin loaded liposphere gel. There was reduction in the level of TNF-α, IL-17 and IL-22 compared to imiquimod group. These results corroborate the premise that liposphere gel containing combination of tacrolimus and curcumin can be an effective strategy for the treatment of psoriasis.

Topics: Administration, Cutaneous; Aminoquinolines; Animals; Chemistry, Pharmaceutical; Curcumin; Delayed-Action Preparations; Dermatologic Agents; Drug Synergism; Enzyme-Linked Immunosorbent Assay; Gels; Imiquimod; Immunosuppressive Agents; Lipids; Male; Mice; Mice, Inbred BALB C; Particle Size; Psoriasis; Tacrolimus; Tissue Distribution

Psoriasis is a chronic autoimmune human skin disorder that is characterized by excessive proliferation of keratinocytes, scaly plaques, severe inflammation and erythema. The pathophysiology of psoriasis involves interplay between epidermal keratinocytes, T lymphocytes, leukocytes and vascular endothelium. Increased leukocyte recruitment and elevated levels of cytokines, growth factors and genetic factors like interleukin (IL)-1β, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2, coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR) and vitamin D receptor (VDR) are the most critical factors governing the exacerbation of psoriasis. In the present study, an attempt was made to elucidate the preventive role of herbal extracts of four dermo-protective Ayurvedic plants, Tinospora cordifolia (TC), Curcuma longa (CL), Celastrus paniculatus (CP) and Aloe vera (AV), against psoriasis-like dermatitis. Parkes (P) strain mice were initially induced with psoriasis-like dermatitis using topical application of imiquimod (IMQ, 5 %), followed by subsequent treatment with the herbal extracts to examine their curative effect on the psoriasis-like dermatitis-induced mice. The extracts were orally/topically administered to mice according to their ED/LD50 doses. Phenotypical observations, histological examinations, and semi-quantitative reverse transcription PCR (RT-PCR) analyses of the skin and blood samples of the control, IMQ-treated and herbal extract-treated psoriasis-like dermatitis-induced mice lead to the conclusion that the combination extract from all the plants was instrumental in downregulating the overexpressed cytokines, which was followed by the CL extract. Moreover, lesser yet positive response was evident from CP and TC extracts. The results suggest that these plants can prove to have tremendous preventive potential against the disease and can open the way to new therapeutic strategies for psoriasis treatment.

Topics: Aloe; Aminoquinolines; Animals; Celastrus; Curcuma; Cytokines; Dermatitis, Contact; Drug Evaluation, Preclinical; Gene Expression; Imiquimod; Male; Mice; Plant Extracts; Plant Stems; Plants, Medicinal; Psoriasis; Skin; Tinospora

Curcumin has been confirmed to have anti-inflammatory properties in addition to the ability to decrease the expression of pro-inflammatory cytokines in keratinocytes. It was suggested that the interleukin-23 (IL-23)/IL-17A cytokine axis played a critical role in the pathogenesis of 12-O-tetradecanoyl phorbol 12-myristate 13-acetate (TPA)-induced K14-VEGF transgenic psoriasis-like mice model. Here, we report that topical use of a curcumin gel formulation inhibited TPA-induced Th1 inflammation in K14-VEGF transgenic mice ears but not Th17 inflammation as expected. Real-time PCR showed that mRNA levels of IL-23, IL-17A, IL-22, IL-6 and TNFα cytokines failed to increase after TPA-induction in K14-VEGF transgenic mice ear skin; but the mRNA level of IFNγ increased significantly at the same time. Furthermore, TPA-induction up-regulated the TCRγδ protein but failed to impact the CCR6 protein, which means that the proliferation of γδ T cells is incapable of IL-17A production. We find that curcumin is capable of relieving TPA-induced inflammation by directly down-regulating IFNγ production. In conclusion, curcumin inhibits TPA-induced Th1 inflammation in K14-VEGF transgenic mice which has not been previously described.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytokines; Disease Models, Animal; Gels; Inflammation; Mice, Transgenic; Nuclear Receptor Subfamily 1, Group F, Member 3; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, CCR6; RNA, Messenger; Skin; Tetradecanoylphorbol Acetate; Th1 Cells

Curcumin, a selective phosphorylase kinase inhibitor, is a naturally occurring phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties in addition to the ability to decrease the expression of pro-inflammatory cytokines in keratinocytes. The interleukin-23 (IL-23)/IL-17A cytokine axis plays a critical role in the pathogenesis of psoriasis. Here, we report that topical use of a curcumin gel formulation strongly inhibited imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which was based on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in BALB/c mouse ear was significantly inhibited following curcumin treatment. Real-time PCR showed that mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α cytokines were decreased significantly by curcumin in ear skin, an effect similar to that of clobetasol. In addition, we found that curcumin may enhance the proliferation of epidermis γδ T cells but inhibit dermal γδ T cell proliferation. We inferred that curcumin was capable of impacting the IL-23/IL-17A axis by inhibiting IL-1β/IL-6 and then indirectly down-regulating IL-17A/IL-22 production. In conclusion, curcumin can relieve the IMQ-induced psoriasis-like inflammation in a mouse model, similar to the effects of clobetasol. Therefore, we have every reason to expect that curcumin will be used in the treatment of psoriasis in the future.

Topics: Aminoquinolines; Animals; Cell Proliferation; Curcumin; Ear; Gene Expression Regulation; Imiquimod; Inflammation; Interleukin-1beta; Interleukin-6; Mice; Mice, Inbred BALB C; Nuclear Receptor Subfamily 1, Group F, Member 3; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, CCR6; RNA, Messenger; Skin

Psoriasis is a chronic inflammatory skin disease featuring abnormal keratinocyte proliferation and differentiation. A genetic risk factor for psoriasis (PSORS4) is a deletion of LCE3B and LCE3C genes encoding structural proteins in terminally differentiated keratinocytes. Because analogs of 1,25-dihydroxyvitamin D3 (1,25D) are used in psoriasis treatment, we hypothesized that 1,25D acts via the vitamin D receptor (VDR) to upregulate expression of LCE 3A/3D/3E genes, potentially mitigating the absence of LCE3B/LCE3C gene products. Results in a human keratinocyte line, HaCaT, suggested that 1,25D, low affinity VDR ligands docosahexaenoic acid and curcumin, along with a novel candidate ligand, delphinidin, induce LCE transcripts as monitored by qPCR. Further experiments in primary human keratinocytes preincubated with 1.2 mM calcium indicated that 1,25D and 10 μM delphinidin upregulate all five LCE3 genes (LCE3A-E). Competition binding assays employing radiolabeled 1,25D revealed that delphinidin binds VDR weakly (IC50 ≈ 1 mM). However, 20 μM delphinidin was capable of upregulating a luciferase reporter gene in a VDRE-dependent manner in a transfected keratinocyte cell line (KERTr). These results are consistent with a scenario in which delphinidin is metabolized to an active compound that then stimulates LCE3 transcription in a VDR/VDRE-dependent manner. We propose that upregulation of LCE genes may be part of the therapeutic effect of 1,25D to ameliorate psoriasis by providing sufficient LCE proteins, especially in individuals missing the LCE3B and 3C genes. Results with delphinidin further suggest that this compound or its metabolite(s) might offer an alternative to 1,25D in psoriasis therapy.

Topics: Anthocyanins; Calcitriol; Calcium; Cell Line; Cornified Envelope Proline-Rich Proteins; Curcumin; Docosahexaenoic Acids; HEK293 Cells; Humans; Keratinocytes; Psoriasis; Receptors, Calcitriol; Risk; Up-Regulation

Psoriasis is a benign, chronic skin disease characterized by keratinocyte hyperproliferation and abnormal differentiation. Curcumin, a selective phosphorylase kinase inhibitor, is a natural phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties as well as the ability to inhibit proliferation and decrease the expression of pro-inflammatory cytokines in psoriatic keratinocytes. However, the pro-apoptotic effect of curcumin in keratinocytes remains unclear. In the present study, we investigated the effect of curcumin on apoptosis induction in TNF-α-treated HaCaT cells. These results show that curcumin exhibited a significant pro-apoptotic effect on HaCaT cells only in the presence of TNF-α and/or TRAIL. The pro-apoptotic effect of curcumin resulted from the increased expression of TRAIL-R1/R2 and the decreased expression of anti-apoptotic proteins. Our results indicate that both curcumin and TNF-α up-regulated the expression of TRAIL-R1/R2. In addition, the expression of anti-apoptotic proteins (IAP1, IAP2, Bcl-X(L)) was up-regulated by TNF-α but suppressed by curcumin in HaCaT cells. Because these proteins are regulated by NF-κB, we examined the role of curcumin in NF-κB activation. As expected, curcumin inhibited TNF-α-induced activation of NF-κB, including NF-κB-P65. Curcumin also inhibited the TNF-α-induced production of IL-6/IL-8 in HaCaT cells. These results imply that curcumin-induced apoptosis of HaCaT cells only occurs when TNF-α or/and TRAIL are present. Therefore, we believe that curcumin is able to reverse the anti-apoptotic function of TNF-α in HaCaT cells and thus expect curcumin to be successful in the treatment of psoriasis.

Topics: Apoptosis; Cell Line; Curcumin; Humans; Interleukin-6; Interleukin-8; Keratinocytes; NF-kappa B; Psoriasis; Receptors, TNF-Related Apoptosis-Inducing Ligand; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha; Up-Regulation