Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy

Guo, Xin; Xue, Mei; Li, Chunjun; Yang, Weng Lang; Wang, Shanshan; Ma, Zhuo; Zhang, Xiaona; Wang, Xiaoyu; Zhao, Ran; Chang, Baocheng; Chen, Liming

doi:10.1016/j.jep.2016.08.029

Cited by 60 publications

(42 citation statements)

References 47 publications

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“…Moreover, our results revealed that there were significant differences in myocardial cells between the diabetic and non-diabetic groups. Guo et al [21] have shown that in the diabetic cardiomyopathy, the myocardium fibers are disordered, extensively collapsed, and degenerated. Similar results in the present study demonstrated the successful establishment of diabetic cardiomyopathy rat models.…”

Section: Discussionmentioning

confidence: 99%

Effects of 1,25-dihydroxyvitamin D3 on pathological changes in rats with diabetic cardiomyopathy

Zeng

Xiao

et al. 2017

Lipids Health Dis

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BackgroundThe role of 1,25-dihydroxyvitamin D3 (vitamin D) in the apoptosis of diabetic cardiomyopathy (DCM) is unclear. This study is to investigate the effects of vitamin D on the pathological changes in rats with DCM.MethodsRats were randomly divided into the control, model, and treatment groups. DCM model was established by the high-fat and -sugar diet. Plasma glucose, body weight, heart weight, heart weight index, and serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were determined. Heart tissue morphology was detected with histochemical staining. Expression levels of Fas and FasL were detected with RT-PCR and immunohistochemistry.ResultsCompared with the control group, the body weights and heart weights were significantly declined, while the plasma glucose levels and heart weight indexes were significantly elevated, in the model group (P < 0.05). However, vitamin D significantly reversed the pathological changes in DCM rats (P < 0.05). Moreover, the serum levels of LDH and CK were significantly increased in the models, which were significantly decreased by vitamin D (P < 0.05). HE staining showed that, vitamin D significantly alleviated the histological changes of myocardial cells in DCM rats. In addition, the mRNA and protein expression levels of Fas and FasL were significantly elevated in the models (P < 0.05), which were significantly declined by vitamin D (P < 0.05).ConclusionVitamin D could alleviate pathological changes, reduce Fas/FasL expression, and attenuate myocardial cell apoptosis in DCM rats, which might be used as a potential effective therapy for the disease.

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Section: Discussionmentioning

confidence: 99%

Effects of 1,25-dihydroxyvitamin D3 on pathological changes in rats with diabetic cardiomyopathy

Zeng

Xiao

et al. 2017

Lipids Health Dis

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“…Furthermore, triptolide (20 ng/ml) attenuated inflammation of H9c2 rat cardiac cell exposure to high glucose by inhibiting NF- κ B activation. Guo et al [ 66 ] showed that the left ventricle pathological structure and function of STZ-induced mice were significantly improved by triptolide (50, 100 or 200 μ g/kg/d p.o.) treatment for 8 weeks.…”

Section: Herbal Medicines: Promising Therapeutic For Dcmmentioning

confidence: 99%

Roles and Mechanisms of Herbal Medicine for Diabetic Cardiomyopathy: Current Status and Perspective

Tian

Zhao

Liu

et al. 2017

Oxidative Medicine and Cellular Longevity

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Diabetic cardiomyopathy is one of the major complications among patients with diabetes mellitus. Diabetic cardiomyopathy (DCM) is featured by left ventricular hypertrophy, myocardial fibrosis, and damaged left ventricular systolic and diastolic functions. The pathophysiological mechanisms include metabolic-altered substrate metabolism, dysfunction of microvascular, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, cardiomyocyte apoptosis, mitochondrial dysfunction, and impaired Ca2+ handling. An array of molecules and signaling pathways such as p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and extracellular-regulated protein kinases (ERK) take roles in the pathogenesis of DCM. Currently, there was no remarkable effect in the treatment of DCM with application of single Western medicine. The myocardial protection actions of herbs have been gearing much attention. We present a review of the progress research of herbal medicine as a potential therapy for diabetic cardiomyopathy and the underlying mechanisms.

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“…To date, researchers have identified the effects of TP on inflammation, cancer, the immune system, and diabetic cardiomyopathy. 13 , 14 , 15 , 16 However, there are relatively few studies on the effects of TP on DKD and TP’s mechanism of action is still not clear and definite.…”

Section: Introductionmentioning

confidence: 99%

Triptolide Restores Autophagy to Alleviate Diabetic Renal Fibrosis through the miR-141-3p/PTEN/Akt/mTOR Pathway

Wang

Han

et al. 2017

Molecular Therapy - Nucleic Acids

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112

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Fibrosis is the major pathological feature of diabetic kidney disease (DKD). Autophagy, a process to maintain metabolic homeostasis, is obviously inhibited in DKD. Triptolide (TP) is a traditional Chinese medicine extract known for immune suppression and anti-inflammatory and anti-cancer activities. In this study, we investigated the effects of TP on autophagy and fibrosis in DKD. TP restored autophagy and alleviated fibrosis in DKD rats and high-glucose-incubated human mesangial cells. After we applied 3-methyladenine (an autophagy inhibitor) and autophagy-related gene 5-small interfering RNA (siRNA), we found that the improvement of fibrosis on TP was related to the restoration of autophagy. In addition, miR-141-3p levels were increased under high glucose but reduced after TP treatment. miR-141-3p overexpression aggravated the fibrosis and restrained the autophagy further, while miR-141-3p inhibition imitated the effects of TP. As an action target, phosphatase and tensin homolog (PTEN) showed corresponding opposite changes. After PTEN-siRNA transfection, the effects of TP on autophagy and fibrosis were inhibited. PTEN levels were downregulated, with downstream phosphorylated protein kinase B (Akt) and the mammalian target of rapamycin (mTOR) upregulated in high glucose, which were reversed by TP treatment. These findings indicate that TP alleviates fibrosis by restoring autophagy through the miR-141-3p/PTEN/Akt/mTOR pathway and is a novel therapeutic option for DKD.

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Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy

Cited by 60 publications

References 47 publications

Effects of 1,25-dihydroxyvitamin D3 on pathological changes in rats with diabetic cardiomyopathy

Effects of 1,25-dihydroxyvitamin D3 on pathological changes in rats with diabetic cardiomyopathy

Roles and Mechanisms of Herbal Medicine for Diabetic Cardiomyopathy: Current Status and Perspective

Triptolide Restores Autophagy to Alleviate Diabetic Renal Fibrosis through the miR-141-3p/PTEN/Akt/mTOR Pathway

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