Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat mesenteric arteries

Li, Rachel Wai-sum; Yang, Cui; Shan, Luchen; Zhang, Zaijun; Wang, Yuqiang; Kwan, Yiu Wa; Lee, Shuncheng; Hoi, Maggie Pui Man; Chan, Shun‐Wan; Cheung, Alex Chun; Cheung, Kwok-Kin; Leung, George Pak-Heng

doi:10.1016/j.ejphar.2015.04.041

Cited by 18 publications

(8 citation statements)

References 32 publications

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“…Besides, some studies have indicated that the TMP can inhibit platelet aggregation, dilate small arteries, improve microcirculation, and can be used as a supplement in the clinic for treating cerebral thrombosis, coronary disease, and angina (Hongyan, 2015;M. Li et al, 2004; R. W. Li et al, 2015). In terms of cardiomyocytes, a previous study demonstrated that the TMP could elicit disparate responses in cardiac contraction and intracellular Ca 2+ transients in isolated adult rat ventricular myocytes (Hintz & Ren, 2003).…”

Section: Introductionmentioning

confidence: 99%

Retracted: Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a

Dong

Liu

Han

et al. 2019

Journal Cellular Physiology

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Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease. Tetramethylpyrazine (TMP, also known as ligustrazine) is the main active ingredient isolated from the rhizome of Ligusticum chuanxiong Hort. A previous study reported that the TMP could exert cardioprotective activity. This study aimed to explore the molecular mechanism of the protective effects of TMP on cardiomyocyte damage caused by hypoxia. The viability and apoptosis of cardiomyocytes H9c2 were detected using cell counting kit‐8 assay and annexin V‐FITC/PI staining, respectively. Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of microRNA‐449a (miR‐449a). Cell transfection was performed to upregulate the expression level of miR‐449a or downregulate the expression level of sirtuin 1 (Sirt1). The protein expression levels of Sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (PI3K/AKT) pathway were evaluated using western blot analysis. We found that the hypoxia incubation inhibited H9c2 viability, induced cell apoptosis, and inactivated the PI3K/AKT pathway. TMP treatment partially relieved the hypoxia‐caused H9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the PI3K/AKT pathway. Moreover, TMP partially alleviated the upregulation of miR‐449a in H9c2 cells caused by hypoxia. Overexpression of miR‐449a weakened the effects of TMP on hypoxia‐treated H9c2 cells. Furthermore, Sirt1 was a target gene of miR‐449a. Knockdown of Sirt1 also weakened the effects of TMP on hypoxia‐treated H9c2 cells. In conclusion, TMP partially relieved hypoxia‐caused cardiomyocytes H9c2 viability loss and apoptosis at least through downregulating miR‐499a, upregulating Sirt1, and then activating the PI3K/AKT pathway.

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Section: Introductionmentioning

confidence: 99%

Retracted: Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a

Dong

Liu

Han

et al. 2019

Journal Cellular Physiology

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“…ADTM inhibited platelet aggregation and thrombus formation by targeting ERp57 both in vitro and in vivo [10]. ADTM also conferred relaxation effects on rat mesenteric arteries [11]. Further study showed that ADTM inhibited the growth of breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II

et al. 2016

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The mitochondrial respiratory chain, including mitochondrial complex II, has emerged as a potential target for cancer therapy. In the present study, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), DT-010, was synthesized. Our results showed that DT-010 is more potent than its parental compounds separately or in combination, in inhibiting the proliferation of MCF-7 and MDA-MB-231 cells by inducing cytotoxicity and promoting cell cycle arrest. It also inhibited the growth of 4T1 breast cancer cells in vivo. DT-010 suppressed the fundamental parameters of mitochondrial function in MCF-7 cells, including basal respiration, ATP turnover, maximal respiration. Treatment with DT-010 in MCF-7 and MDA-MB-231 cells resulted in the loss of mitochondrial membrane potential and decreased ATP production. DT-010 also promoted ROS generation, while treatment with ROS scavenger, NAC (N-acetyl-L-cysteine), reversed DT-010-induced cytotoxicity. Further study showed that DT-010 suppressed succinate-induced mitochondrial respiration and impaired mitochondrial complex II enzyme activity indicating that DT-010 may inhibit mitochondrial complex II. Overall, our results suggested that the antitumor activity of DT-010 is associated with inhibition of mitochondrial complex II, which triggers ROS generation and mitochondrial dysfunction in breast cancer cells.

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“…TMP, also known as ligustrazine is known to possess a wide range of biological activities including antioxidant, anti-inflammatory, antitumor, properties and provide cyto-protection to kidneys, brain and heart [23,[54][55][56][57]. TMP is also known to improve microcirculation and can be potentially used to treat thrombosis as they attenuate platelet aggregation [58,59].…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine reverses high-glucose induced hypoxic effects by negatively regulating HIF-1α induced BNIP3 expression to ameliorate H9c2 cardiomyoblast apoptosis

et al. 2020

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Background: Diabetic patients are highly vulnerable to hypoxic injury, which is associated with hypoxia induced BNIP3 expression that subsequently activate apoptosis. Our previous research show that Tetramethylpyrazine (TMP), a food flavoring agent, represses the hypoxia induced BNIP3 expression attenuate myocardial apoptosis. In this study, we evaluate the effect of TMP to provide protection against hypoxia aggravated high-glucose associated cellular apoptosis. Methods: The cytoprotective effect of TMP against high glucose induced cellular damages was determined on embryo derived H9c2 cardiomyoblast cells that were subjected to 5% hypoxia for 24 h and subjected to different duration of 33 mM high glucose challenge. Further, the involvement of HIF-1α and BNIP3 in cellular damage and the mechanism of protection of TMP were determined by overexpression and silencing HIF-1α and BNIP3 protein expression. Results: The results show that hypoxic effects on cell viability aggravates with high glucose challenge and this augmentative effect is mediated through BNIP3 in H9c2 cardiomyoblast cells. However, TMP administration effectively reversed the augmented HIF-1α levels and BNIP3 elevation. TMP improved the survival of H9c2 cells and effectively suppressed apoptosis in H9c2 cells. Further comparison on the effects of TMP on H9c2 cells challenged with high glucose and those challenged with hypoxia show that TMP precisely regulated the hypoxic intensified apoptotic effects in high-glucose condition. Conclusion: The results clearly show that flavoring agent-TMP attenuates cytotoxicity amplified by hypoxia challenge in high glucose condition by destabilizing HIF-1α.

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Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat mesenteric arteries

Cited by 18 publications

References 32 publications

Retracted: Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a

Retracted: Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a

A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II

Tetramethylpyrazine reverses high-glucose induced hypoxic effects by negatively regulating HIF-1α induced BNIP3 expression to ameliorate H9c2 cardiomyoblast apoptosis

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