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Ergot alkaloids in sclerotia collected in Japan: synthetic profiles and induction of apoptosis by Clavine-type compounds

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Abstract

The genus Claviceps (Clavicipitaceae) is famous for producing ergot alkaloids (EAs) in sclerotia. EAs can cause ergotism, resulting in convulsions and necrosis when ingested, making these compounds a serious concern for food safety. Agroclavine (2), a typical Clavine-type EA, is a causative agent of ergotism and is listed as a compound to be monitored by the European Food Safety Authority. Clavine-type EAs are known to cause cytotoxicity, but the mechanism has not been elucidated. We performed annexin V and PI double-staining followed by flow cytometric analysis to detect apoptosis in HepG2 and PANC-1 cells after exposure to Clavine-type EAs. Clavine-type EAs reduced cell viability and induced apoptosis in both cell lines. We then performed LC–MS analysis of EAs from 41 sclerotia samples of Claviceps collected in Japan. 24 out of 41 sclerotia extracts include peptide-type EAs (ergosine/inine: 4/4′, ergotamine: 5, ergocornine/inine: 6/6′, α-ergocryptine/inine: 8/8′, and ergocristine/inine: 9/9′) and 19 sclerotia extracts among 24 sclerotia detected peptide type EAs include Clavine-type EAs (pyroclavine: 1, agroclavine: 2, festuclavine: 3) by LC–MS. We then performed a metabolomic analysis of the EAs in the sclerotia using principal component analysis (PCA). The PCA score plots calculated for EAs suggested the existence of four groups with different EA production patterns. One of the groups was formed by the contribution of Clavine-type EAs. These results suggest that Clavine-type EAs are a family of compounds requiring attention in food safety and livestock production in Japan.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number 16K07238.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo, Japan

    Yuji Doi, Daigo Wakana, Fumiaki Sato, Hisashi Takeda & Tomoo Hosoe

  2. Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan

    Satoshi Kitaoka

  3. Department of Environmental Science, Ishikawa Prefectural University, Nonoichi, Ishikawa, Japan

    Eiji Tanaka

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  1. Yuji Doi
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  2. Daigo Wakana
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  6. Hisashi Takeda
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Correspondence to Tomoo Hosoe.

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Doi, Y., Wakana, D., Kitaoka, S. et al. Ergot alkaloids in sclerotia collected in Japan: synthetic profiles and induction of apoptosis by Clavine-type compounds. J Nat Med 77, 306–314 (2023). https://doi.org/10.1007/s11418-022-01673-8

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  • DOI: https://doi.org/10.1007/s11418-022-01673-8

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