Acne is a chronic skin disease related to sebum and dead skin cells [1]. Usually beginning when hormone levels change during adolescence, acne occurs most commonly on the face, which has a high density of sebaceous glands, but also occurs at other sites, such as the neck, back, and chest [2]. In many cases, acne disappears upon reaching adulthood, although in some individuals, it lasts into adulthood [3]. In severe cases, the skin can become scarred. Severe acne can also cause psychological problems for young people who are sensitive about their appearance [4]. Acne is caused by a variety of factors and manifests with various clinical symptoms. Follicular hyperkeratinization, overgrowth of Propionibacterium acnes, inflammatory responses, and other genetic and environmental factors are involved [1]. Interleukin (IL)-1α and IL-6 are predominant in the inflammatory lesions of acne vulgaris. When the skin is affected by pathogens or damaged by stresses, these cytokines promote an inflammatory reaction [5]. IL-6 is a proinflammatory cytokine that mediates the immune response after stimulation by pathogen-associated molecular patterns. IL-1α accelerates the production of keratin 16, which is expressed in wounded or aberrant skin, leading to abnormalities in architecture and hyperkeratinization [2]. The keratinocytes in damaged epidermis express IL-1α [6], which stimulates the proliferation of neighboring cells and causes the skin to thicken. This may lead to hyperproliferation of keratinocytes and contribute to hyperkeratinization, aggravating acne [7,8]. Therefore, inhibition of P. acnes-induced IL-6 and IL-1α expression could relieve the symptoms of acne [9].Isoflavone is a flavonoid of soybean that is known as a phytoestrogen because it has a similar structure and activity to estrogen [10]. The isoflavone content of soy is ~0.1-0.4%. The soy isoflavones comprise genistein, daidzein, glycitein, and glycosides (Fig. 1A). The effect of isoflavones on health has been investigated [10]. Isoflavones are widely used in foods and cosmetics to alleviate the effects of skin aging and inflammation while 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...

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