The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models

Abstract

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.

Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells

“…This compound has shown a potential to increase intracellular ATP and mitochondrial spare capacity in human primary myotubes cultured in low glucose media [46]. Thus, our results are in agreement with the current literature suggesting that naturally derived compounds can play a role in improving skeletal muscle function by enhancing ATP production and ameliorating mitochondrial dysfunction [17]. This also explains the increasing interest in understanding the therapeutic advantages of combining rooibos compounds to understand its therapeutic effects in ameliorating diverse metabolic complications [47,48].…”

“…Recently, researchers have reported that regular intake of polyphenols has been linked with the reduced risk of life-threatening diseases, including diabetes and other metabolic complications [10][11][12]. In fact, natural compounds such as genipin, resveratrol, quercetin, ursolic acid, and cinnamon have been reported to enhance insulin sensitivity and improve mitochondrial function in various preclinical models of metabolic disease [12][13][14][15][16][17]. Previous studies have shown that rooibos-rich polyphenolic compounds such as aspalathin and nothofagin can attenuate inflammation, oxidative stress, and insulin resistance in vitro and in vivo [11,[18][19][20].…”

Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells

“…In fact, there is a need to develop bioactive compounds found in foods or beverages to useful nutraceuticals that could be effectively used to manage metabolic diseases, such as T2D [11]. This is supported by growing preclinical evidence indicating that potential nutraceutical compounds, including dietary flavones found in daily consumed foods such as fruits and vegetables, as well as beverages such as tea, can modulate diverse biochemical reactions that are essential for improving metabolic function [26][27][28][29]. However, although such bioactive properties are acknowledged, certain critical issues, such as the determining the quantity of these active compounds in foods, as well as establishing their oral bioavailability, need to be resolved to better understand the therapeutic effects.…”

Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models

“…Here, injection with the isoflavone puerarin, at 100 mg/kg for 4 weeks, could downregulate the expression of a range of genes involved in mitochondrial biogenesis and oxidative phosphorylation, such as PGC-1α, NRF1/2, and transcription factor A (TFAM) in HFD-fed Wistar rats [ 13 ], whereas treatment with HFD containing the phenylpropanoid chicoric acid, at 0.03%, w/w for 6 weeks, was associated with improved glucose and insulin metabolism, while also reversing mitochondrial biogenesis and oxidative phosphorylation within the skeletal muscle in C57BL/6 mice fed HFD for 10 weeks [ 34 ]. Collaboratively, our group has increasingly reported on the potential therapeutic effects of bioactive compounds with abundant antioxidant effects, including polyphenols which are highly present in fruits and vegetables, in improving skeletal muscle function by ameliorating insulin resistance and targeting improving mitochondrial function [ 58 , 59 ].…”