Biological activity of hesperidin and its potential efficacy in treating exercise-induced asthma
Exercise induced asthma (EIA) refers to temporary airway narrowing that occurs during intense exercise, which can occur alone or accompanied by respiratory discomfort symptoms. EIA, as a chronic respiratory disease, not only induces discomfort symptoms such as excessive wheezing, stomach pain, and difficulty breathing, but also has a negative impact on physical and mental health. For example, in terms of physiology, EIA can cause respiratory inflammation, decreased lung ventilation function, decreased maximum oxygen uptake, increased uric acid levels, imbalanced cortisol secretion, and increased muscle oxidative stress damage. In severe cases, it can lead to chronic obstructive pulmonary disease, pulmonary arterial hypertension, and pulmonary heart disease, and even induce sudden death during exercise; In terms of psychological or mental health, EIA can lead to a decrease in sleep quality, reduce athletes’ positive emotions and happiness index, exacerbate depressive tendencies, disrupt the psychological rhythm of competition preparation, and increase the risk of psychological dysfunction during important events. The above-mentioned problems of EIA athletes will further weaken their athletic ability, hinder the normal performance of their competitive level, and ultimately lose their competitive advantage on the field.
Tangeretin, also known as 5,6,7,8,4 ‘- pentamethoxyflavone, is a widely present compound of methoxyflavones (PMFs) in citrus fruits (sweet oranges, wide skinned citrus, etc.) (see Figure 1). Due to its unique biochemical structure, hesperidin has low polarity and strong lipid solubility, and is easily soluble in substances such as benzene and ether. Therefore, it is more likely to penetrate the phospholipid bilayer and enter the cell membrane to exert its corresponding effects. Research shows that hesperidin has the biological activity of more than 80% of the active substances of polymethoxyflavones, and has positive effects on a variety of chronic diseases, such as type 2 diabetes, cardiovascular diseases, malignant tumors and neurodegenerative diseases, and has been widely used in many fields such as biology, medicine and health food. In addition, hesperidin has unique advantages such as stable physical and chemical properties, excellent drug like properties, good oral utilization rate, and “zero” doping prohibited substances. Compared with other nutrients or compound nutritional supplements, hesperidin is more suitable for athletes to use.

Research suggests that hesperidin may have enormous potential for application in the field of sports science. Our research team has taken the lead in exploring the application of hesperidin the field of sports. Animal experiments have shown that hesperidin can significantly improve the exercise endurance of Kunming mice, improve antioxidant enzyme activity, and significantly alleviate oxidative stress damage induced by exhaustive exercise; Human experiments have found that after taking oral hesperidin (200mg/d) for 5 weeks, the subjective fatigue of weightlifters is significantly relieved, and the serum cortisol and uric acid levels on an empty stomach in the morning are significantly reduced; After supplementing with hesperidin (200mg/d) for 4 weeks, the serum testosterone levels of track and field athletes significantly increased, and their body composition improved significantly; In addition, hesperidin can effectively alleviate the cortisol stress response and oxidative stress damage caused by intense exercise, accelerate the elimination of fatigue, and promote the recovery of the body. Although hesperidin is rich in various biological activities, its application in the field of sports is still in the exploratory stage. There are few reports on the use of hesperidin to intervene in the treatment of EIA. Therefore, this article summarizes, analyzes, and generalizes the pathogenesis of EIA, the biological activity of hesperidin, and its potential efficacy in EIA by reviewing relevant research literature at home and abroad. The aim is to provide a reference for the development of hesperidin related research in the field of sports science in China, as well as to provide research ideas and references for the application of hesperidin intervention therapy for EIA.

Compared with other compound supplements, hesperidin has many advantages such as diverse biological activities, stable physical and chemical properties, and no banned substances. Based on the positive effects of hesperidin applied to athletes in the early stage, we believe that hesperidin may be more suitable for use by athletes. However, before the large-scale promotion and application of dietary supplements or intervention drugs for hesperidin, the following three issues need to be addressed: first, the extraction of hesperidin. The content of hesperidin in plants is low and distributed discretely. If large-scale industrialization occurs, it will inevitably cause significant damage or waste of related plant resources, and even lead to the disappearance or extinction of some plants. Due to its tendency to form complexes with other secondary metabolites, minerals, fibers, etc., the extraction process of hesperidin is complex, and separation and purification are difficult. Secondly, the issue of low water solubility. Due to its small size, poor water solubility, and easy rapid degradation and metabolism in the body, hesperidin often cannot fully exert its active advantages in the body. The use of nanomedicine technology (such as spherical nanoparticles, polyester nanoparticles, etc.) can target and enhance drug bioavailability and pharmacokinetics. However, it is currently unclear whether this technology can be effectively used for hesperidin supplements or drug development. Thirdly, security issues. The preliminary animal toxicology test results indicate that daily supplementation of 1-5 mg/kg hesperidin has almost no negative effects on the body; Our team’s preliminary research also confirmed that participants did not experience any physical discomfort symptoms (such as vomiting, nausea, allergies, etc.) after receiving 4 weeks (200mg/d) or 5 weeks (200mg/d) of hesperidin intervention. However, the duration of such studies is relatively short, and there are currently no reports on the effects of long-term or high-dose supplementation of hesperidin on the body. There is also a lack of systematic pharmacokinetic and toxicological studies, and the safety of hesperidin needs further research and demonstration.
In summary, there is a high degree of fit and compensation between the biological activity of hesperidin and various EIA symptoms or derived problems (such as inflammation, oxidative stress damage, uric acid metabolism disorders, etc.) (see Figure 4). The excellent anti-inflammatory and antioxidant activities of hesperidin, as well as its regulatory effects on uric acid, dopamine, melatonin, and other indicators, suggest that hesperidin may have potential positive effects on EIA and may provide a new approach for athlete EIA intervention treatment. Future research should focus on the specific mechanism of action of hesperidin intervention therapy for EIA, and provide theoretical support for promoting the use of hesperidin intervention therapy for EIA through systematic pharmacological mechanism research, clinical trial research, and product development research.