Delphinidin attenuates pathological cardiac hypertrophy via the AMPK/NOX/MAPK signaling pathway

Ren

Korean J Physiol Pharmacol

et al. 2021

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.

Section: Discussionmentioning

confidence: 99%

“…Cardiac fibrosis is an important pathophysiological changes in cardiac aging and observed in several cardiac diseases [ 8 , 14 ]. Oxidative stress can up-regulate cardiac fibrotic signaling pathway [ 8 , 17 ]. For example, ROS can induce cardiac fibrosis via enhancing the expression of profibrotic TGF-β1 [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Mangiferin ameliorates cardiac fibrosis in D-galactose-induced aging rats by inhibiting TGF-β/p38/MK2 signaling pathway

Ren

Korean J Physiol Pharmacol

et al. 2021

“…•− , which was reflective of reduced Nox activity, particularly Nox2 [118]. Interestingly, Ang II-mediated hypertrophy was attenuated by delphinidin, which was reflective of reduced activation of ERK1/2, p38MAPK and JNK.…”

Section: Flavonoidsmentioning

confidence: 94%

“…•− production and Nox activity. It is likely that AMP-activated protein kinase (AMPK), a cardio-protective enzyme [119], is downregulated due to TAC, which is reversed by delphinidin [118]. Upregulation of AMPK leads to inhibition of GTP-binding protein Rac1, a key regulatory subunit of both Nox1 and Nox2 [120].…”

Section: Flavonoidsmentioning

confidence: 99%

Protective Role of Polyphenols in Heart Failure: Molecular Targets and Cellular Mechanisms Underlying Their Therapeutic Potential

Najjar

Feresin

2021

IJMS

Heart failure (HF) is a leading cause of death in the United States, with a 5-year mortality rate of 50% despite modern pharmacological therapies. Plant-based diets are comprised of a diverse polyphenol profile, which lends to their association with reduced cardiovascular disease risk. Whether a polyphenol-rich diet can slow the progression of or reverse HF in humans is not known. To date, in vitro and in vivo studies have reported on the protective role of polyphenols in HF. In this review, we will discuss the major mechanisms by which polyphenols mitigate HF in vitro and in vivo, including (1) reduced cardiac inflammation and oxidative stress, (2) reduced mitochondrial dysfunction, (3) improved Ca2+ homeostasis, (4) increased survival signaling, and (5) increased sirtuin 1 activity.

“…Delphinidin is an anthocyanidin flavonoid that contributes to the intense blue coloration in many fruits and vegetables, such as blackcurrant, eggplant, black grapes, red cabbage, and blackberries, and is abundant in pomegranate fruit extract [108,109]. Delphinidin is an anthocyanidin exhibiting potent antioxidant, anti-inflammatory, and antitumor properties.…”

Section: Delphinidinmentioning

confidence: 99%

Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals

Bhattacharjee

Dashwood

2020

Antioxidants

Epigenetics has provided a new dimension to our understanding of nuclear factor erythroid 2–related factor 2/Kelch-like ECH-associated protein 1 (human NRF2/KEAP1 and murine Nrf2/Keap1) signaling. Unlike the genetic changes affecting DNA sequence, the reversible nature of epigenetic alterations provides an attractive avenue for cancer interception. Thus, targeting epigenetic mechanisms in the corresponding signaling networks represents an enticing strategy for therapeutic intervention with dietary phytochemicals acting at transcriptional, post-transcriptional, and post-translational levels. This regulation involves the interplay of histone modifications and DNA methylation states in the human NFE2L2/KEAP1 and murine Nfe2l2/Keap1 genes, acetylation of lysine residues in NRF2 and Nrf2, interaction with bromodomain and extraterminal domain (BET) acetyl “reader” proteins, and non-coding RNAs such as microRNA (miRNA) and long non-coding RNA (lncRNA). Phytochemicals documented to modulate NRF2 signaling act by reversing hypermethylated states in the CpG islands of NFE2L2 or Nfe2l2, via the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), through the induction of ten-eleven translocation (TET) enzymes, or by inducing miRNA to target the 3′-UTR of the corresponding mRNA transcripts. To date, fewer than twenty phytochemicals have been reported as NRF2 epigenetic modifiers, including curcumin, sulforaphane, resveratrol, reserpine, and ursolic acid. This opens avenues for exploring additional dietary phytochemicals that regulate the human epigenome, and the potential for novel strategies to target NRF2 signaling with a view to beneficial interception of cancer and other chronic diseases.