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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.

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??M. 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.

SUBMITTER: Saito H

PROVIDER: S-EPMC7468911 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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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.

Saito Hiroki H Toyoda Yu Y Hirata Hiroshi H Ota-Kontani Ami A Tsuchiya Youichi Y Takada Tappei T Suzuki Hiroshi H

Nutrients 20200814 8

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 ...[more]

PMID: 32824087

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Project description:Two types of cerumen occur in humans: the wet type with brownish, sticky earwax, and the dry type with a lack of or reduced ceruminous secretion. The wet type is common in populations of European and African origin, while the dry type is frequently seen in Eastern Asian populations. An association between axillary odor and the wet-type earwax was first identified approximately 70 years ago. The data were based on a phenotypical analysis of the two phenotypes among the Japanese by a researcher or by self-declaration of the subjects examined, and were not obtained using definite diagnostic methods. Recently, we identified a single-nucleotide polymorphism (SNP; rs17822931) of the ABCC11 gene as the determinant of the earwax types. In the present study, to determine whether the SNP can serve as a diagnostic marker for axillary osmidrosis (AO), we examined genotypes at rs17822931 in 79 Japanese AO individuals. AO was defined here as a clinical condition of individuals with a deep anxiety regarding axillary odor and had undergone the removal of bilateral axillary apocrine glands.A comparison of the frequencies of genotypes at rs17822931 in the 79 AO individuals and in 161 Japanese from the general population showed that AO was strongly associated with the wet earwax genotype. A total of 78 (98.7%) of 79 AO patients had either the GG or GA genotype, while these genotypes were observed in 35.4% (57/161) of the subjects from the general population (p < 1.1 x 10(-24), by Fisher's exact test).The strong association between the wet-earwax associated ABCC11-genotypes (GG and GA) and AO identified in this study indicates that the genotypes are good markers for the diagnosis of AO. In addition, these results suggest that having the allele G is a prerequisite for the axillary odor expression. In other words, the ABCC11 protein may play a role in the excretory function of the axillary apocrine gland. Together, these results suggest that when an AO individual visiting a hospital is diagnosed with dry-type earwax by ABCC11-genotyping, surgical removal of their axillary glands may not be indicated.

Project description:Apocrine osmidrosis (AO) is a chronic, recurrent, and disturbing disease characterized by malodorous secretion from apocrine glands. Despite various conservative and nonsurgical treatments, surgical removal of apocrine glands remains the cornerstone for AO treatment. Conventional suction-assisted cartilage shaver is effective; however, there are several risks and complications. Hence, we modified the conventional method to achieve better effectiveness and reduce complications. This paper aims to evaluate the clinical effectiveness and the complications arising from the modified suction-assisted cartilage shaver for AO. Thirty-nine patients (M/F=11/28, average age 26.3 years) received this surgical treatment for AO from 2013 to 2017 in the Department of Dermatology at Kaohsiung Chang Gung Memorial Hospital, Taiwan. A suction-assisted cartilage shaver was introduced for the ultimate removal of the subcutaneous tissue containing the apocrine glands. A 0.5 cm incision was made in the center of the identified elliptical surgical area at each axilla. After defatting, the incision was closed primarily. The defatting skin was anchored to the axillary fascia by using 4-0 sutures without drains. We then evaluated the clinical efficacy and complications. The mean duration of follow-up was 31.8 months (12-68 months). Among patients receiving the modified cartilage shaving for AO, 92.3% achieved excellent-to-good results, 5.1% had acceptable results, and 2.6% had fair results. None of them experienced poor clinical efficacy. There was no skin necrosis, hematoma, nor wound infection after the surgery. There were no recurrences in all these patients 2 years after the surgery. This modified suction-assisted cartilage shaver for AO results in good efficacy, a low complication rate, and a low recurrence rate. The method is superior to the conventional one due to tissue glue-free procedure, greater comfort in postoperative care, minimal wounds, less hematoma, and less skin necrosis. The clinical study registration number of this study is NCT03793374.

Project description:Axillary osmidrosis (AO) is a common disease that causes patients to develop malodor and occurs worldwide. There is a lack of uniform standards to evaluate the severity of the odor and identify a sensitive and convenient method to determine the therapeutic effect of AO treatments in a clinical setting. In the present study, the association between pH value and disease severity was investigated and the potential pathogenic bacteria and probiotic pathogens of AO were further examined. A total of 32 patients with bilateral AO and 32 normal healthy controls were recruited for the present study. The odor was investigated using the traditional method (TM) and our groups newly developed Lu swab method (LSM) and according to the results, the cases were assigned a score on a 4-point scale. The patients' scores and pH value were recorded. The microbiological compositions of the affected sites were determined using 16S rDNA sequencing. The mean LSM score was higher compared with the mean TM score (P<0.05). Furthermore, the mean axillary pH value was higher in patients with AO compared with that in healthy subjects (P<0.0001), and the mean pH value of patients with high disease severity was higher compared with that in patients with moderate disease severity (P<0.001). In the microecological flora, the proportion of Staphylococcus species on patients with AO was significantly lower compared with that on normal controls (P<0.0001), while the proportion of Corynebacterium and Anaerococcus was significantly higher compared with that on normal controls (P<0.01 and P<0.001, respectively). In conclusion, LSM provided a higher sensitivity for evaluating odor severity than the TM and may be suitable for use in a clinical setting. The pH value was positively associated with AO severity. Staphylococcus may be an appropriate probiotic for the treatment of AO, while Corynebacterium and Anaerococcus may be causative pathogens of AO. The present study was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR2000037275).

Dataset Information

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.

Publications

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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