Metabolomic study on the antihypertensive effect of S-1-propenylcysteine in spontaneously hypertensive rats using liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.
Aged garlic extract (AGE) has been shown to improve hypertension in both clinical trials and experimental animal models. However, the active ingredient of AGE remains unknown. In the present study, we investigated the antihypertensive effects of AGE and its major constituents including S-1-propenylcysteine (S1PC) and S-allylcysteine (SAC) using spontaneously hypertensive rats (SHR) and found that S1PC is an active substance to lower blood pressure in SHR. In addition, the metabolomics approach was used to investigate the potential mechanism of the antihypertensive action of S1PC in SHR. Treatment with AGE (2g/kg body weight) or S1PC (6.5mg/kg body weight; equivalent to AGE 2g/kg body weight) significantly decreased the systolic blood pressure (SBP) of SHR after the repeated administration for 10 weeks, whereas treatment with SAC (7.9mg/kg body weight; equivalent to AGE 2g/kg body weight) did not decrease the SBP. After the treatment for 10 weeks, the plasma samples obtained from Wistar Kyoto (WKY) rats and SHR were analyzed by means of ultra high performance liquid chromatography coupled with high-resolution quadrupole-Orbitrap mass spectrometry. Multivariate statistical analysis of LC-MS data showed a clear difference in the metabolite profiles between WKY rats and SHR. The results indicated that 30 endogenous metabolites significantly contributed to the difference and 7 of 30 metabolites were changed by the S1PC treatment. Furthermore, regression analysis showed correlation between SBP and the plasma levels of betaine, tryptophan and 3 LysoPCs. This metabolomics approach suggested that S1PC could exert its antihypertensive effect by affecting glycine, serine and threonine metabolism, tryptophan metabolism and glycerophospholipid metabolism.
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan. Electronic address: matsutomo_t@wakunaga.co.jp.
Toshiaki
T
Matsutomo
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Mitsuyasu
M
Ushijima
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Yukihiro
Y
Kodera
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Masashi
M
Nakamoto
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Miyuki
M
Takashima
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Naoaki
N
Morihara
Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Akitakata-shi, Hiroshima 739-1195, Japan.
Koichi
K
Tamura
D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002853:Chromatography, Liquid / Q000379:methods*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D020404:Glycerophospholipids / Q000097:blood / Q000378:metabolism; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D051381:Rats; D011918:Rats, Inbred SHR; D015203:Reproducibility of Results
D000596:Amino Acids; D000959:Antihypertensive Agents; D005227:Fatty Acids; D020404:Glycerophospholipids; C065299:S-allylcysteine; D003545:Cysteine
Hypertension; LC–MS; Metabolomics; Plasma; S-1-Propenylcysteine