Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

Zheng, Chang‐Bo; Lo, Chun-Yin; Meng, Zhaoyue; Li, Zhichao; Zhong, Mingkui; Zhang, Peng; Lü, Jun; Zhao-xiang, Yang; Fu, Yan; Zhang, Yunting; Huang, Yü; Yao, Xiaoqiang

doi:10.3389/fphar.2017.00222

Cited by 20 publications

(26 citation statements)

References 27 publications

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“…; Zheng et al. ), downregulation of SOCE response as seen in direct co‐culture suggests that direct interaction with macrophages could play a role in preventing the development of hypertrophy in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 98%

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Hitscherich

Xie

et al. 2019

Physiol Rep

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Following myocardial infarction ( MI ), myocardial inflammation plays a crucial role in the pathogenesis of MI injury and macrophages are among the key cells activated during the initial phases of the host response regulating the healing process. While macrophages have emerged as attractive effectors in tissue injury and repair, the contribution of macrophages on cardiac cell function and survival is not fully understood due to complexity of the in vivo inflammatory microenvironment. Understanding the key cells involved and how they communicate with one another is of paramount importance for the development of effective clinical treatments. Here, novel in vitro myocardial inflammation models were developed to examine how both direct and indirect interactions with polarized macrophage subsets present in the post‐ MI microenvironment affect cardiomyocyte function. The indirect model using conditioned medium from polarized macrophage subsets allowed examination of the effects of macrophage‐derived factors on stem cell‐derived cardiomyocyte function for up to 3 days. The results from the indirect model demonstrated that pro‐inflammatory macrophage‐derived factors led to a significant downregulation of cardiac troponin T ( cTnT ) and sarcoplasmic/endoplasmic reticulum calcium ATP ase (Serca2) gene expression. It also demonstrated that inhibition of macrophage‐secreted matricellular protein, osteopontin ( OPN ), led to a significant decrease in cardiomyocyte store‐operated calcium entry ( SOCE ). In the direct model, stem cell‐derived cardiomyocytes were co‐cultured with polarized macrophage subsets for up to 3 days. It was demonstrated that anti‐inflammatory macrophages significantly increased cardiomyocyte Ca 2+ fractional release while macrophages independent of their subtypes led to significant downregulation of SOCE response in cardiomyocytes. This study describes simplified and controlled in vitro myocardial inflammation models, which allow examination of potential beneficial and deleterious effects of macrophages on cardiomyocytes and vise versa. This can lead to our improved understanding of the inflammatory microenvironment post‐ MI , otherwise difficult to directly investigate in vivo or by using currently available in vitro models.

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Section: Discussionmentioning

confidence: 98%

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Hitscherich

Xie

et al. 2019

Physiol Rep

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“…Gastrodin (p-hydroxymethylphenyl-b-D-glucopyranoside) is the main bioactive ingredient of herbal Chinese medicine Gastrodia elata. It is clinically used to treat neurological and cardiovascular diseases, such as cardiac hypertrophy, hypertension, migraine, convulsions, dementia, and epilepsy [7,8]. The mechanism underlying the effects of gastrodin on the nervous and vascular system may be related to gamma-aminobutyric acid, glutamate, and calcitonin gene-related peptide.…”

Section: Introductionmentioning

confidence: 99%

Gastrodin Alleviates Vascular Dementia in a 2-VO-Vascular Dementia Rat Model by Altering Amyloid and Tau Levels

et al. 2019

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Vascular dementia (VaD) is the second most common type of dementia and has become a major public health challenge as the global population ages. VaD is caused by cerebrovascular disease, and most patients with VaD have been reported to also have Alzheimer's pathologies, which is the formation of neurofibrillary tangles and amyloid plaques that are mainly composed of hyperphosphorylated Tau and amyloid β (Aβ) respectively. However, the mechanisms of VaD are not completely understood, and very few drugs are available to treat this condition. Gastrodin (Gas) is the main bioactive component of the traditional Chinese herbal plant named Tian Ma (Gastrodia elata), and it has been used to treat neurasthenia in the clinical practice of Chinese Medicine for many years. Here, we hypothesize that Gas alleviates VaD in a rat model of permanent bilateral common carotid artery occlusion (2-VO)-induced VaD. Based on the results of the Morris water maze test and attention set shift test, either 22.5 or 90 mg/kg/day Gas improved the executive dysfunc-tion and memory impairment of 2-VO rats following an intragastric administration for 4 weeks. Both 22.5 and 90 mg/kg/ day Gas reduced Aβ 1-40 and Aβ 1-42 plaques in plasma and hippocampus of 2-VO rats. Mechanistically, in 2-VO rats, treatment with Gas (90 mg/kg/day) suppressed Aβ plaque deposition by decreasing the hippocampus levels of phosphorylated Tau. Thus, Gas ameliorated the cognitive deficits of 2-VO rats by inhibiting the abnormal phosphorylation of Aβ and Tau.

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“…Overexpression of STIM-1 resulted in hypertrophic arterial remodeling and cardiac hypertrophy in chronic ethanol-induced hypertensive rats [26]. For example, gastrodin, an agent used to treat hypertension, was found to suppress SOCE by reducing the expression of STIM-1 in a phenyl-ephrine-induced mouse model of cardiac hypertrophy [27]. Studies have also reported that SOCE plays a significant role in vascular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells

et al. 2020

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Codonopsis lanceolata has been widely used as an anti-inflammatory and anti-lipogenic agent in traditional medicine. Recently, C. lanceolata was reported to prevent hypertension by improving vascular function. This study evaluated the effects of C. lanceolata and its major component lancemaside A on cytosolic calcium concentration in vascular endothelial cells and vascular smooth muscle cells. Cytosolic calcium concentration was measured using fura-2 AM fluorescence. C. lanceolata or lancemaside A increased the cytosolic calcium concentration by releasing Ca2+ from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca2+ entry into endothelial cells and vascular smooth muscle cells from extracellular sources. The C. lanceolata- and lancemaside A-induced cytosolic calcium concentration increases were significantly inhibited by lanthanum, an inhibitor of non-selective cation channels, in both endothelial cells and vascular smooth muscle cells. Moreover, C. lanceolata and lancemaside A significantly inhibited store-operated Ca2+ entry under pathological extracellular Ca2+ levels. In Ca2+-free extracellular fluid, increases in the cytosolic calcium concentration induced by C. lanceolata or lancemaside A were significantly inhibited by U73122, an inhibitor of phospholipase C, and 2-APB, an inositol 1,4,5-trisphosphate receptor antagonist. In addition, dantrolene treatment, which inhibits Ca2+ release through ryanodine receptor channels, also inhibited C. lanceolata- or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway. These results suggest that C. lanceolata and lancemaside A increase the cytosolic calcium concentration through the non-selective cation channels and phospholipase C/inositol 1,4,5-trisphosphate pathways under physiological conditions and inhibit store-operated Ca2+ entry under pathological conditions in endothelial cells and vascular smooth muscle cells. C. lanceolata or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.

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Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy

Cited by 20 publications

References 27 publications

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Gastrodin Alleviates Vascular Dementia in a 2-VO-Vascular Dementia Rat Model by Altering Amyloid and Tau Levels

Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells

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