Therapeutic effects of shikonin on skin lesions in mouse models of allergic dermatitis and wound

Abstract

Aim: The aim of this study was to examine the beneficial effects of shikonin on skin lesions in mouse models of allergic dermatitis and wound. Methods: Mouse models of allergic dermatitis and wound were generated by spreading an allergic-inducing reagent on the dorsal skin and earflaps, and by punching the dorsal skin, respectively. The effects of shikonin on allergic dermatitis was evaluated on frequency of scratching, clinical severity of dermatitis and immunohistochemistry. The effect of shikonin on wound healing compared with steroid was evaluated by the size of the wound area. Results: Shikonin treatment not only improved allergic dermatitis, but also prevented the onset of allergic dermatitis. Furthermore, shikonin promoted wound healing in a mouse model of skin wound. In contrast, steroid (betamethasone) treatment, which is often applied to treat allergic dermatitis, delayed wound healing in the mouse model of allergic dermatitis. Conclusion: Shikonin can be used as a new therapeutic agent for the treatment of allergic dermatitis including atopic dermatitis.

The emerging role of PKM in keratinocyte homeostasis and pathophysiology

“…PKM2 predominates in highly proliferative tissues of both healthy and pathological nature, including the epidermis, and its expression may increase in response to states of disease or stress, including skin disorders [1,19]. For example, Liu et al.…”

“…Enhanced aerobic glycolysis was evidenced by an increase in glucose uptake and lactate production both in vitro and in vivo using experimental models of psoriasis. (D) Under inflammatory conditions, inhibition of PKM2 using pharmacological (benserazide or shikonin) or genetic (shRNA or Cre-loxP) approaches led to a reduction in both keratinocyte inflammation and proliferation, concomitant with a reduction in glucose uptake and lactate production [19,[22][23][24]. (E, F) In the study by Nold et al, HaCaT cells were subjected to CRISPR/Cas9-mediated editing of the PKM exon 9 or exon 10 3 0 splice site.…”

“…PKM2 predominates in highly proliferative tissues of both healthy and pathological nature, including the epidermis, and its expression may increase in response to states of disease or stress, including skin disorders [1,19]. For example, Liu et al [1] demonstrated that PKM2 overexpression reinforces glycolytic metabolism and keratinocyte hyperproliferation, which are key facets of psoriasis (Fig.…”

“…Supportively, treatment with shikonin, a well-established PKM2 inhibitor [20,21], has demonstrated promise for attenuating numerous skin pathologies, often by reducing inflammation and/or proliferation. Shikonin's benefits ranged from suppressing epidermal carcinogenesis [22,23] to improving psoriasis [1,8], allergic dermatitis [19] and wound healing [19,24], including human burn skin [24] (Fig. 1D).…”

Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing

“…Re-epithelialization was scored as: (0) absent, bright-red wound; (1) moderate presence of epithelialization surrounding granulation tissue, pink wound; (2) the presence of epithelialization exceeds that of granulation tissue, pale wound; and (3) fully healed wound [27][28][29]. Inflammation of the wound was determined by the presence of tissue bulging accompanied by erythema, and scored as (0) absent, (1) scant presence in the wound surroundings, (2) moderate presence outside the edges of the wound, and (3) completely surrounding the wound [30]. Each parameter was presented as a global score calculated by averaging the scores of all evaluated time-points.…”