Abstract
Aim:
Cinnamon extracts rich in procyanidin oligomers have shown to improve pancreatic β-cell function in diabetic db/db mice. The aim of this study was to identify the active compounds in extracts from two species of cinnamon responsible for the pancreatic β-cell protection in vitro.
Methods:
Cinnamon extracts were prepared from Cinnamomum tamala (CT-E) and Cinnamomum cassia (CC-E). Six compounds procyanidin B2 (cpd1), (−)-epicatechin (cpd2), cinnamtannin B1 (cpd3), procyanidin C1 (cpd4), parameritannin A1 (cpd5) and cinnamtannin D1 (cpd6) were isolated from the extracts. INS-1 pancreatic β-cells were exposed to palmitic acid (PA) or H2O2 to induce lipotoxicity and oxidative stress. Cell viability and apoptosis as well as ROS levels were assessed. Glucose-stimulated insulin secretion was examined in PA-treated β-cells and murine islets.
Results:
CT-E, CC-E as well as the compounds, except cpd5, did not cause cytotoxicity in the β-cells up to the maximum dosage using in this experiment. CT-E and CC-E (12.5–50 μg/mL) dose-dependently increased cell viability in both PA- and H2O2-treated β-cells, and decreased ROS accumulation in H2O2-treated β-cells. CT-E caused more prominent β-cell protection than CC-E. Furthermore, CT-E (25 and 50 μg/mL) dose-dependently increased glucose-stimulated insulin secretion in PA-treated β-cells and murine islets, but CC-E had little effect. Among the 6 compounds, trimer procyanidins cpd3, cpd4 and cpd6 (12.5–50 μmol/L) dose-dependently increased the cell viability and decreased ROS accumulation in H2O2-treated β-cells. The trimer procyanidins also increased glucose-stimulated insulin secretion in PA-treated β-cells.
Conclusion:
Trimer procyanidins in the cinnamon extracts contribute to the pancreatic β-cell protection, thus to the anti-diabetic activity.
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Acknowledgements
We thank Prof S SEINO for his gift of MIN6 cells. This work was supported by a grant from the National Natural Science Foundation (No 81473262 and 21172044), the National Science and Technology Major Project (Key New Drug Creation and Manufacturing Program, 2012ZX09301001-001 and 2013ZX09103001-001), the Natural Science Foundation of Shanghai, China (No 15ZR1441200) and Shanghai Three-year Plan on Promoting TCM Development (No ZY3-LCPT-2-1003).
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Supplementary information is available on the website of Acta Pharmacologica Sinica.
Supplementary information
Supplementary Figure S1
Identification of CC-E and CT-E. (TIF 248 kb)
Supplementary Figure S2
CC-E, CT-E and procyanidin oligomers protected MIN6 cells from PA-induced dysfunction and apoptosis. (TIF 811 kb)
Supplementary Table S1
Identification of major peaks in total ion chromatogram of CC-E (DOC 28 kb)
Supplementary Table S2
Identification of major peaks in total ion chromatogram of CT-E (DOC 30 kb)
Supplementary Table S3
The purity of cpd1 to 6. (DOC 31 kb)
Supplementary Table S4
HPLC chromatogram of cpd1 to 6. (DOC 161 kb)
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Sun, P., Wang, T., Chen, L. et al. Trimer procyanidin oligomers contribute to the protective effects of cinnamon extracts on pancreatic β-cells in vitro. Acta Pharmacol Sin 37, 1083–1090 (2016). https://doi.org/10.1038/aps.2016.29
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DOI: https://doi.org/10.1038/aps.2016.29
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