Herbal medicine for psoriasis and their molecular targets: A systematic review

Psoriasis is an incurable, chronic, recurrent immune-mediated inflammatory dermatosis characterized by epidermal hyperplasia and excessive infiltration of inflammatory cells into the dermis and neovascularization. The study aimed to provide a systematic review on the in vitro, in vivo, and clinical studies to support traditional uses of herbal medicine for psoriasis treatment. The systematic review was performed by combining three databases, that is, PubMed, ScienceDirect, and Scopus, using the search terms “Psoriasis” AND “Herbal medicine” AND/OR “Traditional medicine.” Full-text articles included after the screening were further evaluated by applying the predefined eligibility criteria. One hundred and twenty research articles were included in the analysis. The included articles involve 94 herbs used as a single herbal extract (n=58 plants) or isolated compounds (n=54 compounds) or as compositions in traditional medicine formulas (n=24 formulas). Most were related to plants or recipes used in Traditional Chinese Medicine (TCM) (63 articles and 207 plants). Research targeting inflammatory and proliferative processes in disease pathogenesis, development, and progression has been an extensive area. The antipsoriasis activity of most plants was mainly through the effects on inflammatory molecules and signaling pathways and immune cells (T-cells, dendritic cells, monocytes, neutrophils, and macrophages), as well as apoptotic molecules and signaling pathways. Plants targeting other signaling molecules should be further investigated.


INTRODUCTION
Psoriasis is an incurable, chronic, recurrent immunemediated inflammatory dermatosis characterized by epidermal hyperplasia and excessive infiltration of inflammatory cells into the dermis and neovascularization (Mason et al., 2013). Clinical presentation includes erythematous scaly rash patches (itching and flaking skin) that affect the scalp, trunk, extensor surfaces of the limbs, and the genital area. The global prevalence rate is approximately 2-3% (Parisi et al., 2013). Although the disease seldom leads to death, it significantly impairs the quality of life due to chronic complications, that is, pruritic erythema and thick loose scales, as well as comorbidities such as arthritis, cardiovascular diseases, metabolic disorders, and psychological depression (Scheiba et al., 2011). Multiple factors such as genetics, inflammation, metabolism, autoimmunity, environment, and infection are associated with psoriasis (Ayala-Fontanez et al., 2016).
Current knowledge on the pathogenesis of psoriasis, however, remains incomplete. Although the molecular mechanisms involved are complex, growing evidence suggests that significant pathological changes are abnormal proliferation and differentiation of epidermal keratinocytes, excessive infiltration of the immune/ inflammatory cells--T cells (Th17, Th1, and Th2), dendritic cells (DCs), macrophages and neutrophils and increased skin angiogenesis (Chamian et al., 2004). The sequence of pathological events in psoriasis is thought to start with an initiation phase in which triggering factors (e.g., skin trauma, infection, drugs, strong sunlight, physiological stress, and smoking) lead to activation of the immune system, followed by the maintenance phase consisting of the chronic progression of the disease (Rendon et al., 2019). The premature maturation of keratinocytes induced by an inflammatory cascade in the dermis results in rapid changes in skin cells. The immune cells move from the dermis to the epidermis and secrete pro-inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-22, IL-23, IL-17A, and IFN-γ (Chan et al., 2006). These inflammatory signals then stimulate keratinocytes to proliferate and secrete cytokines such as IL-1, IL-6, and TNF-α, which signal downstream inflammatory cells to arrive at the site of inflammation and stimulate additional inflammation (Albanesi et al., 2018). Besides, a defect in regulatory T cells and regulatory cytokine IL-10 is also suggested to be involved in psoriasis pathogenesis (Owezarczyk-Saczonek et al., 2018).
The current treatment of psoriasis is limited by adverse drug reactions/toxicity, disease recurrence, and drug resistance. There is no satisfactory or effective cure for psoriasis. The available treatments, both local and systemic, which have to some extent, proved effective are coal tar, Dithranol (anthralin), calcipotriol, corticosteroids, photochemotherapy (PUVA, psoralens with long-wave ultraviolet radiation), retinoids, methotrexate, and other cytostatic drugs (e.g., hydroxyurea and cyclosporine). All have limited clinical efficacy with adverse drug reactions. Patients with mildto-moderate psoriasis are usually treated with topical treatments, while systemic therapy, monoclonal antibodies, or phototherapy is reserved for patients with the moderate-to-severe disease (Martin et al., 2019). Identification of new and effective antipsoriatic agents with few adverse effects, particularly those from herbal medicine remains a research hotspot in dermatology to date.
The study aimed to provide a systematic review and analysis of the evidence-based research (in vitro, in vivo, and clinical studies) of herbal medicine for psoriasis treatment.

MATERIALS AND METHODS
The systematic review was performed by combining three databases, that is, PubMed, ScienceDirect, and Scopus. The search terms applied were "Psoriasis" AND "Herbal medicine" AND/OR "Traditional medicine." All articles were retrieved and downloaded to the EndNote X9 database (Thomson Reuters Company, Canada) for further analysis. They were initially screened by titles and abstracts to exclude irrelevant articles. Full-text articles included after the screening were further evaluated by applying the predefined eligibility criteria. The inclusion criteria were articles (i) published during 2001 and March 2020; (ii) available as full texts in English; and (iii) with in vitro/in vivo/ex vivo/clinical studies related to herbal or traditional medicine with antipsoriasis activity. The exclusion criteria were articles: (i) related to other skin diseases; or (ii) duplicated articles; or (iii) with unclear methodology or insufficient information, or (iv) review articles, letters to the editor, editorials, systematic analysis, or meta-analysis.
Two reviewers extracted data independently and resolved the disparity by discussion and suggestion from the third reviewer. The information obtained for analysis were the first author's name and year of publication, name of plant and part used, traditional use for psoriasis or other diseases, and/or pharmacological activity, tested extract/compound/formulation, objective(s) of the study, type of study (in vitro/in vivo/clinical), and key results and conclusions.

RESULTS
A total of 1,822 articles from PubMed, ScienceDirect, and Scopus databases were downloaded to the EndNote database. Five hundred and seventy-four articles were excluded, and further analysis of the titles and abstracts of the remaining 1,248 articles led to the exclusion of 917 articles (excluded, based on title and abstract). Finally, 120 articles were included in the analysis. The flow diagram of the study inclusion and exclusion is presented in Figure 1, and the study summary is provided in Tables 1 and 2.
The included articles involve 94 herbs used as a single herbal extract (n=58 plants) or isolated compounds (n=54 compounds) or as compositions in traditional medicine formulas (n=24 formulas). Table 3 provides detailed information on the herbal composition in traditional medicine formulas or decoction. Most were related to plants or recipes used in Traditional Chinese Medicine (TCM) (63 articles and 207 plants). Most studies were conducted in vitro (n=31), followed by in vivo (n=30) in animals, and clinical studies in patients with different types of psoriasis (n=18).
In vitro: Human buffy coat Supporting traditional use: inhibition of 5-LOX and COX-1 complemented with an anti-inflammatory activity at the level of NF-  Aloe vera Safe and effective alternative treatment for psoriasis (significant clearing of psoriasis plaques-82.8%, and decreased of PASI score) (Syed et al., 1996) Aloe polysaccharide To investigate the mechanism underlying antipsoriasis activity In vitro: HaCaT cell Potential candidate for psoriasis through antiinflammatory activity (inhibition of TNF17α induced proliferation of keratinocytes and over activation of the NF-signaling pathway.  Extract (aqueous) To investigate preventive role against psoriasis-like dermatitis In vivo: Balb/c mice (IMQ-induced psoriasis model) Marked attenuation of symptoms and processes underlying psoriasis-like dermatitis. (Arora et al., 2016) Alpha Oasis (AO) extract consisting of 10 medicinal herbs* Medicinal herb for antiinflammatory.
Alpha Oasis extract To investigate anti-inflammatory activity on inhibition of pro-inflammatory factors TNF-α by macrophage cells.
In vivo: Balb/c mice (oxazolone-induced inflammation) Potential for inflammatory diseases including psoriasis through inhibiting TNF-α secretion of macrophages. (Ye et al., 2016) In vitro: Macrophage cells To investigate antipsoriasis action through anti-inflammatory activity.
In vivo: Male C57/BL6 mice (IMQ-induced psoriasis model) Antipsoriasis action: Inhibition of LPS /IMQ signaling transduction via inducing autophagic proteolysis of myeloid differentiation factor 88 (MyD88), and thus, inhibition of the production of multiple pro-inflammatory cytokines in dendritic cells.   To investigate the effect on suppression of Th17 cell differentiation and antipsoriasis activity.

TCM formula
To investigate potential active constituents and mechanism of antipsoriasis action.
In vitro: HaCaT cell Potential for treatment psoriasis by acting on multiple targets and pathways synergistically through inhibition of IL-17-related inflammatory pathways. Eleven out of 75 isolated compounds might be active constituents.  In vivo: Balb/c mice (IMQ-induced psoriasis model) Betulinic acid (pentacyclic triterpenoid from plant species, e.g., birch tree, birch bark oil, and paeoniaceae) Anti-inflammatory, antica ncer, antifibrotic, anti-angiogenesis, anti-oxidant.

Acetyl-11-keto-βboswellic acid
To investigate antipsoriasis action on activation of dendritic cells To investigate activity in chronic psoriatic dermatitis through antiinflammatory activity In vivo: Balb/c mice (Oxazolone-induced mouse dermatitis model for chronic psoriatic dermatitis) Improvement of contact dermatitis or psoriasis through regulation of COX-2 produced by macrophage cells and TNF-α and IL-4 produced by Th cells.  Cimicifuga simplex (root) TCM for anti-inflammatory, antiviral. 9,19-Cycloartenol glycoside G3 compound To investigate antipsoriasis activity through an inhibitory effect on immune response (RORϒ IL-17 Th17 and CD4 CD25) In vivo: Mice Anti-inflammatory effect on suppression of pathogenic CD4+ T cell differentiation and IL-17 + RORγt + /IL-10 + FoxP3 + ratio.  Citrus plants (fruit peel) and Silkworm Bombyx mori TCM for anti-inflammation, anticancer, obesity, hyperglycemia, hyperlipidemia.

Naringin extract, Sericin
To investigate antipsoriasis activity mechanism of action through antiinflammatory activity In vitro: Human PBMCs Potential for use as a complementary therapy with conventional treatment of psoriasis: -each and combination: downregulation of proinflammatory cytokines (TNF-, IL-6, IL-23, IL-12p40) associated with psoriasis.  Cnidium officinale (rhizome) Female genital antiinflammatory diseases. Anti-anemia, antifungal, sedative, smooth muscle relaxing.

Extract (methanol) and isolated compounds
To investigate protective effects in skin disorder models through antiinflammatory activity In vivo: Balb/c mice (IMQinduced psoriasis model) Potential for psoriasis treatment by reduction of inflammatory signals including IFN-γ, c-fos, and IκB-α.   Traditional medicines in Egypt, Nordic countries, and Turkey for inflammation skin diseases, such as ulcer, punctured abscesses, and/or burns.

Rosin (water-boiled)
To investigate antipsoriasis activity through anti-inflammatory activity In vivo: Balb/c mice Antipsoriasis activity through inhibition of differentiation and cytokine expression of the inflammatory cells, in particular, Th17cell differentiation and cytokine secretion of IL-23, IL17A, and IL-17F in the IL-23/IL-17.  Cortex mountan (root bark) TCM for inflammatory diseases. Paeonol compound To investigate antipsoriasis activity and mechanism of action through antiinflammatory activity. Ayurvedic medicine for psoriasis, abdominal pain, liver disorders, diabetic wounds, rheumatism, anorexia, menstrual difficulties. Anticancer.

Curcumin compound
To investigate the mechanism of antipsoriasis activity To develop HA-modified ethosomes as a novel nano-topical delivery system ( to improve permeation of curcumin) targeting CD44 in the inflamed epidermis and evaluate the antipsoriasis activity In vivo: C57BL/6 mice (IMQ-induced psoriasis, Skin retention, and Permeability models) HA-modified ethosomes with propylene glycol was successfully developed as a novel drug carrier for curcumin. Targeting CD44 protein, which is overexpressed in inflamed psoriatic skin. (Zhang et al., 2019) In vitro: HaCaT Extract (aqueous) To investigate preventive role against psoriasis-like dermatitis

Diarylheptanoid compound
To investigate the effects on major immunological functions of dendritic cells.

In vitro: Dendritic cells from mouse bone marrow and spleen
Modulation of multiple functions of dendritic cells in the immuno-pathogenesis of psoriasis, including antigen uptake, maturation, migration, pro-inflammatory cytokines production, and finally attenuated the proliferation and differentiation of Th subsets and their effector cytokine production.  In vivo: C57BL/6 male mice Dang-Gui-Liu-Huang Tang (consisting of 7 herbs)* TCM for psoriasis Berberine: GI disorders, bacterial diarrhea. Antihyperglycemic, anticancer, antidepression.  Extract (alcohol) To investigate antipsoriasis activity and underlying mechanism of antiinflammatory action.

4-Methylthiobutylisothioc yanate (MTBI)
To investigate the effects of MTB1 and synthesized compounds on the growth and cell cycle of HaCaT keratinocytes and THP-1 monocytes

Extract (ethanol)
To investigate antipsoriasis activity and underlying mechanism of action through the immunomodulatory activity In vivo: Balb/c mice (IMQinduced psoriasis model) Antipsoriasis activity through the suppression of Th17 differentiation and the activation of dendritic cells.  Evodia rutaecarpa (fruit) TCM for antiinflammatory, antiallergic and immunosuppressive.

Rutaecarpine compound
To investigate the function and mechanism of antipsoriasis activity To investigate the target genes and pathways involved in antiangiogenesis in psoriasis.
In vitro: Chick embryos (Embryonic chick chorioallantoic membrane (CAM) assay) Both: anti-angiogenesis activity. Antiangiogenesis activity of tryptanthrin: G2/M phase arrest, suppression of migration and tube formation through inhibition of Akt and FAK pathway. (Chang et al., 2015) In  In vitro: HUVEC Anti-inflammatory activity: suppression of TNF-α induced VCAM-1 expression via inhibition of AP-1/c-Jun activation. (Chang et al., 2010) Topical ointment To evaluate safety and efficacy in psoriasis Clinical: Patients with psoriasis (plaque-type) (n=51) A novel, safe, and effective therapy for plaque-type psoriasis. (Lin et al., 2008) Extract (methanol) To investigate antipsoriasis activity and underlying mechanism of action through anti-inflammatory activity To investigate the antipsoriasis effect on TJs function and expression of claudin-1 (role as a barrier in human epidermal cells) in psoriatic plaque In vitro: Human keratinocytes Extract: enhancing claudin-1 expression and tight junction function in HaCaT cell. 3 compounds: synergistic effect on upregulating tight junction function. (Lin et al., 2013) In vitro: Human skin Extract and its three major ingredients (Indirubin, Indigo, Tryptanthrin) To investigate the effect on superoxide anion generation and elastase release and signaling pathways involved in its anti-inflammatory activity Effective and safe for therapy of nail psoriasis: -reducing NAPSI scores were superior to the control group (olive oil), with no adverse events during the 24 weeks of treatment. (Lin et al., 2014) Lindioil (extract in oil for topical use) To compare efficacy and safety with standard current topical medication calcipotriol solution Clinical: Patients with nail psoriasis (n=33) Safe and effective alternative therapy for psoriatic nails, with the greatest efficacy on onycholysis and sublingual hyperkeratosis, which arise from hyperproliferation, hyperkeratosis, and parakeratosis of the nail bed, through: -regulating proliferation and differentiation of epidermal keratinocytes -restoring the epidermal barrier function -inhibiting of inflammatory reactions  Topical ointment To evaluate clinical efficacy and safety on treating plaque-type psoriasis and to analyze the histological change in skin tissues Clinical: Patients with plaque-type psoriasis (n=14) Topical Indigo Naturalis ointment: a novel, safe and effective therapy for psoriasis, at least in part by modulating the proliferation and differentiation of keratinocytes in the epidermis, as well as inhibiting the infiltration of T-lymphocytes and subsequent downregulation of IL-17 pathway. (Lin et al., 2007)  In vivo: Balb/c mice (IMQ-induced psoriasis model) Antipsoriasis activity through suppression of the function of activated dendritic cells: -decreasing IL-23 expression -suppressing the expression and secretion of IL-6, IL-12 p40, IL-23, IL-1β, tumor necrosis factor-α Mrna and proteins.  In vitro: PBMCs Paeonia lactiflora (root) TCM for anti-inflammation and immunomodulation Paeoniflorin: inflammatory diseases, including rheumatoid arthritis, hepatic fibrosis, and colitis.

Paeoniflorin (main active ingredient)
To investigate the mechanism of antipsoriasis activity

Balb/c & C57BL/6 mice (IMQ-induced psoriasis model)
Antipsorosis activity by inhibiting Th17 cell response (STAT3 phosphorylation and ROR t expression) and cytokine secretion. To investigate the underlying mechanism of antipsoriasis action In vitro: HaCaT cell A promising candidate for inflammatory skin disorders including psoriasis by inhibition of translocation of NF-B and production of inflammatory cytokines (IL-8, IL23, TNF-α, and ICAM-1). (Dou et al., 2017) of angiogenesis (Costa et al., 2007).

The role of herbal medicine in psoriasis
Complementary and alternative medicine is a common option in self-medicating patients who have psoriasis, with 30-40% of patients using or having used these remedies in combination with conventional psoriasis therapy (Jensen et al., 1990). Herbs used in traditional medicines for psoriasis include mainly those from Asia, particularly China (traditional Chinese medicine: TCM), India (Ayurveda), and Thailand. Some are also used in traditional medicines in European countries and Mexico (Shenefelt, 2011). Nevertheless, their traditional use was, in most cases, arbitrary, without scientific proof of their To investigate the potential antiinflammatory activity to support antipsoriasis activity.
In vivo: Swiss male mice (Croton oil-induced ear edema model) All: effective in reducing edema and cellular migration of polymorphonuclear leukocytes, supporting the use in inflammatory skin disorders, including psoriasis. (Cabrini et al., 2011) Berberis aristata (root) Ayurvedic medicine for skin diseases.

Extract loaded transferosomal gel
To investigate antipsoriasis activity through anti-inflammatory action.

Hesperidin compound To investigate antipsoriatic activity
In vivo: Balb/c mice (IMQ-induced psoriasis model) Therapeutic value for the prevention and treatment of psoriasis: improvement of psoriasis-like skin lesion, reduced epidermal thickness, decreased proliferation, and differentiation of epidermal cells, inhibited expression of inflammatory factors, reduced local skin lesions and serum insulin and glucose levels, modulated signaling pathway and regulates keratinocyte metabolism.  Convallaria majalis (seed) Slowing and regulating heart rate.

Convallatoxin (98%)
To investigate the mechanism of antipsoriasis action In vitro: HaCaT cell Potential for treatment of psoriasis by suppression of keratinocyte hyper-proliferation through ROS-mediated necroptosis. Antipsoriasis activity on both mouse models. (Jiang et al., 2020) In vivo: Balb/c mice (IMQ-and TPA-induced psoriasis models)

Gloriosa superba (root) and
Catharanthus roseus (  Regulation of mitosis and inhibition of the excessive expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in the skin lesions and promotion of the restoration of apoptotic Bcl-2 expression (recovery of the balance between skin cell proliferation, differentiation, and apoptosis). (Shi et al., 2019b) Luteolin flavonoid from Bryophyta, Pteridophyta, Pinophyta, Magnoliophyta Antioxidant, antiinflammatory, antimicrobial, anticancer, antiangiogenesis.

Luteolin compound
To evaluate clinical efficacy and potential in treating psoriasis and to explore the mechanism of action (anti-inflammatory action)

In vitro: HaCaT cell
Reduction of lesions and symptoms through reversing the effects of IFN-γ, inhibition of expression and exosome secretion of HSP90, and regulation of the proportion of immunocytes. (Lv et al., 2020)

Decoction and fractions
To investigate potential antipsoriatic activity and chemical profile In vivo: Balb/c mice (IMQ-induced psoriasis model) Decoction: primary and dichloromethane extract secondary to significantly contribute to antipsoriais activity. Decoction: reestablish skin physiology by decreasing dryness and enhancing skin barrier functions with the best anti-oxidant activity.

Periplogenin (topical)
To investigate antipsoriasis activity and underlying mechanism of action In vitro: HaCat cell Antipsoriasis action through induction of ROS-miediated necroptosis. Potential utilize of inducing ROS-mediated necroptosis as a novel therapeutic strategy for psoriasis treatment. (Zhang et al., 2016) In vivo: Balb/c mice (IMQ-induced and TPA-induced psoriasis models)  To investigate effects on cell proliferation, cell cycle, and apoptosis, including the effect on YAP (yeast-associated protein) expression In vitro: HaCaT cell Potential for treatment of psoriasis: -inhibition of cell proliferation, apoptosis, and cell cycle arrest (G0/1) -prevention of abnormal epidermis proliferation by modulating YAP expression (Jia et al., 2020) Cryptotanshinone compound To investigate antipsoriasis activity and mechanism of action In vivo: C57BL/6J mice (IMQ-induced psoriasis model) Potential for treatment of psoriasis: mainly through modulating STAT3 and inducing G0/G1 arrest. (Tang et al., 2018) Salvia miltiorrhiza Radix (root) -TCM for prevention of psoriasis) Tanshinone IIA To investigate the cellular mechanism that leads to cell cycle arrest and apoptosis in psoriasis Safe and effective therapy for plaque-type psoriasis  Sinapis Alba Linn (mustard seed for spice and TCM)

Respiratory and GI diseases
Mustard seed was ground using a mechanical blender and added to the normal forage at the desired concentration of 5%. Forage pellets were then made and stored in a dry and strictly sanitary condition at room temperature. Stubborn skin ulcers. Antiviral, anticancer, antibacterial, immunomodulatory, insecticidal.

Extract (ethanol) and its constituents
To investigate the effect on cutaneous wound healing In vitro: HaCaT & RAW 264.7 cells Potential use for psoriasis treatment for wound healing effect: -increasing phosphorylation of ERK and Akt -inhibiting NO and PGE2 release and mRNA expression of inflammatory mediators -enhancing motility of keratinocytes -improving cutaneous wound healing in SD rats  In vivo: Sprague-Dawley (SD) rats  The combined use of TCM with acitretin capsule: a safe and effective therapy for psoriasis, and worthy of application in clinical practice. (Zhang et al., 2009) Tinospora cordifolia (root, stem, leaf) Ayurvedic medicine for psoriasis Extract (aqueous) To investigate preventive role against psoriasis-like dermatitis In vivo: Balb/c mice (IMQ-induced psoriasis model) Marked attenuation of symptoms and processes underlying psoriasis-like dermatitis (Arora et al., 2016) Tuhuai formulation (mainly consisting of 6 herbs)* TCM for psoriasis Topical extract (ethanol) To investigate antiproliferative and anti-inflammatory activities and mechanisms of action Effective antipsoriasis: reduction of PASI scores. miR-146a and miR-99a: potential biomarkers for disease activity and clinical efficacy in psoriasis patients treated with Zhuhuang  In vitro: Human PBMCs Zanthoxylum nitidum (root) Anti-inflammatory, antimalarial, antifungal, antiangiogenesis, anticancer.

Nitidine chloride
To investigate antipsoriasis activity and mechanism of action In vitro: HaCaT Antipsorosis activity through inhibition of HaCaT cell proliferation, induction of apoptosis (S phase) through JNK signaling pathway.  In vivo: Balb/c mice IMQ-induced psoriasis and TPAinduced epidermal hyperplasia models)   (Deyrieux et al., 2007). The principal model for in vivo studies is the imiquimod (IMQ)-induced psoriasis-like model in mice. IMQ is a toll-like receptor (TLR7/8) agonist which is a potent immune activator that causes activation and maturation of DCs when applied to the skin of mice . IMQ-induced psoriasis-like mouse model has been widely used to mimic inflammation-type psoriasis critically dependent on the IL-17 and IL-23 cytokine axis, and these models are of benefit for facilitating research on the mechanisms of potential treatments for psoriasis (Rodriguez et al., 2017). Clinical studies to evaluate the clinical efficacy of herbal medicines in patients with different types of psoriasis are usually based on the primary efficacy parameters, including Psoriasis Area and Severity Index (PASI), DAS28 score, and Disease Activity in Psoriatic Arthritis (DAPSA) (Feldman and Krueger, 2005;Tucker et al., 2019).

Plants that modulate inflammation and immune response
Plants that interfere with the production or activity of proinflammatory cytokines/mediators through various signaling pathways and steps in the immune cells and/or keratinocytes include Acanthus mollis (Bader et al., 2016a), Artemisia arborescens (Bader et al., 2016a), Aloe vera , alpha oasis (Ye et al., 47 2016). The main component, paeoniflorin suppressed IL-22 and P38 MAPK pathways . Aloe vera (leave) and C. longa (rhizome) have been used in TCM, traditional Ayurvedic medicine, and traditional medicine in other countries for psoriasis, bacterial infections, inflammation, as well as for anti-oxidant activities and wound-healing promoters (Shedoeva et al., 2019). The topical application of the extract or cream was shown to be a potential candidate for psoriasis both in experimental or clinical studies through anti-inflammatory activity (inhibition of TNF-α induced proliferation of keratinocytes and over activation of the NFpathway) (Arora et al., 2016;Syed et al., 1996). C. longa has been used for psoriasis, abdominal pain, liver disorders, diabetic wounds, rheumatism, anorexia, menstrual difficulties, and cancer. The active compound curcumin was shown to act on psoriasis through inhibiting hKv1.3 channel, activation of T-cells, and expression of inflammatory cytokines IL-2 and IFN-γ .
Curcumin-loaded hyaluronan (HA)-modified ethosomes (HA-ES) was successfully developed with propylene glycol as a novel drug carrier for curcumin to targeting CD44 protein in the inflamed psoriasis cells . Tripterygium wilfordii Hook f. has been used in TCM for psoriasis, as well as dermatitis, asthma, systemic lupus erythematosus, rheumatoid arthritis, nephritis, Bechet's disease, and for prevention of transplant rejection. The plant contains multiglycosides which exert antipsoriasis activity through down-regulation of the function of Th17 cells (via inhibition of STAT3 phosphorylation) . Triptolide compound was shown to regulate IL-12/IL-23 production in LPS stimulated mouse peritoneal macrophage and inhibit p40 expression and IL12p40 transcription (Zhang et al., 2010).

Conclusion
Herbal medicines have a potential role in the treatment of psoriasis. Bioactive natural products are considered to be promising prototypes for the development of new therapeutic agents for psoriasis. The antipsoriasis activities of several plants used in traditional medicine for psoriasis have been confirmed in different experimental models in conjunction with their underlying mechanisms of action at the molecular and cellular levels. Research targeting inflammatory and proliferative processes in disease pathogenesis, development, and progression has been an extensive area. Blocking the generation of an inflammatory infiltrate by interfering with critical molecules of the adhesion process is an attractive strategy to treat psoriasis (for example, the approved drug efalizumab) (Parisi et al., 2013). Controlling these pro-inflammatory cytokines in DCs would be a breakthrough for psoriasis treatment. Investigation of anti-angiogenesis activities remains attractive to researchers. Herbs//herbal medicine targeting other signaling molecules should be further investigated.