| Curcumin is a naturally occurring phytochemical present in Turmeric (a plant native to south India) and is a scarce diketones pigment. As a selective phosphorylase kinase inhibitor, curcumin is able to inhibit activation of kinds of serine/threonine protein kinase, such as Protein Kinase A, Protein Kinase C, Serine/arginine-Rich Protein specific Kinase, phosphorylase kinase, and tyrosine kinase, impact the intra-cellular signal transduction, exhibits multi-bioactivities:pro-apoptosis, anti-proliferation, anti-oxidant, anti-inflammatory, anti-microbial and anti-carcinogenic and so on.For curcumin’s water-insoluble character is concerned, it still have no intravenous administration application been reported. And almost existing clinical research data are based on oral administration for the way. But the poor bioavailability of curcumin was disappointing. The data from a curcumin phase I clinical study show that oral administration of curcumin3.6g/day was only able to reach a11.1±0.6nmol/L of the peak plasma concentration, while below this dose is not undetectable. For these reasons, even if curcumin has made clear its pharmacological effects in vitro and in vivo studies, it throws a gloom over curcumin’s applied research due to its poor bioavailability.Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders characterized by hyperproliferative keratinocytes and massive infiltration of leukocytes. It affects approximately25million people in North America and Europe and is likely the most prevalent immune-mediated skin disease in adults. Although the pathogenesis of psoriasis is not fully understood, there is growing evidence to indicate that the interleukin-23(IL-23)/IL-17A cytokine axis plays a critical role in the disease development. The high levels of IL-23, IL-21, IL-22and IL-17expression in psoriatic lesional skin can be detected both in mRNA and protein. And IL-23-induced changes in mouse skin share many characteristics with human psoriasis, such as erythema, epidermal hyperplasia (acanthosis sign), parakeratosis and infiltration of leukocytes, while the dermis layer of the inflammation and echinoderms sign is contributed by cytokine IL-22, this process needs participation of CCR6. IL-23-induced skin inflammation due to cytokines of IL-17family and their downstream implementation. There are still more cytokines, such as TNF-a, IL-1a, IL-1β, IL-6, IL-8, VEGF, and TGF-P, who involved in the pathogenesis of psoriasis.Numerous of cytokines participated pathogenesis of psoriasis and involved extremely complex signal transduction. It is well known that cytokines, such as IL-17A, IL-17F, TNF-a, and IL-6, related to the activation of NF-κB. The multi-targeted role of curcumin made it possible to impact on psoriasis complex signal transduction network, such as the inhibition of NF-κB activation, inhibition of STAT3phosphorylation. Taking into account the potential applications value of curcumin in the treatment of psoriasis and the superficial features of psoriatic lesions, this study designed to verified the basis of pharmacological effects of curcumin on KC cells, evaluated to therapeutic effect of topical administration of curcumin in psoriatic on psoriasis model in mice.Our results showed that the expression of anti-apoptotic proteins (IAP1, IAP2, Bcl-XL) was up-regulated by TNF-a but suppressed by curcumin in HaCaT cells. Because these proteins are regulated by NF-κB, we examined the role of curcumin in NF-κB activation. As expected, curcumin inhibited TNF-a-induced activation of NF-κB, including NF-κB-P65. Curcumin also inhibited the TNF-a-induced production of IL-6/IL-8in HaCaT cells. Poor absorption of curcumin contributes to its low bioavailability and then makes it extremely difficult to play a role in target cell. Reference to previous research foundation, in the original formula on the basis of using the other transdermal accelerator: azone, and adjust the proportion of the formula, we worked out successfully a stable curcumin gel preparation. With this curcumin gel preparation, we evaluated the treatment effects of curcumin on imiquimod induced psoriasis-like mouse mode, and obtained the exciting results. We found that topical use of a curcumin gel formulation strongly inhibited imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which was based on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in BALB/c mouse ear was significantly inhibited following curcumin treatment. Real-time PCR showed that mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6and TNF-a cytokines were decreased significantly by curcumin in ear skin, an effect similar to that of clobetasol. In addition, we found that curcumin may enhance the proliferation of epidermis y8T cells but inhibit dermal γδ T cell proliferation.This study investigated the effect of curcumin on psoriasis treatment and assessed its mechanism in vitro and vivo. And to achieve this target, a curcumin topical gel preparation was studied and improved. We observed the effects of curcumin in a psoriasis-like mouse model and its role on IL-23/IL-17A/IL-22axis first time, and compared with steroid hormones parallelly. For sure, all above that found the theoretical and experimental basis for the curcumin future development direction. |
PDF Full Text Request