Sheep skin collagen peptide exerts an anti-fatigue effect by ...

Highlights

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  Sheep skin collagen peptide can extend the exhaustion swimming time in mice.

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  SSCPs improve energy metabolism via the AMPK/PGC-1α axis.

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  SSCPs can regulate the NRF2/HO-1 axis to reduce oxidative stress caused by exercise.

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  SSCPs can mitigate mitochondrial dysfunction caused by oxidative stress.

Abstract

The development of bioactive substances to mitigate exercise-induced fatigue is crucial for enhancing physical recovery and performance. This study explores the anti-fatigue effects and mechanisms of collagen peptides derived from sheep skin. The mechanism of anti-fatigue focuses on AMPK/PGC-1α and NRF2/HO-1 pathways. These peptides, characterized by elevated levels of arginine and branched-chain amino acids, demonstrate significant anti-fatigue properties. Mice administered collagen peptides exhibited a prolonged swimming time of 15 min, reflecting a 55% increase compared to the control group (n = 8). This enhanced endurance is likely due to an increase in slow-twitch muscle fibers, which are more resistant to fatigue. Further analysis revealed that the peptide administration group showed increased expression of AMPK and PGC-1α at both the gene and protein levels. Collagen peptides also promoted energy metabolism and ATP content in C2C12 muscle cells in vitro, as well as in skeletal muscle in vivo. Additionally, these peptides facilitated the nuclear accumulation of NRF2 protein and reduced the expression of Keap-1. This led to an improvement in the body's antioxidant capacity, evidenced by elevated expression of SOD, GSH-Px, and HO-1. Moreover, collagen peptides reduced MDA accumulation and enhanced mitochondrial function by activating the NRF2/HO-1 axis. Consequently, collagen peptides exhibit anti-fatigue effects through two primary mechanisms: enhancing energy metabolism via the AMPK/PGC-1α axis and reducing oxidative damage through the NRF2/HO-1 axis.

Introduction

Fatigue is a multifaceted condition characterized by an overall decline in vitality, muscular strength and cognitive abilities. It may arise due to a multitude of causes, encompassing intense physical exertion, extended periods of physical engagement, enduring mental strain, and various pathological states. Exercise-induced fatigue, commonly referred to as muscle fatigue, is specifically identified by the muscles' diminished capacity to sustain the necessary level of contraction following vigorous exercise. This state is distinguished by a decrement in muscle efficacy and an encompassing sense of exhaustion. In contemporary society, the issue of fatigue associated with sports has emerged as a notable concern, adversely affecting individuals' routine functions and holistic health. Consequently, the identification of bioactive compounds possessing anti-fatigue attributes is crucial for enhancing the quality of life.

Several foodborne active ingredients have demonstrated anti-fatigue effects, including bioactive peptides, amino acids, polysaccharides, and polyphenols. For instance, ginseng polysaccharide significantly prolongs swimming time in exhaustive swimming mice (Yu et al., 2022). Collagen peptides, as bioactive components, offer various health benefits. Ren et al. reported that supplementation with tilapia skin collagen peptide significantly extended exhaustive swimming time in loaded mice (Qu et al., 2022). Zhu et al. analyzed that activation of energy metabolism in skeletal muscle of mice after gavage of maca hydrolysate may upregulate mitochondrial biogenesis and function (Zhu et al., 2021). Ren et al. showed that supplementation with tilapia skin collagen peptide significantly prolonged exhaustive swimming time in loaded mice (Ren et al., 2020). This effect is attributed to multiple mechanisms, including decreased serum metabolite levels, improved glycogen supply, and enhanced endogenous antioxidant enzyme activity. As the impact of fatigue on the daily lives of individuals intensifies, there is an escalating curiosity regarding the potential therapeutic efficacy of natural compounds, including collagen peptides.

Peptides are known to alleviate fatigue by regulating energy metabolism, reducing metabolite accumulation, and inhibiting oxidative stress (Coggan et al., 1989; Wang et al., 2021a). The relationship between energy metabolism and fatigue is complex, involving energy production, neuroendocrine regulation, and psychological factors (Lei et al., 2024; Zhang et al., 2017). ATP, the primary energy source in the body, is predominantly produced in mitochondria through the tricarboxylic acid cycle and the electron transport chain. Activation of the AMPK/PGC1-α pathway in skeletal muscle promotes mitochondrial biogenesis, which can enhance exercise capacity (Qu et al., 2022; Zhao et al., 2023). Disruption of body balance due to metabolite accumulation can affect energy metabolism and muscle function, leading to chronic inflammation, oxidative stress, and cellular damage, which contributes to fatigue (Li et al., 2018). The NRF2 signaling pathway regulates oxidative stress; under stress conditions, NRF2 translocates to the nucleus and, in conjunction with other factors, regulates the expression of various antioxidant enzymes, enhancing the body's antioxidant capacity (Wang et al., 2021b; Yan et al., 2024). Nevertheless, the question of whether sheep skin collagen peptides (SSCPs) possess anti-fatigue attributes, as well as the underlying mechanisms of their potential anti-fatigue effects, remains to be elucidated.

This study aims to investigate the anti-fatigue effects of collagen peptide through the AMPK/PGC-1α and NRF2/HO-1 pathways. The peptide-treated group exhibited a swimming time twice as long as the control group. This improvement is likely due to an increase in the number of slow-twitch muscle fibers, which are more resistant to fatigue, and enhanced energy metabolism. Our findings suggest that SSCPs promote ATP production in C2C12 myotubes by activating AMPK and PGC-1α gene and protein expression. Additionally, SSCPs reduce Keap-1 expression, disrupting its binding to NRF2 and inhibiting NRF2 ubiquitination and degradation. This results in NRF2 nuclear translocation and increased expression of antioxidant factors. Consequently, SSCPs enhance energy metabolism via the AMPK/PGC-1α axis and reduce oxidative damage through the NRF2/HO-1 pathway, thus exerting their anti-fatigue effects.

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Section snippets

Materials and chemicals

SSCPs were provided by Zhongtai Kangyuan Biotechnology Co., LTD. Mouse C57BL/6 mice were purchased from Liaoning Changsheng Biotechnology Co., LTD. C2C12 cells were obtained from Wuhan Pricella Biotechnology Co., Ltd. Lactic acid (LA, A019-2-1), blood urea nitrogen (BUN, C013-2-1), lactate dehydrogenase (LDH, A020-2-2), ATP content (A095-1-1), and antioxidant enzyme detection kits were procured from Nanjing Jiancheng Bioengineering Institute. All other reagents used in this study were of

High levels of arginine and branched-chain amino acids in SSCPs

The amino acid composition of SSCPs is detailed in Fig. 1D. The content of hydrolyzed amino acids in SSCPs was found to be 912.68 ± 17.05 mg/g. The specific amino acid composition ratios are provided in Table S1. Notably, arginine and branched-chain amino acids (BCAAs) are present in high concentrations in SSCPs. Arginine constitutes 9.5% of SSCPs, while BCAAs make up 11.3%.

Efficient free radical scavenging by SSCPs

DPPH and ABTS assays measure the ability of SSCPs to scavenge free radicals. The antioxidant capacity of SSCPs was

Discussion

As the attention on anti-fatigue functional products increases, the development of food-derived natural active components with anti-fatigue properties is of particular importance. However, whether SSCPs possess anti-fatigue activity and the underlying mechanisms remain to be elucidated. This study conducts in vivo validation of the activity of SSCPs and explores their potential in vitro activity mechanisms. Studies have shown that SSCPs have high levels of arginine and branched-chain amino

Conclusion

In summary, this study investigated the anti-fatigue effects of SSCPs and their underlying mechanisms. Mice in the SSCP group exhibited a 55% increase in swimming time compared to the control group. SSCPs were shown to eliminate exercise-induced ROS in vivo by promoting NRF2 nuclear translocation and reducing mitochondrial oxidative DNA damage caused by free radicals. Furthermore, SSCPs enhance mitochondrial biogenesis and energy metabolism through the AMPK/PGC-1α axis. These results suggest

CRediT authorship contribution statement

Xiaoyu Ma: Writing – original draft, Visualization, Methodology, Data curation. Quanxi Wang: Software, Methodology, Data curation. Qi Yang: Resources, Methodology, Data curation. Ximing Yang: Supervision, Methodology. Xinran Liu: Software, Methodology. Baifeng Fu: Methodology, Data curation. Shuzhen Cheng: Writing – review & editing, Investigation, Conceptualization. Ming Du: Writing – review & editing, Investigation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgment

This study was supported by the Dalian High-level Innovative Talent Team Project (2023RG005).

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