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Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy.
Nutr Metab Cardiovasc Dis. 2018 09; 28(9):952-961.NM

Abstract

BACKGROUND AND AIM

The association of diabetes mellitus (DM) and poor metabolic control with high incidence of cardiovascular diseases is well established. The aim of this study was to investigate the potential cardioprotective effect of crocin (Crocus sativus L. extract) on diabetic heart dysfunction and to elucidate the mediating molecular mechanisms.

METHODS AND RESULTS

Streptozotocin (STZ)-induced diabetic rats were treated with two different concentrations of crocin (10 or 20 mg/kg), while isolated cardiac myocytes exposed to 25 mM glucose, were treated with 1 or 10 μM of crocin. Treatment of STZ-diabetic rats with crocin resulted in normalization of plasma glucose levels, inhibition of cardiac hypertrophy and fibrosis, and improvement of cardiac contractile function. Heat Shock Response was enhanced. Myocardial AMPK phosphorylation was increased after treatment with crocin, resulting in normalization of autophagy marker proteins (LC3BII/LC3BI ratio, SQSTM1/p62 and Beclin-1), while the diabetes-induced myocardial apoptosis was decreased. Similar results regarding the effect of crocin on autophagy and apoptosis pathways were obtained in isolated cardiac myocytes exposed to high concentration of glucose.

CONCLUSION

The results suggest that crocin improves the deteriorated cardiac function in diabetic animals by enhancing the heat shock response, inhibiting apoptosis and normalizing autophagy in cardiac myocytes. Thus, treatment with crocin may represent a novel approach for treating diabetic cardiomyopathy.

Authors+Show Affiliations

Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.Emeritus Professor of Hematology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece. Electronic address: lazou@bio.auth.gr.

Pub Type(s)

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

Language

eng

PubMed ID

30017436

Citation

Feidantsis, K, et al. "Treatment With Crocin Improves Cardiac Dysfunction By Normalizing Autophagy and Inhibiting Apoptosis in STZ-induced Diabetic Cardiomyopathy." Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, vol. 28, no. 9, 2018, pp. 952-961.
Feidantsis K, Mellidis K, Galatou E, et al. Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy. Nutr Metab Cardiovasc Dis. 2018;28(9):952-961.
Feidantsis, K., Mellidis, K., Galatou, E., Sinakos, Z., & Lazou, A. (2018). Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy. Nutrition, Metabolism, and Cardiovascular Diseases : NMCD, 28(9), 952-961. https://doi.org/10.1016/j.numecd.2018.06.005
Feidantsis K, et al. Treatment With Crocin Improves Cardiac Dysfunction By Normalizing Autophagy and Inhibiting Apoptosis in STZ-induced Diabetic Cardiomyopathy. Nutr Metab Cardiovasc Dis. 2018;28(9):952-961. PubMed PMID: 30017436.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy. AU - Feidantsis,K, AU - Mellidis,K, AU - Galatou,E, AU - Sinakos,Z, AU - Lazou,A, Y1 - 2018/07/14/ PY - 2018/03/19/received PY - 2018/06/05/revised PY - 2018/06/07/accepted PY - 2018/7/19/pubmed PY - 2019/3/15/medline PY - 2018/7/19/entrez KW - Apoptosis KW - Autophagy KW - Cardiac function KW - Crocin KW - Diabetes KW - Heat shock response SP - 952 EP - 961 JF - Nutrition, metabolism, and cardiovascular diseases : NMCD JO - Nutr Metab Cardiovasc Dis VL - 28 IS - 9 N2 - BACKGROUND AND AIM: The association of diabetes mellitus (DM) and poor metabolic control with high incidence of cardiovascular diseases is well established. The aim of this study was to investigate the potential cardioprotective effect of crocin (Crocus sativus L. extract) on diabetic heart dysfunction and to elucidate the mediating molecular mechanisms. METHODS AND RESULTS: Streptozotocin (STZ)-induced diabetic rats were treated with two different concentrations of crocin (10 or 20 mg/kg), while isolated cardiac myocytes exposed to 25 mM glucose, were treated with 1 or 10 μM of crocin. Treatment of STZ-diabetic rats with crocin resulted in normalization of plasma glucose levels, inhibition of cardiac hypertrophy and fibrosis, and improvement of cardiac contractile function. Heat Shock Response was enhanced. Myocardial AMPK phosphorylation was increased after treatment with crocin, resulting in normalization of autophagy marker proteins (LC3BII/LC3BI ratio, SQSTM1/p62 and Beclin-1), while the diabetes-induced myocardial apoptosis was decreased. Similar results regarding the effect of crocin on autophagy and apoptosis pathways were obtained in isolated cardiac myocytes exposed to high concentration of glucose. CONCLUSION: The results suggest that crocin improves the deteriorated cardiac function in diabetic animals by enhancing the heat shock response, inhibiting apoptosis and normalizing autophagy in cardiac myocytes. Thus, treatment with crocin may represent a novel approach for treating diabetic cardiomyopathy. SN - 1590-3729 UR - https://www.unboundmedicine.com/medline/citation/30017436/Treatment_with_crocin_improves_cardiac_dysfunction_by_normalizing_autophagy_and_inhibiting_apoptosis_in_STZ_induced_diabetic_cardiomyopathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-4753(18)30193-5 DB - PRIME DP - Unbound Medicine ER -