As per studies, psoriasis is an autoimmune disease that causes redness, scaling, and thickening of the affected skin due to the skin's activated dendritic cells interacting with the surrounding keratinocytes on the skin's surface (23).
Psoriasis model is dependent on mouse tail model, which is an ideal model for inducing psoriasis due to the ease of obtaining psoriasiform skin in these animals with the psoriasis phenotype. Mouse model have the same pathophysiological features that seen in human like cutaneous inflammation, hyperkeratosis and dendritic cells CD4 cells manifestation and anti-oxidant system (14).
Imiquimod which is a TLR7/8 agonist specific for toll-like receptors can stimulate innate response through Dendritic cells, monocytes, and macrophages activation and promotes signalling of cytokines cascade through the expression of several inflammatory cytokines in the body. Thus, the Th-1-driven immune response is augmented, resulting in antitumor and antiviral effects (24). Even though the IMQ model induces psoriasis-like symptoms, they resolve spontaneously after six days of treatment. Due to the instability of the adoptive response, these findings indicated that mice are not genetically compromised and are capable of reversing the inflammatory process in response to IMQ stimulation (14,25). As a result, we administered IMQ to mice's dorsal shaved skin for 12 consecutive days. In The current study, the Imiquimod treatment resulted in significant and greater changes in spleen mass index when comparing with control group which was already demonstrated by several other authors (23,27,28)
ELISA readings for spleen tissue inflammatory biomarkers revealed that Imiquimod could significantly increase all tested pro inflammatory biomarkers and inflammatory cell signals, and it produced a picture of plaque psoriasis in mice similar to that observed in humans with plaque psoriasis. Numerous authors have previously discussed these findings, which demonstrated the effect of Imiquimod on tissue inflammatory biomarkers (27,28,29).
Numerous mechanisms against inflammation and immune suppression made highly potent topical corticosteroids the gold standard for Psoriasis treatment due to their efficacy (30). The action mechanisms of Clobetasol are classified as genomic and non-genomic. The genomic pathway referred to Glucocorticoid receptors on the plasma membrane. Upon binding to its receptors, a steroid molecule migrates into the nucleus and stimulates the formation of anti-inflammatory transcription factors called Glucocorticoids Response Elements, which are then released into the cytoplasm. (31). The non-genomic route is responsible for glucocorticoids' rapid action. It has been demonstrated that glucocorticoids increase the expression of Annexin A1, a protein that binds to phospholipids and inhibits the synthesis of pro-inflammatory prostanoids. In addition, it inhibits the expression and activation of pro-inflammatory cytokines, decreases nitric oxide expression, and affects the function of mast cells (32). Glucocorticoids promote anti-inflammatory gene transcription while inhibiting pro-inflammatory gene transcription.
In the current investigation, Clobetasol significantly inhibited the inflammatory response induced by Imiquimod. When treated with Clobetasol, inflammatory cytokines such as IL-17, IL-23, TNF-, and NF-K were significantly reduced compared to induction group II. Despite the fact that topical Clobetasol is an effective treatment for psoriasis, it has been found to cause adverse effects such as skin striae, degeneration, and telangiectases, in addition to their systemic adverse effects (34). This limitation renders steroidal drugs unsuitable for long-term use, and the demand for new drugs with fewer side effects is growing.
Lycopene is one of the nutraceuticals that can be used to prevent or treat certain diseases, such as psoriasis (35). It has numerous beneficial effects for the skin, including a powerful antioxidant effect and a protective function against the damaging effects of UV radiation through the activation of DNA repair pathways (36). Lycopene through different study prove the positive impact on plaque type psoriasis in mice regarding clinical and histological examination with better response to higher dose of Lycopene (42).
According to ELISA-based histochemical analysis, it is evident that IL-23/IL-17 play a crucial role in Imiquimod-induced psoriasis in mice. Upon activation, dermal dendritic cells release IL-23, which promotes the activation and differentiation of T-17 helper cells. These helper cells then secrete pro-inflammatory cytokines that activate and mobilise other immune cells and promote keratinocyte proliferation (38). IL-17 activates the nuclear factor-K (NF-K) and JUN amino-terminal kinase (JNK) signalling pathways in a TNF- associated factor upon binding to its receptor. During this study, Lycopene improved the spleen levels of Interleukin 17, Interleukin-23, and NF-K, particularly at high doses (Group V). TNF-, one of the cytokines involved in psoriatic inflammation, is regarded as the master pro-inflammatory marker of the innate immune system because of its multiple origins and targets. Typically, T cells, macrophages, monocytes, keratinocytes, natural killer (NK), and antigen-presenting cells release this protein. It stimulates the proliferation of keratinocytes, angiogenesis via VEGF, and the production of pro-inflammatory cytokines. In this study, Lycopene at two different doses significantly reduced TNF- levels compared to the Imiquimod group (Group II). These findings were consistent with other studies that demonstrated a suppressive effect of lycopene on IL-17 and TNF- in pregnant mice (39), and Intracellular adhesion molecules activated by IL-23 cytokines (15). Yang et al. (2017) suggested that lycopene exerts its anti-inflammatory effect by inhibiting NF-K in endothelial cells (40).
Combining steroidal and non-steroidal treatment for the treatment of psoriasis in order to avoid the adverse effects of excessive doses of steriods and achieve a better result through synergism has been widely used (41). In the present study, the Combination group (Group VI) demonstrated the greatest improvement in clinical severity score and the greatest ameliorative effect on histological features and the Baker scoring system. In addition, when applied topically for six consecutive days to Psoriasis induced by Imiquimod, the combination of Lycopene 0.25 mg/ml and 0.05% Clobetasol inhibited spleen inflammatory biomarkers better than Clobetasol alone. These effects may be attributable to the synergistic anti-inflammatory effect of Clobetasol and Lycopene, which is advantageous for preventing the spread of psoriasis and reducing its symptoms.