Genkwanin glycosides are major active compounds in Phaleria nisidai extract mediating improved glucose homeostasis by stimulating glucose uptake into adipose tissues
Natural remedies are used as standalone treatments or complementary to modern medicine to control type 2 diabetes. In Palau, the traditional leaf decoction of Phaleria nisidai (PNe) is selected to treat hyperglycemia and its efficacy has been supported by a small clinical trial. As part of a reverse pharmacology approach, we here investigated the anti-diabetic potential of PNe and its bioactive compounds to alleviate insulin resistance in diet-induced obese, male mice. Dietary supplementation with PNe improves insulin sensitivity and promotes glucose uptake into adipose depots. In vitro, PNe triggers glucose disposal into murine and human adipocytes by upregulating Glut1 expression through PKC-ERK1/2 signaling. To identify active constituents in PNe, we conducted bioactivity-guided fractionations and deciphered genkwanin flavone glycosides as bioactive principles. Moreover, we demonstrate that the aglycone genkwanin (GE) improves insulin resistance to a comparable extent to the anti-diabetic drug, metformin. Our findings present GE as promising glucoregulatory phytochemical that facilitates glucose uptake into adipocytes, thereby reducing systemic glucose load and enhancing insulin sensitivity.
Authors
- Vissarion Efthymiou (ORCID: https://orcid.org/0000-0003-4327-7977)
- Victor Yano
- Caroline Moser
- Christian Wolfrum (ORCID: https://orcid.org/0000-0002-3862-6805)
- Carla Horváth
- Alexandra Kellenberger
- Adriano Rutz (ORCID: https://orcid.org/0000-0003-0443-9902)
- Lucia Balážová (ORCID: https://orcid.org/0000-0001-6765-7486)
- Hua Dong (ORCID: https://orcid.org/0000-0002-8235-726X)
- Jean‐Luc Wolfender (ORCID: https://orcid.org/0000-0002-0125-952X)
- Christopher Kitalong (ORCID: https://orcid.org/0000-0001-6312-3452)
- Isabel Reinisch (ORCID: https://orcid.org/0000-0002-3587-4635)
- Emerson Ferreira Queiroz (ORCID: https://orcid.org/0000-0001-9567-1664)
- Miroslav Baláž (ORCID: https://orcid.org/0000-0002-5740-4896)
- Joëlle Houriet (ORCID: https://orcid.org/0000-0003-4548-3168)
- Laurence Marcourt (ORCID: https://orcid.org/0000-0002-9614-1099)
- Aron N. Horvath (ORCID: https://orcid.org/0000-0002-4399-3095)
- Bertrand Graz (ORCID: https://orcid.org/0000-0003-2839-725X)
Institutions
- University of Geneva (CH)
- Nanyang Technological University (SG)
- ETH Zurich (CH)
- The Geneva Association (CH)
- Palau International Coral Reef Center (PW)
- Biomedical Research Center of the Slovak Academy of Sciences (SK)
- Universitätsklinik Balgrist (CH)
- Comenius University Bratislava (SK)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-16
- DOI
- https://doi.org/10.1038/s41467-025-62689-8
- Citations
- 3
- Primary Topic
- Tannin, Tannase and Anticancer Activities
- Type
- article
- Field-Weighted Citation Impact
- 3.79
Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eidgenössische Technische Hochschule Zürich
- Université de Genève
- Innosuisse - Schweizerische Agentur für Innovationsförderung