Structures and biological activities of new carnosic acid- and carnosol-related compounds generated by heat treatment of rosemary
Introduction
Chronic oxidative stress is increased in metabolic syndromes and type-2 diabetes mellitus (T2DM), and this increase appears to underlie the development of T2DM and diabetic complications. Increased oxidative stress also appears to be a deleterious factor that leads to insulin resistance, dyslipidemia, β-cell dysfunction, and impaired glucose tolerance, ultimately leading to T2DM (Boden et al., 2015). Exactly how to reduce the harmful effects of oxidative stress, hyperglycemia, and dyslipidemia by daily food intake is an important topic (Tangvarasittichai, 2015; Esposito et al., 2013). Peroxisome proliferator-activated receptor (PPAR) γ is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. Activation of PPARγ enhances adipocyte differentiation and, thus, causes insulin sensitization and improved glucose metabolism. Currently, PPARγ agonists such as rosiglitazone are used clinically to treat patients with T2DM (Berger et al., 2005; von Bibra et al., 2008; Yang et al., 2015). In addition, rosiglitazone has been reported to reduce the risk of cardiovascular disease by increasing antioxidant production (von Bibra et al., 2008; Yang et al., 2015). Thus, PPARγ agonists play critical regulatory roles in energy homeostasis and metabolic functions. Many chemical reactions may occur when food materials are heated during cooking (e.g., boiling, frying, and heating in a pan). The compounds produced by heating food may possess pharmaceutical benefits. Rosemary is an herb that is widely used in cooking in daily life. Carnosic acid (CA) and carnosol (CS) are components of rosemary that are reported to possess antioxidant activity (Frankel et al., 1996) and PPARγ agonistic activity (Rau et al., 2006). In this study, we identified five compounds generated by heating rosemary by comparing high-performance liquid chromatography with diode-array detection (HPLC-DAD) data from unheated and heated extracts. We report the isolation, structural determination, and antioxidative and PPARγ agonistic activities of these compounds.
Section snippets
Searching, isolation, and structural determination of compounds generated by heat treatment of rosemary
Both dried and heated rosemary powder were extracted with CH2Cl2-MeOH (1:1), and each extract was analyzed using a DAD ODS HPLC system. By comparing the DAD chromatography of two extracts (Fig. S-1).
To isolate these compounds, 35 g of dried rosemary powder was heated and extracted with CH2Cl2-MeOH (1:1). The CH2Cl2-MeOH (1:1) extract (4.22 g) was next purified by silica gel column chromatography (hexane-EtoAc, 10:1). In this chromatography, 4 compounds (2–5) were eluted in fractions (fr.)
Discussion
In this study, we found five CA- and CS-related compounds (1–5) from rosemary after heat treatment. Maillard-reaction and caramelization-reaction products are known heat-generated compounds from food materials (Martins et al., 2000), while few other compounds have been reported. Therefore, our results supported the possibility that the heat treatment of food materials could be a new way to explore bioactive substances. Surprisingly, 3 compounds (1, 2, and 4) were previously reported as natural
Spectroscopic analysis
HR-ESI-MS spectra were obtained on a JMS-T100LP mass spectrometer (Jeol, Tokyo, Japan), using reserpine as an external standard. HR-EI-MS spectra were obtained on a JMS-AX505 mass spectrometer (Jeol, Tokyo, Japan). NMR spectra were measured in CDCl3 with an AVANCE400 instrument (Bruker BioSpin, Karlsruhe, Germany), using the residual solvent peak as an internal standard (δC 77.0, δH 7.26 ppm).
HPLC-DAD conditions for searching generated compounds produced by heat treatment
Three grams of dried rosemary (purchased from GABAN Co., ltd, Tokyo, Japan) was powdered in a mixer and
Author contribution statement
KS designed the research. ST and FH supervised the research. YB, YS, RH, YM, and DY performed the experiments. KS and YB wrote the paper.
Role of the funding source
This work was supported by JSPS KAKENHI [grant number 15K00798].
Declaration of interest
The authors declare no conflict of interest.
Acknowledgements
We thank for Miss Chihiro Takeuchi, Miss Nayoko Tsuda, Miss Satsuki Kato, Miss Natsuka Saito, Miss Misa Sumiya, Miss Shizuka Suzuki, and Miss Midori Matsuyuki for their contributions to the experiments conducted in this study. In addition, we appreciate Dr. Susan Hall (The University of North Carolina at Chapel Hill) for critically reading the manuscript.
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