Composition and method

Abstract

A composition and a method for use in neuroprotection or improving cognitive ability, enhancing athletic performance or improving muscle function, combatting inflammation, combatting aging, extending lifespan or improving healthspan, managing stress or improving mood. The composition comprises: salidroside or a pharmaceutically acceptable salt, ester, or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

Description

Composition and Method Technical Field

[0001] This invention belongs to the technical field of dietary or nutritional supplements; specifically, the compositions involved contain rhodioloside or its pharmaceutically acceptable salts, esters or derivatives; and ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs or derivatives. Background Technology

[0002] Rhodiola rosea has historically been used as a valuable herbal supplement due to its remarkable adaptogenic properties. Rhodioloside is the main active compound isolated from the Rhodiola rosea plant. Rhodioloside possesses various pharmacological effects, including anti-fatigue, immunomodulatory, and free radical scavenging. As a compound with broad pharmacological activity, rhodioloside exhibits multifaceted health-promoting effects. It has a significant anti-fatigue effect, helping to alleviate fatigue after stress and improving physical endurance and vitality. Rhodioloside also plays an important role in immunomodulation, enhancing the body's immune function and increasing its resistance to disease. Furthermore, by acting at the cellular level, rhodioloside slows down the cellular aging process, scavenges free radicals, and protects the body from free radical damage, thereby helping to maintain skin elasticity and bodily function. Therefore, rhodioloside has broad application prospects in health products, pharmaceuticals, and cosmetics.

[0003] Ergothioneine is a natural compound with excellent antioxidant and anti-inflammatory properties. It primarily exerts its antioxidant function in mitochondria, protecting mitochondrial components from oxidative damage, and also demonstrates outstanding anti-inflammatory and anti-aging effects.

[0004] As we age, our bodies may experience a "precipitous decline in aging." Signs of aging include loose skin, weakened muscles, osteoporosis, decreased vision and hearing, weakened immunity, and cognitive decline. Other symptoms may include graying hair, tooth loss, memory loss, and slowed reaction time. There are many reasons why people are increasingly focused on anti-aging, including our lifestyles, advancements in medical science, and the desire for longevity and health. The pursuit of longevity is a significant factor. In the past, average lifespans were relatively short, and many people faced health problems or even died in middle age. However, advancements in modern medicine and technology have allowed people to enjoy life for longer. This pursuit of longevity is driven by a desire for more time and opportunities to achieve unfulfilled goals and dreams. Anti-aging is not only about longevity but also about reducing the risk of disease. Many age-related diseases, such as heart disease, cancer, and diabetes, are related to the body's aging process. By taking anti-aging measures, people can reduce their risk of developing these diseases. Therefore, anti-aging focuses not only on extending life but also on improving the quality of life. Therefore, extending lifespan or improving healthy lifespan is crucial for maintaining a positive mindset and quality of life.

[0005] Human stress response refers to a series of spontaneous adaptive physical and psychological responses to sudden or intense external stimuli (such as threats, challenges, or stressful situations). The hypothalamic-pituitary-adrenal (HPA) axis, a crucial component of the neuroendocrine system, participates in controlling the stress response through the interaction of a series of hormones, regulating various bodily activities such as digestion, the immune system, mood, sexual behavior, and energy storage and consumption. These regulatory outcomes include physiological changes, such as increased heart rate, elevated blood pressure, and elevated blood sugar levels to provide emergency energy; and psychological adjustments, such as improved concentration, increased alertness, and faster decision-making, to cope with external stimuli. The stress response is a self-protective mechanism developed through long-term human evolution, but prolonged or excessive stress can have negative health effects.

[0006] Psychological problems refer to abnormalities or distress in an individual's thinking, emotions, or behavior. These abnormalities may stem from multiple factors, including physiological, environmental, social, and psychological factors, affecting an individual's daily life, work, and learning abilities. Emotional stress refers to a state of tension, anxiety, or unease experienced when facing various life events or challenges, usually accompanied by physiological reactions such as increased heart rate and elevated blood pressure. In today's society, with the accelerated pace of life and intensified work competition, people generally face psychological and emotional stress from work, family, and interpersonal relationships. These stimuli can trigger stress responses in the body, affecting not only individual mental health but also potentially leading to physical illness and a decline in social function, becoming a social problem that urgently needs attention and resolution. This invention discovers that the combination of rhodioloside and ergothioneine may play a preventive and ameliorative role in neuroprotection and cognitive improvement, particularly in preventing and improving neurological damage or degeneration. This is of great significance to people facing various pressures and cognitive challenges in modern society and has significant application potential in the field of health care.

[0007] During exercise, muscle cells produce a large number of free radicals, which can lead to cell damage and inflammatory responses, thereby affecting athletic performance and recovery. Therefore, combining the potential benefits of rhodioloside and ergothioneine to develop a compound supplement that can effectively enhance athletic performance and improve muscle function will meet the market's broad demand for improving athletic ability and promoting recovery.

[0008] This study also found that the combination of rhodioloside and ergothioneine can be effectively applied to stress management or mood improvement, anti-inflammation, anti-aging or life extension or improved healthy lifespan. This composition and its application and method will have broad market demand. Summary of the Invention

[0009] To achieve the above objectives, in one aspect, the present invention provides a composition comprising rhodioloside or a pharmaceutically acceptable salt, ester, or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

[0010] In some embodiments, the composition is used for neuroprotection or improvement of cognitive function, enhancement of motor performance or improvement of muscle function, anti-inflammatory, anti-aging, life extension or improvement of healthy lifespan, stress management or improvement of mood.

[0011] In some implementation schemes, cognitive abilities include learning ability, recall ability, spatial perception ability, attention allocation ability, memory, emotion regulation ability, concentration ability, problem-solving agility, resistance to distractions, sustained attention, reaction ability, brain activity, and alertness. Enhancing athletic performance includes increasing running or swimming distance, increasing exercise time, increasing running or swimming speed, improving exercise endurance or power, reducing post-exercise inflammation and muscle fatigue, and improving muscle contraction during exercise. Improving muscle function includes alleviating or preventing muscle dysfunction, improving mitochondrial function in muscles, improving insulin resistance in muscles, increasing muscle mass, increasing muscle strength and endurance, improving glucose transport and metabolism in skeletal muscle, alleviating or preventing muscle injury, and reducing muscle fatigue. Anti-inflammatory effects include protecting cells and tissues, reducing the risk of chronic inflammation, improving immune function, relieving pain and discomfort, preventing or alleviating inflammation of the skin, cells, and nerves, and protecting endothelial cells. Anti-aging includes preventing, reducing, or delaying cellular aging, skin aging, or photoaging; stress management includes preventing, reducing, or eliminating oxidative, environmental, inflammatory, and psychological stress responses or pressures, improving or enhancing the recovery or restoration of oxidative, environmental, inflammatory, and psychological stress responses or pressures, and increasing the body's or mind's resistance to oxidative, environmental, inflammatory, and psychological stress responses or pressures; mood improvement includes relieving anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

[0012] In some implementations, neuroprotection or improved cognitive function is achieved by reducing plasma levels of neurofilament light chains, improving the recognition of novel objects, increasing brain-derived neurotrophic factor (BDNF), reducing neuroinflammation, reducing oxidative damage to neurons, and enhancing synaptic plasticity. Enhanced athletic performance or improved muscle function is achieved by promoting muscle protein synthesis, improving blood circulation and oxygen supply, providing antioxidant protection and reducing free radical damage, regulating hormone levels, and increasing nerve conduction velocity. Anti-inflammatory effects are achieved by inhibiting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-8 (IL-8), or by increasing anti-inflammatory cytokines. Anti-aging effects are achieved by enhancing mitochondrial biogenesis, alleviating mitochondrial dysfunction, reducing oxidative stress, enhancing cell function or cell repair, increasing cell activity, and raising p-AKT, AKT, and p-AMPK protein levels. Extended lifespan or improved healthy lifespan is achieved by improving mitochondrial function and enhancing antioxidant capacity. Stress management or improved mood is achieved by regulating the HPA axis to reduce cortisol levels, mitigating cellular oxidative damage, and reducing depressive-like behaviors.

[0013] In some embodiments, rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives are administered in doses of 1-2000 mg daily. In some embodiments, rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives may be administered in doses of 2-2000 mg, 5-1800 mg, 10-1500 mg, 15-1200 mg, 20-1000 mg, 25-800 mg, 30-500 mg, or 1-1000 mg, 5-800 mg, 5-300 mg, 5-100 mg, 10-500 mg, 10-300 mg, 10-100 mg, 15-100 mg, 20-80 mg daily.

[0014] In some embodiments, ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is administered in doses of 1-1000 mg daily. In some embodiments, ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof may be administered in doses of 2-1000 mg, 5-800 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, or 25-80 mg daily.

[0015] In some embodiments, the ratio of rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives to ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs, or derivatives is 1:50 to 500:1. In some embodiments, the ratio of rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives to ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs, or derivatives may be 1:20 to 300:1, 1:10 to 200:1, 1:5 to 100:1, 1:10 to 80:1, 1:1 to 80:1, 3:10 to 80:1, 3:1 to 50:1, 5:10 to 25:1, 5:1 to 25:1, 1:10 to 10:1, or 1:4 to 6:1.

[0016] In some embodiments, the composition is formulated as a nutritional supplement, food, beverage, or animal feed.

[0017] In some embodiments, the composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, syrups, injections, or functionalized food compositions.

[0018] In some embodiments, the composition is prepared as a solid or liquid formulation.

[0019] In another aspect, the present invention provides a nutritional supplement, food, beverage, or animal feed comprising the composition described above.

[0020] In some embodiments, the composition is present in the nutritional supplement, food, beverage, or animal feed at a weight ratio of 0.1% to 95%. In some embodiments, the weight ratio of the composition in the nutritional supplement, food, beverage, or animal feed may be 0.5% to 90%, 1% to 85%, 5% to 80%, 10% to 75%, 15% to 70%, 20% to 65%, 25% to 60%, 30% to 55%, or 35% to 50%.

[0021] In some implementations, nutritional supplements, foods, beverages, and animal feeds also contain dietaryly or pharmaceutically acceptable carriers.

[0022] On the other hand, the present invention provides a method for neuroprotection or improvement of cognitive ability, enhancement of motor performance or improvement of muscle function, anti-inflammatory, anti-aging, life extension or improvement of healthy lifespan, stress management or improvement of mood, the method comprising: administering a composition to a subject in need, the composition comprising rhodioloside or a pharmaceutically acceptable salt, ester or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof.

[0023] In some implementation schemes, cognitive abilities include learning ability, recall ability, spatial perception ability, attention allocation ability, memory, emotion regulation ability, concentration ability, problem-solving agility, resistance to distractions, sustained attention, reaction ability, brain activity, and alertness. Enhancing athletic performance includes increasing running or swimming distance, increasing exercise time, increasing running or swimming speed, improving exercise endurance or power, reducing post-exercise inflammation and muscle fatigue, and improving muscle contraction during exercise. Improving muscle function includes alleviating or preventing muscle dysfunction, improving mitochondrial function in muscles, improving insulin resistance in muscles, increasing muscle mass, increasing muscle strength and endurance, improving glucose transport and metabolism in skeletal muscle, alleviating or preventing muscle injury, and reducing muscle fatigue. Anti-inflammatory effects include protecting cells and tissues, reducing the risk of chronic inflammation, improving immune function, relieving pain and discomfort, preventing or alleviating inflammation of the skin, cells, and nerves, and protecting endothelial cells. Anti-aging includes preventing, reducing, or delaying cellular aging, skin aging, or photoaging; stress management includes preventing, reducing, or eliminating oxidative, environmental, inflammatory, and psychological stress responses or pressures, improving or enhancing the recovery or restoration of oxidative, environmental, inflammatory, and psychological stress responses or pressures, and increasing the body's or mind's resistance to oxidative, environmental, inflammatory, and psychological stress responses or pressures; mood improvement includes relieving anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

[0024] In some implementations, neuroprotection or improved cognitive function is achieved by reducing plasma levels of neurofilament light chains, improving the recognition of novel objects, increasing brain-derived neurotrophic factor (BDNF), reducing neuroinflammation, reducing oxidative damage to neurons, and enhancing synaptic plasticity. Enhanced motor performance or improved muscle function is achieved by promoting muscle protein synthesis, improving blood circulation and oxygen supply, providing antioxidant protection and reducing free radical damage, regulating hormone levels, and increasing nerve conduction velocity. Anti-inflammatory effects are achieved by inhibiting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-8 (IL-8), or by increasing anti-inflammatory cytokines. Anti-aging is achieved by enhancing mitochondrial biogenesis, alleviating mitochondrial dysfunction, reducing oxidative stress, enhancing cell function or cell repair, enhancing cell activity, and increasing the levels of p-AKT, AKT, and p-AMPK proteins; the extension of lifespan or improvement of healthy lifespan is achieved by improving mitochondrial function and enhancing antioxidant capacity; stress management or mood improvement is achieved by regulating the HPA axis to reduce cortisol levels, reduce cellular oxidative damage, and reduce depressive-like behaviors.

[0025] In some embodiments, rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives are administered in doses of 1-2000 mg daily. In some embodiments, rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives may be administered in doses of 2-2000 mg, 5-1800 mg, 10-1500 mg, 15-1200 mg, 20-1000 mg, 25-800 mg, 30-500 mg, or 1-1000 mg, 5-800 mg, 5-300 mg, 5-100 mg, 10-500 mg, 10-300 mg, 10-100 mg, 15-100 mg, 20-80 mg daily.

[0026] In some embodiments, ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is administered in doses of 1-1000 mg daily. In some embodiments, ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof may be administered in doses of 2-1000 mg, 5-800 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, or 25-80 mg daily.

[0027] In some embodiments, the ratio of rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives to ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs, or derivatives is 1:50 to 500:1. In some embodiments, the ratio of rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives to ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs, or derivatives may be 1:20 to 300:1, 1:10 to 200:1, 1:5 to 100:1, 1:10 to 80:1, 1:1 to 80:1, 3:10 to 80:1, 3:1 to 50:1, 5:10 to 25:1, 5:1 to 25:1, 1:10 to 10:1, or 1:4 to 6:1.

[0028] In some implementations, the subjects are humans or mammals.

[0029] In some embodiments, the composition is administered orally, intravenously, intramuscularly, intraperitoneally, or sublingually.

[0030] In some implementations, application may be performed once daily or every other day, or at a suitable frequency. In some implementations, application may continue for a period of time, such as 3 days to 1 week, 2 weeks to 7 weeks, or 4 weeks to 14 weeks.

[0031] In some embodiments, the composition is formulated as a nutritional supplement, food, beverage, or animal feed.

[0032] In some embodiments, the composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, syrups, injections, or functionalized food compositions.

[0033] In another aspect, the present invention provides the use of a composition in the preparation of a nutritional supplement, food, beverage, or animal feed for neuroprotection or improvement of cognitive ability, enhancement of motor performance or improvement of muscle function, anti-inflammatory, anti-aging, life extension or improvement of healthy lifespan, stress management or improvement of mood, the composition comprising rhodioloside or a pharmaceutically acceptable salt, ester or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog or derivative thereof.

[0034] In some implementation schemes, cognitive abilities include learning ability, recall ability, spatial perception ability, attention allocation ability, memory, emotion regulation ability, concentration ability, problem-solving agility, resistance to distractions, sustained attention, reaction ability, brain activity, and alertness. Enhancing athletic performance includes increasing running or swimming distance, increasing exercise time, increasing running or swimming speed, improving exercise endurance or power, reducing post-exercise inflammation and muscle fatigue, and improving muscle contraction during exercise. Improving muscle function includes alleviating or preventing muscle dysfunction, improving mitochondrial function in muscles, improving insulin resistance in muscles, increasing muscle mass, increasing muscle strength and endurance, improving glucose transport and metabolism in skeletal muscle, alleviating or preventing muscle injury, and reducing muscle fatigue. Anti-inflammatory effects include protecting cells and tissues, reducing the risk of chronic inflammation, improving immune function, relieving pain and discomfort, preventing or alleviating inflammation of the skin, cells, and nerves, and protecting endothelial cells. Anti-aging includes preventing, reducing, or delaying cellular aging, skin aging, or photoaging; stress management includes preventing, reducing, or eliminating oxidative, environmental, inflammatory, and psychological stress responses or pressures, improving or enhancing the recovery or restoration of oxidative, environmental, inflammatory, and psychological stress responses or pressures, and increasing the body's or mind's resistance to oxidative, environmental, inflammatory, and psychological stress responses or pressures; mood improvement includes relieving anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

[0035] In some implementations, neuroprotection or improved cognitive function is achieved by reducing plasma levels of neurofilament light chains, improving the recognition of novel objects, increasing brain-derived neurotrophic factor (BDNF), reducing neuroinflammation, reducing oxidative damage to neurons, and enhancing synaptic plasticity. Enhanced athletic performance or improved muscle function is achieved by promoting muscle protein synthesis, improving blood circulation and oxygen supply, providing antioxidant protection and reducing free radical damage, regulating hormone levels, and increasing nerve conduction velocity. Anti-inflammatory effects are achieved by inhibiting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-8 (IL-8), or by increasing anti-inflammatory cytokines. Anti-aging effects are achieved by enhancing mitochondrial biogenesis, alleviating mitochondrial dysfunction, reducing oxidative stress, enhancing cell function or cell repair, increasing cell activity, and raising p-AKT, AKT, and p-AMPK protein levels. Extended lifespan or improved healthy lifespan is achieved by improving mitochondrial function and enhancing antioxidant capacity. Stress management or improved mood is achieved by regulating the HPA axis to reduce cortisol levels, mitigating cellular oxidative damage, and reducing depressive-like behaviors.

[0036] In some embodiments, rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives are administered in doses of 1-2000 mg daily. In some embodiments, rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives may be administered in doses of 2-2000 mg, 5-1800 mg, 10-1500 mg, 15-1200 mg, 20-1000 mg, 25-800 mg, 30-500 mg, or 1-1000 mg, 5-800 mg, 5-300 mg, 5-100 mg, 10-500 mg, 10-300 mg, 10-100 mg, 15-100 mg, 20-80 mg daily.

[0037] In some embodiments, ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof is administered in doses of 1-1000 mg daily. In some embodiments, ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof may be administered in doses of 2-1000 mg, 5-800 mg, 8-500 mg, 10-300 mg, 15-200 mg, 20-100 mg, or 25-80 mg daily.

[0038] In some embodiments, the ratio of rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives to ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs, or derivatives is 1:50 to 500:1. In some embodiments, the ratio of rhodioloside or its pharmaceutically acceptable salts, esters, or derivatives to ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs, or derivatives may be 1:20 to 300:1, 1:10 to 200:1, 1:5 to 100:1, 1:10 to 80:1, 1:1 to 80:1, 3:10 to 80:1, 3:1 to 50:1, 5:10 to 25:1, 5:1 to 25:1, 1:10 to 10:1, or 1:4 to 6:1.

[0039] In some embodiments, the composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, syrups, injections, or functionalized food compositions. Attached Figure Description

[0040] Figure 1 shows the baseline level of NFL in mouse plasma before the start of the experiment.

[0041] Figure 2 shows the level of NFL in the plasma of mice in each group after 8 weeks of treatment.

[0042] Figure 3 shows the discrimination level of new objects in each group of mice after 8 weeks of treatment.

[0043] Figure 4 shows the performance results of each group of experimental animals in the measurement of maximum aerobic speed.

[0044] Figure 5 shows the exercise endurance results of each group of experimental animals in the exhaustion time test.

[0045] Figure 6 shows the results of forelimb muscle strength measurement in the grip test for each group of experimental animals.

[0046] Figure 7 shows the results of TNF-α in the experimental group.

[0047] Figure 8 shows the results of IL-6 in the experimental group.

[0048] Figure 9 shows the results of IL-8 in the experimental group.

[0049] Figure 10 shows the cell viability of each experimental group under CoCl2 damage.

[0050] Figure 11 shows the fluorescence intensity of the ROS probe DCFH-DA in each experimental group under CoCl2 damage.

[0051] Figure 12 shows the relative p-AKT / AKT protein ratio in each experimental group under CoCl2 damage.

[0052] Figure 13 shows the non-weakened stage of nematodes in each experimental group.

[0053] Figure 14 shows the relative fluorescence density of ROS probes in nematodes of each experimental group.

[0054] Figure 15 shows the serum TNF-α levels in each experimental group.

[0055] Figure 16 shows the serum AST levels in each experimental group.

[0056] Figure 17 shows the serum ALT levels in each experimental group.

[0057] Figure 18 shows the serum cortisol levels in each experimental group.

[0058] Figure 19 shows the SOD levels in each experimental group.

[0059] Figure 20 shows the immobility time of the forced swimming experiment for each experimental group.

[0060] Figure 21 shows the immobility time in the tail suspension experiment for each experimental group.

[0061] Figure 22 shows the levodopa levels in the serum of each experimental group.

[0062] Figure 23 shows the serum cortisol levels in each experimental group. Detailed Implementation

[0063] The present invention will now be further described with reference to preferred embodiments thereof. While the invention will be described in conjunction with preferred embodiments, it should be understood that they are not intended to limit the invention to these embodiments. Rather, the invention is intended to cover alternatives, modifications, and equivalents that may be included within the spirit and scope of the invention as defined in the claims.

[0064] As used herein, the term “or” is intended to include both “and” and “or”. In other words, the term “or” can also be replaced with “and / or”.

[0065] As used herein, unless the context clearly indicates otherwise, the singular forms “a / an” and “the” are intended to include the plural forms as well.

[0066] As used herein, the terms “comprising” or “including” or variations thereof refer to items that are included in the context of the term in their non-restrictive sense, but do not exclude items not specifically mentioned. It also includes the more restrictive verbs 'consistently composed of' and 'comprises of'.

[0067] As used herein, the terms “subject” or “mammal” are used interchangeably to refer to any animal to which the methods and compositions of this disclosure may be applied or administered. Animals may suffer from illness or other diseases, but they do not need to be sick to benefit from the methods and compositions of this disclosure. Therefore, any animal may utilize the disclosed compositions or become a recipient of the disclosed methods. Although the animal subject is preferably human, the methods and compositions of this invention are equally applicable to veterinary medicine, for example, for the treatment of domesticated species such as canines, felines, rodents, and various other pets; livestock such as cattle, horses, sheep, goats, pigs, etc.; and wild animals such as non-human primates in the wild or in zoos.

[0068] As used herein, the term "administration" refers to the process of delivering the disclosed composition or active ingredient to a subject. The compositions of the present invention are preferably administered via oral, intravenous, intramuscular, intraperitoneal, subcutaneous, topical, or sublingual routes, but may also be administered via other conventional routes to achieve the desired effect.

[0069] As used herein, the term "pharmaceutically acceptable" means pharmaceutically, physiologically, dietaryally, or cosmetically acceptable, and refers to combinations of compositions or reagents, materials or compositions and / or dosage forms thereof that are suitable for contact with human and animal tissues, compatible with other components of the composition, without excessive toxicity, irritation, allergic reactions or other problems or complications, and commensurate with a reasonable benefit / risk ratio, within the bounds of reasonable medical judgment.

[0070] In some embodiments, the compositions of the present invention can be prepared together with dietaryly or pharmaceutically acceptable carriers. These carriers include non-toxic, compatible substances commonly used in health foods and dietary supplements, animal feeds, and pharmaceutical preparations, such as sugars, starches, cellulose and their derivatives, powdered tragacanth gum, malt, gelatin, talc, oils, glycols, polyols, esters, agar, alginic acid, pyrogen-free water, isotonic saline, petrolatum, silicone oil, olive oil, and palm wax.

[0071] In some embodiments, the compositions of the present invention may be administered together with other supplements, such as vitamins, minerals, nootropics, and other supplements known in the art.

[0072] Various forms and formulations of the compositions are considered. The compositions will be formulated as nutritional supplements or dietary supplements, (medical) foods, beverages, animal feeds, in liquid or solid form. For oral administration, the compositions of the present invention may be in any suitable form, including solutions, tablets, gel capsules, capsules, or alternative nutritional foods or supplements.

[0073] The dosage of the active ingredient in this invention depends on the specific formulation and form. The dosage can also vary depending on factors such as the subject's sensitivity, age, sex, weight, and specific response. One or more doses can be administered once or multiple times daily or at a suitable frequency for any period of time. For example, an effective dose can be administered daily for one day, several days, multiple days, or indefinitely. In some embodiments, administration can continue for several days or longer, such as weeks or months.

[0074] The following examples illustrate selected embodiments of the present invention and are not intended to limit the scope of the invention. Example 1

[0075] One part of rhodioloside and one part of ergothioneine are mixed evenly in a three-dimensional mixer to obtain the composition described in Example 1. Example 2-18

[0076] Examples 2-18 were prepared in the same manner as in Example 1. The weight parts of rhodioloside and ergothioneine are shown in the table below:

[0077] [Corrected according to Rule 26, 2001.12.2025]

[0078] The nutritional supplements, foods, beverages, and animal feeds of the present invention comprise the compositions of the present invention and suitable dietaryally or pharmaceutically acceptable carriers. Example 19

[0079] C57BL / 6 mice, 6 weeks old and weighing 18-22 g, were selected. The mice were placed in an animal laboratory with a temperature of 22-25℃, humidity of 40%-60%, and a 12-hour light / 12-hour dark cycle (lights on at 8:00 AM and off at 8:00 PM). They were allowed free access to food and water and were allowed to acclimatize to the environment for one week before the experiment began.

[0080] A neurological model was established in mice by inducing neurological damage through chemical methods, specifically by intraperitoneal injection of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP selectively destroys dopaminergic neurons in the substantia nigra, leading to neurological damage symptoms similar to Parkinson's disease in mice.

[0081] Mice were randomly divided into the following groups: baseline group G0, control group G1, and test groups G2-G12, with 10 mice in each group. Mice in the baseline group (G0) and control group (G1) were administered saline via gavage. Mice in group G2 were administered the composition of Example 4 at a total dose of 50 mg / kg; mice in group G3 were administered the composition of Example 1 at a total dose of 50 mg / kg; mice in group G4 were administered the composition of Example 12 at a total dose of 50 mg / kg; mice in groups G5-G7 were administered rhodioloside at doses of 40 mg / kg, 25 mg / kg, and 10 mg / kg, respectively; mice in groups G8-G10 were administered ergothioneine at doses of 10 mg / kg, 25 mg / kg, and 40 mg / kg, respectively; mice in group G11 were administered rhodioloside at a dose of 50 mg / kg; and mice in group G12 were administered ergothioneine at a dose of 50 mg / kg. Except for mice in the baseline group, all other groups received intraperitoneal injections of MPTP solution at a dose of 30 mg / kg for 5 consecutive days. Mice in the baseline group received an equal volume of saline intraperitoneally. After injection, behavioral changes in the mice were observed to confirm successful model establishment. Except for the baseline group, mice in other groups that successfully established the model were administered saline or appropriate supplements via gavage for 8 weeks. The concentration designs for each group are shown in the table below:

[0082] [Corrected according to Rule 26, 2001.12.2025]

[0083] Mice were evaluated and tested before the start of the experiment (baseline period) and at week 8 of the experiment.

[0084] Detection of Neurofilament Light Chain (NFL) Levels in Blood: Blood samples were collected from mice in the baseline group (G0), control group, and test groups (G1 to G10) before the start of the experiment (baseline period) and at week 8. 0.5 ml of blood was collected from the orbital venous plexus of mice using a 1 ml syringe and placed in a microcentrifuge tube containing EDTA anticoagulant. The tube was gently inverted 8-10 times to mix. The plasma was then centrifuged at 3000 rpm for 10 minutes at 4°C to separate the plasma. The plasma samples were aliquoted into sterile EP tubes (100 μl per tube), clearly labeled with sample number, collection time, etc., and stored at -80°C for analysis. The neurofilament light chain (NFL) levels in plasma were detected using enzyme-linked immunosorbent assay (ELISA). As a component of neurons, NFL levels are elevated by all factors that cause neuronal or axonal damage; therefore, NFL levels can, to some extent, indicate cognitive functions such as attention allocation, memory, and emotion regulation. NFL data were analyzed using SPSS statistical software. Two-way ANOVA was used for comparisons among multiple groups. If a difference was statistically significant, further pairwise comparisons were performed between groups (using the LSD method). A p-value < 0.05 was considered statistically significant.

[0085] As shown in Figure 1, before the experiment, the results of the detection of NFL levels in the plasma of G0 baseline group and MPTP-induced model mice showed that compared with the baseline group, the NFL level in the model group was significantly increased by 89%, indicating that the MPTP-induced neurological injury model was successfully established (p<0.05). As shown in Figure 2, after 8 weeks of intervention with a combination containing different proportions of rhodioloside and EGT, the NFL levels in the mouse plasma were significantly reduced (p<0.05). Compared with the G1 group, the NFL levels in the G2-G4 groups decreased by 29%, 27%, and 31%, respectively. The G11 group decreased by 18%, and the G12 group decreased by 13%. This indicates that treatment with different proportions of rhodioloside and ergothioneine can protect and improve the cognitive function of mice. Example 20

[0086] C57BL / 6 mice, 6 weeks old and weighing 18-22 g, were selected. The mice were placed in a breeding environment with a temperature of 22-25℃, humidity of 40%-60%, and a 12-hour light / 12-hour dark cycle (lights on at 8:00 am and off at 8:00 pm) for 1 week to acclimatize before being divided into experimental groups.

[0087] Mice were randomly divided into the following groups: control group G1 and test groups G2-G12, with 10 mice in each group. Control group G1 was administered saline via gavage. Group G2 mice were administered the composition of Example 4 at a total dose of 50 mg / kg; Group G3 mice were administered the composition of Example 1 at a total dose of 50 mg / kg; Group G4 mice were administered the composition of Example 12 at a total dose of 50 mg / kg; Groups G5-G7 mice were administered rhodioloside at doses of 40 mg / kg, 25 mg / kg, and 10 mg / kg, respectively; Groups G8-G10 mice were administered ergothioneine at doses of 10 mg / kg, 25 mg / kg, and 40 mg / kg, respectively; Group G11 mice were administered rhodioloside at a dose of 50 mg / kg; and Group G12 mice were administered ergothioneine at a dose of 50 mg / kg. All mice were administered saline or appropriate supplements via gavage for 4 weeks. The concentration design for each group was the same as in Example 19.

[0088] Novel Object Recognition (NOR) Behavioral Experiment: A self-made behavioral testing box with dimensions of 40 cm × 25 cm × 20 cm (length × width × height) was used. Before the experiment, the testing box was thoroughly cleaned with 70% ethanol to remove any residual odor, and allowed to dry completely after the ethanol had evaporated. The experimental environment was kept quiet, with suitable lighting, and the temperature controlled at 22-24℃. Two days before the formal experiment, mice were placed in the testing box for 5 minutes each day to acclimatize to the environment without any objects inside. On the third day, training was conducted. The mice were placed in the testing box with their backs to the tester. Two identical objects (object A and object B) were placed inside the box. The objects were black plastic cubes, measuring 5 cm × 5 cm × 5 cm, placed in opposite adjacent corners, 5 cm from the box walls. The mice were allowed to explore freely for 5 minutes, during which their exploratory behavior was recorded. Exploratory behavior was defined as the mouse's head or nose facing the object at a distance of no more than 1 cm or touching the object; sitting on the object was not considered exploratory behavior. A high-definition camera was used to record the mice's behavior for subsequent analysis. Sixty minutes after training, a test was conducted. One object in the test box was replaced with a new object (object B, a white plastic cylinder, 4 cm in diameter and 6 cm in height). The mice were placed back in the test box, and the exploration time for the new object (object B) and the familiar object (object A) within 5 minutes was recorded, denoted as TN (exploration time for the new object) and TF (exploration time for the familiar object), respectively. The discrimination rate for each mouse was calculated as TN / (TN + TF). Analysis of the discrimination rate reflects the compound's effect on improving cognitive function. Data analysis was performed using GraphPad Prism 7.0 statistical software. Two-way ANOVA was used for comparisons among multiple groups. If the difference was statistically significant, further pairwise comparisons were performed between groups (using the LSD method). P < 0.05 was considered statistically significant.

[0089] As shown in Figure 3, the discrimination rates of mice were significantly increased after intervention with combinations containing different proportions of rhodioloside and EGT (P<0.05). Compared with group G1, the discrimination rates of mice in groups G2-G4 increased by 33%, 43%, and 29%, respectively. Group G11 saw an increase of 20%, and group G12 an increase of 22%. The results indicate that combinations of different proportions of rhodioloside and ergothioneine can improve the learning ability, recall ability, and spatial perception ability of mice, thus improving cognitive function. Example 21

[0090] Forty male C57BL / 6J mice (18–22 g, approximately 6–8 weeks old) were housed in a cage with a normal photoperiod (12 hours on, 12 hours off, lights on from 8:00 AM to 8:00 PM). The temperature was maintained at 22 ± 2℃, and the relative humidity was kept at 45–65%. All mice had free access to food and water. Mice were allowed one week to acclimatize before being used in any experiments.

[0091] The experiment was divided into 4 groups, with 8 mice in each group, as follows: Group 1 (control group): Mice were given oral saline (vehicle) from 9:30 AM to 11:30 AM daily, followed by food, for 1 week; Group 2 (composition of Example 12, total dose of 100 mg / kg): Administered from 9:30 AM to 11:30 AM daily, followed by food, for 1 week; Group 3 (composition of Example 1, total dose of 100 mg / kg): Administered from 9:30 AM to 11:30 AM daily, followed by food, for 1 week; Group 4 (composition of Example 4, total dose of 100 mg / kg): Administered from 9:30 AM to 11:30 AM daily, followed by food, for 1 week; The dosage of the supplement for each group is shown in the table below:

[0092] [Corrected according to Rule 26, 2001.12.2025]

[0093] Maximum Aerobic Speed ​​(MAS): MAS was measured on a treadmill (Exer-6 M treadmill; Columbus Instruments, Ohio, USA) according to the instruction manual. Mice were gradually adapted to the treadmill by increasing the speed and duration of exercise (four habituation sessions). The MAS measurement protocol began with a warm-up time (6 m·min). -1 Next 5 minutes, 8 m·min -1 Next 2 minutes, 10 m·min -1 (Next 2 minutes). Then, the treadmill speed increases by 2 m / min. −1 Run until exhaustion (defined as being unable to start running again after 10 seconds). The rate of exhaustion is considered MAS (Time of Exhaustion). Exhaustion test: The time to exhaustion was tested on a treadmill. After the warm-up step (6 minutes) -1 The next 5 minutes and 10 m·min -1 (In the next 5 minutes), increase running speed by 2 m / min. -1The mice were then run at this speed until they reached 70% of their maximum sustained energy (MAS). Exhaustion was defined as the inability to return to the treadmill after 10 seconds. Grasp test: A dedicated grip tester was used, ensuring accurate instrument calibration. The experimental environment was kept quiet and at a suitable temperature (20-26℃), and the mice were allowed to acclimatize for 5-10 minutes. The mice's forepaws were placed on the metal grid of the grip tester, and they were gently pulled backward. The maximum pull force when releasing the grid was recorded. Each mouse underwent three tests, with 1-2 minutes between each test. The maximum pull force was recorded each time, and the average value was calculated. After the tests, the instruments were cleaned and disinfected to prevent cross-infection. Exhaustion time and maximum pull force were analyzed using GraphPad Prism 7.0 statistical software. Two-way ANOVA was used for comparisons between multiple groups. If the differences were statistically significant, further pairwise comparisons were performed between groups (using the LSD method). A p-value < 0.05 was considered statistically significant.

[0094] After intervention with a combination containing different proportions of rhodioloside and EGT, the exhaustion time and maximum tensile strength of mice were significantly improved, indicating that the mice's motor performance and muscle function were enhanced. Example 22

[0095] The treatment of the experimental mice was the same as in Example 21. The experiment was divided into 6 groups, with 8 mice in each group, as follows: Group G1 (control group): mice were orally administered an equal volume of physiological saline (vehicle); Group G2: mice were administered rhodioloside 50 mg / kg; Group G3: mice were administered ergothioneine 50 mg / kg; Group G4 (the composition of Example 12, total dose 50 mg / kg); Group G5 (the composition of Example 1, total dose 50 mg / kg); Group G6 (the composition of Example 4, total dose 50 mg / kg); the treatment of the experimental groups was the same as in Example 21, and the dosage of supplements administered to each group is shown in the table below:

[0096] [Corrected according to Rule 26, 2001.12.2025]

[0097] The methods for maximal aerobic speed measurement (MAS), exhaustion time test, and grip strength test were the same as in Example 21. The results are shown in Figures 4-6. Figure 4 shows the performance of each group of experimental animals in the maximal aerobic speed measurement. Figure 5 shows the exercise endurance results of each group of experimental animals in the exhaustion time test. Figure 6 shows the measurement results of forelimb muscle strength of each group of experimental animals in the grip strength test. Compared with the control group, the use of rhodioloside alone (G2 group) improved maximal aerobic speed (MAS), exhaustion time, and grip strength by 52%, 16%, and 38%, respectively. The use of ergothioneine alone (G3 group) improved MAS, exhaustion time, and grip strength by 42%, 20%, and 23%, respectively. The improvement of the combination of rhodioloside and ergothioneine compared with the control group was significantly greater than that of the individual groups (G2 and G3 groups), especially in the G5 group, which showed improvements of 140%, 48.3%, and 101.9% in MAS, exhaustion time, and grip strength, respectively. Compared with the use of rhodioloside or ergothioneine alone, the combination of rhodioloside and ergothioneine improved these three indicators by more than 10%. The 1:1 ratio of rhodioloside to ergothioneine showed the best effect, improving these three indicators by more than 20%.

[0098] The above results indicate that the rhodioloside and ergothioneine composition of the present invention has a significant synergistic effect in enhancing athletic performance and improving muscle function, and its effect is significantly better than that of either single component used alone. Example 23

[0099] Cell culture: The normal human epidermal keratinization (NHEK) cell line was preserved in a humid environment (95% air and 5% carbon dioxide, 37°C) and cultured in DMEM supplemented with 10% heat-inactivated fetal bovine serum (FBS), 2 mM glutamine and 1% penicillin / streptomycin.

[0100] Medium-wave ultraviolet stimulation: NHEK cells were seeded in 12-well plates (50,000 cells / mL) until the cells reached approximately 80% confluence. The cells were washed once with phosphate-buffered saline (PBS) at room temperature, and then 0.5 mL of PBS was added to the cells before ultraviolet irradiation. Cells were exposed to 50 mJ / cm². 2Irradiated with UVB for 2 minutes. Immediately after irradiation, the PBS was replaced with the following solutions: Group 1 (control group): culture medium. Group 2 (experimental group 1): culture medium containing the solution from Example 12, with rhodioloside concentration of 0.5 μg / mL and EGT concentration of 2 μg / mL. Group 3 (experimental group 2): culture medium containing the solution from Example 1, with rhodioloside concentration of 1.25 μg / mL and EGT concentration of 1.25 μg / mL. Group 4 (experimental group 3): culture medium containing the solution from Example 4, with rhodioloside concentration of 2 μg / mL and EGT concentration of 0.5 μg / mL. The concentration designs of rhodioloside or EGT in other groups are shown in the table below:

[0101] [Corrected according to Rule 26, 2001.12.2025]

[0102] After changing the culture medium, return the cells to 37°C for 24 hours. Collect the cell culture supernatant and store at -80°C before use.

[0103] Detection of inflammatory factors: Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in the cell culture supernatant of each group were detected using an ELISA kit. Statistical analysis: Data analysis was performed using Graphpad Prism 7 software. Results are expressed as standard deviation (x ± s), and significance analysis was performed using a two-way ANOVA test.

[0104] NHEK cells incubated with medium containing different proportions of rhodioloside and EGT showed a significant decrease in the levels of TNF-α, IL-6, and IL-8 induced by UVB, compared to those treated with rhodioloside or EGT alone, indicating that the combination has a good anti-inflammatory effect. Example 24

[0105] Cell Culture: Human normal epidermal keratinocytes (NHEK) were cultured using the method described in Example 23. UVB Stimulation: Cell plating and UV stimulation were performed using the method described in Example 23. Immediately after irradiation, PBS was replaced with the following solutions: Group 1 (Control Group): Culture medium. Group 2 (Experimental Group 1): Culture medium containing the solution from Example 12, with rhodioloside concentration of 5 μg / mL and EGT concentration of 20 μg / mL. Group 3 (Experimental Group 2): Culture medium containing the solution from Example 1, with rhodioloside concentration of 12.5 μg / mL and EGT concentration of 12.5 μg / mL. Group 4 (Experimental Group 3): Culture medium containing the solution from Example 4, with rhodioloside concentration of 20 μg / mL and EGT concentration of 5 μg / mL. The concentrations of rhodioloside or EGT in other groups are shown in the table below.

[0106] [Corrected according to Rule 26, 2001.12.2025]

[0107] After changing the culture medium, the cells were stored at 37°C for 24 hours. The cell culture supernatant was collected and stored at -80°C before use.

[0108] The methods for detecting and statistically analyzing inflammatory factors are the same as in Example 23.

[0109] Figures 7-9 show the results of TNF-α, IL-6, and IL-8 in the experimental groups. NHEK cells incubated with medium containing different proportions of rhodioloside and EGT showed significantly lower levels of TNF-α, IL-6, and IL-8 induced by UVB compared to either rhodioloside or EGT alone (p < 0.05). Compared to group 1, TNF-α levels in groups 2-4 decreased by approximately 35%, 37%, and 31%, respectively; group 5 decreased by approximately 12%; and group 6 decreased by approximately 17%. IL-6 levels in groups 2-4 decreased by approximately 35%, 45%, and 27%, respectively; group 5 decreased by approximately 7%; and group 6 decreased by approximately 17%. IL-8 levels in groups 2-4 decreased by approximately 64%, 59%, and 52%, respectively; group 5 decreased by approximately 21%; and group 6 decreased by approximately 40%. This indicates that the combination has a better anti-inflammatory effect compared to using either the group alone. Example 25

[0110] Cell Culture: The HT22 cell line is a mouse hippocampal neuronal cell line derived from HT4. Under normal adherent growth conditions, double antibodies can be cultured in standard DMEM medium with added serum. Cells are stored in a humid environment (95% air and 5% carbon dioxide, 37°C), and cell morphology is examined under a microscope. Cell counts are performed on the cell suspension using a hemocytometer (Marienfeld, Germany) to monitor cell number.

[0111] Cobalt chloride (CoCl2) hypoxia model and in vitro stimulation: HT22 cells were seeded in 24-well plates (1×10⁻⁶ cells / wells). 4Cells were cultured at a concentration of 1 cell / mL until confluence reached approximately 80%. The old culture medium was removed, and the prepared rhodioloside / EGT / rhodioloside and EGT mixture was added. HT22 cells were then placed statically in a medium containing rhodioloside / EGT / rhodioloside and EGT for 1 hour, followed by treatment with cobalt chloride (50 µM) for 24 hours. Groups included a control group, CoCl2, CoCl2 with 2 μM rhodioloside, CoCl2 with 20 µM rhodioloside, CoCl2 with 200 µM rhodioloside, CoCl2 with 2 μM EGT, CoCl2 with 20 μM EGT, CoCl2 with 200 μM EGT, CoCl2 with 1 µM rhodioloside and 1 µM EGT, CoCl2 with 10 µM rhodioloside and 100 µM EGT, and CoCl2 with 100 µM rhodioloside and 100 µM EGT. After 24 hours, cell viability was measured using the CCK-8 assay. Cell supernatant was collected, and lactate dehydrogenase (LDH) levels were measured. Intracellular reactive oxygen species (ROS) and calcium levels were detected using appropriate specific labeled probes. 2+ And mitochondrial membrane potential (MMP). Intracellular p-AKT, AKT and p-AMPK protein levels were analyzed by Western blot.

[0112] Cell viability assay (CCK-8 assay): After 24 h of CoCl2 hypoxia injury, 10 µL of CCK-8 solution was added to every 100 µL of the system, and incubated for 4 h. The absorbance was measured at 450 nm using enzyme labeling. The cell viability calculation formula was: Cell viability = (Absorbance of experimental group / Absorbance of control group) × 100%. LDH assay: According to the kit manufacturer's instructions, soluble LDH in the culture medium supernatant was measured using ELISA. Finally, the absorbance value was obtained at 450 nm using the enzyme label, and the LDH content in the supernatant was calculated based on the standard curve. Intracellular ROS assay: According to the kit manufacturer's instructions, when reactive oxygen species are present in the cells, DCFH (2,7-dichlorofluorescein diacetate) is oxidized to generate a strong green fluorescent substance DCF (dichlorofluorescein). Its fluorescence has a large peak near the excitation wavelength of 502 nm and the emission wavelength of 530 nm, and the fluorescence intensity is directly proportional to the intracellular reactive oxygen species level. Intracellular Ca 2+ Detection: Detection of intracellular Ca 2+Concentration changes were observed, with an excitation wavelength of 488 nm and an emission wavelength of 525-530 nm. Intracellular MMP detection: JC-1 is an ideal fluorescent probe for detecting mitochondrial membrane potential (ΔΨm). JC-1 dye exhibits a potential dependence on accumulation within mitochondria. In normal mitochondria, JC-1 aggregates in the mitochondrial matrix, forming polymers that emit strong red fluorescence (Ex = 585 nm, Em = 590 nm). In unhealthy mitochondria, due to a decrease or loss of membrane potential, JC-1 exists only as monomers in the cytoplasm, producing green fluorescence (Ex = 514 nm, Em = 529 nm). Therefore, color changes directly reflect changes in mitochondrial membrane potential. The degree of mitochondrial depolarization can also be measured by the ratio of red to green fluorescence intensity. p-AKT, AKT, and p-AMPK protein levels: Changes in the type and expression of p-AKT and AKT proteins were identified and semi-quantitatively analyzed by transferring electrophoretically separated components from the gel to a solid support (such as an NC or PVDF membrane), followed by detection with specific antibodies. β-actin was used as an internal parameter. Graphpad 8.0 software was used for data analysis. Results are expressed as standard deviation (x ± s), and two-way ANOVA was used for significance analysis.

[0113] Figure 10 shows the percentage of cell viability in each experimental group. CoCl2 hypoxia damage leads to decreased cell viability. Among the single-treatment groups, the 20 µM EGT group and the 20 µM rhodioloside group significantly improved cell viability. Among the combination groups, the 10 µM EGT + 10 µM rhodioloside group showed the best effect in improving cell viability, and was superior to the single-treatment groups (20 µM EGT group and 20 µM rhodioloside group) at the same molar dose. The cell viability of the 10 µM EGT + 10 µM rhodioloside group was increased by approximately 11% compared to both the 20 µM EGT group and the 20 µM rhodioloside group. This indicates that the combination treatment can better alleviate cell damage. Therefore, subsequent studies used effective doses of 20 µM EGT and 20 µM rhodioloside, and 10 µM EGT + 10 µM rhodioloside for experiments.

[0114] Figure 11 shows the fluorescence intensity of the intracellular ROS probe (DCFH-DA) in each experimental group. The intracellular ROS content in the 10µM EGT+10µM rhodioloside group was significantly lower than that in the EGT group and the rhodioloside group. The ROS content in the 10µM EGT+10µM rhodioloside group was reduced by 32.2% and 34.3% compared with the 20µM EGT group and the 20µM rhodioloside group, respectively. This indicates that the combined treatment can alleviate oxidative stress caused by hypoxia.

[0115] Figure 12 shows the relative p-AKT / AKT protein expression ratios for each experimental group. The ratios in the 10µM EGT + 10µM rhodioloside groups were higher than those in the single-use groups. The relative p-AKT / AKT ratio in the 10µM EGT + 10µM rhodioloside groups was approximately 20% higher than that in the 20µM EGT and 20µM rhodioloside groups. This indicates that the combination therapy can more effectively activate the AKT pathway, provide a strong survival signal, and directly inhibit apoptosis.

[0116] Furthermore, this study found that the combined intervention of EGT and rhodioloside reduced LDH release more effectively than the single component, indicating that the combined use of EGT and rhodioloside has a protective effect on hypoxic nerve cells and reduces cell membrane damage. The combined use of EGT and rhodioloside also reduced calcium ion content more effectively than the single component, indicating that the combined treatment can alleviate intracellular calcium overload caused by hypoxia. The combined use of EGT and rhodioloside also effectively increased mitochondrial membrane potential more effectively than the single component, indicating that the combined treatment can effectively maintain or restore mitochondrial membrane potential (ΔΨm), thereby inhibiting hypoxia-induced mitochondrial dysfunction. In addition, it activated AMPK to effectively respond to energy stress and restore energy homeostasis.

[0117] After intervention, HT22 cells in the rhodioloside and ergothioneine groups showed lower levels of LDH, ROS, and intracellular calcium compared to the CoCl2 group. 2+ All levels decreased, while MMP recovered, indicating that HT22 cells suffered relatively mild damage, mitochondrial function improved, and cells were protected. Furthermore, while AKT levels remained constant, p-AKT and p-AMPK levels increased in HT22 cells, indicating enhanced cellular antioxidant capacity. By activating upstream signaling pathways of AKT and AMPK, HT22 cells were protected from CoCl2-mimicked hypoxia damage by stabilizing mitochondrial function, alleviating oxidative stress, inhibiting calcium overload, and directly blocking apoptosis. Experimental results show that the combination of rhodioloside and ergothioneine at different ratios can prevent, alleviate, or delay cellular senescence. Example 26

[0118] *C. elegans*: *C. elegans* was cultured in NGM agar (NaCl 3 g, peptone 2.5 g, agar 17 g, CaCl2 1 mL, MgSO4 1 mL, K2HPO4-KH2PO4 buffer 25 mL, cholesterol solution 1 mL) at a temperature controlled between 16-25℃. Subsequently, lyophilized *E. coli* OP50 sterilized by ultraviolet light was added.

[0119] Rhodioloside / EGT Treatment: Assay plates were prepared by adding 600 µL of nematode growth medium (NGM) agar (without peptone and CaCl2) containing 0.3% Tween 20 and amphotericin B (1 µg / mL) and ampicillin (100 µg / mL) and 2'-deoxy-5-fluorinated uridine (120 µM) with or without rhodioloside (1 mM, 10 mM, or 100 mM), with or without EGT (1 mM, 10 mM, or 100 mM), with or without rhodioloside (0.5 mM and 5 mM or 50 mM), and with or without rhodioloside (0.5 mM and 5 mM or 50 mM) to 6-well plates. Lifetime and non-fragile span analyses were performed to detect mitochondrial function-related parameters, including reactive oxygen species (ROS) and mitochondrial membrane potential (MMP).

[0120] Lifespan and non-deterioration period determination: Incucyte ® The S3 live-cell analysis system (Sartorius, Göttingen, Germany) was used to automatically monitor the lifespan and non-debilitating phase of *Caenorhabditis elegans*. In the experiment, worms were synchronized by hypochlorite treatment and hatched into L1 larvae on standard NGM agar plates. Post-laying L4 larvae were transferred to standard plates containing fluorouracil (FUdR) to assess oviposition defects. On day 3 post-laying, worms were transferred to experimental plates. In an incubator at 20°C, using a 4× objective phase-contrast and green fluorescence channel, the lifespan and non-debilitating phase of *Caenorhabditis elegans* were analyzed using Incucyte. ® The S3 live cell analysis system acquires plate images every 12 hours. Images are acquired from each well at regular intervals. The worm's posture and position are recorded in each frame, and changes are detected by overlaying two consecutive images. The worm's posture changes over time, eventually ceasing to change, indicating worm death. Before death, most older worms only move their heads or tails, a condition defined as weakness.

[0121] Mitochondrial ROS: To examine the effect of rhodioloside / EGT / combined intake on mitochondrial ROS, CellROX was used. ® Green (Invitrogen, Carlsbad, CA, USA) staining. Simply put, CellROX... ®Green was a freshly prepared 5 mM stock solution, diluted 1:500 in M9 buffer before treatment. Animals were then transferred to plates with or without rhodioloside / EGT / rhodioloside and EGT staining solutions and stained at 20°C for 2 hours. Animals were mounted on poly-L-lysine-coated slides and observed under a fluorescence microscope (Zeiss Axioscope, Oberkochen, Germany). Mitochondrial ROS were relatively quantified using ImageJ software. At least 15 worms were observed in each experiment.

[0122] MMP Detection: MMP was determined by staining with tetramethylrhodamine methyl ester (TMRM). TMRM (final concentration: 30 µM) was added to NGM agar plates with or without rhodioloside / EGT / rhodioloside and EGT. Dead *E. coli* OP50 was then seeded and dried in the dark for 24 hours. Synchronized animals were transferred to TMRM plates and incubated at 20°C for 15 hours. The animals were then mounted on poly-L-lysine-coated slides and observed under a fluorescence microscope (Zeiss Axioscope, Oberkochen, Germany). Fluorescence intensity was measured using ImageJ software.

[0123] Data analysis was performed using Graphpad 8.0 software. The results are expressed as standard deviation (x±s), and significance analysis was conducted using two-way ANOVA.

[0124] Survival rates of nematodes treated with different concentrations of EGT, rhodioloside, and EGT + rhodioloside were observed. We found that the highest survival rates were ranked as follows: 5 mM EGT + 5 mM rhodioloside > 10 mM rhodioloside > 10 mM EGT. This indicates that the combination of EGT and rhodioloside effectively improves survival rates and is superior to either EGT or rhodioloside alone. Therefore, subsequent studies used effective doses of 10 mM EGT, 10 mM rhodioloside, and 5 mM EGT + 5 mM rhodioloside for experiments.

[0125] Figure 13 shows the non-weakness curves of nematodes treated with EGT, rhodioloside, and EGT+rhodioloside. It can be seen that 10 mM EGT and 10 mM rhodioloside have similar effects, while the non-weakness period is prolonged in the 5 mM EGT + 5 mM rhodioloside group, indicating that the combination can significantly improve the quality of life under stress or during aging.

[0126] Figure 14 shows the ROS content in nematodes treated with EGT, rhodioloside, and EGT+rhodioloside. The ROS content in the EGT+rhodioloside group was significantly lower than that in the EGT and rhodioloside groups, decreasing by 20.5% and 17.3%, respectively. This indicates that the combined treatment can alleviate overall oxidative stress levels, effectively remove excess ROS caused by hypochlorite, and protect biomolecules from oxidative damage.

[0127] Nematodes treated with hypochlorite exhibit abnormally elevated mitochondrial membrane potential due to stress damage. EGT, rhodioloside, and EGT can all alleviate the abnormality of MMP. The combined use of EGT and rhodioloside can restore MMP to normal levels, indicating that the combined use protects mitochondrial function and directly acts on the core of cellular energy—mitochondria—maintaining their healthy state. This is fundamental to maintaining cell vitality, reducing ROS production, and delaying weakness.

[0128] After intervention with different proportions of rhodioloside and EGT, the lifespan and non-debilitating period of *C. elegans* were prolonged, mitochondrial ROS levels were reduced, and lower MMP fluorescence intensity was observed, indicating that different combinations of rhodioloside and EGT can prolong lifespan and improve healthy lifespan, thus having an anti-aging effect. Example 27

[0129] Experimental animals and housing conditions: Forty 5-week-old Kunming mice were housed in separate cages of five at 22±2℃ and 45-65% relative humidity; the light and dark cycle was 12 hours per day, with lights turned on at 8:00 AM and off at 8:00 PM. All mice had free access to food and water during the housing period. Mice were allowed at least one week to acclimatize to the new housing conditions before the start of the experiments.

[0130] Supplementation: After acclimatization, mice were randomly divided into groups of 8 mice each based on their body weight. Group 1 was the saline group; Group 2 was the rhodioloside group (26 mg / kg); Group 3 was the ergothioneine group (26 mg / kg); Group 4 was the rhodioloside and ergothioneine group (13 mg / kg + 13 mg / kg); the remaining 8 mice served as the negative control group, receiving saline supplementation (Group 5). All supplements and saline were administered via gavage, with the same volume of saline administered as the other groups. Supplements were administered daily from 9:00 AM to 11:00 AM for 28 days.

[0131] Exhaustion Swimming Test: Thirty minutes after the last day of drug administration, mice (excluding the negative control group) were placed in a vertical, transparent container (30 cm × 25 cm × 15 cm) filled with water at 23 ± 1℃ and swam for 90 minutes. After swimming, blood samples were collected by enucleation. After serum separation, the levels of cytokines tumor necrosis factor-α, interleukin-6, and interleukin-8; aspartate aminotransferase and alanine aminotransferase; and cortisol in the serum were tested according to the detection methods provided by the ELISA kit. After blood collection, the mice were euthanized and dissected. The same liver lobules from each mouse were accurately separated and weighed, homogenized with PBS at a 1:9 ratio, and centrifuged at 3000g for 15 minutes. The supernatant was extracted, and the malondialdehyde (MDA), glutathione (Glutathione), and superoxide dismutase (SOD) activity in the liver homogenate were measured using the respective kits according to the ELISA kit manufacturers' instructions.

[0132] Data analysis: Graphpad 8.0 software was used for data analysis. The results are expressed as standard deviation (x ± s), and two-way ANOVA test was used for significance analysis.

[0133] As shown in Figures 15-19, Figure 15 shows the serum TNF-α level in each experimental group, Figure 16 shows the serum AST level in each experimental group, Figure 17 shows the serum ALT level in each experimental group, Figure 18 shows the serum cortisol level in each experimental group, and Figure 19 shows the SOD level in each experimental group. After supplementation, mice in the rhodioloside and ergothioneine groups, under exercise stimulation, showed a 37%, 39%, 37%, 30%, 32%, and 37% decrease in serum levels of cytokines tumor necrosis factor-α, interleukin-6, interleukin-8, aspartate aminotransferase, alanine aminotransferase, and cortisol, respectively, compared to group 1. Liver malondialdehyde levels decreased by 44%, while glutathione content and superoxide dismutase activity increased by 61% and 40%, respectively. Furthermore, the results in the rhodioloside and ergothioneine groups were significantly better than those in the rhodioloside or ergothioneine groups alone, indicating that the body experienced less inflammatory and oxidative stress and had a better ability to adapt to stress. Example 28

[0134] Experimental animals and housing conditions: Forty 11-week-old adult C57BL / 6J mice were housed in separate cages of five at 22 ± 2℃ and 45-65% relative humidity; the light and dark cycle was 12 h / 12 ​​h, with lights turned on at 8:00 AM and off at 8:00 PM. All mice had free access to food and water during the housing period. Mice were allowed at least one week to acclimatize to the new housing conditions before the start of the experiments.

[0135] Depressive-like behavior induction: Thirty-two pre-fed 12-week-old mice were randomly induced to exhibit depressive-like behavior using lipopolysaccharide (LPS). 0.5 mg / kg of LPS was dissolved in sterile, endotoxin-free saline and administered subcutaneously. Twenty-four hours after administration, all mice underwent behavioral tests. Changes in immobility time in forced swimming and tail suspension tests were observed over two days. Significantly prolonged immobility time in both tests indicated depressive behavioral changes, necessitating supplementation.

[0136] Forced swimming test: The forced swimming test is a commonly used research method for assessing the degree of depression in mice. The test observes the mice's struggle to escape in the water, determining their depressive-like behavior and the degree of depression. Generally, mice will struggle vigorously in the water, demonstrating a strong desire to escape; conversely, remaining still is considered depressive-like behavior, and the duration of this behavior indicates the degree of depression; the longer the duration, the more severe the depression. In the experiment, the test mice are placed vertically in a transparent container (30 cm × 25 cm × 15 cm) filled with water at 23 ± 1℃, and allowed to acclimatize for 1 minute. The immobility time is then recorded over the next 5 minutes. The immobility time is recorded and analyzed using EthoVision XT video tracking software.

[0137] Tail suspension test: Similar to the forced swimming test, the tail suspension test is also commonly used to detect the degree of depression in mice. The mouse is suspended upside down 40 cm off the ground, 1 cm from the tip of its tail, using medical tape. Normally, the mouse will struggle violently after being lifted off the ground; conversely, immobility is interpreted as depressive-like behavior, and the duration of this behavior indicates the degree of depression; the longer the duration, the more severe the depression. After the mouse has adapted for 1 minute, the immobility time over 5 minutes is recorded and analyzed using EthoVision XT video tracking software.

[0138] Supplementation: All mice exhibiting depressive-like behavioral changes were randomly divided into four groups of eight mice each. Group 1 was the saline group; Group 2 was the rhodioloside group (26 mg / kg, Group 2); Group 3 was the ergothioneine group (26 mg / kg, Group 3); Group 4 was the rhodioloside and ergothioneine group (13 mg / kg + 13 mg / kg, Group 4); the remaining eight un-LPS-induced mice served as the negative control group and were supplemented with saline (Group 5). All supplements and saline were administered via gavage after a two-hour fast, with the saline volume being the same as in the other groups. Supplements were administered daily from 9:00 AM to 11:00 AM for one week.

[0139] Sample Collection: After supplementation administration, all mice underwent forced swimming and tail suspension tests, and immobility time was observed. Following the observation period, blood samples were collected from the mice via enucleation. Serum was separated, and serum levodopa and cortisol levels were measured using an ELISA kit.

[0140] Results analysis: The observed immobility times of each group were analyzed using Graphpad 8.0 software. The results are expressed as standard deviation (x ± s), and significance analysis was performed using two-way ANOVA.

[0141] As shown in Figures 20-23, Figure 20 shows the immobility time in the forced swimming test for each experimental group, Figure 21 shows the immobility time in the tail suspension test for each experimental group, Figure 22 shows the serum levodopa level for each experimental group, and Figure 23 shows the serum cortisol level for each experimental group. After intervention with the rhodioloside and ergothioneine, mice in the rhodioloside and ergothioneine groups showed significantly shorter immobility times in the forced swimming and tail suspension tests (48% and 51%, respectively) compared to the control group (Group 1). Serum levodopa levels increased by 114%, and cortisol levels decreased by 49%. These results were significantly better in the rhodioloside and ergothioneine groups than in the rhodioloside or ergothioneine groups alone, indicating a reduction in depressive-like behavior and improved mood in the mice.

[0142] While specific embodiments and examples of the invention have been described herein, those skilled in the art will understand that any modifications and variations can be made without departing from the principles of the invention. The above embodiments and descriptions do not limit the scope of the invention. Any combination of embodiments of the invention, as well as any obvious extensions or analogies thereof, are within the scope of the invention. Furthermore, the invention covers any arrangement intended to achieve the same purpose, and all such variations and modifications falling within the scope of the appended claims.

Claims

1. A composition, characterized in that, The composition comprises rhodioloside or a pharmaceutically acceptable salt, ester, or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

2. The composition according to claim 1, characterized in that, The composition is used for neuroprotection or improvement of cognitive ability, enhancement of motor performance or improvement of muscle function, anti-inflammatory, anti-aging, life extension or improvement of healthy lifespan, stress management or improvement of mood.

3. The composition according to claim 1 or 2, characterized in that, The cognitive abilities mentioned include learning ability, recall ability, spatial perception ability, attention allocation ability, memory, emotion regulation ability, concentration ability, problem-solving agility, resistance to interference, sustained attention, reaction ability, brain activity, and alertness; the enhanced athletic performance mentioned includes increasing exercise time, improving exercise endurance or explosive power, reducing post-exercise inflammation and muscle fatigue, and improving muscle contraction during exercise; the improved muscle function mentioned includes alleviating or preventing muscle dysfunction, improving mitochondrial function in muscles, improving insulin resistance in muscles, increasing muscle mass, increasing muscle strength and endurance, improving glucose transport and metabolism in skeletal muscle, and alleviating or preventing muscle damage. The anti-inflammatory effects include protecting cells and tissues, reducing the risk of chronic inflammation, improving immune function, relieving pain and discomfort, preventing or alleviating inflammation of the skin, cells, and nerves, and protecting endothelial cells; the anti-aging effects include preventing, reducing, or delaying cellular aging, skin aging, or photoaging; the stress management effects include preventing, reducing, or eliminating oxidative, environmental, inflammatory, and psychological stress responses or pressures, improving or enhancing the recovery or restoration of oxidative, environmental, inflammatory, and psychological stress responses or pressures, and increasing the body's or mind's resistance to oxidative, environmental, inflammatory, and psychological stress responses or pressures; the mood-improving effects include relieving anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

4. The composition according to any one of claims 1 to 3, characterized in that, The neuroprotection or improvement of cognitive ability is achieved by reducing the level of neurofilament light chains in plasma, improving the recognition rate of new objects, increasing brain-derived neurotrophic factor (BDNF), reducing neuroinflammation, reducing oxidative damage to neurons, and enhancing synaptic plasticity. The enhancement of motor performance or improvement of muscle function is achieved by promoting muscle protein synthesis, improving blood circulation and oxygen supply, antioxidation and reducing free radical damage, regulating hormone levels, and increasing nerve conduction velocity. The anti-inflammatory effect is achieved by inhibiting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-8 (IL-8), or by increasing anti-inflammatory cytokines. The anti-aging effect is achieved by enhancing mitochondrial biogenesis, alleviating mitochondrial dysfunction, reducing oxidative stress, enhancing cell function or cell repair, enhancing cell activity, and increasing the levels of p-AKT, AKT, and p-AMPK proteins. The extension of lifespan or improvement of healthy lifespan is achieved by improving mitochondrial function and enhancing antioxidant capacity. The stress management or improvement of mood is achieved by regulating the HPA axis to reduce cortisol levels, reducing cellular oxidative damage, and reducing depressive-like behaviors.

5. The composition according to any one of claims 1 to 4, characterized in that, The rhodioloside or its pharmaceutically acceptable salts, esters or derivatives are administered at a dose of 1-2000 mg per day.

6. The composition according to any one of claims 1 to 5, characterized in that, The ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs or derivatives are administered in doses of 1-1000 mg per day.

7. The composition according to any one of claims 1 to 6, characterized in that, The ratio of the rhodioloside or its pharmaceutically acceptable salt, ester or derivative to the ergothioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative is 1:50 to 500:

1.

8. The composition according to any one of claims 1 to 7, characterized in that, The composition is formulated into nutritional supplements, food, beverages, and animal feed.

9. The composition according to any one of claims 1 to 8, characterized in that, The composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, syrups, injections, or functional food compositions.

10. A method for neuroprotection or improving cognitive ability, enhancing motor performance or improving muscle function, anti-inflammatory, anti-aging, prolonging life or improving healthy lifespan, stress management or improving mood, characterized in that, The method includes administering a composition to a subject in need, the composition comprising rhodioloside or a pharmaceutically acceptable salt, ester, or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

11. The method according to claim 10, characterized in that, The cognitive abilities mentioned include learning ability, recall ability, spatial perception ability, attention allocation ability, memory, emotion regulation ability, concentration ability, problem-solving agility, resistance to interference, sustained attention, reaction ability, brain activity, and alertness; the enhanced athletic performance mentioned includes increasing exercise time, improving exercise endurance or explosive power, reducing post-exercise inflammation and muscle fatigue, and improving muscle contraction during exercise; the improved muscle function mentioned includes alleviating or preventing muscle dysfunction, improving mitochondrial function in muscles, improving insulin resistance in muscles, increasing muscle mass, increasing muscle strength and endurance, improving glucose transport and metabolism in skeletal muscle, and alleviating or preventing muscle injury. The anti-inflammatory effects include protecting cells and tissues, reducing the risk of chronic inflammation, improving immune function, relieving pain and discomfort, preventing or alleviating inflammation of the skin, cells, and nerves, and protecting endothelial cells; the anti-aging effects include preventing, reducing, or delaying cellular aging, skin aging, or photoaging; the stress management effects include preventing, reducing, or eliminating oxidative, environmental, inflammatory, and psychological stress responses or pressures, improving or enhancing the recovery or restoration of oxidative, environmental, inflammatory, and psychological stress responses or pressures, and increasing the body's or mind's resistance to oxidative, environmental, inflammatory, and psychological stress responses or pressures; the mood improvement effects include relieving anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

12. The method according to claim 10 or 11, characterized in that, The neuroprotection or improvement of cognitive ability is achieved by reducing the level of neurofilament light chains in plasma, improving the recognition rate of new objects, increasing brain-derived neurotrophic factor (BDNF), reducing neuroinflammation, reducing oxidative damage to neurons, and enhancing synaptic plasticity. The enhancement of motor performance or improvement of muscle function is achieved by promoting muscle protein synthesis, improving blood circulation and oxygen supply, antioxidation and reducing free radical damage, regulating hormone levels, and increasing nerve conduction velocity. The anti-inflammatory effect is achieved by inhibiting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-8 (IL-8), or by increasing anti-inflammatory cytokines. The anti-aging effect is achieved by enhancing mitochondrial biogenesis, alleviating mitochondrial dysfunction, reducing oxidative stress, enhancing cell function or cell repair, enhancing cell activity, and increasing the levels of p-AKT, AKT, and p-AMPK proteins. The extension of lifespan or improvement of healthy lifespan is achieved by improving mitochondrial function and enhancing antioxidant capacity. The stress management or improvement of mood is achieved by regulating the HPA axis to reduce cortisol levels, reducing cellular oxidative damage, and reducing depressive-like behaviors.

13. The method according to any one of claims 10 to 12, characterized in that, The rhodioloside or its pharmaceutically acceptable salts, esters or derivatives are administered at a dose of 1-2000 mg per day.

14. The method according to any one of claims 10 to 13, characterized in that, The ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs or derivatives are administered in doses of 1-1000 mg per day.

15. The method according to any one of claims 10 to 14, characterized in that, The ratio of the rhodioloside or its pharmaceutically acceptable salt, ester or derivative to the ergothioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative is 1:50 to 500:

1.

16. The method according to any one of claims 10 to 15, characterized in that, The subjects are humans or mammals.

17. The method according to any one of claims 10 to 16, characterized in that, The composition is administered orally, intravenously, intramuscularly, intraperitoneally, or sublingually.

18. The method according to any one of claims 10 to 17, characterized in that, The composition is formulated into nutritional supplements, food, beverages, and animal feed.

19. The method according to any one of claims 10 to 18, characterized in that, The composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, syrups, injections, or functional food compositions.

20. The use of a composition in the preparation of nutritional supplements, foods, beverages, or animal feeds for neuroprotection or improvement of cognitive function, enhancement of motor performance or improvement of muscle function, anti-inflammatory, anti-aging, life extension or improvement of healthy lifespan, stress management or improvement of mood, characterized in that, The composition comprises rhodioloside or a pharmaceutically acceptable salt, ester, or derivative thereof; and ergothioneine or a pharmaceutically acceptable salt, acid, ester, analog, or derivative thereof.

21. The use according to claim 20, characterized in that, The cognitive abilities mentioned include learning ability, recall ability, spatial perception ability, attention allocation ability, memory, emotion regulation ability, concentration ability, problem-solving agility, resistance to interference, sustained attention, reaction ability, brain activity, and alertness; the enhanced athletic performance mentioned includes increasing exercise time, improving exercise endurance or explosive power, reducing post-exercise inflammation and muscle fatigue, and improving muscle contraction during exercise; the improved muscle function mentioned includes alleviating or preventing muscle dysfunction, improving mitochondrial function in muscles, improving insulin resistance in muscles, increasing muscle mass, increasing muscle strength and endurance, improving glucose transport and metabolism in skeletal muscle, and alleviating or preventing muscle injury. The anti-inflammatory effects include protecting cells and tissues, reducing the risk of chronic inflammation, improving immune function, relieving pain and discomfort, preventing or alleviating inflammation of the skin, cells, and nerves, and protecting endothelial cells; the anti-aging effects include preventing, reducing, or delaying cellular aging, skin aging, or photoaging; the stress management effects include preventing, reducing, or eliminating oxidative, environmental, inflammatory, and psychological stress responses or pressures, improving or enhancing the recovery or restoration of oxidative, environmental, inflammatory, and psychological stress responses or pressures, and increasing the body's or mind's resistance to oxidative, environmental, inflammatory, and psychological stress responses or pressures; the mood improvement effects include relieving anxiety, stress, depression, obsessive-compulsive disorder, or bipolar disorder.

22. The use according to claim 20 or 21, characterized in that, The neuroprotection or improvement of cognitive ability is achieved by reducing the level of neurofilament light chains in plasma, improving the recognition rate of new objects, increasing brain-derived neurotrophic factor (BDNF), reducing neuroinflammation, reducing oxidative damage to neurons, and enhancing synaptic plasticity. The enhancement of motor performance or improvement of muscle function is achieved by promoting muscle protein synthesis, improving blood circulation and oxygen supply, antioxidation and reducing free radical damage, regulating hormone levels, and increasing nerve conduction velocity. The anti-inflammatory effect is achieved by inhibiting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-8 (IL-8), or by increasing anti-inflammatory cytokines. The anti-aging effect is achieved by enhancing mitochondrial biogenesis, alleviating mitochondrial dysfunction, reducing oxidative stress, enhancing cell function or cell repair, enhancing cell activity, and increasing the levels of p-AKT, AKT, and p-AMPK proteins. The extension of lifespan or improvement of healthy lifespan is achieved by improving mitochondrial function and enhancing antioxidant capacity. The stress management or improvement of mood is achieved by regulating the HPA axis to reduce cortisol levels, reducing cellular oxidative damage, and reducing depressive-like behaviors.

23. The use according to any one of claims 20 to 22, characterized in that, The rhodioloside or its pharmaceutically acceptable salts, esters or derivatives are administered at a dose of 1-2000 mg per day.

24. The use according to any one of claims 20 to 23, characterized in that, The ergothioneine or its pharmaceutically acceptable salts, acids, esters, analogs or derivatives are administered in doses of 1-1000 mg per day.

25. The use according to any one of claims 20 to 24, characterized in that, The ratio of the rhodioloside or its pharmaceutically acceptable salt, ester or derivative to the ergothioneine or its pharmaceutically acceptable salt, acid, ester, analog or derivative is 1:50 to 500:

1.

26. The use according to any one of claims 20 to 25, characterized in that, The composition is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions, syrups, injections, or functional food compositions.

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