TY - JOUR
T1 - Dynamics of the Cellular Metabolism of Leptosperin Found in Manuka Honey
AU - Kato, Yoji
AU - Kawai, Masaki
AU - Kawai, Shota
AU - Okano, Yayako
AU - Rokkaku, Natsumi
AU - Ishisaka, Akari
AU - Murota, Kaeko
AU - Nakamura, Toshiyuki
AU - Nakamura, Yoshimasa
AU - Ikushiro, Shinichi
N1 - Funding Information:
This work was supported in part by tthe JSPS KAKENHI Grant-in-Aid for Scientific Research (B) (Y.K., A.I., T.N., Y.N., and S.I., 17H01960).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/10/2
Y1 - 2019/10/2
N2 - Leptosperin (methyl syringate β-d-gentiobioside) is abundantly found in manuka honey, which is widely used because of its antibacterial and possible anti-inflammatory activities. The aim of this study was to examine the molecular mechanism underlying the metabolism of leptosperin. Five phytochemicals (leptosperin, methyl syringate (MSYR), glucuronate conjugate of MSYR (MSYR-GA), sulfonate conjugate of MSYR (MSYR-S), and syringic acid (SYR)) were separately incubated with HepG2 and Caco-2 cells. After incubation, we found that the concentration of MSYR decreased, whereas the concentrations of SYR, MSYR-GA, and MSYR-S increased. By profiling with inhibitors and carboxylesterases (CES1, 2), we found that the conversion from MSYR to SYR was mediated by CES1. Lipopolysaccharide-stimulated RAW264.7 cells restored MSYR-GA to MSYR possibly by the secreted β-glucuronidase. All of the mice administered with leptosperin, MSYR, or manuka honey showed higher MSYR (13.84 ± 11.51, 14.29 ± 9.19, or 6.66 ± 2.30 nM) and SYR (1.85 ± 0.66, 6.01 ± 1.20, or 8.16 ± 3.10 nM) levels in the plasma compared with that of the vehicle controls (3.33 ± 1.45 (MSYR) and 1.85 ± 0.66 (SYR) nM). The findings of our study indicate that the unique metabolic pathways of these compounds may account for possible functionalities of manuka honey.
AB - Leptosperin (methyl syringate β-d-gentiobioside) is abundantly found in manuka honey, which is widely used because of its antibacterial and possible anti-inflammatory activities. The aim of this study was to examine the molecular mechanism underlying the metabolism of leptosperin. Five phytochemicals (leptosperin, methyl syringate (MSYR), glucuronate conjugate of MSYR (MSYR-GA), sulfonate conjugate of MSYR (MSYR-S), and syringic acid (SYR)) were separately incubated with HepG2 and Caco-2 cells. After incubation, we found that the concentration of MSYR decreased, whereas the concentrations of SYR, MSYR-GA, and MSYR-S increased. By profiling with inhibitors and carboxylesterases (CES1, 2), we found that the conversion from MSYR to SYR was mediated by CES1. Lipopolysaccharide-stimulated RAW264.7 cells restored MSYR-GA to MSYR possibly by the secreted β-glucuronidase. All of the mice administered with leptosperin, MSYR, or manuka honey showed higher MSYR (13.84 ± 11.51, 14.29 ± 9.19, or 6.66 ± 2.30 nM) and SYR (1.85 ± 0.66, 6.01 ± 1.20, or 8.16 ± 3.10 nM) levels in the plasma compared with that of the vehicle controls (3.33 ± 1.45 (MSYR) and 1.85 ± 0.66 (SYR) nM). The findings of our study indicate that the unique metabolic pathways of these compounds may account for possible functionalities of manuka honey.
KW - carboxylesterase
KW - leptosperin
KW - metabolism
KW - methyl syringate
KW - syringic acid
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U2 - 10.1021/acs.jafc.9b03894
DO - 10.1021/acs.jafc.9b03894
M3 - Article
C2 - 31496237
AN - SCOPUS:85072849318
SN - 0021-8561
VL - 67
SP - 10853
EP - 10862
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
IS - 39
ER -