Title:Qingxiong Ointment and its Active Ingredient, Shikonin Treat Psoriasis
through HIF-1 Signaling Pathway
Volume: 30
Issue: 24
Author(s): Bin Zhang, Ge Yan, Fei Li, Ye Tang, Guangyao Xu, Yanan Zhang and Kan Ze*
Affiliation:
- Derpartment of Surgery VIII (Dermatology and Sores), Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai
University of Traditional Chinese Medicine, Shanghai 200071, China
Keywords:
Qingxiong ointment, shikonin, psoriasis, network pharmacology, HIF-1 signaling pathway, skin disorder.
Abstract:
Background: Psoriasis is a common chronic inflammatory skin disorder. Qingxiong ointment (QX)
is a natural medicinal combination frequently employed in clinical treatment of psoriasis. However, the active
ingredients of QX and its precise mechanisms of improving psoriasis remain unclear. This study elucidated the
effects of QX on an Imiquimod (IMQ)-induced mouse model of psoriasis while also exploring the regulation
of the active ingredient of QX, shikonin, on the HIF-1 signaling pathway in HaCaT cells.
Methods: A mouse model of psoriasis was established through topical application of IMQ, and the local therapeutic
effect of QX was evaluated using dorsal skin tissue with mouse psoriatic lesion and Psoriasis Area
Severity Index (PASI) scores, hematoxylin-eosin (HE) staining, and immunohistochemical staining. Elisa and
qPCR were employed to identify changes in the expression of inflammation-related factors in the mouse dorsal
skin. Immunofluorescence was used to assess changes in the expression of T cell subsets before and after
treatment with various doses of QX. HPLC was used to analyze the content of shikonin, and network pharmacology
was employed to analyze the main targets of shikonin. Immunofluorescence was used to identify the effects
of shikonin on the HIF-1 signaling pathway in IL6-induced psoriasis HaCaT cells. Finally, qPCR was
used to identify the differential expression of the HIF-1 signaling pathway in skin tissues.
Results: QX significantly reduces PASI scores on the backs of IMQ-induced psoriasis mice. HE staining reveals
alleviated epidermal thickness in the QX group. Immunohistochemical analysis shows a significant reduction
in ICAM, KI67, and IL17 expression levels in the QX group. Immunofluorescence results indicate
that QX can notably decrease the proportions of CD4+ T cells, γδ T cells, and CD8+ T cells while increasing
the proportion of Treg cells. Network pharmacology analysis demonstrates that the main targets of shikonin
are concentrated in the HIF-1 signaling pathway. Molecular docking results show favorable binding affinity between
shikonin and key genes of the HIF-1 signaling pathway. Immunofluorescence results reveal that
shikonin significantly reduces p-STAT3, SLC2A1, HIF1α, and NOS2 expression levels. qPCR results show
significant downregulation of the HIF-1 signaling pathway at cellular and tissue levels.
Conclusion: Our study revealed that QX can significantly reduce the dorsal inflammatory response in the
IMQ-induced psoriasis mouse model. Furthermore, we discovered that its main component, shikonin, exerts
its therapeutic effect by diminishing the HIF-1 signaling pathway in HaCaT cells.
