Recent reports have highlighted the potential anti-obesity effects of epicatechin (EC) in regulating metabolism. Most studies have primarily used rodent models housed at standard temperatures (ST) 22°C ± 2°C. However, these mice may experience chronic cold exposure at ST, which can influence energy metabolism. Housing mice at thermoneutrality (TN) 28°C ± 2°C could provide a more accurate representation of human temperature conditions. Additionally, many studies focus solely on male animals, overlooking the significance of considering sex differences in the investigation of physiological and metabolic dysregulation. In our trial, we used both male and female C57Bl/6 mice, including lean and obese individuals. The mice were treated with either 12 mg or 20 mg of EC/kg of body weight (administered by gavage) over 12 weeks, five days a week, and were housed at either ST or TN. Contrary to previous reports, we found no anti-obesity effects from EC in either male or female mice at both doses. The mice exhibited similar weight gain, adipose tissue sizes, biochemical profiles, and liver fat accumulation when compared to obese, untreated animals. Furthermore, obese male mice supplemented with 20 mg of EC and housed at TN showed increased subcutaneous white adipose tissue (scWAT) weight and worsened glucose tolerance compared to their non-EC-treated counterparts. In conclusion, epicatechin administered by gavage did not improve obesity, liver steatosis, or insulin resistance in either male or female obese mice housed at ST or TN. This suggests that the route of administration and the EC dosage could influence its anti-obesity effects.

The inhibition of kynurenine aminotransferase II (KATII) is a target for treating several diseases with an excess of kynurenic acid (KYNA). KATII inhibitors exist, but they have adverse side effects, given their irreversible inhibition mechanism. This study aimed to discover potent and safe inhibitors of KATII by using computational and in vitro methods. We identified herbacetin and (-)-Epicatechin as reversible KATII inhibitors from a small library of natural compounds, whose Glide docking scores (-8.66 kcal mol-1 and-8.16 kcal mol-1, respectively) and MM/GBSA binding energies (-50.30 kcal mol-1 and -51.35 kcal mol-1, respectively), which are higher scores than the standard inhibitor, PF-04859989 (-7.12 kcal mol-1 and -38.41 kcal mol-1, respectively). The ADMET analysis showed that herbacetin and (-)-Epicatechin have suitable pharmacokinetic parameters, are moderately bioavailable, and have a safe toxicity profile. Their KATII inhibitory activity is in the range of IC50 values of 5.98± 0.18 µM and 8.76 ± 0.76 µM, respectively. Furthermore, the MTT assay for cell toxicity showed that the two compounds do not alter HepG2 cell viability at their required concentration for KATII inhibition. These results show that herbacetin and(-)-Epicatechin are suitable for KATII inhibition and appropriate candidates for further development of KATII inhibitors.

Epicatechin has been described as a polyphenol compound that promotes skeletal muscle restructuring, by expressing muscle regulation factors, activation of satellite cells and modulation of the main pathways associated with catabolism. However, the literature shows contrasting results of therapeutic effects and treatment protocols. Thus, the aim of this systematic review was to analyze the current literature addressing the molecular mechanism and clinical protocol of epicatechin on skeletal muscular atrophy in humans and animals. A search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library databases. The qualitative analysis showed a prevalence of the inhibitory action of epicatechin in myostatin expression and atrogenes FOXO, MAFbx and MuRF1. Epicatechin showed positive effects on increased follistatin and on the activation of the myogenic regulatory factors (Myf5, MyoD and myogenin). In addition, the studies evidenced the impact of epicatechin on the mitochondrias' biosynthesis in muscle fibers, activation of the signaling pathway of AKT/mTOR protein synthesis, and improvement of skeletal musculature performance, particularly when associated with physical training. Epicatechin showed promising clinical applicability through beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization allowing to draw more specific conclusions on its therapeutic use.