D-chiro-inositol enriched Fagopyrum tataricum (L.) Gaench extract alleviates mitochondrial malfunction and inhibits ER stress/JNK associated inflammation in the endothelium. (25th March 2018)

• Record Type: Journal Article
• Authors: Zhang, Bobo; Gao, Caifeng; Li, Yunlong; Wang, Min
• Is Part Of: Journal of ethnopharmacology. Volume 214(2018)
• Page Start: 83
• Page End: 89
• Publication Date: 2018-03-25
• Subjects: CMC-Na carboxymethylcellulose sodium -- DCI D-chiro-inositol -- DHE dihydroethidium -- Drp1 dynamin-related protein 1 -- ER endoplasmic reticulum -- FFAs free fatty acids -- HFD high fat diet -- IRE-1α inositol-requiring enzyme-1α -- JNK Jun n-terminal kinase -- Mdivi-1 mitochondrial division inhibitor-1 -- Met metformin Mfn2 mitofusin2 -- PA palmitate acid -- RAECs rat aortic primary endothelial cells -- RIPA Radio Immunoprecipitation Assay buffer -- ROS reactive oxygen species -- TBBE tartary buckwheat bran extract -- UPR unfolded protein response -- VCAM-1 vascular cell adhesion molecule-1 -- Δψm mitochondria membrane potential; D-chiro-inositol enriched tartary buckwheat extract -- Mitochondrial malfunction -- ER stress -- JNK -- Caspase-3; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2017.12.002
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Tartary buckwheat is a food medicine dual-use crop with healing effects on cardiovascular diseases and type2 diabetes. It has been proposed that endothelial dysfunction is the initial lesion in these diseases and it's associated with mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation. D-chiro-inositol (DCI) is a bioactive compound of Tartary buckwheat and is always deficit in type2 diabetes. However, it remains unknown whether DCI-enriched Tartary buckwheat extract can ameliorate mitochondrial dysfunction, ER stress and inflammation in the endothelium. Material and methods: Endothelial cells were treated with palmitic acid (PA) and mice were fed with high fat diet (HFD). The effects of DCI-enriched Tartary buckwheat bran extract (TBBE) on superoxide anion generation, dynamin-related protein 1 (Drp1), mitofusin2 (Mfn2), inositol-requiring enzyme-1α (IRE1α) and Jun n-terminal kinase (JNK) activation and inflammation in the endothelium against lipotoxicity were investigated. Results: In endothelial cells, TBBE significantly inhibited oxidative stress. Meanwhile, in HFD-fed mice and PA-induced cells, TBBE regulated Drp1 phosphorylation and inhibited its activation, implying the protective effect of TBBE on mitochondrial morphology. As a result, TBBE protected mitochondrial function. Additionally, TBBE inhibited ER stress and reduced the production of IL-6 and VCAM-1, associated with JNK pathway, thereby inhibiting the caspase-3 activation in vivo and in vitro . Conclusions: Taken together, this study indicated the beneficial role of TBBE in endothelial inflammation, with emphasis on mitochondrial dysfunction, ER stress and JNK activation. Graphical abstract: The proposed working pathway for the suppressive effect of TBBE on inflammation in the endothelium. TBBE inhibited mitochondrial dysfunction and ER stress by combating oxidative stress, leading to the inhibition of JNK activation by down-regulation of its phosphorylation. Therefore, TBBE protected endothelial function by the prevention of inflammatory responses and the suppression of apoptosis.