Novel inhibitors for histidine decarboxylase from plant components

Main Article Content

Yoko Nitta Hiroe Kikuzaki Hiroshi Ueno



Histamine is a bioactive amine that affects a wide range of biological activities in the human body.  In this review, we discuss the active components of spices and herbs that can inhibit histidine decarboxylase (HDC), an enzyme that catalyzes synthesis of histamine.  We screened 21 spices and 122 medicinal plants by carrying out inhibition assays with recombinant human HDC.  Among spices, flavonoid glycosides of allspice, quercetin 3-O-b-D-glucuronide 6"-methyl ester and quercetin 3-O (2-O-galloyl) glucoside, at 1 mM inhibited HDC by 64 and 55%, respectively.  Among medicinal plants, ellagitannins of meadowsweet, rugosin D, rugosin A, rugosin A methyl ester, and tellimagrandin II inhibited HDC significantly with Ki values of approximately 0.35-1 mM.  These results indicate that plant components are promising sources for novel inhibitors of HDC.

Article Details

How to Cite
NITTA, Yoko; KIKUZAKI, Hiroe; UENO, Hiroshi. Novel inhibitors for histidine decarboxylase from plant components. International Biology Review, [S.l.], v. 1, n. 2, aug. 2017. ISSN 2572-7168. Available at: <>. Date accessed: 19 nov. 2017. doi:
histamine; inhibitors; flavonoid glycoside; ellagitannin; medicinal plant
Review Articles


1. Savany A, Cronenberger L. Purification and detection of multiple forms of histidine decarboxylase in rat gastric mucosa. Biochim Biphys Acta. 1978;526:247-58.

2. Hammar L, Hjerten S. Purification and immunochemical analysis of histidine decarboxylase from murine mastocytoma. Agents and Actions. 1980;10(1/2):92-3.

3. Martin SAM, Bishop JO. Purification and characterization of histidine decarboxylase from mouse kidney. Biochem J. 1986;234:349-54.

4. Dartsch C, Chen D, Hakanson R, Persson L. Histidine decarboxylase in rat stomach ECL cells: relationship between enzyme activity and different molecular forms. Regul Pept. 1999;81(1-3):41-8.

5. Safina F, Tanaka S, Inagaki M, Tsuboi K, Sugimoto Y, Ichikawa A. Expression of L-histidine decarboxylase in mouse male germ cells. J Biol Chem. 2002;277(16):14211-5.

6. Ercan-Sencicek AG, Stillman AA, Ghosh AK, Bilguvar K, O'Roak BJ, Mason CE, et al. L-histidine decarboxylase and Tourette's syndrome. N Engl J Med. 2010;362(20):1901-8.

7. Taguchi Y, Watanabe T, Kubota H, Hayashi H, Wada H. Purification of histidine decarboxylase from the liver of fetal rats and its immunochemical and immunohistochemical characterization. J Biol Chem. 1984;259(8):5214-21.

8. Ohmori E, Fukui T, Imanishi N, Yatsunami K, Ichikawa A. Purification and characterization of L-histidine decarboxylase from mouse mastocytoma P-815 cells. J Biochem. 1990;107:834-9.

9. Komori H, Nitta Y, Ueno H, Higuchi Y. Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase. J Biol Chem. 2012;287(34):29175-83.

10. Ohshita J, Okigami H, Nitta Y, Ueno H. Evaluation of inhibitory effects of spice-derived natural extracts on histidine decarboxylase. J Home Econ Jpn. 2007;58:17-22.

11. Nitta Y, Kikuzaki H, Ueno H. Inhibitory activity of Pimenta dioica extracts and constituents on recombinant human histidine decarboxylase. Food Chemistry. 2009;113(2):445-9.

12. Rodriguez-Caso C, Rodriguez-Agudo D, Sanchez-Jimenez F, Medina MA. Green tea epigallocatechin-3-gallate is an inhibitor of mammalian histidine decarboxylase. Cell Mol Life Sci. 2003;60(8):1760-3.

13. Nitta Y, Kikuzaki H, Ueno H. Food components inhibiting recombinant human histidine decarboxylase activity. J Agric Food Chem. 2007;55(2):299-304.

14. Nitta Y, Ito K, Ueno H. Inhibitory activity of medicinal plants toward human histidine decarboxylase. J Home Econ Jpn. 2008;12:1011-6.

15. Nitta Y, Kikuzaki H, Azuma T, Ye Y, Sakaue M, Higuchi Y, et al. Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylase. Food Chem. 2013;138(2-3):1551-6.

16. Nitta Y, Yasukata F, Kitamoto N, Ito M, Sakaue M, Kikuzaki H, et al. Inhibition of Morganella morganii Histidine Decarboxylase Activity and Histamine Accumulation in Mackerel Muscle Derived from Filipendula ulumaria Extracts. J Food Prot. 2016;79(3):463-7.

17. FDA. Fish and Fishery Products Hazards and Controls Guidance - Fourth Edition. 2016.

18. Moilanen J, Karonen M, Tahtinen P, Jacquet R, Quideau S, Salminen JP. Biological activity of ellagitannins: Effects as anti-oxidants, pro-oxidants and metal chelators. Phytochemistry. 2016;125:65-72.

Most read articles by the same author(s)

Obs.: This plugin requires at least one statistics/report plugin to be enabled. If your statistics plugins provide more than one metric then please also select a main metric on the admin's site settings page and/or on the journal manager's settings pages.