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Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.
Acta Pharmacol Sin. 2015 Mar; 36(3):323-33.AP

Abstract

AIM

Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats.

METHODS

Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins.

RESULTS

DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine.

CONCLUSION

Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

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Authors+Show Affiliations

Liu ZW
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
Wang JK
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
Qiu C
Department of Biostatistics & Bioinformatics, School of Public Health & Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
Guan GC
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
Liu XH
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
Li SJ
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.
Deng ZR
Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an 710000, China.

MeSH

AlkaloidsAnimalsApoptosisCardiotonic AgentsCaspase 3Caspase 8Cells, CulturedDiabetes Mellitus, ExperimentalDiabetic CardiomyopathiesMaleMyeloid Differentiation Factor 88Myocytes, CardiacOxidative StressQuinolizinesRats, Sprague-DawleyReactive Oxygen SpeciesSignal TransductionToll-Like Receptor 4Ventricular Dysfunction, LeftVentricular Function, LeftMatrines

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25619390

Citation

Liu, Zhong-wei, et al. "Matrine Pretreatment Improves Cardiac Function in Rats With Diabetic Cardiomyopathy Via Suppressing ROS/TLR-4 Signaling Pathway." Acta Pharmacologica Sinica, vol. 36, no. 3, 2015, pp. 323-33.
Liu ZW, Wang JK, Qiu C, et al. Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway. Acta Pharmacol Sin. 2015;36(3):323-33.
Liu, Z. W., Wang, J. K., Qiu, C., Guan, G. C., Liu, X. H., Li, S. J., & Deng, Z. R. (2015). Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway. Acta Pharmacologica Sinica, 36(3), 323-33. https://doi.org/10.1038/aps.2014.127
Liu ZW, et al. Matrine Pretreatment Improves Cardiac Function in Rats With Diabetic Cardiomyopathy Via Suppressing ROS/TLR-4 Signaling Pathway. Acta Pharmacol Sin. 2015;36(3):323-33. PubMed PMID: 25619390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway. AU - Liu,Zhong-wei, AU - Wang,Jun-kui, AU - Qiu,Chuan, AU - Guan,Gong-chang, AU - Liu,Xin-hong, AU - Li,Shang-jian, AU - Deng,Zheng-rong, Y1 - 2015/01/26/ PY - 2014/05/23/received PY - 2014/10/14/accepted PY - 2015/1/27/entrez PY - 2015/1/27/pubmed PY - 2016/3/29/medline SP - 323 EP - 33 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 36 IS - 3 N2 - AIM: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. RESULTS: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. CONCLUSION: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway. SN - 1745-7254 UR - https://www.unboundmedicine.com/medline/citation/25619390/Matrine_pretreatment_improves_cardiac_function_in_rats_with_diabetic_cardiomyopathy_via_suppressing_ROS/TLR_4_signaling_pathway_ DB - PRIME DP - Unbound Medicine ER -