Preclinical Evaluation of a Food-Derived Functional Ingredient to Address Skeletal Muscle Atrophy

Abstract

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.

Characterising the efficacy and bioavailability of bioactive peptides identified for attenuating muscle atrophy within a Vicia faba-derived functional ingredient

“…A predictive machine learning approach was used to predict peptides with two different activities, anti-inflammatory and protein synthesis, both these activities were chosen based on the activity of the natural hydrolysate, NPN_1 (PeptiStrong™) that was created to reduce inflammation and improve protein synthesis ( Cal et al., 2020 ). To predict anti-inflammatory activity, we focused on TNF-α reduction and used an untargeted approach ( Fig.…”

“…NPN_1 was prepared as previously described by Cal et al. (2020) ( Cal et al., 2020 ). Briefly, commercially obtained protein powder from V. faba (60–63% protein content; AGT Foods Europe, The Netherlands) was solubilised in an alkalising solution and homogenised by agitation.…”

“…Phosphorylation of S6 was measured as described by Cal et al. (2020) ( Cal et al., 2020 ). Briefly, C2C12 ​cells (8000 ​cells/cm 2 ) were seeded in growth medium in a 96-well plate.…”

“…Recently, a functional ingredient, NPN_1, derived from the V. faba was shown to address skeletal muscle loss ( Cal et al., 2020 ). In this study, Cal et al. (2020) reported beneficial effects on protein synthesis, protein degradation and TNF-α secretion in vitro .…”

Using Artificial Intelligence to Reduce Global Healthcare Costs through Discovery and Development of Nutritional Interventions

“…Another AI discovery characterised a functional ingredient, again derived from rice, that significantly improved physical strength and mobility in a double-blind placebo with an immuno-impaired ageing population [33]. Additionally, a similar approach identified a peptide within the pea plant that reduced cellular ageing in a double-blind placebo clinical trial [34], while other research proved that a peptide hydrolysate from fava bean has the ability to prolong muscle health [35]. Such examples demonstrate that the complexity of understanding the clinical benefits of plants can begin to be solved by the latest ML algorithms and that plant-derived functional ingredients can now be developed in a scientific manner at a minute fraction of the costs traditionally associated with pharmaceutical development.…”