Biochanin A Attenuates Psoriasiform Inflammation by Regulating Nrf2/HO-1 Pathway Activation and Attenuating Inflammatory Signalling.

Abstract

Psoriasis is a long-term inflammatory skin condition marked by an overabundance of keratinocytes and the release of pro-inflammatory cytokines in the outer layer of skin. For the comprehensive management of intermediate to advanced psoriasis, innovative biological treatments have been developed. Products for the superficial therapy of mild to moderate psoriasis are still necessary, though. Trifolium pratense contains the isoflavone biochanin A (BCA), which exhibits antiviral, antioxidant, anti-carcinogenic, and anti-inflammatory properties, and helps protect the integrity and function of the endothelium. Although investigations have not shown that BCA is effective in treating psoriasis, it has been shown to slow down the breakdown of the skin barrier by regulating keratinocyte growth. We sought to clarify the basic mechanisms behind BCA's impact on psoriasis in vitro and in vivo using experimental research via regulating Nrf2/HO-1 signaling pathway. By subjecting human primary keratinocytes to psoriasis-related cytokines, psoriasis-like keratinocytes were produced. The CCK8 test was used in this investigation to assess cell viability. BCA reduced keratinocyte growth and inflammatory cascade stimulation produced by TNF-α and IL-6, according to in vitro investigations conducted on HaCaT cells. The in vivo findings showed that six days of BCA therapy significantly decreased the skin, hematological indicators, levels of NO, TBARS, histopathological, and pro-inflammatory factors of COX-2, iNOS, NF-κB pathway. It additionally influenced the protein content of pro-inflammatory cytokines such as IL-17, IL-23, IL-1β in the epidermis along with IL-6, TNF-α among the epidermis and serum. In addition, in contrast to the IMQ group, BCA improved the skin's level of Nrf2/HO-1 protein, anti-inflammatory cytokine IL-10, and antioxidant indicators like SOD, CAT, GST, GSH, GR, and Vit-C. Ultimately, our research shows that BCA was effective in treating psoriasis in pre-clinical animal models by activating the Nrf2/HO-1 pathway, leading to an increase in antioxidant and anti-inflammatory markers.