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      Soy Isoflavone Genistein Inhibits an Axillary Osmidrosis Risk Factor ABCC11: In Vitro Screening and Fractional Approach for ABCC11-Inhibitory Activities in Plant Extracts and Dietary Flavonoids

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          Abstract

          Axillary osmidrosis (AO) is a common chronic skin condition characterized by unpleasant body odors emanating from the armpits, and its aetiology is not fully understood. AO can seriously impair the psychosocial well-being of the affected individuals; however, no causal therapy has been established for it other than surgical treatment. Recent studies have revealed that human ATP-binding cassette transporter C11 (ABCC11) is an AO risk factor when it is expressed in the axillary apocrine glands—the sources of the offensive odors. Hence, identifying safe ways to inhibit ABCC11 may offer a breakthrough in treating AO. We herein screened for ABCC11-inhibitory activities in 34 natural products derived from plants cultivated for human consumption using an in vitro assay system to measure the ABCC11-mediated transport of radiolabeled dehydroepiandrosterone sulfate (DHEA-S—an ABCC11 substrate). The water extract of soybean ( Glycine max) was found to exhibit the strongest transport inhibition. From this extract, via a fractionation approach, we successfully isolated and identified genistein, a soy isoflavone, as a novel ABCC11 inhibitor with a half-maximal inhibitory concentration value of 61.5 μM. Furthermore, we examined the effects of other dietary flavonoids on the ABCC11-mediated DHEA-S transport to uncover the effects of these phytochemicals on ABCC11 function. While further human studies are needed, our findings here about the natural compounds will help develop a non-surgical therapy for AO.

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          Bioactive flavonoids in medicinal plants: Structure, activity and biological fate

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            Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements.

            The pharmacokinetic behavior of naturally occurring isoflavones has been determined for the first time in healthy adults. We compared plasma kinetics of pure daidzein, genistein and their beta-glycosides administered as a single-bolus dose to 19 healthy women. This study demonstrates differences in the pharmacokinetics of isoflavone glycosides compared with their respective beta-glycosides. Although all isoflavones are efficiently absorbed from the intestinal tract, there are striking differences in the fate of aglycones and beta-glycosides. Mean time to attain peak plasma concentrations (t(max)) for the aglycones genistein and daidzein was 5.2 and 6.6 h, respectively, whereas for the corresponding beta-glycosides, the t(max) was delayed to 9.3 and 9.0 h, respectively, consistent with the residence time needed for hydrolytic cleavage of the glycoside moiety for bioavailability. The apparent volume of distribution of isoflavones confirms extensive tissue distribution after absorption. Plasma genistein concentrations are consistently higher than daidzein when equal amounts of the two isoflavones are administered, and this is accounted for by the more extensive distribution of daidzein (236 L) compared with genistein (161 L). The systemic bioavailability of genistein [mean AUC = 4.54 microg/(mL x h)] is much greater than that of daidzein [mean AUC = 2.94 microg/(mL x h)], and bioavailability of these isoflavones is greater when ingested as beta-glycosides rather than aglycones as measured from the area under the curve of the plasma appearance and disappearance concentrations. The pharmacokinetics of methoxylated isoflavones show distinct differences depending on the position of the methoxyl group in the molecule. Glycitin, found in two phytoestrogen supplements, underwent hydrolysis of the beta-glycoside moiety and little further biotransformation, leading to high plasma glycitein concentrations. Biochanin A and formononetin, two isoflavones found in one phytoestrogen supplement, were rapidly and efficiently demethylated, resulting in high plasma genistein and daidzein concentrations typically observed after the ingestion of soy-containing foods. These differences in pharmacokinetics and metabolism have implications for clinical studies because it cannot be assumed that all isoflavones are comparable in their pharmacokinetics and bioavailability. An analysis of 33 phytoestrogen supplements and extracts revealed considerable differences in the isoflavone content from that claimed by the manufacturers. Plasma concentrations of isoflavones show marked qualitative and quantitative differences depending on the type of supplement ingested. These studies indicate a need for improvement in quality assurance and standardization of such products.
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              Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature

              Soyfoods have long been recognized as sources of high-quality protein and healthful fat, but over the past 25 years these foods have been rigorously investigated for their role in chronic disease prevention and treatment. There is evidence, for example, that they reduce risk of coronary heart disease and breast and prostate cancer. In addition, soy alleviates hot flashes and may favorably affect renal function, alleviate depressive symptoms and improve skin health. Much of the focus on soyfoods is because they are uniquely-rich sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor modulators. Despite the many proposed benefits, the presence of isoflavones has led to concerns that soy may exert untoward effects in some individuals. However, these concerns are based primarily on animal studies, whereas the human research supports the safety and benefits of soyfoods. In support of safety is the recent conclusion of the European Food Safety Authority that isoflavones do not adversely affect the breast, thyroid or uterus of postmenopausal women. This review covers each of the major research areas involving soy focusing primarily on the clinical and epidemiologic research. Background information on Asian soy intake, isoflavones, and nutrient content is also provided.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                14 August 2020
                August 2020
                : 12
                : 8
                : 2452
                Affiliations
                [1 ]Frontier Laboratories for Value Creation, Sapporo Holdings Ltd., 10 Okatome, Yaizu, Shizuoka 425-0013, Japan; hiroki.saito@ 123456sapporoholdings.co.jp (H.S.); hiroshi.hirata@ 123456sapporoholdings.co.jp (H.H.); ami.ota@ 123456sapporoholdings.co.jp (A.O.-K.); yoichi.tsuchiya@ 123456sapporoholdings.co.jp (Y.T.)
                [2 ]Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; tappei-tky@ 123456umin.ac.jp (T.T.); suzukihi-tky@ 123456umin.ac.jp (H.S.)
                Author notes
                [* ]Correspondence: ytoyoda-tky@ 123456umin.ac.jp
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-7411-0531
                https://orcid.org/0000-0002-3868-9320
                Article
                nutrients-12-02452
                10.3390/nu12082452
                7468911
                32824087
                e582e797-d28b-4273-bb9f-8d55d6944e2d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 July 2020
                : 12 August 2020
                Categories
                Article

                Nutrition & Dietetics
                axillary osmidrosis treatment,bioactivity investigation of food extract,body odor,food ingredient,functional food,glycine max,health promotion,mrp8,phytochemicals,transporter

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