Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

Abstract

<jats:p>A large number of diverse mechanisms that lead to cytoprotection have been described to date. Perhaps, not surprisingly, the role of mitochondria in these phenomena is notable. In addition to being metabolic centers, due to their role in cell catabolism, ATP synthesis, and biosynthesis these organelles are triggers and/or end-effectors of a large number of signaling pathways. Their role in the regulation of the intrinsic apoptotic pathway, calcium homeostasis, and reactive oxygen species signaling is well documented. In this review, we aim to characterize the prospects of influencing cytoprotective mitochondrial signaling routes by natural substances of plant origin, namely, flavonoids (e.g., flavanones, flavones, flavonols, flavan-3-ols, anthocyanidins, and isoflavones). Flavonoids are a family of widely distributed plant secondary metabolites known for their beneficial effects on human health and are widely applied in traditional medicine. Their pharmacological characteristics include antioxidative, anticarcinogenic, anti-inflammatory, antibacterial, and antidiabetic properties. Here, we focus on presenting mitochondria-mediated cytoprotection against various insults. Thus, the role of flavonoids as antioxidants and modulators of antioxidant cellular response, apoptosis, mitochondrial biogenesis, autophagy, and fission and fusion is reported. Finally, an emerging field of flavonoid-mediated changes in the activity of mitochondrial ion channels and their role in cytoprotection is outlined.</jats:p>

Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns

“…Synthesis of ATP by catabolism of carbon-rich sources via oxidative phosphorylation is one of the major roles of mitochondria. The integrity of the inner mitochondrial membrane is very much essential to normal physiological and biophysical functioning [ 93 ]. Mitochondrial damage during oxidative insult like the accumulation of cardiotoxins or due to ischemia/reperfusion is considered a key event leading to cardiomyocytes dysfunction and apoptosis [ 94 ].…”

Fisetin Inhibits NLRP3 Inflammasome by Suppressing TLR4/MD2-Mediated Mitochondrial ROS Production

“…Fisetin (3,7,3′,4′-tetrahydroxy flavone) is a flavonol that is ubiquitous in trees, fruits, and vegetables [ 16 , 17 ]. It has been reported that fisetin has numerous pharmacological properties, including anticancer [ 18 ], antioxidative [ 19 ], antimelanogenic [ 20 ], and anti-inflammatory [ 21 ] activities.…”

The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

“…Such bioactivities were mediated through the interference with the inflammation and apoptosis processes [ 10 , 27 , 30 , 31 , 32 ]. Moreover, phenolic compounds and flavonoids in particular are known for their anti-inflammatory activity [ 87 , 88 ] besides which they have the ability to reduce apoptosis in normal cells triggered by various stimuli [ 89 ]. Therefore, the isolated compounds as well as the other compounds which we identified them previously in C. annua extract (mainly phenolics) [ 29 ] were scrutinized using protein-ligand docking to predict their binding interactions towards the caspase-3 (PDB:6 CKZ) and IFN-γ (PDB: 2R3Z) proteins obtained from the Protein Data Bank (MOE ® -2019) in a trial to link these phytochemicals with the experimental results.…”