Improvement effects of a novel Chinese herbal formula in imiquimod and IL-23-stimulated mouse models of psoriasis

Abstract

Background: Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades.

Aims: To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats.

Methods: Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined.

Results: The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application.

Conclusions: ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.

Keywords: IL-23/Th17 axis; Imiquimod; Inflammation skin disease formula; Jak/Stat pathway; MAPK pathway; Psoriasis.

Fig. 1

Effects of ISDF on IMQ-induced mouse psoriasis model. A The procedure of IMQ inducement and ISDF treatment in mice. B Body weight. C Dorsal skin thickness. D PASI score. E Represent photos. F H&E-stained photos. Magnification at 100 × . G Epidermal thickness (indicated by arrow). Data were presented as mean ± SEM (n = 8). *p < 0.05 and **p < 0.01 compared with the IMQ group

Fig. 2

Effects of ISDF on inflammatory response induced by IMQ in mice. A Serum levels of IL-17A, IL-22 and IL-6. B Skin levels of IL-17A, IL-22 and IL-4. C Gene expression of IL-4, IL-6, IL-1β and TNF. D, E Protein expression of NF-κB and MAPK pathways. D Western blotting bands. E Results of quantitative analysis. Data were presented as mean ± SEM (n = 8). *p < 0.05 and **p < 0.01 compared with the IMQ group

Fig. 3

Effects of ISDF on IL-23-induced mouse psoriasis model. A The procedure of IL-23 inducement and ISDF treatment in mice. B Body weight. C Dorsal skin thickness. D Represent photos. E PASI score. F H&E-stained photos. Magnification at 100 × . G Epidermal thickness (indicated by arrow)

Fig. 4

Effects of ISDF on inflammatory response induced by IL-23 in mice. A Serum levels of IL-17A and IL-22, and the level of IL-23 in the injected skin. B, C Protein expression of Jak/Stat3 pathways. B Results of quantitative analysis. C Western blotting bands. Data were presented as mean ± SEM (n = 8). *p < 0.05 and **p < 0.01 compared with the IL-23 group

Fig. 5

The pharmacokinetics study of ISDF in rats. A Chromatogram of plasma of untreated rats at 278 nm. B Chromatogram of baicalin standard at 278 nm. C Chromatogram of plasma of the ISDF-treated rats at 278 nm. D Plasma concentration–time curve of baicalin in the ISDF-treated rats. E Chromatogram of erythrocytes of untreated rats at 264 nm. F Chromatogram of erythrocytes of the ISDF-treated rats at 264 nm. G Chromatogram of berberine standard at 264 nm. H Erythrocytes concentration–time curve of berberine in the ISDF-treated rats

Fig. 6

Action mechanisms of ISDF in the IMQ/IL-23-induced psoriasis mice model