Abstract
Microorganisms and plants produce bioactive metabolites that are potentially useful in the treatment of disease. We have designed and synthesized DHMEQ as a specific inhibitor of NF-κB based on the structure of epoxyquinomicin. It directly binds to NF-κB components to inhibit DNA-binding and was shown to be endowed with inhibiting activity in various inflammatory and cancer models in experimental animals. It was also effective to improve the success of islet transplantation especially when administered to donor mice. We have also isolated from the leaves of Ervatamia microphylla conophylline, a compound that induces differentiation of beta cells from the precursor cells and was recently found to suppress islet fibrosis in diabetes model rats.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Umezawa K, Kawakami M, Watanabe T (2003) Molecular design and biological activities of protein-tyrosine phosphatase inhibitors. Ther Pharmacol 99:15–24
Suzuki E, Sugiyama C, Umezawa K (2009) Inhibition of inflammatory mediator secretion by (-)-DHMEQ in mouse bone marrow-derived macrophages. Biomed Pharmacother 63:351–358
Takahashi T, Matsumoto S, Matsushita M, Kamachi H, Tsuruga Y, Kasai H, Watanabe M, Ozaki M, Furukawa H, Umezawa K, Todo S (2010) Donor pretreatment with DHMEQ improves islet transplantation. J Surg Res 163: e23–34
Umezawa K (2011) Possible role of peritoneal NF-κB in peripheral inflammation and cancer: lessons from the inhibitor DHMEQ. Biomed Pharmacother 65:252–259
Umezawa K, Hiroki A, Kawakami M, Naka H, Takei I, Ogata T, Kojima I, Koyano T, Kowithayakorn T, Pang HS, Kam TS (2003) Induction of insulin production in rat pancreatic acinar carcinoma cells by conophylline. Biomed Phamacother 57:341–350
Ogata T, Li L, Yamada S, Yamamoto Y, Tanaka Y, Takei I, Umezawa K, Kojima I (2004) Promotion of B cell differentiation by conophylline in fetal and neonatal rat pancreas. Diabetes 53:2596–2602
Fujii M, Takei I, Umezawa K (2009) Antidiabetic effect of plant extract containing conophylline by oral administration in streptozotocin-treated and Goto-Kakizaki rats. Biomed Pharmacother 63:710–716
Hisanaga E, Park KY, Yamada S, Hashimoto H, Takeuchi T, Mori M, Seno M, Umezawa K, Takei I, Kojima I (2008) A simple method to induce differentiation of murine bone marrow mesenchymal cells to insulin-producing cells using conophylline and betacellulin-delta4. Endocrine J 55:535–543
Saito R, Yamada S, Yamamoto Y, Kodera T, Hara A, Tanaka Y, Kimura F, Takei I, Umezawa K, Kojima I (2012) Conophylline suppresses pancreatic stellate cells and improves islet fibrosis in Goto-Kakizaki rats. Endocrinology 153:621–630
Atsumi S, Nagasawa A, Koyano T, Kowithayakorn T, Umezawa K (2003) Suppression of TGF-β signaling by conophylline via upregulation of c-Jun expression. Cell Mol Life Sci 60:2516–2525
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sidthipong, K., Todo, S., Takei, I. et al. Screening of new bioactive metabolites for diabetes therapy. Intern Emerg Med 8 (Suppl 1), 57–59 (2013). https://doi.org/10.1007/s11739-013-0922-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11739-013-0922-1