Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Abstract

Psoriasis is a chronic autoimmune disease featured by patches on the skin. It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features. Apigenin (API) is a natural flavonoid with anti-inflammatory and immunoregulatory properties. Therefore, we speculated that API can ameliorate psoriasis, and determined its effect on the development of psoriasis by using imiquimod (IMQ)-induced psoriasis mouse model. Our results showed that API attenuated IMQ-induced phenotypic changes, such as erythema, scaling and epidermal thickening, and improved splenic hyperplasia. Abnormal differentiation of immune cells was restored in API-treated mice. Mechanistically, we revealed that API is a key regulator of signal transducer activator of transcription 3 (STAT3). API regulated immune responses by reducing interleukin-23 (IL-23)/STAT3/IL-17A axis. Moreover, it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB (NF-κB) pathway. Furthermore, API reduced expression of inflammatory cytokines through inactivation of NF-κB. Taken together, our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Bitter Phytochemicals as Novel Candidates for Skin Disease Treatment

“…In the skin, apigenin showed beneficial effects in addressing inflammatory conditions and certain types of skin cancer. In a mouse model of imiquimod-induced psoriasis-like skin lesions, apigenin decreased erythema, scaling, and Psoriasis Area and Severity Index (PASI) score, and it also inhibited NF-kB activation and the IL-23/STAT3/IL-17A pathway [154]. Furthermore, apigenin decreased protein expressions of TNF-α, IL-1β, and IL-6 at the skin level [154].…”

“…In a mouse model of imiquimod-induced psoriasis-like skin lesions, apigenin decreased erythema, scaling, and Psoriasis Area and Severity Index (PASI) score, and it also inhibited NF-kB activation and the IL-23/STAT3/IL-17A pathway [154]. Furthermore, apigenin decreased protein expressions of TNF-α, IL-1β, and IL-6 at the skin level [154]. Similarly, in a mouse model of induced atopic dermatitis, apigenin decreased skin lesions, alleviated cutaneous symptoms, and reduced IgG1 and IgE levels in mouse serum [155].…”

“…TAS2R14 [132,142] TAS2R39 [132] Psoriasis [154] Atopic dermatitis [155] Melanoma [156][157][158][159][160][161][162] Negative impact on the reproductive system [273,274] Low water and non-polar solubility [275] Poor oral bioavailability [276] Amarogentin TAS2R1 [43],TAS2R4 [43], TAS2R39 [43],TAS2R43 [43], TAS2R46 [43],TAS2R47 [43],…”