Navigating Calcium and Reactive Oxygen Species by Natural Flavones for the Treatment of Heart Failure

Abstract

Heart failure (HF), the leading cause of death among men and women world-wide, causes great health and economic burdens. HF can be triggered by many factors, such as coronary artery disease, heart attack, cardiomyopathy, hypertension, obesity, etc., all of which have close relations with calcium signal and the level of reactive oxygen species (ROS). Calcium is an essential second messenger in signaling pathways, playing a pivotal role in regulating the life and death of cardiomyocytes via the calcium-apoptosis link mediated by the cellular level of calcium. Meanwhile, calcium can also control the rate of energy production in mitochondria that are the major resources of ROS whose overproduction can lead to cell death. More importantly, there are bidirectional interactions between calcium and ROS, and such interactions may have therapeutic implications in treating HF through finely tuning the balance between these two by certain drugs. Many naturally derived products, e.g., flavones and isoflavones, have been shown to possess activities in regulating calcium and ROS simultaneously, thereby leading to a balanced microenvironment in heart tissues to exert therapeutic efficacies in HF. In this mini review, we aimed to provide an updated knowledge of the interplay between calcium and ROS in the development of HF. In addition, we summarized the recent studies (in vitro, in vivo and in clinical trials) using natural isolated flavones and isoflavones in treating HF. Critical challenges are also discussed. The information collected may help to evoke multidisciplinary efforts in developing novel agents for the potential prevention and treatment of HF.

A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment

“…( Mukund et al, 2017 ; Jaiswal et al, 2019 ; Kim and Park, 2020 ; Javed et al, 2021 ). Apigenin and genistein have been launched into market as dietary supplements for decades; meanwhile, they are also actively tested in clinical trials, especial for genistein as more clinical trials use it as a candidate for the treatment of various diseases including malignant cancers ( Yu et al, 2021 ). Thus, in the current mini-review, we attempted to have an overview of the progress made in the past decade of the studies (2012–2021) of apigenin and genistein in the treatment of PCa, including resistant forms of PCa, as flavonoids have also shown promising therapeutic application in resistant cancers ( Ye et al, 2019 ).…”

Editorial: Novel Small-Molecule Agents in Overcoming Multidrug Resistance in Cancers

“…Ji et al conducted an interesting comparison of the flavones apigenin and genistein, two isomers that show similar yet different activities and mechanisms in prostate cancer. Importantly, genistein has been extensively studied in lab and in clinical trials for many diseases including cancers ( Russo et al, 2016 ; Yu et al, 2021 ), and it has been used as nutritional supplement on market for decades. Genistein appears to be a more promising drug candidate and lead compound than its counterpart apigenin, since much more combinational regimens were developed and evaluated using genistein as a chemo-sensitizer.…”