Antipsoriatic Agents Research Articles

Recent advancements in novel formulations of anti-psoriatic agents for effective delivery: clinical importance and patent survey.

Objectives An autoimmune-mediated dermatological ailment featuring recurrent episodes is acknowledged as psoriasis. Around the world, 2-3% of people suffer from this autoimmune skin condition. The primary goal of the current review is to analyse and determine the effectiveness of conventional and emerging nano technological strategies to alleviate psoriasis and discuss future perspectives. Evidence acquisition A thorough search of numerous electronic databases, including Science Direct, Scopus, Google Scholar, Clinical Trials, Google Patents, Research Gate, and PubMed, yielded all the data used in this review paper about the management of psoriasis via various anti-psoriatic agent and nanotechnology approaches. Keywords such as topical, liposomes, niosomes, micro needles, clinical trials, patents, pathogenesis, biosimilars, cytokines, and other pertinent words were investigated. Results Nano technological approaches are gaining prominence since they enable targeted delivery, rapid onset of action with limited systemic exposure. Researchers have investigated innovative, alternative therapeutic approaches that are both secure and efficient for treating psoriatic conditions. Further, the potential role of numerous psoriatic conventional therapies has been explored. The patents granted or in process to address psoriasis via topical route have been well explored. Modern nanotechnology has made it possible for pharmaceuticals to be delivered with improved physical, chemical, pharmacokinetic, and pharmacodynamic qualities. Despite extensive research complete cure for psoriasis is hampered. Conclusion Relying on the extensive literature review, it can be inferred that nanoparticles based novel delivery strategies have the possibility of enhancing the pharmacological activity and eliminating or resolving problems associated with this ailment. The different drug delivery systems available for the treatment of psoriasis along with the clinical trials in different stages, patents in process and granted, the commercialized status of therapeutic molecules, and the future of research in this area have been thoroughly reviewed.

Nano-based formulations of thymoquinone are new approaches for psoriasis treatment: a literature review.

Psoriasis, a persistent immune-mediated inflammatory skin condition, affects approximately 2-3% of the global population. Current treatments for psoriasis are fraught with limitations, including adverse effects, high costs, and diminishing efficacy over time. Thymoquinone (TQ), derived from Nigella sativa seeds, exhibits promising anti-inflammatory, antioxidant, and immunomodulatory properties that could prove beneficial in managing psoriasis. However, TQ's hydrophobic nature and poor bioavailability have hindered its usefulness as a therapeutic agent. Recent research has strategically addressed these challenges by developing nano-thymoquinone (nano-TQ) formulations to enhance delivery and efficacy in treating psoriasis. Preclinical studies employing mouse models have demonstrated that nano-TQ effectively mitigates inflammation, erythema, scaling, epidermal thickness, and cytokine levels in psoriatic lesions. Various nano-TQ formulations, including nanoemulsions, lipid vesicles, nanostructured lipid carriers, and ethosomes, have been explored to improve solubility, facilitate skin penetration, ensure sustained release, and achieve site-specific targeting. Although clinical trials are currently scarce, the outcomes from in vitro and animal models are promising. The potential co-delivery of nano-TQ with other anti-psoriatic agents also presents avenues for further investigation.

In Vitro and In Vivo Antipsoriatic Efficacy of Protected and Unprotected Sugar-Zinc Phthalocyanine Conjugates.

Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose-ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 µM) compared to unprotected glucose conjugate (IC50 = 22.7 µM), protected galactose-ZnPc (IC50 = 7.13 µM), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 µM). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.

Ginsenoside Compound K Reduces Psoriasis-related Inflammation by Activation of the Glucocorticoid Receptor in Keratinocytes.

To investigate the effects and mechanism of Ginsenoside Compound K (GCK) on psoriasis, focusing on the glucocorticoid receptor (GR) in keratinocytes. An imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model was generated to evaluate the anti-inflammatory effect of GCK. Hematoxylin and eosin (H&E) staining was used to assess skin pathological changes. Protein expression of K17 and p-p65 in mice skin was assayed by immunohistochemical. Protein expression and phosphorylation of p65 IκB were assayed by Western blot. Protein expression of K1, K6, K10, K16, K17, and GR were assayed by Western blot and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels of TNF-α, IL-6, CXCL-8, and ICAM-1. Real-time polymerase chain reaction (RT-PCR) was used to quantify TNF-α, IL-6, IL-8, and ICAM-1 mRNA expression. Cell viability was determined by Cell Counting Kit-8(CCK-8) assay. A high-content cell-imaging system was used to assay cell proliferation. Nuclear translocation of p65 and GR was assayed by imaging flow cytometry and immunofluorescence microscopy. Small interfering RNA was used to confirm the role of GR in the anti-inflammatory and immunoregulatory effect of GCK in normal human epidermal keratinecytes (NHEKs). GCK reduced the psoriasis area, severity index, and epidermal thickening in IMQ-induced mice. GCK significantly attenuated the mRNA levels of IL-6, IL-8, TNF-α, and ICAM-1 and reduced epidermal hyperproliferation in the skin of IMQ-induced mice. GCK inhibited in vitro activation of NF-κB, leading to attenuated release of inflammatory mediators (IL-6, IL-8, TNF-α, and ICAM-1) and suppression of NHEK hyperproliferation and abnormal differentiation. These inhibitory effects of GCK were diminished by GR silencing in NHEKs. GCK suppressed psoriasis-related inflammation by suppressing keratinocyte activation, which may be related to promoting GR nuclear translocation and inhibiting NF-κB activation. In summary, GCK appears to be a GR activator and a promising therapeutic candidate for antipsoriatic agents.

Volatile Oil Containing Plants as Phytopharmaceuticals to Treat Psoriasis: A Review.

Psoriasis is a chronic skin condition caused by an autoimmune response that accelerates the life cycle of skin cells, resulting in the characteristic symptoms of scaling, inflammation, and itching. Palliative treatment options for psoriasis often prioritize the use of volatile oils. These oils contain monoterpenes, sesquiterpenes, and phenylpropanoids that are intricately linked to the molecular cascades involved in the pathogenesis and symptoms of psoriasis. To evaluate the antipsoriatic efficacy of volatile oils and their components, we conducted a systematic review of scientific studies. Our literature search encompassed various online databases, including PubMed, BIREME, SCIELO, Open Grey, Scopus, and ScienceDirect. The selected studies included experimental in vitro/in vivo assessments as well as clinical studies that examined the potential of volatile oils and their extracts as antipsoriatic agents. We excluded conference proceedings, case reports, editorials, and abstracts. Ultimately, we identified and evaluated a total of 12 studies for inclusion in our analysis. The data collected, compiled, and analyzed strongly support the interaction between volatile oils and their constituents with the key molecular pathways involved in the pathogenesis of psoriasis and the development of its symptoms. Volatile oils play a significant role in the palliative treatment of psoriasis, while their chemical constituents have the potential to reduce the symptoms and recurrence of this condition. The current review highlights that the constituents found in volatile oils offer distinct chemical frameworks that can be regarded as promising starting points for the exploration and development of innovative antipsoriatic agents.

Tanshinone IIA, a component of the self-made Xiao-Yin decoction, ameliorates psoriasis by inhibiting IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways.

Psoriasis is a persistent inflammatory dermatological disorder. Tanshinone IIA (tan-IIA) is a biologically active compound in the self-made Xiao-Yin decoction (SMXYD) and exhibits diverse biological properties, such as anti-proliferative and anti-inflammatory effects. The objective of this investigation was to assess the potential of tan-IIA as a therapeutic agent against psoriasis. Network pharmacology was employed to ascertain the active constituents and potential pathways associated with SMXYD and psoriasis. We conducted CCK-8, qRT-PCR, and western blotting to assess the proliferation of HaCaT keratinocytes and the expression of IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. Additionally, we used H&E staining, western blotting, and ELISA to evaluate the therapeutic effects and signaling pathways of tan-IIA in psoriasis-like mice induced by imiquimod (IMQ). Network pharmacology analysis identified eight hub compounds. The Th17/IL-17 signaling was found to be a potential therapeutic pathway of SMXYD against psoriasis, with JUN (AP-1) as the core molecule. Next, PTGS2 was selected as the target of tan-IIA against psoriasis using network pharmacology analysis. Molecular docking showed a high affinity between PTGS2 and tan-IIA. Tan-IIA treatment attenuated M-5-induced hyperproliferation and inflammation in HaCaT keratinocytes. Additionally, Tan-IIA downregulated the PTGS2/NF-κB/AP-1 pathway in HaCaT keratinocytes. In the IMQ-induced psoriasis-like mouse, tan-IIA significantly reduced the severity of skin lesions and downregulated the PTGS2/NF-κB/AP-1 pathway. Moreover, the combination of methotrexate (MTX) and tan-IIA further inhibited the IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. The administration of tan-IIA has shown a positive effect on psoriasis by inhibiting the IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. The findings suggest that it has promising qualities that make it a potential candidate for the development of future anti-psoriatic agents.

Cannabidiol Mediates In Vitro Attenuation of Proinflammatory Cytokine Responses in Psoriatic Disease.

Background: Cannabidiol (CBD), a substance that belongs to the phytocannabinoids, appears to exert antioxidant, neuroprotective, antipsychotic, anticonvulsant, and anticancer properties. Recent evidence supports the immunoregulatory effect of CBD on autoimmune and/or inflammatory disease. Psoriasis is a chronic skin disease. The main immune cell population involved in the pathogenesis of the disease is the interleukin- (IL-) 17-producing T helper (Th) 17 subset. Other subpopulations, such as interferon-γ (IFNγ) -producing Th1 and T cytotoxic (Tc) 1, IL-17-producing Tc17, as well as natural killer (NK) and natural killer T cells (NKT) have been implicated in psoriasis development. Purpose: The aim of the present study was to evaluate the in vitro effect of CBD on the aforementioned subpopulations isolated from patients with psoriasis using flow cytometry. Methods: Cells were stimulated in the presence or absence of CBD, stained and examined using surface and intracellular markers. Results: CBD decreased IL-17 production within the CD3, Th, and NKT cell compartments and IFNγ production within the CD3 compartment in cells isolated from patients with psoriasis. Interestingly, CBD supplementation did not inhibit production of proinflammatory cytokines in cells isolated from healthy individuals. On the contrary, IFNγ-producing Th, Tc, and NK cells increased after CBD supplementation. Conclusion: CBD provides anti-inflammatory effects in T cells isolated from patients with psoriasis. Our results could be the impetus for future investigations regarding the immunomodulatory properties of CBD and its utilization for development of CBD-containing antipsoriatic agents.

Sexual dysfunctions in psoriatic patients.

Psoriasis is one the most common skin diseases associated with a great decrease in the quality of patients' lives. We aimed to study sexual dysfunctions in psoriatic patients using the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men via an anonymous online survey. The study included 80 psoriatic patients and 75 controls without dermatoses. There was a downward trend in the total IIEF score in psoriatic men compared to controls. 58% of male patients and 76% of controls had a normal IIEF score. There was no significant difference in IIEF between patients treated and not with systemic agents. 62% of female patients had a decreased FSFI score, whereas in the control group, the majority of subjects (54%) had a normal FSFI score. There was no significant difference in FSFI score between patients and controls. Female patients treated with systemic antipsoriatic agents had significantly worse lubrication, satisfaction with sexual life, and pain. Our study has shown that the majority of questioned female psoriatic patients had sexual dysfunction according to FSFI, particularly they had worse satisfaction with sexual life and less sexual desire compared to women without psoriasis. The majority of male patients did not have sexual dysfunction according to IIEF, however, they had significantly worse overall satisfaction with sexual life and confidence to keep an erection. Systemic antipsoriatic treatment does not probably influence sexual dysfunctions in men but it does in women although we were not able to assess the severity or resolution of lesions after those treatments. However embarrassing, psoriatic patients should be questioned about their sexual lives by dermatologists, and more studies are needed to explore this matter.

Enhancement of Curcumin's Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel.

Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel's 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel's potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis.

How should we do in the selection and follow-up of systemic conventional treatments in psoriasis?

There is an increasing need for appropriate effective treatment and long-term disease control in patients with psoriasis because of the decreased quality of life, increased physicosocial deficits and associated co-morbidities. Systemic conventional treatments that are the first step in the management of moderate-to-severe plaque psoriasis include methotrexate (MTX), acitretin, cyclosporine and fumarates. MTX is considered the gold standard in the treatment of moderate-to-severe chronic plaque type psoriasis. It is also used to treat pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis. Acitretin monotherapy is less effective than other conventional systemic treatments for plaque psoriasis, while superior to generalized, palmoplantar pustular, and hyperkeratotic variants. Cyclosporine is preferred in the presence of unstable acute clinical conditions (erythrodermic or generalized pustular psoriasis) and also in induction phase of rotational and sequential therapy for severe resistant psoriasis, due to its rapid effect. Dimethyl fumarate, which has similar efficacy to MTX, is an appropriate option in the induction and long-term systemic treatment for adult patients with moderate to severe plaque psoriasis without psoriatic arthritis. Although they are often overshadowed by biologics at the stage of preference by most physicians and patients today, they are classical and inexpensive agents with known long-term results. When the appropriate patient profile and psoriasis type are selected at the right time and necessary laboratory and clinical follow-ups are made, each of them is an effective treatment with reliable and satisfactory results. In this article, important points (recommendations according to patient characteristics, psoriasis type and comorbidities) to be considered in clinical practice when using the conventional anti-psoriatic agents in the treatment of psoriasis are overviewed.

Investigation the efficacy of antipsoriatic drugs by blood plasma thermoanalysis

AbstractPsoriasis is an immune cell-mediated mainly inflammatory skin disease where patients may become asymptomatic after systemic drug therapies or nevertheless mild-to-moderate symptoms or exacerbating of either severe symptom should be detected. In addition to know the general change of blood plasma, the aim of the recent study was to detect the effect of antipsoriatic drug treatment to the patients’ symptoms by differential scanning calorimetry (DSC). The study included patients of both sexes who had different symptoms despite treatment with antipsoriatic medication (cytostatic agents, retinoids, biological treatment, n = 10 in each group). After the examination by dermatologist, the definition of symptoms severity was established on PASI (Psoriasis Area Severity Index) score. Blood plasma calorimetric changes were measured with calorimeter device. In the examined psoriatic patients, the thermodynamic parameters: denaturation temperature and calorimetric enthalpy of the transitions in proportion, corresponded to the degree of disease severity after targeted treatments with cytostatic or retinoid agents or following biological response modifier therapy. In conclusion, plasma DSC profiles were associated with response to antipsoriatic agents, which was associated with the presence or absence of symptoms after treatment.

Sericin coated thin polymeric films reduce keratinocyte proliferation via the mTOR pathway and epidermal inflammation through IL17 signaling in psoriasis rat model

Therapeutic treatment forms can play significant roles in resolving psoriatic plaques or promoting wound repair in psoriatic skin. Considering the biocompatibility, mechanical strength, flexibility, and adhesive properties of silk fibroin sheets/films, it is useful to combine them with anti-psoriatic agents and healing stimulants, notably silk sericin. Here, we evaluate the curative properties of sericin-coated thin polymeric films (ScF) fabricated from silk fibroin, using an imiquimod-induced psoriasis rat model. The film biocompatibility and psoriatic wound improvement capacity was assessed. A proteomics study was performed to understand the disease resolving mechanisms. Skin-implantation study exhibited the non-irritation property of ScF films, which alleviate eczema histopathology. Immunohistochemical and gene expression revealed the depletion of β-defensin, caspase-3 and -9, TNF-α, CCL-20, IL-1β, IL-17, TGF-β, and Wnt expressions and S100a14 mRNA level. The proteomics study suggested that ScF diminish keratinocyte proliferation via the mTOR pathway by downregulating mTOR protein, corresponding to the modulation of TNF-α, Wnt, and IL-1β levels, leading to the enhancement of anti-inflammatory environment by IL-17 downregulation. Hematology data demonstrated the safety of using these biomaterials, which provide a potential therapeutic-option for psoriasis treatment due to desirable effects, especially anti-proliferation and anti-inflammation, functioning via the mTOR pathway and control of IL-17 signaling.

The Potentials of Herbal Plant against the Psoriasis

Chronic autoimmune skin disease termed psoriasis is characterised by excessive keratinocyte multiplication, scaly plaques, severe inflammation, and erythema. T lymphocytes, leukocytes, vascular endothelium, and epidermal keratinocytes also contribute in the pathogenesis of psoriasis. Increased leukocyte recruitment and increased levels of cytokines, growth factors, and genetic factors like interleukin (IL)-1, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF), interferon (IFN), transforming growth factor (TGF), toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2. The most important aspects impacting the treatment of psoriasis are coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR), and vitamin D receptor (VDR). Various synthetic medicinal drugs have also been known to have the side effect of psoriasis. Due to their safety and accessibility, herbal medications may indicate the potential as effective anti-psoriatic agents.
 Keywords: Psoriasis, Herbal Drug, Silybum marianum, Thespesia populnea, Mahonia aquifolium

Exploration of and insights into advanced topical nanocarrier systems for the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease with an underlying autoimmune pathogenesis that has brought great distress to patients. Current treatment options include topical therapy, systemic therapy, and phototherapy. By disrupting the stratum corneum, nanocarriers have unique advantages in allowing drug carriers to be tailored to achieve targeted drug delivery, improve efficacy, and minimize adverse effects. Furthermore, despite their limited success in market translatability, nanocarriers have been extensively studied for psoriasis, owing to their excellent preclinical results. As topical formulations are the first line of treatment, utilize the safest route, and facilitate a targeted approach, this study, we specifically describes the management of psoriasis using topical agents in conjunction with novel drug delivery systems. The characteristics, advantages, weaknesses, and mechanisms of individual nanocarriers, when applied as topical anti-psoriatic agents, were reviewed to distinguish each nanocarrier.

Revolutionary nanocarriers-based drug delivery system for antipsoriatic agents: an overview

Revolutionary nanocarriers-based drug delivery system for antipsoriatic agents: an overview

Indonesian Ciplukan Extract Inhibited TGF-β1/NF-κB Pathway in Experimental Psoriasis Mouse Models

Background:The global prevalence of psoriasis, a chronic inflammatory skin disease, has substantially increased in the last decade. The increase activity of Transforming Growth Factor ß1 (TGFß1)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway which cause inflammation, is the major pathological mechanism in psoriasis. Current psoriasis treatment using chemical agents is hampered by the side-effects when used long-term, which underlines the need for alternative, low side-effect anti-psoriatic agents. The extract of Physalis angulata L., also known as Ciplukan in Indonesia, contains Physalins, compounds known for their anti-inflammatory effects, but whose effect on psoriasis has not been studied.
 Objective: This study aimed to investigate the effect of Ciplukan extract (CE) to TGFß1/NF-κB pathway in psoriasis mouse models.
 Methods: This was experimental study with posttest-only control group design. The CE active ingredients were identified using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twenty-five female imiquimod (IMQ) induced psoriasis-like dermatitis mice were allocated into five groups, with three groups receiving 7 days of 400, 800, and 1200 mg/kg bodyweight doses of CE, respectively, and two groups serving as control and IMQ groups. The NF-κB and TGFß1 expressions were evaluated using Allred score based on immunohistochemistry (IHC) staining. Histopathology and clinical psoriasis manifestations were assessed using Baker’s from Hematoxylin Eosin (HE) staining and Psoriasis Area Severity Index (PASI) scores. The Kruskal-Wallis followed by Mann Whitney tests were conducted for data analysis. The p-value < 0.05 was considered to be statistically different. 
 Results: Based on LC-MS/MS test, Physalin B, D, and F were active ingredients from CE in ethyl acetate solution. An improvement in psoriasis inflammation was observed in 400 and 800 mg/kg bodyweight doses of CE, but only the dosage of 800 mg/kg BW significantly decreased of Allred scores from NF-κB and TGFß1 expressions; Baker’s and PASI scores compared to IMQ group (p<0.05). The 1200 mg/kg bodyweight doses of CE associated with acute toxicity signs and mortality, meanwhile dosage of 800 mg/kg BW showed the highest efficacy with lowest toxicity effect.
 Conclusions: Ciplukan extract improved psoriasis manifestations via inhibition effect to TGFß1/NF-κB pathway and the extract might be developed as an alternative anti-psoriasis agent

A bioinformatic approach to establish P38α MAPK inhibitory mechanism of selected natural products in psoriasis

In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38α mitogen-activated protein kinases (P38α MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38α MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38α MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (−9.00 and −8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action.

The hair follicle‐psoriasis axis: Shared regulatory mechanisms and therapeutic targets

It has long been known that there is a special affinity of psoriasis for the scalp: Here, it occurs most frequently, lesions terminate sharply in frontal skin beyond the hair line and are difficult to treat. Yet, surprisingly, scalp psoriasis only rarely causes alopecia, even though the pilosebaceous unit clearly is affected. Here, we systematically explore the peculiar, insufficiently investigated connection between psoriasis and growing (anagen) terminal scalp hair follicles (HFs), with emphasis on shared regulatory mechanism and therapeutic targets. Interestingly, several drugs and stressors that can trigger/aggravate psoriasis can inhibit hair growth (e.g. beta-blockers, chloroquine, carbamazepine, interferon-alpha, perceived stress). Instead, several anti-psoriatic agents can stimulate hair growth (e.g. cyclosporine, glucocorticoids, dithranol, UV irradiation), while skin/HF trauma (Köbner phenomenon/depilation) favours the development of psoriatic lesions and induces anagen in "quiescent" (telogen) HFs. On this basis, we propose two interconnected working models: (a) the existence of a bidirectional "hair follicle-psoriasis axis," along which keratinocytes of anagen scalp HFs secrete signals that favour the development and maintenance of psoriatic scalp lesions and respond to signals from these lesions, and (b) that anagen induction and psoriatic lesions share molecular "switch-on" mechanisms, which invite pharmacological targeting, once identified. Therefore, we advocate a novel, cross-fertilizing and integrative approach to psoriasis and hair research that systematically characterizes the "HF-psoriasis axis," focused on identification and therapeutic targeting of selected, shared signalling pathways in the future management of both, psoriasis and hair growth disorders.

A review on the important phytochemicals and their role in psoriasis

Psoriasis may emerge at any stage of life irrespective of age, sex or geographic location. It is identified as a chronic immune-linked inflammatory skin disease that affects all human races. Psoriasis is often more Caucasian than non-Caucasian groups of human races and in geographic areas, like higher latitudes and Western countries. Therefore, attention should be paid to both genetic and environmental causes of psoriasis. Natural products have significantly contributed and encouraged the advances in skin disease treatment like psoriasis. The maximum number of phytochemicals is now being used worldwide, including various plants, herbs, and formulations. In addition, some phytochemicals like psoralen, aloe-emodin, curcumin etc. have also been isolated in pure form and have also shown their efficacy in the management of psoriasis. The presence of such phytochemicals confirms the effectiveness of few herbal therapies. This paper reviews some of the promising phytochemicals and their potential molecular target sites and mechanism of action, which may aid in designing and producing more precise and selective antipsoriatic agents. Exploring and recognizing phytochemicals as to how they function will facilitate more site-specific delivery methods for psoriasis care.

A computational multi-targeting approach for drug repositioning for psoriasis treatment

BackgroundPsoriasis is an autoimmune inflammatory skin disease that affects 0.5–3% of the world’s population and current treatment options are posed with limitations. The reduced risk of failure in clinical trials for repositioned drug candidates and the time and cost-effectiveness has popularized drug reposition and computational methods in the drug research community.ResultsThe current study attempts to reposition approved drugs for the treatment of psoriasis by docking about 2000 approved drug molecules against fifteen selected and validated anti-psoriatic targets. The docking results showed that a good number of the dataset interacted favorably with the targets as most of them had − 11.00 to − 10.00 kcal/mol binding free energies across the targets. The percentage of the dataset with binding affinity higher than the co-crystallized ligands ranged from 34.76% (JAK-3) to 0.73% (Rac-1). It was observed that 12 out of the 0.73% outperformed all the co-crystallized ligands across the 15 studied proteins. All the 12 drugs identified are currently indicated as either antiviral or anticancer drugs and are of purine and pyrimidine nuclei. This is not surprising given that there is similarity in the mechanism of the mentioned diseases.ConclusionThis study, therefore, suggests that; antiviral and anticancer drugs could have anti-psoriatic effects, and molecules with purine and pyrimidine structural architecture are likely templates to consider in developing anti-psoriatic agents.