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Syringaresinol Protects against Type 1 Diabetic Cardiomyopathy by Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress.
Mol Nutr Food Res. 2020 09; 64(18):e2000231.MN

Abstract

SCOPE

Syringaresinol (SYR) is a phenolic compound, which could be found in various cereals and medicinal plants. It exerts both anti-inflammatory and antioxidant pharmacological properties. However, little is known about the effect of SYR on modulating diabetic cardiomyopathy. The present study aimed to investigate the pharmacodynamic effect of SYR on diabetic cardiomyopathy and the underlying molecular mechanism.

METHODS AND RESULTS

In STZ-induced type 1 diabetic mice, orally administration with SYR in every other day for 8 weeks significantly improves cardiac dysfunction and preventes cardiac hypertrophy and fibrosis. The macrophage infiltration and oxidative stress biomarkers are also suppressed by SYR without affecting hyperglycemia and body weight. In neonatal cardiomyocytes, high glucose-induced cell apoptosis and fibrosis are potently decreased by SYR, and the inflammatory response and oxidant stress are also alleviated by SYR incubation. Mechanistically, SYR may exert protective effects by restoring suppression of antioxidant kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-E2-related factor 2 (Nrf2) system and abnormal activation of transforming growth factor-β (TGF-β)/mothers against decapentaplegic homolog (Smad) signaling pathway in vitro and in vivo.

CONCLUSION

The results indicated that SYR could be a potential therapeutic agent for the treatment of diabetic cardiomyopathy by inhibiting inflammation, fibrosis, and oxidative stress. The signaling pathway of Keap1/Nrf2 and TGF-β/Smad could be used as therapeutic targets for diabetic complications.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, 300100, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Clinical laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300197, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin, 300100, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.Department of Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32729956

Citation

Li, Guangru, et al. "Syringaresinol Protects Against Type 1 Diabetic Cardiomyopathy By Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress." Molecular Nutrition & Food Research, vol. 64, no. 18, 2020, pp. e2000231.
Li G, Yang L, Feng L, et al. Syringaresinol Protects against Type 1 Diabetic Cardiomyopathy by Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress. Mol Nutr Food Res. 2020;64(18):e2000231.
Li, G., Yang, L., Feng, L., Yang, J., Li, Y., An, J., Li, D., Xu, Y., Gao, Y., Li, J., Liu, J., Yang, L., & Qi, Z. (2020). Syringaresinol Protects against Type 1 Diabetic Cardiomyopathy by Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress. Molecular Nutrition & Food Research, 64(18), e2000231. https://doi.org/10.1002/mnfr.202000231
Li G, et al. Syringaresinol Protects Against Type 1 Diabetic Cardiomyopathy By Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress. Mol Nutr Food Res. 2020;64(18):e2000231. PubMed PMID: 32729956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Syringaresinol Protects against Type 1 Diabetic Cardiomyopathy by Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress. AU - Li,Guangru, AU - Yang,Lei, AU - Feng,Lifeng, AU - Yang,Jiu, AU - Li,Yafei, AU - An,Jiale, AU - Li,Dihua, AU - Xu,Yang, AU - Gao,Yang, AU - Li,Jing, AU - Liu,Jie, AU - Yang,Liang, AU - Qi,Zhi, Y1 - 2020/08/09/ PY - 2020/03/09/received PY - 2020/07/03/revised PY - 2020/7/31/pubmed PY - 2021/8/3/medline PY - 2020/7/31/entrez KW - diabetic cardiomyopathy KW - fibrosis KW - inflammation KW - oxidative stress KW - syringaresinol SP - e2000231 EP - e2000231 JF - Molecular nutrition & food research JO - Mol Nutr Food Res VL - 64 IS - 18 N2 - SCOPE: Syringaresinol (SYR) is a phenolic compound, which could be found in various cereals and medicinal plants. It exerts both anti-inflammatory and antioxidant pharmacological properties. However, little is known about the effect of SYR on modulating diabetic cardiomyopathy. The present study aimed to investigate the pharmacodynamic effect of SYR on diabetic cardiomyopathy and the underlying molecular mechanism. METHODS AND RESULTS: In STZ-induced type 1 diabetic mice, orally administration with SYR in every other day for 8 weeks significantly improves cardiac dysfunction and preventes cardiac hypertrophy and fibrosis. The macrophage infiltration and oxidative stress biomarkers are also suppressed by SYR without affecting hyperglycemia and body weight. In neonatal cardiomyocytes, high glucose-induced cell apoptosis and fibrosis are potently decreased by SYR, and the inflammatory response and oxidant stress are also alleviated by SYR incubation. Mechanistically, SYR may exert protective effects by restoring suppression of antioxidant kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-E2-related factor 2 (Nrf2) system and abnormal activation of transforming growth factor-β (TGF-β)/mothers against decapentaplegic homolog (Smad) signaling pathway in vitro and in vivo. CONCLUSION: The results indicated that SYR could be a potential therapeutic agent for the treatment of diabetic cardiomyopathy by inhibiting inflammation, fibrosis, and oxidative stress. The signaling pathway of Keap1/Nrf2 and TGF-β/Smad could be used as therapeutic targets for diabetic complications. SN - 1613-4133 UR - https://www.unboundmedicine.com/medline/citation/32729956/Syringaresinol_Protects_against_Type_1_Diabetic_Cardiomyopathy_by_Alleviating_Inflammation_Responses_Cardiac_Fibrosis_and_Oxidative_Stress_ L2 - https://doi.org/10.1002/mnfr.202000231 DB - PRIME DP - Unbound Medicine ER -