Research Progress on Anti-Fatigue Peptides from Abalone

As a class of small-molecule peptides with anti-fatigue bioactivity, anti-fatigue peptides exert remarkable biological and pharmacological effects in regulating human fatigue status. They are widely sourced from various organisms including animals, plants and microorganisms. In vivo, anti-fatigue peptides can modulate human energy metabolism, relieve fatigue, improve exercise capacity and enhance the body’s antioxidant capacity, which are of great significance for improving quality of life and promoting physical health. Among research on anti-fatigue peptides, abalone-derived anti-fatigue peptides have attracted extensive attention due to their unique source and prominent anti-fatigue efficacy.

As a precious marine biological resource, abalone is rich in high-quality protein, low in fat, and contains abundant amino acids, trace elements and multiple vitamins. Favored by modern people for its high nutritional value and health-care functions, it is regarded as a premium seafood ingredient [1] and gains worldwide popularity. Abundant proteins and peptides exist in the muscle, viscera and other tissues of abalone, among which multiple bioactive anti-fatigue peptides may be contained [2-3]. In-depth research on the sources, characteristics and action mechanisms of abalone anti-fatigue peptides not only facilitates comprehensive understanding of the nutritional and functional components of this marine resource, but also provides critical scientific evidence for the development of anti-fatigue products and pharmaceuticals. Such research boosts the exploitation and utilization of marine biological resources and injects new momentum into human health undertakings, bearing important theoretical and practical values.

Fatigue refers to physical and mental states arising after certain physical or mental activities, mainly manifested as muscle soreness, mental lassitude and declined exercise performance. Persistent fatigue adversely affects human health and may even trigger various chronic diseases. Therefore, exploring effective anti-fatigue interventions has become a research hotspot. Long-term physical exertion induces a series of physiological and biochemical changes in the human body, leading to insufficient energy reserves, bodily dysfunction and subsequent fatigue. If fatigue cannot be eliminated in a timely manner and accumulates to a certain threshold, overwork and even chronic fatigue syndrome may occur, which destabilizes the internal environment, weakens immune function, accumulates metabolic waste, and may further cause organic lesions, posing threats to human physical and mental health. In sports, excessive training or overload work induced by various factors can trigger fatigue. Accordingly, developing functional foods and pharmaceuticals to alleviate fatigue and accelerate physical recovery has become a research focus across multiple disciplines such as sports medicine and military medicine [4].

Prolonged physical exhaustion may lead to multiple disorders related to biological regulation and immune function, including aging, depression, cancer, multiple sclerosis and Parkinson’s disease. Most of these illnesses stem from chronic pain caused by the deficiency of one or several hormones. Additionally, diabetes, hyperthyroidism, anemia, high body mass index and liver diseases are also potential causes of fatigue. The pathogenesis of fatigue is highly complex, usually resulting from combined effects of multiple factors: insufficient energy supply, accumulation of secondary metabolites, oxidative stress, inflammation and immune dysfunction. Recent scientific studies reveal that inadequate energy provision and buildup of secondary metabolites during protein metabolism are the dominant contributors to fatigue onset [5].

The discovery of anti-fatigue peptides offers novel ideas and strategies to address this issue. Research on anti-fatigue peptides not only helps uncover the mechanisms and patterns of fatigue, but also opens new avenues for developing anti-fatigue products and drugs. Against this backdrop, this paper systematically reviews abalone anti-fatigue peptides from the perspectives of their sources, characteristics, action mechanisms, research methodologies, application prospects and future research directions, aiming to provide valuable references and guidance for studies in this field.

1 Sources of Abalone Anti-Fatigue Peptides

1.1 Introduction to Abalone Species

Abalone, also known as sea-ear, belongs to Haliotidae of Gastropoda (correction: the original text mistakenly wrote Cephalopoda; abalone is gastropod mollusk). It is an ancient marine shellfish with significant economic value and health-care functions. Abalone mainly distributes in temperate and cold coastal waters across global oceans, with abundant species in East Asian countries including China, Japan and South Korea. Based on external morphology and shell features, abalones are roughly classified into multiple species such as rim abalones and true abalones. Among them, Haliotis discus hannai, Haliotis diversicolor, Haliotis asinina, Haliotis ovina and Haliotis semistriata are common species along China’s coastal areas [6]. Distinct abalone species differ in morphology, growth habitats and nutritional composition; thus, thorough research on the sources of abalone anti-fatigue peptides helps fully exploit their nutritional and functional properties.

1.2 Growth Environment of Abalone

Abalones inhabit rocky and reef zones with smooth water flow, clean seawater and relatively high salinity, ranging from the low tide line of intertidal zones to waters 10 meters deep [7]. They have strict requirements for water temperature, salinity and water quality: the optimal growth temperature is 15–20 ℃, salinity 3.0%–3.5%, and pH 8.0–8.3. In such habitats, abalones fully absorb abundant nutrients from seawater, resulting in high contents of proteins, polysaccharides, trace elements and other nutrients in their muscle, viscera, gills and other tissues. These environmental conditions directly determine abalone quality and the content of anti-fatigue peptides, laying a material foundation for extracting such peptides.

1.3 Nutritional Components of Abalone

Abalone boasts comprehensive nutrients including proteins, unsaturated fatty acids, trace minerals, nucleic acids and polysaccharides. Protein is its primary nutritional component, featuring balanced amino acid profiles and high bioactivity. Furthermore, abalone muscle contains natural bioactive peptides, minerals and vitamins that exert vital nutritional and health-care effects on humans. Its viscera and gills are also rich in nutrients with high protein and polysaccharide contents, providing abundant raw materials for extracting anti-fatigue peptides. Therefore, abalone is a valuable source of anti-fatigue peptides worthy of in-depth investigation [3,6].

2 Characteristics of Abalone Anti-Fatigue Peptides

2.1 Composition and Structure of Abalone Anti-Fatigue Peptides

Anti-fatigue peptides generally refer to small oligopeptides composed of 2–10 amino acid residues, such as high-F-value oligopeptides from tilapia; polypeptides containing more than 10 amino acid residues also exist, exemplified by soybean peptides [4]. Widely applied in sports fields with remarkable efficacy, anti-fatigue peptides positively regulate bodily immune function and anti-stress capacity. They possess unique physicochemical properties as follows: (1) Most bioactive peptides have low molecular weights, while high-molecular-weight peptides are relatively rare; (2) Compared with intact proteins and free amino acids, they are more easily digested and absorbed without consuming bodily energy or increasing gastrointestinal burden; (3) Diverse peptide species with multiple biological activities; (4) Capability to act as molecular carriers [8].

Abalone peptides are mixed peptides generated via enzymatic hydrolysis or chemical hydrolysis of abalone proteins, mainly consisting of amino acid-rich polypeptides and a small amount of free amino acids. Approximately 40% of abalone peptides have molecular weights below 450 Da, indicating that most abalone peptides are short-chain peptides composed of 2–3 amino acid residues. Their small molecular structures facilitate digestion and absorption in the digestive tract. Abalone peptides contain abundant amino acids dominated by glutamic acid, aspartic acid and arginine; diverse combinations of these amino acids endow abalone peptides with versatile bioactivity and pharmacological properties [9-10]. In addition, abalone peptides exhibit complex spatial conformations including α-helices and β-sheets, whose structural features determine their diverse biological functions in vivo.

2.2 Functional Characteristics of Anti-Fatigue Peptides

Bioactive peptides are recognized as high-quality in vitro nutritional supplements for anti-fatigue purposes, capable of alleviating fatigue and enhancing bodily anti-fatigue capacity. With deepened understanding of the correlations between animal, human physiological activities and diseases, an increasing number of scholars have focused on endogenous metabolic products of organisms. Endogenous bioactive peptides function as hormonal modulators to regulate in vivo biochemical reactions, while exogenous bioactive peptides have been gradually proven to exert anti-fatigue effects. Studies demonstrate that anti-fatigue bioactive peptides not only supply essential amino acids for humans, but also maintain internal homeostasis as well as stable blood glucose and blood lipid levels during exercise. Moreover, they improve multiple bodily functions, including elevating red blood cell count, mitochondrial DNA content and activity of the mitochondrial respiratory chain, boosting exercise willingness and performance, and promoting systemic metabolism and cardiopulmonary function [11].

3 Action Mechanisms of Anti-Fatigue Peptides

Anti-fatigue peptides maintain bodily internal homeostasis, regulate organ functions, accelerate metabolism and improve physical work efficiency. When athletes ingest appropriate hydrolyzed protein peptides, their body mass (especially for lightweight individuals) and muscle strength increase, alongside elevated serum total calcium levels. These effects mitigate or inhibit side effects induced by exercise-triggered negative nitrogen balance, sustain or promote normal protein synthesis, and relieve various exercise-induced physiological changes, ultimately achieving anti-fatigue outcomes [12].

Recent studies confirm that certain bioactive peptides possess anti-fatigue activity, yet their exact underlying mechanisms remain unclear. Research and application of abalone anti-fatigue peptides are relatively limited. Based on comprehensive analysis of existing literature, their anti-fatigue mechanisms may involve the following pathways [13]

3.1 Regulation of Energy Metabolism

Adenosine triphosphate (ATP), creatine phosphate, glycogen and blood glucose are core energy suppliers throughout all life stages. Insufficient energy provision is a key factor leading to declined exercise performance and fatigue. Therefore, effective replenishment of bodily energy substrates is essential to sustain normal physical activity, creating growing demand for nutritional supplements, especially functional foods such as low-fat high-protein health products. Characterized by rapid digestion, absorption and utilization, bioactive peptides can quickly supply energy to the human body, qualifying them as high-quality anti-fatigue functional ingredients [14].

Carbohydrates serve as the primary energy source for humans; when carbohydrate reserves are depleted, the body catabolizes fat and protein as alternative energy substrates. Accordingly, maintaining stable blood glucose during training is critical to improving athletic performance. The main carbohydrate stores in the human body are muscle glycogen and liver glycogen. Muscle glycogen acts as the primary energy source in the early stage of exercise, and its gradual depletion impairs athletic performance. When muscle glycogen is exhausted, liver glycogen decomposes to stabilize blood glucose. Generally, higher glycogen storage correlates with stronger exercise tolerance; massive glycogen consumption inevitably induces fatigue. Thus, muscle glycogen, liver glycogen and blood glucose are key indicators linked to exercise fatigue [15].

Jia et al. [16] intragastrically administered chickpea oligopeptides to mice regularly and found that hepatic and muscle glycogen contents of mice after exhaustive exercise were significantly higher than those in the blank control group. Wei et al. [17] fed mice perilla seed peptides for 28 consecutive days prior to weight-loaded swimming tests; results showed that hepatic and muscle glycogen levels in the high-dose group increased markedly, proving that perilla seed peptides boost bodily energy supply to exert anti-fatigue effects.

3.2 Scavenging of Metabolic Waste Products

Anti-fatigue peptides slow the accumulation of fatigue-inducing substances in vivo. Physical exhaustion is usually accompanied by drastically elevated blood lactic acid and blood urea nitrogen (BUN) concentrations. Anti-fatigue peptides can significantly reduce circulating lactic acid and BUN levels in exercising organisms, thereby alleviating fatigue sensations [12].

Miao et al. [18] conducted anti-fatigue research by intragastrically feeding hemp seed oligopeptides to mice periodically. After exhaustive swimming, the medium- and high-dose groups exhibited remarkably lower blood lactic acid concentrations and lactic acid production rates compared with the blank group. Li et al. [19] administered tuna protein peptide products to mice and observed prolonged weight-loaded swimming time, as well as significantly decreased serum lactic acid and BUN levels in the medium-dose group. Furthermore, when carbohydrate supply is insufficient under fatigue conditions, proteins participate in energy metabolism. Since peptides are absorbed faster than intact proteins, peptide supplementation rapidly provides nitrogen sources to relieve fatigue.

3.3 Elimination of Free Radicals

Strenuous or prolonged exercise enhances oxidative phosphorylation to sustain continuous energy supply, resulting in massive generation of oxygen free radicals. Unremoved excess free radicals trigger lipid peroxidation. Their abnormal accumulation damages tissues and organs and may even cause cell death. Lipids are critical components of cell and organelle membranes; lipid peroxidation impairs cellular and subcellular structures. Mitochondria are the primary site of free radical production. Excessive free radicals disrupt mitochondrial membranes in muscle cells, hinder ATP synthesis, cause energy shortage and ultimately induce fatigue.

Multiple studies verify that anti-fatigue peptides efficiently eliminate metabolic waste to relieve fatigue. Additionally, they scavenge in vivo free radicals, suppress lipid peroxidation, and prevent structural damage and functional disorders of cells, thus realizing anti-fatigue efficacy [20-21].

3.4 Promotion of Damaged Tissue Repair

Exhaustive exercise destroys the structure and function of mitochondrial membranes, reducing energy production and triggering exercise-induced fatigue [22]. Yu [11] compared the mRNA expression level of cytochrome c oxidase subunit I (COX I) in skeletal muscle across mouse groups and found significantly upregulated COX I mRNA in medium- and high-dose treatment groups, indicating improved overall mitochondrial function during exercise and anti-fatigue effects. Jia [23] administered high-F-value corn peptides to rats before exhaustive exercise; compared with the control group, rats receiving corn peptides showed increased expression of mitochondrial fusion protein Mfn2 and decreased expression of mitochondrial fission protein Drp1 in skeletal muscle.

3.5 Modulation of Cellular Metabolic Enzymes

Cells contain abundant enzymes associated with energy metabolism, including pyruvate kinase (PK), malate dehydrogenase (MDH), succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Investigating the activity and content of energy metabolic enzymes facilitates in-depth understanding of anti-fatigue mechanisms. SDH and MDH, key enzymes in the tricarboxylic acid cycle, enhance aerobic metabolism capacity when activated; PK, the rate-limiting enzyme of glycolysis, improves anaerobic exercise performance [13].

Chen et al. [24] intragastrically administered wild hazelnut small-molecule peptides to mice. After exercise, medium- and high-dose groups showed significantly lower muscle CK levels and higher activities of serum SOD, GSH-Px and catalase (CAT) relative to the control group. Wang et al. [25] treated mice with sheep placenta peptides before weight-loaded swimming tests; results demonstrated reduced malondialdehyde (MDA) content and elevated SOD and GSH-Px activities, confirming anti-fatigue bioactivity.

4 Research Methodologies for Anti-Fatigue Peptides

4.1 Extraction of Abalone Anti-Fatigue Peptides

Enzymatic hydrolysis represents the dominant method for preparing abalone anti-fatigue peptides. This technique yields large quantities of small peptides with low production costs and eco-friendly reaction conditions, and has been widely adopted in the food industry. Commonly used proteases for hydrolysis include trypsin, pepsin, neutral protease, alkaline protease, papain, bacillus subtilis protease, flavourzyme and compound proteases. Studies reveal that combined application of two or more proteases often achieves superior hydrolysis efficiency compared with single enzymes [26].

Li et al. [27] hydrolyzed tuna meat using a combination of trypsin and flavourzyme to prepare tuna protein peptides. Subsequent weight-loaded swimming tests on mice showed that swimming time in low-, medium- and high-dose groups extended by 9.46%, 30.66% and 21.17% respectively versus the control group. Appropriate pretreatment of raw materials such as ultrasonic or microwave treatment shortens hydrolysis duration and optimizes hydrolysis outcomes [26]. Chen et al. [28] applied ultrasonic-assisted enzymatic hydrolysis to Babylonia areolata, increasing short-peptide yield by 1.1 times compared with non-ultrasonic treatment. Wang et al. [29] utilized microwave pretreatment to boost the hydrolysis efficiency of soft-shelled turtle protein. Furthermore, numerous scholars have optimized hydrolysis parameters to obtain high-activity anti-fatigue peptides via single-factor experiments, orthogonal tests and response surface methodology. Lou [30] optimized parameters including pH, hydrolysis temperature and enzyme dosage through orthogonal design, taking gelatin hydrolysis degree and superoxide anion radical scavenging capacity of hydrolysates as evaluation indicators, and acquired samples with optimal anti-fatigue performance.

4.2 Purification of Abalone Anti-Fatigue Peptides

Separation and purification of abalone anti-fatigue peptides aim to obtain samples with higher activity or purity while maximizing product yield. Summarizing extraction and analytical methods for abalone peptides, structural analysis and structure-activity relationship research are core segments of related studies, all of which rely on separation and purification technologies. Therefore, purification techniques are indispensable for research on abalone anti-fatigue peptides. Major targeted separation and purification technologies include electrophoresis, chromatography and membrane separation [12].

4.3 Activity Evaluation Methods for Abalone Anti-Fatigue Peptides

Fatigue involves complex physiological and biochemical processes. In 1996, China’s Ministry of Health issued the Procedures and Detection Methods for Functional Evaluation of Health Foods, which standardized testing protocols for anti-fatigue efficacy, categorized into two major types: exercise tests (weight-loaded swimming test, rod-climbing test) and biochemical indicators (blood lactic acid, blood urea nitrogen, hepatic/muscle glycogen, blood glucose, LDH, hemoglobin, creatine phosphate, etc.), with exercise tests serving as primary assessment tools. Exercise trials and biochemical detection must be combined. Animals require preliminary screening prior to exercise testing. A test substance is confirmed to possess anti-fatigue activity if one or more exercise tests and two or more biochemical indicators show positive results [31].

Two mainstream evaluation systems are applied: anti-fatigue endurance exercise tests and biochemical indicator detection. Common endurance tests include mouse rod-climbing assay and weight-loaded swimming assay. Typical biochemical indicators encompass serum CK, BUN, blood testosterone, blood lactic acid and glycogen. Quantifying these indicators post-exercise assesses fatigue severity and physical recovery degree. Combined utilization of these methods comprehensively evaluates the anti-fatigue efficacy of abalone peptides from multiple dimensions.

5 Application Prospects of Abalone Anti-Fatigue Peptides

As promising bioactive ingredients, abalone anti-fatigue peptides attract extensive attention for their research trends. Future research directions mainly focus on the following aspects [6]

5.1 In-Depth Exploration of Anti-Fatigue Mechanisms

Subsequent research needs to thoroughly elucidate the action mechanisms of abalone anti-fatigue peptides, including their regulatory effects on oxidative stress, modulation of energy metabolism and pathways improving exercise performance. Clarifying these mechanisms will provide solid scientific evidence for their practical application.

5.2 Development of Diversified Products

Future research will prioritize developing diversified products containing abalone anti-fatigue peptides, covering food, health food and pharmaceutical sectors. Further exploration of key technologies such as peptide extraction, purification, product preparation and storage stability will meet the demand for bioactive ingredients across different fields.

5.3 Innovative Research Based on Biotechnology

Biotechnological approaches will be adopted to innovate research on abalone anti-fatigue peptides, including the application of genetic engineering and optimization of biosynthetic pathways. These technologies offer novel strategies for large-scale peptide production and promote their popularization in anti-fatigue fields.

5.4 Combined Research of Abalone Anti-Fatigue Peptides with Other Bioactive Ingredients

Follow-up studies will focus on combining abalone anti-fatigue peptides with other natural bioactive components to explore their synergistic mechanisms and targeted efficacy for specific populations, providing theoretical and practical support for developing market-competitive anti-fatigue products.

6 Conclusions

6.1 Summary of Major Research Progress on Abalone Anti-Fatigue Peptides

As potential anti-fatigue bioactive peptides, abalone anti-fatigue peptides exert remarkable anti-fatigue effects in vivo. Studies on abalone proteins and peptides confirm that raw materials for extracting anti-fatigue peptides are abundant, including abalone muscle and viscera [2-3], laying a solid resource foundation for further exploitation. In addition, abalone anti-fatigue peptides feature low molecular weight, easy absorption and favorable stability, supporting their broad application in food, health food and pharmaceutical industries.

In terms of action mechanisms, abalone anti-fatigue peptides play vital roles in regulating oxidative stress, modulating energy metabolism and enhancing exercise capacity. Elucidation of these mechanisms establishes a theoretical basis for understanding their biological functions and clinical translation. Continuous improvement of research methodologies also provides robust technical support for studies on abalone anti-fatigue peptides, covering extraction, purification, structural identification and activity evaluation.

Future research needs to further clarify the molecular and cellular mechanisms of abalone anti-fatigue peptides, comprehensively revealing their functional pathways and key regulatory nodes. Meanwhile, research on application prospects should be strengthened to develop diversified products and offer more solutions for human fatigue management. In summary, abalone anti-fatigue peptides boast broad research prospects and exert far-reaching significance for advancing the whole anti-fatigue research field.

6.2 Significance and Prospects for Human Health and Fatigue Management

Abalone anti-fatigue peptides carry profound theoretical and practical value for human health and fatigue intervention. First, accelerated living pace and rising occupational and life stress in modern society lead to prevalent fatigue problems. Research and application of abalone anti-fatigue peptides provide novel interventions for mitigating human fatigue, delivering reliable health support and improving work efficiency and quality of life.

Furthermore, current reports on the exact in vivo action mechanisms of abalone anti-fatigue peptides remain scarce. They possess wide application prospects in food, health food and pharmaceutical industries. Exploitation of abalone anti-fatigue peptides drives industrial upgrading and innovation, enriches dietary structures and enhances the nutritional functionality of food products. As raw materials for health foods and pharmaceuticals, they offer new strategies for human health management and adjuvant treatment of diseases, greatly improving public physical conditions [32].

Research and application of abalone anti-fatigue peptides are of great significance with extensive market prospects, pioneering new directions for human health and fatigue regulation. It is predictable that abalone anti-fatigue peptides will generate substantial application value in food, health food and pharmaceutical sectors and achieve remarkable breakthroughs in anti-fatigue research.

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