Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

Abstract

Psoriasis is an uncontrolled, long-lasting inflammatory dermatosis distinguished by thickened, erythematous, and flaky skin lesions. Massive amounts of inflammatory cytokines are produced when immune system imbalances are driven by genetic and environmental triggers. Vinpocetine (VNP), a man-made analogue of the compound vincamine found in the dwarf periwinkle herb, has robust anti-inflammatory, immunomodulatory, and anti-oxidative effects; alleviates the epidermal penetration of immune cells, such as eosinophils and neutrophils; and abolishes the generation of pro-inflammatory molecules.

Objective: This study was aimed at exploring the effects of long-term topical VNP, both alone and co-administered with clobetasol propionate, in an imiquimod-induced mouse model of psoriasiform dermatitis.

Methods: The study protocol consisted of 48 Swiss albino mice, randomly divided into six groups of eight mice each. In group I, petroleum jelly was administered daily for 8 days. In group II, imiquimod was administered topically at 62.5 mg daily for 8 days. In groups III, VI, V, and VI, 0.05% clobetasol propionate, 1% VNP, 3% VNP, and 3% VNP plus 0.05% clobetasol were administered topically for an additional 8 days after the induction, thus resulting in a total trial length of 16 days.

Results: Topical VNP at various doses alleviated the severity of imiquimod-induced psoriatic lesions-including erythema, silvery-white scaling, and thickening-and reversed the histopathological abnormalities. Moreover, imiquimod-exposed animals treated with VNP showed markedly diminished concentrations of inflammatory biomarkers, including tumour necrosis factor-α, interleukin (IL)-8, IL-17A, IL-23, IL-37, nuclear factor-kappa B (NF-κB), and transforming growth factor-β1.

Conclusion: This research provides new evidence that VNP, alone and in combination with clobetasol, may serve as a potential adjuvant for long-term management of autoimmune and autoinflammatory skin diseases, particularly psoriasis, by attenuating psoriatic lesion severity, suppressing cytokine generation, and limiting NF-κB-mediated inflammation.

Keywords: Antipsoriatic therapy; Imiquimod; Immune-mediated dermatoses; Inflammatory skin diseases; Mouse model of psoriasis; Vinpocetine.

Figure 1

Severity of imiquimod-triggered psoriasiform dermatitides. Scale bars = 100 mm.

Figure 2

Degree of imiquimod-induced erythema. A: No lesion (0 days), B: slightly pink (2nd day), C: pink (4th day), D: red (6th day), E: dark red (8th day). Scale bars = 100 mm.

Figure 3

Severity scores of psoriasiform skin lesions in mouse groups. Scale bars = 100 mm.

Figure 4

A: Effects of the investigated drugs on erythema. B: Effects of the investigated drugs on scaling. C: Effects of the investigated drugs on dorsal skin thickness. D: Effects of the investigated drugs on right ear skin thickness. Data are presented as mean ± SD. IMQ = imiquimod, CLO = clobetasol, and CLO + VNP = clobetasol plus vinpocetine. ∗p < 0.001 compared with healthy controls; ∗∗p < 0.01 compared with the IMQ 5% induction group; #p < 0.05 compared with the 0.05% CLO group, n = 8.

Figure 5

A: Effects of the investigated drugs on total cumulative PASI scores after a continuous 16-day therapeutic regimen. B: Effects of the investigated drugs on Baker's scores after a continuous 16-day therapeutic regimen. Data are presented as mean ± SD. ∗p < 0.001 compared with healthy controls; ∗∗p < 0.01 compared with the IMQ 5% induction group; #p < 0.05 compared with the 0.05% CLO group, n = 8.

Figure 6

Mean tissue concentrations of TNF-α and IL-17A. IMQ = imiquimod, CLO = clobetasol, VNP = vinpocetine, CLO + VNP = clobetasol plus vinpocetine. Data are shown as mean ± SD. ∗p < 0.001 compared with the control group; ∗∗p < 0.01 compared with the IMQ induction group; #p < 0.05 compared with the 0.05% CLO group, n = 8.

Figure 7

Mean tissue concentrations of IL-8, NF-κB, and TGF-β1. IMQ = imiquimod, CLO = clobetasol, VNP = vinpocetine, CLO + VNP = clobetasol plus vinpocetine. Data are shown as mean ± SD. ∗p < 0.001 compared with the control group; ∗∗p < 0.01 compared with the IMQ induction group; #p < 0.05 compared with the 0.05% CLO group, n = 8.

Figure 8

Histological skin sections of mouse groups stained with haematoxylin and eosin at 10× magnification. Group 1 (control) showed normal skin structures, including the keratin skin layers (yellow line), epidermis (red line), dermis (green line), and sebaceous glands (blue line). Group II (IMQ group) tissue demonstrated hallmarks of psoriasis, including marked epidermal inflammatory processes (yellow line), prominent rete processes thinning (red line), intense hyperkeratotic lesions (green line), and marked acanthotic alterations (blue line). Group III (CLO group) showed mild psoriasis inflammation (yellow line), moderate rete peg lengthening (red line), mild hyperkeratotic lesions (green line), and mild acanthotic changes (blue line). Mice subjected to 1% VNP (group IV) exhibited modest inflammation (yellow line), mild extension of rete pegs (red line), minor hyperkeratotic lesions (green line), and modest acanthotic modifications (blue line). Group V (3% VNP) mice had mild skin inflammation (yellow line), absence of rete ridge processes (red line), absence of hyperkeratotic signs (green line), and absence of acanthotic alterations (blue line). Mice in group V (CLO + VNP) displayed modest epidermal inflammation (yellow line), absence of rete ridge processes (red line), absence of hyperkeratotic signs (green line), and a lack of acanthotic changes (blue line).