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Study of the metabolism of S-allylmercaptocysteine to elucidate its metabolites and metabolic pathway in rats

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Abstract

S-allylmercaptocysteine (SAMC) is one of the characteristic sulfur constituents in aged garlic extract and has been shown to exert various pharmacological actions. However, because of the short half-life of SAMC, its metabolic profile and mode of action remain largely unclear. We investigated the metabolism of SAMC with the aim to identify its metabolites and metabolic pathway. After intravenous administration of SAMC to rats, the plasma and urine were examined using liquid chromatography–mass spectrometry (LC–MS) at various time points. The analysis of plasma led us to identify four SAMC metabolites, S-3-hydroxypropylcysteine, S-2-carboxyethylcysteine, S-3-hydroxypropylglutathione and N-acetyl-S-3-hydroxypropylcysteine. The ex vivo and in vitro metabolic studies using rat plasma and S9 fraction from liver or kidney revealed that SAMC was rapidly converted to diallylpolysulfides that are volatile and thus dissipate via lung and skin during circulation. We also found that diallylpolysulfides were further metabolized to glutathione S-conjugates, cysteine S-conjugates, and N-acetylated forms in the metabolic studies. In addition, we identified two N-acetylcysteine S-conjugates, N-acetyl-S-3-hydroxypropylcysteine and N-acetyl-S-2-carboxyethylcysteine in rat urine, the amount of which was estimated to be 10.7% of SAMC being administered. The present findings serve as the key step to elucidate the entire metabolism of SAMC and its mode of pharmacological action.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors deeply thank Dr. Takami Oka of Wakunaga Pharmaceutical Co., Ltd, for his helpful advice, encouragement and critical reading of the manuscript.

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  1. Central Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda–cho, Akitakata–shi, Hiroshima, 739-1195, Japan

    Masato Nakamoto & Kayo Kunimura

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  1. Masato Nakamoto
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Correspondence to Masato Nakamoto.

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Nakamoto, M., Kunimura, K. Study of the metabolism of S-allylmercaptocysteine to elucidate its metabolites and metabolic pathway in rats. Eur Food Res Technol 249, 1377–1389 (2023). https://doi.org/10.1007/s00217-023-04220-1

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  • DOI: https://doi.org/10.1007/s00217-023-04220-1

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