Orobol, A Derivative of Genistein, Inhibits Heat-Killed Propionibacterium acnes-Induced Inflammation in HaCaT Keratinocytes

Acne is a chronic skin disease that typically occurs in the teens and twenties, and its symptoms vary according to age, sex, diet, and lifestyle. The condition is characterized by hyperproliferation of keratinocytes in the epidermis, sebum overproduction, excessive growth of Propionibacterium acnes, and P. acnes-induced skin inflammation. Interleukin (IL)-1α and IL-6 are predominant in the inflammatory lesions of acne vulgaris. These cytokines induce an inflammatory reaction in the skin in the presence of pathogens or stresses. Moreover, IL-1α accelerates the production of keratin 16, which is typically expressed in wounded or aberrant skin, leading to abnormalities in architecture and hyperkeratinization. Orobol (3’,4’,5,7-tetrahydroxyisoflavone) is a metabolite of genistein that inhibited the P. acnes-induced increases in IL-6 and IL-1α levels in human keratinocytes (HaCaTs) more effectively compared with salicylic acid. In addition, orobol decreased the IL-1α and IL-6 mRNA levels and inhibited the phosphorylation of inhibitor of kappa-B kinase, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and mitogen-activated protein kinase induced by P. acnes. Finally, the expression of Ki67 was decreased by orobol. Thus, orobol ameliorated the inflammation and hyperkeratinization induced by heat-killed P. acnes and thus has potential for use in functional foods and cosmetics.