molecules Review Polyphenols and Their Effects on Muscle Atrophy and Muscle Health Takeshi Nikawa * , Anayt Ulla and Iori Sakakibara   Citation: Nikawa, T.; Ulla, A.; Sakakibara, I. Polyphenols and Their Effects on Muscle Atrophy and Muscle Health. Molecules 2021, 26, 4887. https://doi.org/10.3390/ molecules26164887 Academic Editors: Yusaku Miyama, Jun Watanabe and Hiroko Isoda Received: 12 July 2021 Accepted: 9 August 2021 Published: 12 August 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Department of Nutritional Physiology, Institute of Medical Nutrition, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; anayatullah1988@gmail.com (A.U.); sakakibara.iori@tokushima-u.ac.jp (I.S.) * Correspondence: nikawa@tokushima-u.ac.jp; Tel.: +81-88-633-9248; Fax: +81-88-633-7086 Abstract: Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxida- tive stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphe- nols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabu- lar form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies. Keywords: antioxidants; polyphenols; flavonoid; muscle atrophy; proteolysis; mitochondrial dys- function; mitochondrial biogenesis; myogenesis; oxidative stress 1. Introduction The skeletal muscle is a plastic organ and the most abundant tissue in vertebrates. It plays a significant role in metabolism, movement, respiration, protection, daily physical activities, and the maintenance of posture and balance [1]. Generally, a healthy skele- tal muscle always maintains a good equilibrium between protein synthesis and protein degradation. Any physiological (aging) or pathological conditions that interfere with the catabolic and anabolic symmetry of proteins will lead to a reduced cross-sectional area (CSA) of muscle fibers and decreased muscle strength and mass, resulting in muscle atrophy. The three main conditions that trigger muscle atrophy are (I) disuse, including immobilization, denervation, bed rest, space flight, and aging; (II) chronic disease, includ- ing chronic heart failure, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, and cancer; and (III) medications, such as glucocorticoids [2,3]. Atrophy of the muscle reduces the quality of life and movement independence of the patients, thus imposing an additional financial burden on the health care system and causing increased morbidity and mortality. Hence, maintaining healthy muscles is necessary for preventing metabolic diseases and achieve healthy aging. Muscle mass is maintained via the regulation of various anabolic pathways. Among them, the PI3K/Akt/mTOR pathway is the most important, in which insulin/IGF-1 acts Molecules 2021, 26, 4887. https://doi.org/10.3390/molecules26164887 https://www.mdpi.com/journal/molecules