The therapeutics effects of monobenazone on treatment of psoriasis induced in mice

Abstract

This study investigates the efficacy of monobenazone, a novel topical agent, in treating psoriasis-like lesions in an imiquimod (IMQ)-induced murine model. Female BALB/c mice were allocated to four groups: negative control, IMQ-treated positive control, monobenazone treatment, and clobetasol propionate treatment. The Psoriasis Area and Severity Index (PASI), histopathological analysis, and cytokine quantification (TNF-α and IL-6) were used to assess treatment outcomes. Monobenazone significantly reduced PASI scores and ameliorated histopathological features, including acanthosis and dermal inflammation, compared to the positive control. Furthermore, monobenazone treatment resulted in decreased levels of pro-inflammatory cytokines TNF-α and IL-6. These findings suggest that monobenazone exhibits therapeutic potential in mitigating psoriasis-like symptoms, potentially through modulation of inflammatory responses. While promising, further research is necessary to elucidate its mechanism of action and clinical applicability as a novel psoriasis treatment.

Introduction

Psoriasis is a chronic, immune-mediated, inflammatory skin disorder characterized by the hyperproliferation and abnormal differentiation of keratinocytes with the appearance of erythematous and scaling plaques. It is a multifaceted disease that affects an approximate 2–3% of people worldwide, causing considerable impairment in the quality of life of many patients either physically or psychologically [1].

Psoriasis typically presents as well-circumscribed, erythematous plaques covered with silvery-white scales. Although these lesions can appear anywhere on the body, common sites of involvement include the elbows, knees, scalp, and lower back. Clinical manifestations can vary greatly among patients, ranging from small, localized patchy areas to widespread involvement of the skin [2].

The pathogenesis is an aberrant immune response in which the activation of T cells, particularly T-helper 17 and T-helper 1 cells, lies at the core. These activated T cells produce pro-inflammatory cytokines, such as interleukin-17, interleukin-22, interferon-γ, and tumor necrosis factor-α [3].

The crosstalk between immune cells and keratinocytes is the crux of triggering and sustaining a psoriatic lesion. By the release of pro-inflammatory mediators at that site, immigrant immune cells activate T cells and other immune cells at the site. These cytokines allow for excessive proliferation and abnormal differentiation of keratinocytes, resulting in epidermal hyperplasia and scaling of the psoriatic plaques. Activated keratinocytes secrete chemokines and other inflammatory mediators to attract and activate more immune cells, closing a vicious, self-sustaining circuit of inflammation [4].

Treatment of psoriasis includes multivariate approaches that are targeted at anti-inflammatory effects, control of symptoms, and improvement in quality of life. Generally, psoriasis treatments fall into four categories: topical therapies, phototherapy, systemic medications, and biologic agents. The choice of the treatment modality depends on numerous factors, most significantly disease severity, extent of the involved skin surface area, comorbidities, and patient preferences [5].

Although available with various other modalities, the management of psoriasis still remains unsatisfactory for many a patient. It is associated with resistance against treatment, loss of effectiveness with time, and adverse drug effects. This is also a chronic disease that obviously needs long-term therapy, which usually becomes more of a burden to the patients. Hence, development of new therapeutic modalities capable of ensuring effective, safe, and convenient long-term management of psoriasis continues [6].

Monobenzone is a depigmenting agent whose major use until today has been in the treatment of vitiligo. Recently, there is interest in its mechanism of action, its side effects, and a possible application in other dermatological disorders like psoriasis [7].

The primary mechanism of action of monobenzone involves the selective destruction of melanocytes, the pigment-producing cells in the skin. Monobenzone is metabolized by tyrosinase, an enzyme crucial for melanin synthesis, into reactive quinone products. These reactive metabolites cause oxidative damage to melanocytes, leading to their destruction. Additionally, monobenzone has been shown to induce autoimmune responses against melanocytes, further contributing to depigmentation [8].

Monobenzone’s ability to generate reactive oxygen species (ROS) and induce cellular stress extends beyond melanocytes. Recent studies have suggested that monobenzone can affect other skin cells, including keratinocytes, through similar oxidative mechanisms. This broader impact on skin cell populations has led to investigations into its potential effects on inflammatory skin conditions like psoriasis [9].

While monobenzone’s primary use remains in vitiligo treatment, its mechanism of action has sparked interest in its potential applications for other dermatological conditions. The ability of monobenzone to modulate skin cell behavior and potentially influence inflammatory processes has led to investigations into its effects on conditions like psoriasis [10].

The exploration of monobenzone’s potential in psoriasis treatment represents a novel approach, leveraging its immunomodulatory and anti-inflammatory properties beyond its traditional role as a depigmenting agent. This unconventional application underscores the importance of understanding drug mechanisms across different dermatological conditions and highlights the potential for repurposing existing medications to address unmet therapeutic needs [11].

Keratinocytes, the predominant cell type in the epidermis, play a crucial role in the pathophysiology of psoriasis. Once considered passive bystanders in the disease process, keratinocytes are now recognized as active participants in the initiation, maintenance, and resolution of psoriatic inflammation. Understanding their role is essential for comprehending the potential therapeutic effects of agents like monobenzone on psoriasis [12].

In psoriasis, keratinocytes exhibit accelerated proliferation and aberrant differentiation. This results in epidermal hyperplasia (acanthosis), retention of nuclei in the stratum corneum (parakeratosis), incomplete cornification, and altered expression of keratins and other differentiation markers. These changes contribute to the characteristic thickened, scaly appearance of psoriatic plaques [13].

Activated keratinocytes in psoriatic lesions produce a range of pro-inflammatory cytokines and chemokines, including IL-1α, IL-1β, IL-6, IL-8, TNF-α, IL-17C (an IL-17 family member produced by keratinocytes), and chemokines like CXCL1, CXCL2, and CCL20. These factors contribute to the recruitment and activation of immune cells, perpetuating the inflammatory cycle [14]. The dysregulated proliferation and differentiation of keratinocytes in psoriasis lead to an altered epidermal barrier function. This compromised barrier can allow for increased penetration of environmental antigens and microbes, potentially triggering or exacerbating inflammatory responses [14].

Keratinocytes in psoriatic skin show altered responses to growth factors and cytokines. They become hyperresponsive to proliferative signals and less sensitive to anti-proliferative signals, contributing to the characteristic epidermal hyperplasia seen in psoriatic lesions [15].

Understanding the central role of keratinocytes in psoriasis pathogenesis has led to the development of targeted therapies aimed at modulating keratinocyte function. These approaches include agents that normalize keratinocyte proliferation and differentiation, as well as those that target specific cytokine pathways involved in keratinocyte-immune cell interactions [16].

The exploration of monobenzone’s potential effects on keratinocytes and its implications for psoriasis treatment represents a novel area of research. While monobenzone is primarily known for its effects on melanocytes, recent studies suggest that its actions may extend to other skin cell types, including keratinocytes [17].

Monobenzone’s ability to generate reactive oxygen species (ROS) and induce cellular stress could potentially affect keratinocyte function. In the context of psoriasis, where keratinocytes are hyperproliferative and show aberrant differentiation, monobenzone-induced stress might paradoxically lead to beneficial effects by altering keratinocyte behavior [18].

The oxidative stress induced by monobenzone could potentially modulate signaling pathways involved in keratinocyte proliferation and differentiation. This modulation might help normalize the hyperproliferative state of psoriatic keratinocytes, potentially reducing epidermal thickness and scaling [19].

Monobenzone’s effects on cellular stress responses might influence the production of pro-inflammatory cytokines and chemokines by keratinocytes. By altering the inflammatory milieu, monobenzone could potentially disrupt the self-perpetuating cycle of inflammation characteristic of psoriasis [20].

The immunomodulatory effects of monobenzone, observed in its use for vitiligo treatment, might extend to the immune environment in psoriatic skin. This could potentially influence the interactions between keratinocytes and immune cells, modulating the inflammatory response. It impact on keratinocytes might affect the expression of antimicrobial peptides (AMPs) and other innate immune mediators. Given the role of AMPs in psoriasis pathogenesis, this could have implications for disease activity and progression [21].

Material and methods

Animal models and the ethical approach

This study, therefore, focused on the model monobenazone murine model to investigate the therapeutic effect of monobenazone on psoriasiform skin lesions. All animal experiments are conducted in conformity with the observation and guidelines imposed by IACUC, hence approved by Ethical Review Committee. Female BALB/c mice of 6–8 weeks of age were obtained from an in house approved animal facility and acclimatized for one week under normal laboratory conditions: a 12-hour light/dark cycle with ad libitum access to food/water.

Mice were obtained from Alnahrain-Biological Technical Center, Baghdad. The animals were housed in the same center in controlled conditions at a temperature of 22 ± 2 °C and 50 ± 10% humidity with a 12-h light/dark cycle. The mice had ad libitum access to food and water.

At the end of the treatment period, mice were anaesthetized with isoflurane at 4% concentration and a maintenance dose of 2% in oxygen at a flow rate of 2 L/min, given via inhalation using a precision vaporizer. After establishing the depth of unconsciousness after 2–3 min of anesthesia, euthanasia was carried out by cervical dislocation. This method was selected in accordance with the AVMA Guidelines for the Euthanasia of Animals to ensure minimal distress and pain.

Induction of psoriasis-like skin lesion

Psoriasiform skin lesions were induced in mice by topical application of imiquimod (IMQ) cream (5%) on shaved dorsal skin. IMQ was applied daily for 7 consecutive days to induce inflammation and hyperproliferation typical of psoriasis. Severity of skin lesions was scored by the Psoriasis Area and Severity Index (PASI) which assessed erythema, thickness, and scaling scored from 0 to 4 [22].

Treatment groups and drug administration

Mice were assigned randomly into four groups (n = 8 for each group) as follows: Control Negative Group: Treated with no drugs. Control Positive Group: Treated with IMQ only. Monobenazone Treatment Group: treated topically with monobenazone 1% w/w once daily for 7 days, starting in combination with IMQ application. Clobetasol Propionate Treatment Group: treated topically with clobetasol propionate 0.05% w/w once daily for 7 days, starting in combination with IMQ application.

Histopathological examination scoring of psoriasiform skin lesions

The inflammatory status of the dorsal skin was clinically scored using the PASI clinical scoring system daily for all 8 days. The erythema, induration, and desquamation of the skin on the back of each mouse were assessed subjectively every day for three parameters. The scores are from 0 to 4: 0—none, 1—slight, 2—moderate, 3—marked, 4—very marked.

Thus, the total score ranged between 0 and 12. All measurements were performed by two investigators independently; values were then averaged. (n = 6 for all scores). Animals were sacrificed after treatment. Skin samples obtained were carried out for histopathological studies. Samples were fixed in 10% neutral buffered formalin for 24 h, followed by dehydration with a gradient of ethanol, followed by clarification in xylene and embedding in paraffin. Sections 5 µm thick were cut from tissue blocks on a rotary microtome.

H&E-stained sections were prepared to evaluate the thickness of epidermis and acanthosis, and for dermal inflammation. Histopathological changes had been evaluated by an independent blinded pathologist and graded according to a standardized scoring system which took into account epidermal thickness, parakeratosis, grade of inflammatory cell infiltration, and vascular changes [23].

Cytokine Assay For cytokine analysis, skin tissues were homogenized by the addition of 500 µL of ice-cold PBS with protease inhibitors to about 50 mg of skin tissue, followed by further homogenization on ice using a tissue homogenizer. The homogenates were further centrifuged at 12,000×g at 4 °C for 15 min followed by supernatant collection.

The concentrations of TNF-α and IL-6 were assessed in the supernatants by a commercially available enzyme-linked immunosorbent assay kit according to the manufacturer’s instructions (R&D Systems, Minneapolis, MN, USA). The resulting concentrations were determined as pg/mg of total protein after the normalization of the total protein amount using the Bradford assay.

Statistical analyses

Data Analysis Statistical analyses were done using GraphPad Prism Software version 9.0 (GraphPad Software, San Diego, CA, USA). The results are expressed as mean ± standard deviation (SD). One-way analysis of variance (ANOVA) was used to determine the statistical significance followed by Tukey’s post hoc test for multiple comparisons. For non-normally distributed data, Kruskal-Wallis test followed by Dunn’s post hoc test was applied. Correlation analyses were done using Pearson’s correlation coefficient. A p-value < 0.05 was considered statistically significant [24].

Results

Scoring of psoriasis-like skin lesions

The signs of erythema, thickness and scales on the back skin were seen two or three days after the application of IMQ. All the three parameters along with the cumulative score showed the gradual increase in the observed physical factors with the maximum score at day 8 as compared to the control group.

The PASI score of the control group was maintained around 0 throughout the experiment indicating normal baseline skin condition In contrast, the groups treated with imiquimod exhibited a significant increase in PASI scores, correlating with the severity of induced psoriasis-like lesions, which provided a clear delineation of the inflammatory response triggered by imiquimod and underscored the appropriate establishment of the disease model, Table 1 and Fig. 1.

Table 1 Represent severity of skin inflammation of all groups

Fig. 1

Comparative analysis of skin inflammation severity across different treatment groups

The histo-pathological slide examination revealed significant differences in epidermal thickness, inflammatory cell infiltration, and vascular changes across the treatment groups.

However, there are numerous instances of severe irregular acanthosis, marked degeneration, and depletion of dermal fibrous tissue, along with a scarcity of hair follicles. The epidermis displays severe mitotic figures of basal epithelial cells, a normal keratin layer, and vacuolated keratocytes, while the dermal fibrous tissues show significant degeneration and tissue depletion. These observations are based on H&E staining at 100x magnification

Some of the important parameters observed were parakeratosis, acanthosis, and Munro’s microabscesses. Such features are typical of psoriatic lesions and hence meet the established pathological criteria.

Key parameters such as parakeratosis, acanthosis, and Munro’s microabscesses were observed. These are hallmark features of psoriatic lesions, in line with the established pathological criteria. The keratinocytes in this slide (Fig. 5) show signs of reduced hyperproliferation compared to typical psoriatic lesions. The epidermis appears thinner, suggesting a normalization of keratinocyte activity. There is no clear evidence of excessive keratinocyte proliferation, which is typically seen in untreated psoriatic skin. The organization of the epidermis appears improved, though not fully normalized, indicating ongoing remodeling processes. This suggests that the monobenzone treatment has been effective in regulating keratinocyte behavior, a key factor in psoriasis pathology.

Histological evaluation

The Table 2 show the histopathological score of the 4 groups as follows.

Table 2 Histopathological scores for skin tissue across different treatment groups

0 = for normal skin 1 = for mild inflammation, characterized by the presence of a small number of inflammatory cells, minimal tissue damage, and relatively intact skin architecture. 2 = for moderate inflammation, characterized by the presence of a moderate number of inflammatory cells, moderate tissue damage, and some disruption of the normal skin architecture. 3 = for severe inflammation, characterized by the presence of a large number of inflammatory cells, significant tissue damage, and substantial disruption of the normal skin architecture. 4 = for the most severe degree of inflammation and tissue damage, with a large number of inflammatory cells, significant destruction of the normal skin architecture, and extensive tissue damage observed in the imiquimod-treated control group [25].

The groups evaluated where classified as:

• Control Negative: Represents normal skin with no inflammation or tissue damage.

• Control Positive (Imiquimod): Exhibits the most severe inflammation and tissue damage. Monobenazone: Shows moderate inflammation and tissue damage. Clobetasol Propionate: Displays mild inflammation and tissue damage.

Data summary

See Table 2.

Visual analysis

The following visualizations provide a clear representation of the histopathological scores.

This Bar Plot: Shows the total histopathological scores for each group, highlighting the severity of inflammation and tissue damage.

• The Control Positive (Imiquimod) group exhibits the highest level of inflammation and tissue damage, with a total score of 15.

• The Monobenazone group shows moderate inflammation with a total score of 9.

• The Clobetasol Propionate group has the lowest inflammation among the treated groups, with a total score of 5.

• The Control Negative group maintains normal skin conditions with a total score of 0. This evaluation provides insights into the effectiveness of different treatments in managing skin inflammation and tissue damage.

Cytokines results

See Fig. 8.

TNF-alpha and IL-6 levels across groups

See Table 3.

TNF-alpha analysis

As shown in Table 3 Negative control vs. Positive control: Negative control: 64.95 ± 5.94 Ng/L and Positive control: 124.32 ± 7.34 Ng/L. The positive control shows a substantial increase (91.4% higher) in TNF-alpha levels compared to the negative control, indicating a significant inflammatory response in the disease model while comparing Treatment groups vs. Positive control we found that Clobetasol.-treated (GII): 77.79 ± 10.46 Ng/L Monobenazone-treated (GIII): 90.53 ± 8.92 Ng/L Both treatments reduced TNF-alpha levels compared to the positive control, with clobetasol. showing a greater reduction (37.4% decrease) than monobenazone (27.2% decrease) on the other hand comparing Treatment groups vs. Negative control it was found that Clobetasol.-treated levels are 19.8% higher than the negative control. Monobenazone-treated levels are 39.4% higher than the negative control. Neither treatment fully restored TNF-alpha to baseline (negative control) levels.

Table 3 Quantitative comparison of pro-inflammatory cytokine expression (TNF-α and IL-6) in control and experimental treatment groups

IL-6 analysis

On comparing Negative control vs. Positive control it found that Negative control: 35.086 ± 1.701 Ng/L Positive control: 51.71 ± 4.39 Ng/L The positive control shows a 47.4% increase in IL-6 levels compared to the negative control, indicating elevated inflammation in the disease model. And after treatment the Treatment groups vs. Positive control: Clobetasol.-treated (GII) was 39.46 ± 4.43 Ng/L and Monobenazone-treated (GIII): 42.54 ± 3.81 Ng/L both treatments reduced IL-6 levels compared to the positive control, with clobetasol. showing a slightly greater reduction (23.7% decrease) than monobenazone (17.7% decrease).

Now if we analyze the results from Treatment groups vs. Negative control: Clobetasol.-treated levels are 12.5% higher than the negative control. Monobenazone-treated levels are 21.2% higher than the negative control. Neither treatment fully restored IL-6 to baseline (negative control) levels, but both came closer than with TNF-alpha.

So the cytokines results show that Clobetasol. appears to be more effective in reducing both TNF-alpha and IL-6 levels compared to monobenazone. For TNF-alpha, clobetasol. reduced levels by 37.4% vs. 27.2% for monobenazone (relative to positive control). For IL-6, clobetasol. reduced levels by 23.7% vs. 17.7% for monobenazone (relative to positive control). Both treatments were more effective in normalizing IL-6 levels than TNF-alpha levels.

Overall observations shows that both clobetasol. and monobenazone demonstrate anti-inflammatory effects by reducing TNF-alpha and IL-6 levels. Clobetasol. appears to be more potent in reducing inflammatory markers, particularly TNF-alpha.

Monobenazone shows a moderate anti-inflammatory effect, positioning it as a potential alternative treatment. Neither treatment fully normalizes cytokine levels to those of the negative control, suggesting room for improvement or potential combination therapies. In conclusion, while both treatments show promise in reducing inflammatory markers, clobetasol. demonstrates superior efficacy in this study. However, monobenazone’s moderate effect and potentially more consistent results (as suggested by lower SDs) indicate it could be a valuable alternative, especially if it has a better side effect profile or other advantages not captured in this data set. Further research into the broader effects, safety profiles, and potential synergies of these treatments would be beneficial.

Discussion

The present study investigates the therapeutic potential of monobenazone in the treatment of psoriasis-like skin lesions using an imiquimod (IMQ)-induced murine model. Our findings provide compelling evidence for the efficacy of monobenazone in ameliorating psoriatic symptoms, offering new insights into potential treatment strategies for this chronic inflammatory skin condition.

The histopathological examination revealed significant differences between the control groups and the monobenazone-treated group. The IMQ-induced psoriasis model successfully replicated key features of human psoriasis, including severe irregular acanthosis, elongated dermal papillae, and subepithelial fibrous connective tissue degeneration. These observations align with previous studies utilizing the IMQ-induced psoriasis model [26] confirming the validity of our experimental approach.

Therapeutically, monobenzone (1% w/w) was used in one single dose; it is thus crucial that one realizes the existence of other critical and sometimes necessary dose dependencies in clinical translatability. A multiple concentration study falls out of the scope of the current study; therefore, it’s further encouragement toward dose-response studies.

Monobenazone treatment resulted in a notable reduction of psoriasis-like features, as evidenced by the partial resolution of acanthosis and the normalization of dermal structures. This improvement, while not as pronounced as that observed with the reference drug clobetasol propionate, suggests that monobenazone possesses significant therapeutic potential. The variability in treatment response across different histological slides indicates that the efficacy of monobenazone may depend on factors such as the severity of the initial lesion or local differences in drug penetration and metabolism.

The observed reduction in epidermal thickness following monobenazone treatment is particularly noteworthy, as epidermal hyperproliferation is a hallmark of psoriasis [27]. This finding suggests that monobenazone may modulate keratinocyte proliferation and differentiation, key processes in psoriasis pathogenesis. Future studies should investigate the molecular mechanisms underlying this effect, potentially focusing on the regulation of keratinocyte cell cycle and differentiation markers such as Ki67, K16, and involucrin [28].

Our histopathological analysis revealed a reduction in inflammatory cell infiltration in monobenazone-treated skin compared to the IMQ-treated positive control. This observation is crucial, as the influx of immune cells, particularly T cells and neutrophils, plays a central role in perpetuating the inflammatory cascade in psoriasis [29]. The ability of monobenazone to mitigate this inflammatory infiltrate suggests that it may possess immunomodulatory properties, which warrant further investigation.

Interestingly, we also observed changes in dermal vasculature, with a reduction in the dilation of blood vessels in monobenazone-treated skin. Vascular changes are a well-documented feature of psoriatic lesions, contributing to the characteristic erythema and facilitating the influx of inflammatory cells [30]. The apparent normalization of vascular structures following monobenazone treatment could be an important aspect of its therapeutic action, potentially involving modulation of angiogenic factors such as VEGF [31].

This study, though it measured TNF-α and IL-6 as primary markers, has to take into consideration other important cytokines that play a huge role in psoriasis pathogenesis, such as IL-17 and IL-23, which should be investigated in future studies to fully elucidate the mechanisms of monobenzone.

The significant reduction in pro-inflammatory cytokines TNF-α and IL-6 following monobenazone treatment provides strong evidence for its anti-inflammatory properties. These cytokines are key players in the pathogenesis of psoriasis, with TNF-α, in particular, being a successful target for biological therapies [32].

The ability of monobenazone to suppress these cytokines suggests that it may act on multiple levels of the inflammatory cascade.

While the reduction in cytokine levels was less pronounced than that achieved with clobetasol propionate, it is important to note that the mechanisms of action likely differ between these two compounds. Clobetasol propionate, as a potent corticosteroid, exerts broad anti-inflammatory effects through glucocorticoid receptor-mediated pathways [33]. In contrast, the mechanism by which monobenazone modulates inflammatory mediators remains to be elucidated. Future studies should explore whether monobenazone acts directly on immune cells, affects cytokine signaling pathways, or modulates the expression of pro-inflammatory genes [34].

The efficacy of monobenazone, while not surpassing that of clobetasol propionate in this study, presents several potential advantages that merit further investigation. Unlike topical corticosteroids, which are associated with skin atrophy and other adverse effects with long-term use [35], monobenazone may offer a more favorable safety profile. This could be particularly beneficial for sensitive areas or for maintenance therapy.

Moreover, the unique mechanism of action of monobenazone could potentially complement existing therapies. Combination approaches, such as using monobenazone in conjunction with low-potency corticosteroids or vitamin D analogs, might yield synergistic effects while minimizing side effects. Such combination strategies have shown promise in psoriasis management [36] and should be explored in future studies with monobenazone.

The results of this study are fully complemented by figures that provide two important insights into the therapeutic effect of monobenazone and its comparison with clobetasol. As can be seen in Fig. 1, the monobenzone therapy clearly reduced the severity of the psoriatic skin inflammation compared to the positive control, though it didn’t to the extent that clobetasol did. Baseline histopathological features in the control negative group (Fig. 2; Table 2) with normal epidermal and dermal structures serve as a comparison for pathological changes induced by imiquimod in the control positive group represented in Fig. 3. These pathological changes include severe acanthosis, parakeratosis, and capillary dilation, underlining the inflammatory response that the disease model had caused. Clobetasol treatment, represented in Fig. 4, evidently improved these pathological changes, with significant anti-inflammatory effects and tissue restoration. Monobenazone treatment, as shown in Fig. 5, revealed promising improvements in histopathological features, including reduced epidermal hyperplasia and normalization of dermal structures, though these were more moderate compared to clobetasol. It can be further emphasized that the comparative analysis of histopathological scores, represented in Figs. 6 and 7, shows that clobetasol exerts the best performance in minimizing both tissue damage and inflammation, while monobenazone is moderate but with notable effects. Finally, the cytokine analysis represented in Fig. 8 indicates significant decreases in TNF-α and IL-6 levels for both treatments, although the most pronounced decreases were observed with clobetasol. These findings together point to the therapeutic potential of monobenazone as an anti-inflammatory agent, although further studies are needed to optimize its efficacy and explore its use in combination therapies.

Fig. 2

Section of skin (Control negative) shows: normal epidermis (E), hair follicles (Black arrows), & dermal fibrous tissue (Asterisk). H&E stain, 100x

Fig. 3

Section of skin (control positive) showing active mitotic figures of basal cells (black arrows) and dilation of dermal capillaries (black arrow). H&E stain, 400x

Fig. 4

The histopathological analysis of skin treated with Clobetasol propionate reveals moderate irregular acanthosis, normal dermal fibrous tissue, and a few mature hair follicles with sebaceous glands

Fig. 5

Represent the effect of monobenazone on psoriatic mice skin. This histological image provides evidence of improvement in psoriatic skin lesions following monobenzone treatment in mice

Fig. 6

Histopathological scores heatmap of skin tissue treatments

Fig. 7

Comparative analysis of total histopathological scores in skin tissue across various treatment modalities

Fig. 8

Comparative analysis of TNF-alpha and IL-6 cytokine levels in various treatment groups

Conclusion

In conclusion, our study demonstrates the promising therapeutic potential of monobenazone in the treatment of psoriasis-like skin lesions. The observed improvements in histopathological features, coupled with the reduction in pro-inflammatory cytokines, suggest that monobenazone may offer a novel approach to managing this challenging skin condition. While further research is needed to fully elucidate its mechanisms of action and optimize its clinical application, monobenazone represents an exciting avenue for future development in psoriasis therapy. The effect of monobenzone might involve key inflammatory pathways, such as NF-κB or the JAK/STAT axis, pivotal in the pathogenesis of psoriasis. Future studies exploring these mechanisms can help explain monobenzone’s action.

As we continue to unravel the complex pathogenesis of psoriasis, targeted approaches like monobenazone may pave the way for more effective and personalized treatment strategies, ultimately improving the quality of life for millions of individuals affected by this chronic inflammatory disease

Limitation

This study did not consider the effects of monobenzone on normal skin. While this would have provided important information on its safety profile, such assessments should be performed during further studies.