A composition for improving cognitive function and relieving sleep disorders based on a three-hub long-life axle and application thereof

Abstract

The present application belongs to the technical field of food, and relates to a composition for improving cognitive function and relieving sleep disorders based on a three-pivot longevity axis and application thereof. The composition comprises ginsenoside, ergothioneine, honokiol and pyrroloquinoline quinone. The composition improves neurodegenerative aging from four dimensions of neuroprotection, sleep improvement, nerve repair promotion and anti-neural inflammation. Meanwhile, the ginsenoside CK activates the AMPK node, the honokiol activates the SIRT3 node, and the pyrroloquinoline quinone activates the PGC-1 alpha node, thereby synergistically activating the AMPK-SIRT1-PGC-1 alpha three-pivot longevity axis to rebuild the energy metabolism and repair capacity of neurons. The ginsenoside, ergothioneine, honokiol and pyrroloquinoline quinone have certain synergistic effects in improving cognitive function, improving memory, relieving sleep disorders and improving neurodegenerative aging.

Description

Technical Field

[0001] This invention belongs to the field of food technology and relates to a composition for improving cognitive function and alleviating sleep disorders based on a three-hub longevity axis and its application, particularly to a composition for improving cognitive function and alleviating sleep disorders based on the synergistic activation of the AMPK-SIRT1-PGC-1α three-hub longevity axis and its application. Background Technology

[0002] Neurodegenerative aging has become a major health problem seriously threatening the quality of life of the elderly. Unlike physiological aging, neurodegenerative aging refers to degenerative changes in the central nervous system that exceed the normal range during aging. Neurodegenerative aging manifests as memory decline, cognitive impairment, and sleep disorders. Its core pathologies include: ATP insufficiency due to the decline of neuronal mitochondrial function; accelerated neuronal damage due to neuroinflammation; oxidative stress leading to neuronal membrane lipid peroxidation and synaptic function decline; and decreased GABAergic system function leading to difficulty falling asleep and poor sleep quality.

[0003] Most existing compositions lack precise design for the specific stage of neurodegenerative aging, failing to achieve organic integration of anti-inflammatory, antioxidant, neurotransmitter regulation and synaptic function protection at the mechanistic level, and also making it difficult to effectively improve daytime cognitive function while improving sleep quality.

[0004] The "tri-hub longevity axis" (AMPK-SIRT1-PGC-1α) is a core network for cellular energy sensing and metabolic regulation. These three components work synergistically through a positive feedback loop to maintain cellular youthfulness. In neurodegenerative aging, neuronal NAD... + Decreased SIRT1 levels lead to reduced SIRT1 activity, triggering a vicious cycle collapse of the tri-hub axis, resulting in neuronal mitochondrial dysfunction, energy metabolism disorders, and decreased synaptic plasticity. Therefore, simultaneously targeting the tri-hub nodes to rebuild the positive feedback loop of this axis is a key strategy for improving neurodegenerative aging.

[0005] Therefore, developing a composition that can intervene in the pathological processes related to neurodegenerative aging through multiple targets and pathways, while alleviating memory decline, cognitive impairment, and sleep disorders, has significant clinical application value and broad market prospects. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a composition for improving cognitive function and alleviating sleep disorders based on a three-hub longevity axis, and its application, particularly a composition for improving cognitive function and alleviating sleep disorders based on the synergistic activation of the AMPK-SIRT1-PGC-1α three-hub longevity axis, and its application.

[0007] To achieve this objective, the present invention employs the following technical solution:

[0008] In a first aspect, the present invention provides a composition for improving cognitive function and alleviating sleep disorders based on a three-hub longevity axis, the composition comprising ginsenosides, ergothionein, magnolol and pyrroloquinoline quinone.

[0009] Ginsenosides, ergothioneine, magnolol, and pyrroloquinoline quinone target different nodes of the three-axis. Ergothioneine (EGT) is one of the few known dietary antioxidants that efficiently accumulates in brain tissue via active transport mediated by the OCTN1 transporter. EGT levels are significantly negatively correlated with dementia risk. EGT specifically scavenges hydroxyl radicals and peroxynitrites in neurons, protecting synaptic function. In addition, EGT can also enhance neuronal NAD through the CSE / H2S / cGPDH pathway. + At certain levels, it provides substrate support for SIRT1 activation. Magnolol and other compounds can cross the blood-brain barrier, improving sleep onset and sleep depth through positive allosteric regulation of GABA-A receptors (non-benzodiazepine dependent), while simultaneously activating neuronal SIRT3 to protect mitochondrial function. SIRT3 complements PGC-1α-driven mitochondrial biogenesis, jointly maintaining neuronal mitochondrial homeostasis. Ginsenoside CK can cross the blood-brain barrier to inhibit excessive microglial activation and reduce neuroinflammation, improving neuronal energy metabolism through AMPK activation. After AMPK activation, it upregulates NAMPT via phosphorylation, increasing NAD. + Levels and activation of SIRT1 initiate a three-axis positive feedback loop. Pyrroloquinoline quinone (PQQ) stimulates nerve growth factor (NGF) synthesis, promoting neuronal survival and synaptic plasticity, and promotes neuronal mitochondrial biogenesis through CREB / PGC-1α.

[0010] Preferably, the composition comprises, by weight parts, 1-20 parts of ginsenoside, 5-100 parts of ergothionein, 10-500 parts of magnolol, and 1-20 parts of pyrroloquinoline quinone.

[0011] The mass fractions of ginsenosides can be selected from 1 part, 2 parts, 5 parts, 8 parts, 10 parts, 12 parts, 15 parts, 18 parts, 20 parts, etc.; the mass fractions of ergothionein can be selected from 5 parts, 10 parts, 15 parts, 20 parts, 30 parts, 40 parts, 50 parts, 60 parts, 70 parts, 80 parts, 90 parts, 100 parts, etc.; the mass fractions of magnolol can be selected from 10 parts, 20 parts, 50 parts, 80 parts, 100 parts, 120 parts, 150 parts, 180 parts, 200 parts, 250 parts, 300 parts, 350 parts, 400 parts, 450 parts, 500 parts, etc.; the mass fractions of pyrroloquinoline quinone can be selected from 1 part, 2 parts, 5 parts, 8 parts, 10 parts, 12 parts, 15 parts, 18 parts, 20 parts, etc. Other specific values ​​within the above ranges can be selected, which will not be elaborated here.

[0012] Preferably, the ginsenoside is ginsenoside CK.

[0013] Preferably, the composition is prepared by a method comprising the following steps: physically mixing the raw materials to obtain the composition.

[0014] In a second aspect, the present invention provides the use of the composition according to the first aspect, which improves cognitive function and alleviates sleep disorders based on a three-hub longevity axis, in the preparation of a product having the effect of improving neurodegenerative aging.

[0015] Preferably, the composition for improving cognitive function and alleviating sleep disorders in the product has a mass percentage content of 0.1-70%, such as 0.1%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, etc. Other specific values ​​within the above range can be selected, and will not be elaborated here.

[0016] Preferably, the improvement of neurodegenerative aging includes improving memory, improving cognitive decline, or improving sleep disorders.

[0017] Preferably, the dosage form of the product includes tablets, capsules, granules, powders, gummies, oral liquids, or beverages.

[0018] Preferably, the product also includes auxiliary materials.

[0019] Preferably, the excipients include any one or a combination of at least two of the following: solvent, emulsifier, dispersant, wetting agent, binder, stabilizer, colorant, diluent, flavoring agent or filler.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The composition of this invention synergistically improves neurodegenerative aging from four dimensions: ① Neuroprotection, with EGT actively accumulating in brain tissue via OCTN1 to clear oxidative damage; ② Improved sleep, with honokiol regulating and improving sleep quality through GABA-A receptor regulation (a non-addictive mechanism); ③ Promotion of nerve repair, with PQQ stimulating NGF synthesis and enhancing synaptic plasticity; ④ Anti-neuroinflammatory, with ginsenoside CK inhibiting excessive microglial activation. More importantly, ginsenoside CK activates AMPK, upregulates NAMPT, and enhances NAD. + -Activation of SIRT1-deacetylation of PGC-1α-increased mitochondrial biogenesis-feedback activation of AMPK, forming a positive feedback loop; and magnolol enhances mitochondrial antioxidant defense through SIRT3, PQQ activates this node by upregulating PGC-1α expression via CREB phosphorylation through the CREB / PGC-1α pathway, and EGT provides alternative NAD. + Supply. The multi-component synergistic reconstruction of the AMPK-SIRT1-PGC-1α tri-axis restores neuronal energy metabolism and repair capabilities. In particular, the active brain tissue uptake characteristics of EGT and the non-addictive sleep-inducing activity of magnolol make this composition superior to existing single-component formulations in both safety and efficacy. Attached Figure Description

[0022] Figure 1 This is the result of the mouse escaping the incubation period.

[0023] Figure 2 This is the result of the number of times the mouse crossed the platform.

[0024] Figure 3 This is the result of the number of times the zebrafish remained still.

[0025] Figure 4 This is the result of the cumulative duration of zebrafish remaining still.

[0026] Figure 5 It is NAD in zebrafish + The result at the horizontal level. Detailed Implementation

[0027] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0028] Example 1

[0029] This embodiment provides a composition for improving cognitive function and alleviating sleep disorders. The composition comprises, by weight parts, 4 parts of ginsenoside CK, 30 parts of ergothioneine, 50 parts of magnolol, and 10 parts of PQQ.

[0030] Its preparation method includes: physically mixing the raw materials to obtain the product.

[0031] Example 2

[0032] This embodiment provides a composition for improving cognitive function and alleviating sleep disorders. The composition comprises, by weight parts, 2 parts of ginsenoside CK, 20 parts of ergothioneine, 40 parts of magnolol, and 8 parts of PQQ.

[0033] The preparation method is the same as in Example 1.

[0034] Example 3

[0035] This embodiment provides a composition for improving cognitive function and alleviating sleep disorders. The composition comprises, by weight parts, 6 parts of ginsenoside CK, 60 parts of ergothioneine, 100 parts of magnolol, and 16 parts of PQQ.

[0036] The preparation method is the same as in Example 1.

[0037] Example 4

[0038] This embodiment provides a composition for improving cognitive function and alleviating sleep disorders. The only difference between this composition and Example 1 is that ginsenoside CK is replaced with an equal amount of ginsenoside Rb1, while the other components and contents remain unchanged.

[0039] The preparation method is the same as in Example 1.

[0040] Example 5

[0041] This embodiment provides a composition for improving cognitive function and alleviating sleep disorders. The only difference between this composition and Example 1 is that ginsenoside CK is replaced with an equal amount of ginsenoside Rb2, while the other components and contents remain unchanged.

[0042] The preparation method is the same as in Example 1.

[0043] Comparative Example 1

[0044] This comparative example provides a composition for improving cognitive function and alleviating sleep disorders, which differs from Example 1 only in that it does not contain ginsenoside CK, and its reduced mass is proportionally allocated to the mass of ergothioneine, magnolol and PQQ.

[0045] The preparation method is the same as in Example 1.

[0046] Comparative Example 2

[0047] This comparative example provides a composition for improving cognitive function and alleviating sleep disorders, which differs from Example 1 only in that it does not contain ergothioneine, and the reduced mass of ergothioneine is proportionally allocated to the mass of ginsenoside CK, magnolol and PQQ.

[0048] The preparation method is the same as in Example 1.

[0049] Comparative Example 3

[0050] This comparative example provides a composition for improving cognitive function and alleviating sleep disorders, which differs from Example 1 only in that it does not contain magnolol, and the reduced mass of magnolol is proportionally allocated to the mass of ginsenoside CK, ergothioneine and PQQ.

[0051] The preparation method is the same as in Example 1.

[0052] Comparative Example 4

[0053] This comparative example provides a composition for improving cognitive function and alleviating sleep disorders, which differs from Example 1 only in that it does not contain PQQ, and its reduced mass is proportionally allocated to the mass of ginsenoside CK, magnolol and ergothioneine.

[0054] The preparation method is the same as in Example 1.

[0055] Test Example 1

[0056] Improved cognitive function

[0057] AlCl3-induced sluggishness model (memory improvement model)

[0058] Animal modeling and drug administration: Mice were randomly divided into a blank control group, a model group, and a sample group, with 6 mice in each group. Except for the blank control group, the other groups were administered AlCl3 by gavage at a dose of 200 mg / kg daily for 50 days to establish an Alzheimer's disease model. Mice in the sample group were administered AlCl3 by gavage at a dose of 40 mg / kg, while the blank control group and the model group were given an equal volume of distilled water. All mice were administered AlCl3 by gavage for 50 consecutive days until the end of the experiment.

[0059] Morris water maze experiment: To assess the spatial, memory, and learning cognitive levels of mice, this study used the Morris water maze experiment for corresponding behavioral observations. Specific components included: ① Adaptation training: The hidden platform was retained, and mice were allowed to swim freely in the pool at the same time each day for three consecutive days; ② Cruise experiment: The hidden platform was removed, and mice were placed into the maze at the same time each day. The escape latency was recorded as the time it took for the mouse to find and remain at the platform. If the animal failed to find the platform within 60 seconds, the escape latency was recorded as 60 seconds. The mouse could then be manually guided to the platform and remain there for 10 seconds. This experiment was conducted for three consecutive days; ③ Spatial exploration experiment: On the last day of the experiment, the hidden platform was removed, and mice were still released from the same entry point. The time the mouse spent in the original platform quadrant and the number of times it traversed the platform were recorded within 60 seconds.

[0060] The results of the mouse escape latency period are as follows Figure 1 As shown in the figure, the number of times the mouse crossed the platform is as follows: Figure 2 As shown, * indicates p < 0.05 compared to the model control group, ** indicates p < 0.01 compared to the model control group, *** indicates p < 0.001 compared to the model control group; # indicates p < 0.05 compared to Example 1, ## indicates p < 0.01 compared to Example 1, and ### indicates p < 0.001 compared to Example 1.

[0061] Experimental results showed that, compared with the blank control group, the escape latency of mice in the model control group was significantly prolonged (p<0.001), and the number of platform crossings was also significantly reduced (p<0.001), indicating a significant decline in cognitive ability. The anti-aging composition of the present invention can significantly improve cognitive ability. If ginsenoside CK is replaced, or if any of the components are missing, the effect will be significantly reduced.

[0062] Test Example 2

[0063] Sleep aid effect

[0064] Zebrafish model: A GABA-based sleep rhythm model

[0065] The laboratory culture temperature was 28.0±1.0℃. An automatic light-dark cycle timer was used, with a 14-hour light / 10-hour darkness cycle. The water used for fish rearing was purified by a fully automatic purification system with a pH of 7.0-8.0. The circulating water was changed daily.

[0066] Six-day-old (6 dpf) wild-type AB strain zebrafish were randomly selected and divided into three groups: a normal group, a model group, and a sample group, with 30 fish in each group. A sleep deprivation model was established by stimulating the zebrafish with continuous LED light (150 lux) for 24 hours. The control group was kept in a normal light-dark alternation environment (14 hours of light; 10 hours of darkness), while the model group and each test sample group received continuous light for 24 hours, with a sample concentration of 28 mg / mL in each test sample group. After treatment, the movement behavior of the zebrafish juveniles was monitored for 1 hour in the dark using the NoldusDanio Vision system, and the number of times they remained still and the cumulative duration of stillness were analyzed using Ethovision XT 15 software.

[0067] The results of the zebrafish stillness count are as follows: Figure 3 As shown, the cumulative duration of zebrafish stillness is as follows: Figure 4As shown, * indicates p < 0.05 compared to the model control group, ** indicates p < 0.01 compared to the model control group, *** indicates p < 0.001 compared to the model control group; # indicates p < 0.05 compared to Example 1, ## indicates p < 0.01 compared to Example 1, and ### indicates p < 0.001 compared to Example 1.

[0068] Experimental results showed that, compared with the normal control group, the model control group had a significantly higher number of periods of stillness (p<0.001) and a significantly lower cumulative duration of stillness (p<0.001), exhibiting fragmented sleep and insomnia. The anti-aging composition of this invention can significantly restore sleep rhythm. If ginsenoside CK is replaced, or if any of the components are missing, the effect will be significantly reduced.

[0069] Test Example 3

[0070] Anti-aging effect test

[0071] Zebrafish model

[0072] Modeling method: 3 dpf AB zebrafish, the concentration of D-galactose in the culture medium was 16 mg / mL, D-galactose treatment was carried out for 5 consecutive days, and the culture medium was changed every day;

[0073] Group processing:

[0074] Normal control group: Zebrafish that have not undergone modeling were cultured in ordinary aquaculture water for 8 days;

[0075] Model group: Zebrafish were cultured in ordinary aquaculture water for 8 days after modeling;

[0076] Sample group: Zebrafish after modeling were cultured in aquaculture water containing the sample for 8 days, with a sample concentration of 28 mg / mL.

[0077] 1. NAD + Level test

[0078] After the administration of the drug, the zebrafish were washed, homogenized, and the supernatant was collected. The solution was then processed according to the enhanced NAD3 regimen. + The test kit (WST-8 method), Beyotime, S0176S was processed.

[0079] The effect of the test substance on NAD in an aging model zebrafish + The influence of level, such as Figure 5As shown, * indicates p < 0.05 compared to the model control group, ** indicates p < 0.01 compared to the model control group, *** indicates p < 0.001 compared to the model control group; # indicates p < 0.05 compared to Example 1, ## indicates p < 0.01 compared to Example 1, and ### indicates p < 0.001 compared to Example 1.

[0080] Experimental results showed that, compared with the normal control group, the model control group had higher levels of NAD+ in zebrafish. + The level was significantly reduced (p<0.001). NAD+ is ubiquitous in the body during the aging process. + The core pathological feature of NAD is insufficient synthesis and excessive consumption. + Progressive decline in NAD levels is one of the core initiating factors of energy metabolism decline, oxidative stress accumulation, and cellular homeostasis imbalance in organisms. The anti-aging composition of this invention can significantly restore NAD in zebrafish. + If ginsenoside CK is replaced, or if any of the ingredients are missing, the effect will be significantly reduced.

[0081] The above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A composition for improving cognitive function and alleviating sleep disorders based on a three-pivot longevity axis, characterized in that, The composition includes ginsenosides, ergothionein, magnolol, and pyrroloquinoline quinone.

2. The composition for improving cognitive function and alleviating sleep disorders according to claim 1, characterized in that, The composition comprises, by weight, 1-20 parts of ginsenoside, 5-100 parts of ergothionein, 10-500 parts of magnolol, and 1-20 parts of pyrroloquinoline quinone.

3. The composition for improving cognitive function and alleviating sleep disorders according to claim 1 or 2, characterized in that, The ginsenoside mentioned is ginsenoside CK.

4. The composition for improving cognitive function and alleviating sleep disorders according to any one of claims 1-3, characterized in that, The composition is prepared by a method comprising the following steps: physically mixing the raw materials to obtain the composition.

5. The use of the composition based on the three-hub longevity axis for improving cognitive function and alleviating sleep disorders according to any one of claims 1-4 in the preparation of a product having the effect of improving neurodegenerative aging.

6. The application according to claim 5, characterized in that, The composition in the product that improves cognitive function and alleviates sleep disorders has a mass percentage of 0.1-70%.

7. The application according to claim 5 or 6, characterized in that, The improvements in neurodegenerative aging include improving memory, improving cognitive decline, or improving sleep disorders.

8. The application according to any one of claims 5-7, characterized in that, The dosage forms of the products include tablets, capsules, granules, powders, gummies, oral liquids, or beverages.

9. The application according to any one of claims 5-8, characterized in that, The product also includes auxiliary materials.

10. The application according to claim 9, characterized in that, The excipients include any one or a combination of at least two of the following: solvents, emulsifiers, dispersants, wetting agents, binders, stabilizers, colorants, diluents, flavoring agents, or fillers.

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