Compositions for the management of sleep disorders

Abstract

The present invention discloses a composition comprising Fisetin, Resveratrol either alone or combinations for modulating sleep, cognition or mood in a subject. More specifically, the invention discloses a method or use of the said composition in the management of sleep, cognition and mood.

Description

COMPOSITIONS FOR THE MANAGEMENT OF SLEEP DISORDERFIELD OF INVENTION

[0001] The present invention in general relates to a composition comprising Fisetin, Resveratrol or combinations thereof More specifically, the invention relates to a composition comprising Fisetm or Resveratrol either alone or in combinations thereof for use in management of sleep in a subject.BACKGROUND OF THE INVENTION

[0002] Sleep is one of the inevitable daily-living activities and it is one of the most important factors contributing to health. Sleep has a positive effect on quality of life and body functions and homeostasis (Sexton-Radek, K., A Pichler-Mowry, R. (2011). Daily Activities and Sleep Quality’ in Young Adults. Perceptual and Motor Skills, 112(2), 426-428). Sleep is essential for the cellular, organic and systemic functions of an organism with its absence being potentially harmful to health and changing feeding behaviour, glucose regulation, blood pressure, cognitive processes and some hormonal axes (Aldahal L, Bahammam AS. Metabolic, endocrine, and immune consequences of sleep deprivation. Open Respir Med J. 2011 ;5:31-43). A sleep disorder or somnipathy, is a medical disorder affecting an individual’s sleep patterns, sometimes impacting physical, mental, social, and emotional functioning. Sleep deprivation as often casually termed as “sleep insufficiency” is experienced when a person either sleep for a shorter time than the body require to stay health or have low-quality sleep due to sleep disruptions. The average daily sleep needed for a healthy adult is 7 to 9 hours. Sleep deprivation can be due to various reasons which can be mental or physical exhaustion, stress, nocturnal working hours, use of alcohol just before sleep, consumption of caffeine before bed time, constant travel and sleeping in a new or unfamiliar place. Few medical conditions like sleep apnea, Alzheimer’s diseases, Parkinson’s disease (Krystal AD. Et al., Psychiatric disorders and sleep. Neurol Clin. 2012 Nov; 30(4): Pages 1389- 413), schizophrenia, restless leg syndrome, narcolepsy, anxiety, insomnia (Krystal AD et al., . Sleep Disturbance in Psychiatric Disorders: Effects on Function and Quality of Life in Mood Disorders Alcoholism Annale of Clinical Psychiatry, 20(l):Pages 39-46, 2008), and Schizophrenia , brain injuries and concussions, cancer, muscle pain or injury (Jain SV, Panjeton GD, Martins YC. Relationship Between Sleep Disturbances andChronic Pain: A Narrative Review. Clinics and Practice. 2024; 14(6):2650-2660), common cold , flu etc. can also lead to sleep deprivation. Sleep deprivation is associated with increased daytime sleepiness, reduced neurocognitive performance, fatigue, , short sleep time, poor sleep quality, muscle atrophy such as sarcopenia and cachexia and increase in hormonal imbalances mainly increase in cortisol levels, reduction in testosterone in men, reduction in Insulin-like growth factor 1, and also decrease in activity of protein synthesis is observed (M. Dattilo et.al, Sleep and muscle recovery’: Endocrinological and molecular basis for a new and promising hypothesis. Medical Hypotheses, Volume 77, Issued, 2011, Pages220-222).

[0003] Sleep deprived subject often complaint about difficulty in falling asleep, having a nightmare, feeling sleepy on awakening in the morning, not feeling like having a sound sleep, feeling fatigue on awakening in the morning, feeling sleepy during daytime, and the like. These may lead to lowering an efficiency of work, or an unexpected accident. Undiagnosed and Untreated sleep disorders may lead to an increased risk of accidents and develop serious complication such as Parkinsons disease, Lewy body dementia, or multiple system atropy, anxiety disorder, bipolar disorder, multiple organ failure syndrome and total sleep deprivation, risk of cerebrovascular accidents and can also lead to cardiovascular disorders (Ruben Victor Rial et. al, The trivial function of sleep, Sleep Medicine Reviews, Volume 11, Issue 4, 2007, Pages 311-325). The symptoms associated with sleep disorders are aggravated by sleep deprivation, physical or emotional stress, traumatic events, and use and abuse of substances or medications. There are few supportive treatments such as cognitive behavioural therapy (CBT-I) that includes different methods such as controlling stimulus, restricting sleep (SRT), and relaxation therapy. These treatments help reduce anxiety, stress, relieve muscle tension, and lower blood pressure. Another treatment called Light-phase shift therapy has proven useful for sleep disturbances associated with circadian rhythm abnormalities. Patients may be exposed to bright light to help normalize their sleep schedule.

[0004] Some of the medicines that are commonly linked to unusual sleep-related behaviours are antipsychotics and psychotropic medications (e.g., anticholinergics), sedatives, and hypnotic agents, particularly the class of Z drugs or nonbenzodiazepine benzodiazepine receptor agonists (e.g., zolpidem and eszopiclone) which now have a black box warning from US Food and Drug Administration (FDA) due to increased risk of complex sleep behaviours.

[0005] Common side effects of prescription sleep aids include drug tolerance, rebound insomnia, difficulty swallowing or breathing, worsening depression, drowsiness, headaches, and nausea. In some cases, these medications can also lead to dependence and addiction (Fulghum et. AL, Understanding the side effects of sleeping pills, WebMD, June 19, 2024). As a result, many people are turning to natural extracts as a safer alternative. Herbal extracts such as mulberry extracts in US20240382549A1 wherein mulberry extract supplement before or during evening meals enhances sleep quality; US 10857195B2 discloses plant extracts mainly Lamiaceae family such as mint, spearmint to enhance cognitive health and promote sleep; Moreover, Traditionally known valerian root, and chamomile have been shown to promote relaxation and improve sleep quality without the risk of side effects associated with prescription medications. Therefore, there exist a need for an alternative natural composition to treat sleep disorders. CN115137779A teaches sleep aiding tea comprising combination of essential oil and its method of preparation from cinnamon oil. lavender oil, bitter orange leaf oil, lemon oil, and rose essential oil to promote sleep; CN 111329937A provides a traditional Chinese medicine anti-insomnia incense stick composition that can be burnt before sleep time to reduce anxiety and promote sleep; CN115700091A is a nerve soothing and sleep-aiding beverage comprising passion fruit, melissa officinalis, chamomile, spine date seed powder, green plum fruit, dragon fruit, and licorice extract; CN112057567A provides a patch formulation for treating Insomnia using various natural extracts mainly chamomile, lavender, tuber fleece flower stem, polygala tenuifolia, schisandra chinensis, astragalus membranaceus, saliva miltiorrhiza, bamboo leaf, melatonin, rehmanniae recen, miltiorrhiza. However, herbs like chamomile showed improved sleep but did not lead to improvement of sleep, percentage of sleep efficiency, and daytime functioning measures kezmi et al., Effects of chamomile (Matricaria chamomilla L.) on sleep: A systematic review and meta-analysis of clinical trials, Complementary Therapies in Medicine, Volume 84,2024, 103071, ISSN 0965-2299.

[0006] Though prior art offers plethora of options containing herbal composition, still there can be a challenge in sourcing and achieving desired yield of actives in the composition. There is a continuous need to develop formulations for management of sleep disorders with a holistic approach and target multiple parameters, that affect sleep disruption, to improve sleep quality and sleep cycles. Thus, the claimed inventionpromotes both or either synthetically or naturally derived flavones / flavonoids from plant extracts to enhance sleep quality, improve and manage sleep related disorders.

[0007] It is the principle object of the invention to disclose a composition comprising comprising Fisetin, Resveratrol or combinations thereof.

[0008] It is another object of the invention to disclose a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in management of sleep in a subject, wherein the composition improves sleep in a subject.

[0009] It is another object of the invention to disclose methods or use of a composition comprises Fisetin, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for modulating sleep, b) administering an effective dose of tire composition to the subject thereby modulation involves improvement in sleep for the said subject.

[0010] It is another object of the invention to disclose a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in improving cognitive functions in a subject.

[0011] It is another object of the invention to disclose a composition comprising Fisetin or Resveratrol either alone or in combinations thereof tor use in improving mood in a subject.

[0012] The present invention solves the above-mentioned objects and provides further related advantages.SUMMARY OF THE INVENTION

[0013] In a most preferred embodiment, the invention discloses comprising Fisetin, Resveratrol or combinations thereof

[0014] In another most preferred embodiment, a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in management of sleep in a subject, wherein the composition improves sleep in the said subject.

[0015] In another most preferred embodiment, a composition comprising Fisetiri or Resveratrol either alone or in combinations thereof for use in improving cognitive functions in a subject. In another most preferred embodiment, a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in improving mood in a subject.

[0016] In another most preferred embodiment, the invention discloses use of a composition comprising Fisetin, Resveratrol or combinations thereof in a subjectcomprising a) identifying the subject for management of sleep, b) administering an effective dose of the composition to the subject thereby improving sleep in the said subject.

[0017] In another most preferred embodiment, the invention discloses a method of modulating sleep comprises Fisetin, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for modulating sleep, b) administering an effective dose of the composition to the subject thereby modulation involves improvement in sleep for the said subject.

[0018] In another most preferred embodiment, the invention discloses a method of improving cognitive function comprises Fisetm, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for improving cognitive functions; b) administering an effective dose of the composition to the subject.

[0019] In another most preferred embodiment, the invention discloses a method of improving mood comprises Fi setin, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for improving mood; b) administering an effective dose of the composition co the subject.

[0020] In another most preferred embodiment, the invention discloses use of a composition comprising Fisetin, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for management of sleep, b) administering an effective dose of the composition to the subject thereby improving sleep in the said subject.BRIEF DESCRIPTION OF DRAWINGS

[0021] Fig. 1 is a graphical representation showing the effect of Fisetin in sleep deprived rats (Groups 1 -4) compared to control. All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01, when compared to control group.

[0022] Fig. 2 is a graphical representation graphical representation showing the effect of Resveratrol in sleep deprived rats (Groups 1, 5-7) compared to control. All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01, when compared to control group.

[0023] Fig. 3 is a graphical representation showing the effect of Fisetin on rats (Groups 1-4) from Open Field test (OFT) in Total box. All the values were expressed in Mean ± SEM (n=6) *P<0.05, **P<0.01.

[0024] Fig. 4 is a graphical representation showing the effect of Resveratrol on rats (Groups I, 5-7) from Open Field test (OFT) in Total box. All the values were expressed in Mean ± SEM (n=6) *P<0.05, **P<0.01.

[0025] Fig. 5 is a graphical representation showing the effect of Fisetin on rats (Groups 1-4) from Open Field test (OFT) in Centre box. All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01, when compared to control group.

[0026] Fig. 6 is a graphical representation showing the effect of Resveratrol on rats (Groups 1, 5-7) from Open Field test (OFT) in Centre box. All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01, when compared to control group.

[0027] Fig. 7 is a graphical representation showing the effect of Fisetin on rats (Groups 1-4) with Urination and Defecation counts.

[0028] Fig. 8 is a graphical representation showing the effect of Resveratrol on rats (Groups 1, 5-7) with Urination and Defecation counts.

[0029] Fig. 9 is a graphical representation showing the effect of Fisetin, Resveratrol on rats (Groups 1-7). All the values were expressed in Mean ± SEM (n=6). *P<0.05. **P<0.01 when compared to control group.

[0030] Fig. 10 is a graphical representation showing the effect of Compounds on rats (Groups 8-11) with entries in open arm from Elevated Plus Maze (EPM) test. All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01, when compared to control group.

[0031] Fig. 11 is a graphical representation showing the effect of Compounds on rats (Groups 8-1 1) with time spent in open arm from Elevated Plus Maze (EPM) test. All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01, when compared to control group.

[0032] Fig. 12 is a graphical representation showing the effect of Compounds on BDNF levels in rats (Groups 8-11). All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01 when compared to control group.

[0033] Fig. 13 is a graphical representation showing the effect of Compounds on Melatonin levels in rats (Groups 8-11). All the values wrere expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01 when compared to control group.

[0034] Fig. 14 is a graphical representation showing the effect of Compounds on NOX- 4 in rats (Groups 8-11 ). All the values were expressed in Mean ± SEM (n=6). *P<0.01, **P<0.001 wrhen compared to control group.

[0035] Fig. 15 is a graphical representation showing the effect of Compounds on rats (Groups 8-11) from Open Field test (OFT) in Total box. All the values were expressed in Mean ± SEM (n=6). *P<0.01, **P<0.001 when compared to control group.

[0036] Fig. 16 is a graphical representation showing the effect of Compounds on rats (Groups 8-11 ) from Open Field test (OFT) in Centre box. All the values were expressed in Mean ± SEM (n=6). *P<0.01, **P<0.001 when compared to control group.

[0037] Fig. 17 is a graphical representation showing the effect of Compounds on rats (Groups 8-11 ) with Urination and Defecation counts.

[0038] Fig. 18 is a graphical representation showing the effect of Compounds on Melatonin levels in rats (Groups 8-1 1). All the values were expressed in Mean ± SEM (n=6). *P<0.05, **P<0.01 when compared to control group.

[0039] Fig. 19 is a graphical representation showing the effect of Compounds on GABAergic levels in rats (Groups 8-1 1). All the values were expressed in Mean ± SEM (n=6). *P<0.05. **P<0.01 when compared to control group.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTSSelected Definitions

[0040] All the terms used in this application carry ordinary' meaning as known in the prior art unless otherwise specified. Few other specific definitions used in this invention are explained below, which applies throughout this specification. Claims provide broader definition unless and otherwise specified.

[0041] Furthermore, the terms "approximately,” "approximate,” "about," and similar terms generally refer to ranges that include the identified value within a margin of 20%, 10%, or preferably 5%, and any values there between.

[0042] As used herein, management or modulation of a condition refers to improvement or positive effect in sleep. An effective dose refers to positive or modulatory effects in sleep / mood / cognitive abilities in a subject covered under this invention.

[0043] As used herein, behavioral parameters refer to assessment of behavioral (cognitive and physical) attributes of the subject covered under this invention.

[0044] As used herein, biological markers refer to honnones or proteins that are responsive or indicative of sleep covered under this invention.

[0045] As used herein, the word “Compounds” can be Fisetin or Resveratrol or combinations as referenced in the respective embodiments.

[0046] As used herein, control or vehicle control is untreated control.

[0047] As used herein, effective dose is the dose required to have positive modulatory’ effect on sleep. The modulatory effect, used herein, is anything that covers a positive effect on sleep / cognilive functions / mood. The effective dose calculated herein for this invention was back calculated for rats from the safety dose of human subjects.[00048 j As used herein, the sources for Fisetin or Resveratrol is not only limited to synthetic source but also from natural sources. Fisetin can be isolated from Strawberry, Apple, Persimmon, Lotus root, onion, grapes, kiwi, peach, cucumber. Resveratrol can be isolated from red grape, white grape, black tea, red tea, green tea, lime blossom, apple juice, peach juice, sweet wine, and blueberry. Without any limitations to the sources listed above, it is obvious to those ordinarily skilled in the art to look for other sources. The isolation and standardization of Fisetin or Resveratrol from natural sources is also obvious to a person ordinarily skilled in the art.

[0049] As used herein, pharmaceutically, nutraceutically and cosmeceutically acceptable excipients and adjuvants are those which commonly used excipients that are known in the respective industry.

[0050] In a most preferred embodiment, the invention discloses a composition comprising Fisetin, Resveratrol or combinations thereof. In a related aspect of the invention, wherein the composition is formulated with pharmaceutically, nutraceutically, cosmeceutically acceptable excipients, adjuvants, diluents or carriers, and administered orally in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, lotions, and eatables.

[0051] In another most preferred embodiment, the invention discloses a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in management of sleep in a subject, wherein the composition improves sleep in the said subject. In related embodiment of the invention, wherein the management of sleep arises in conditions selected from the group consisting of sleep apnea, restless legs syndrome. (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs }. parasomnia, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder Jet lag, shift work disorder, and irregular sleepwake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chronic insomnia. In related embodiment of the invention, wherein the management ofsleep is associated with improvement in the behavioral parameters and modulatory effects on the subject. In related embodiment of the invention, wherein the behavioral parameters is selected from the group consisting of memory, learning, and attention that are associated with sleep. In related embodiment of the invention, wherein the behavioral parameters are assessed selected from the group consisting of Open Field Test (OFT), Elevated Plus Maze, Urination, and Defecation. In related embodiment of the invention, wherein the modulatory effect on biological markers is to improve sleep in the said subject. In related embodiment of tire invention, wherein the biological markers is selected from the group consisting of Melatonin, Brain Derived Neurotrophic Factor (BDNF), NADPH Oxidase NOX-4, and Gamma-Aminobutyric Acid (GABA). In related embodiment of the invention, wherein the subject is a mammal. In related embodiment of the invention, wherein the composition is formulated with pharmaceutically, nutraceutically, cosmeceutically acceptable excipients, adjuvants, diluents or carriers, and administered orally in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, lotions, and eatables.

[0052] In another most preferred embodiment, a method of modulating sleep comprises Fisetin, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for modulating sleep; and b) administering an effective dose of the composition to the subject thereby modulation provides improvement in sleep. In related embodiment of the invention, the modulation of sleep arises in conditions selected from the group consisting of sleep apnea, restless legs syndrome, (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomnia, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chrome insomnia. In related embodiment of the invention, wherein the management of sleep is associated with improvement in the behavioral parameters and modulatory effects on the subject. In related embodiment of the invention, wherein the behavioral parameters is selected from the group consisting of memory, learning, and attention that are associated w ith sleep. In related embodiment of the invention, wherein the behavioral parameters are assessed selected from the group consisting of Open Field Test (OFT), Elevated Plus Maze, Urination, and Defecation, hi related embodiment of the invention, wherein the modulatory effect on biological markers is to improve sleep inthe said subject. In related embodiment of the invention, wherein the biological markers is selected from the group consisting of Melatonin. Brain Derived Neurotrophic Factor (BDNF), NADPH Oxidase NOX-4, and Gamma-Aminobutyric Acid (GABA). In related embodiment of the invention, wherein the subject is a mammal. In related embodiment of the invention, wherein the composition is formulated with pharmaceutically, nulraceulically, cosmeceutically acceptable excipients, adjuvants, diluents or carriers, and administered orally in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, lotions, and eatables.

[0053] In another most preferred embodiment, use of a composition comprising Fisetin or Resveratrol either alone or in combinations thereof in management of sleep in a subject, wherein the composition improves sleep in the said subject. In related embodiment of the invention, the management of sleep arises in conditions selected from the group consisting of sleep apnea, restless legs syndrome, (R'LS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomnia, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chronic insomnia. In related embodiment of the invention, wherein the management of sleep is associated with improvement in the behavioral parameters and modulatory effects on the subject. In related embodiment of the invention, wherein the behavioral parameters is selected from the group consisting of memory', learning, and attention that are associated with sleep. In related embodiment of the invention, wherein the behavioral parameters are assessed selected from the group consisting of Open Field Test (OFT), Elevated Plus Maze, Urination, and Defecation. In related embodiment of the invention, wherein the modulatory' effect on biological markers is to improve sleep in the said subject. In related embodiment of the invention, wherein the biological markers is selected from the group consisting of Melatonin, Brain Derived Neurotrophic Factor (BDNF), NADPH Oxidase NOX-4, and Gamma-Aminobutyric Acid (GABA). In related embodiment of the invention, wherein the subject is a mammal. In related embodiment of the invention, wherein the composition is formulated with pharmaceutically, nutraceutically, cosmeceutically acceptable excipients, adjuvants, diluents or carriers, and administered orally in the form oftablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, lotions, and eatables.

[0054] In another most preferred embodiment, the invention discloses a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in improving cognitive functions in a subject. In related embodiment of the invention, wherein the cognitive functions are selected from the group consisting of memory, focus, attention, and learning. In related embodiment of the invention, wherein the subject is cognitively impaired due to sleep deprivation. In related embodiment of the invention, wherein improvement in cognitive functions is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF) and Gamma-Aminobutyric Acid (GABA). Sleep deprivation can arise due to sleep apnea, restless legs syndrome, (R.LS), narcolepsy, circadian rhythm sleep disorders t CRSDs), parasomnia, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder. Jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chronic insomnia. Cognitive impairment can be the loss of memory and other mental abilities, learning disorders like dyslexia, neuropsychological impairments (such as in attention, working memory or executive function), dementia, and Alzheimer’s disease.

[0055] In another most preferred embodiment, use of a composition comprising Fi setin or Resveratrol either alone or m combinations thereof in improving cognitive functions in a subject. In related embodiment of the invention, wherein the cognitive functions are selected from the group consisting of memory, focus, attention, and learning. In related embodiment of the invention, wherein the subject is cognitively impaired due to sleep deprivation. In related embodiment of the invention, wherein improvement in cognitive functions is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF) and Gamma-Aminobutyric Acid (GABA). Sleep deprivation can arise due to sleep apnea, restless legs syndrome, (R.LS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomnia, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomma and chronic insomnia. Cogniti ve impairment can be the loss of memory and other mental abilities, learning disorders like dyslexia, neuropsychological impairments (such asin attention, working memory’ or executive function), dementia, and Alzheimer’s disease.100056] In another most preferred embodiment, the invention discloses a method of improving cognitive function comprises Fisetin, Resveratrol or combinations thereof in a subject comprising a) identifying the subject for improving cognitive functions; b) administering an effective dose of the composition the subject thereby resulting in improvement in cognitive functions. In related embodiment of the invention, wherein the cognitive function is selected from the group consisting of memory, focus, attention, and learning. In related embodiment of the invention, wherein the subject is cognitively impaired due to sleep deprivation. In related embodiment of the invention, wherein improvement in cognitive functions is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF) and Gamma-Aminobutyric Acid (GABA). Sleep deprivation can arise due to sleep apnea, restless legs syndrome, (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomma, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chronic insomnia. Cognitive impairment can be the loss of memory and other mental abilities, learning disorders like dyslexia, neuropsychological impairments (such as in attention, working memory or executive function), dementia, and Alzheimer’s disease.

[0057] In another most preferred embodiment, the invention discloses a composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in improving mood in a subject. In related embodiment of the invention, wherein improvement of mood arises in conditions selected from the group consisting of stress, anxiety, depression, and trauma. In related embodiment of the invention, wherein the subject is sleep deprived. In related embodiment of the invention, wherein improvement of mood is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF), Gamma-Aminobutyric Acid (GABA), and decreasing NADPH Oxidase NOX-4. In related embodiment of the invention, wherein the subject is a mammal. Sleep deprivation can arise due to sleep apnea, restless legs syndrome. (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomma, anxiety, meatal disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wakerhythm disorder, Insomnia includes transient insomnia, short term insomnia and chronic insomnia.

[0058] In another most preferred embodiment, the invention discloses use of a composition comprising Fiseti n or Resveratrol either alone or in combinations thereof in improving mood in a subject. In related embodiment of the invention, wherein improvement of mood arises in conditions selected from the group consisting of stress, anxiety, depression, and trauma. In related embodiment of the invention, wherein the subject is sleep deprived. In related embodiment of the invention, wherein improvement of mood is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF), Gamma-Aminobutyric Acid (GABA), and decreasing NADPH Oxidase NOX-4. In related embodiment of the invention, wherein the subject is a mammal. Sleep deprivation can arise due to sleep apnea, restless legs syndrome, (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomnia. anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chronic insomnia.

[0059] In another most preferred embodiment, the invention discloses a method of improving mood comprises Fi setin. Resveratrol or combinations thereof in a subject comprising a) identifying the subject for improving mood; b) administering an effective dose of the composition to the subject, thereby resulting in improvement in mood for the said subject. In related embodiment of the invention, wherein improvement of mood arises in conditions selected from the group consisting of stress, anxiety, depression, and trauma. In related embodiment of the invention, wherein the subject is sleep deprived. In related embodiment of the invention, wherein improvement of mood is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF), Gamma-Aminobutyric Acid (GABA), and decreasing NADPH Oxidase NOX-4. In related embodiment of the invention, wherein the subject is a mammal. Sleep deprivation can arise due to sleep apnea, restless legs syndrome, (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomnia, anxiety, mental disorders, and Insomnia. CRSDs includes advanced sleep phase disorder, delayed sleep phase disorder, jet lag, shift work disorder, and irregular sleep-wake rhythm disorder. Insomnia includes transient insomnia, short term insomnia and chronic insomnia.

[0060] In all embodiments of the invention, effective dose of the Compounds is selected from the range 5 mg / Kg to 150 mg / kg of the weight of the subject, or preferably selected from the range 15 mg / Kg to 130 mg / kg of the weight of the subject, or preferably selected from the range 30 mg / Kg to 110 mg / kg of the weight of the subject, or preferably selected from the range 45 mg''Kg to 90 mg / kg of the weight of the subject, or preferably selected from the range 60 mg / Kg to 85 mg / kg of the weight of the subject.

[0061] In few embodiments of the invention, combinations include anything in the range 1 :0.05 or 1:0.5 or 1 : 1.J00062] The preferred embodiments are further described in detail by means of the following examples. The examples are provided solely for illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the present disclosure.EXAMPLES

[0063] The compounds Fisetin, .Resveratrol used in this invention are chemically synthesized and characterized for purity before use,

[0064] Selection of animal models to study sleep management is critical to cover every aspect of sleep disorders, which will become ideal to replicate in human subjects. 8-10 weeks old Wistar rats weighing 120-130 gms were used and divided into following groups as in Table 1. Table 1 is group of animals to analyze animals in sleep deprivation model as in [Paia. 0009]Table 1 : Groups for the Study

[0065] Studies on Sleep Management

[0066] To capture every aspect of effective management of sleep and understand the activities of the compounds, suitable models were selected such as sleep deprived model to simulate insomnia, Intermittent hypoxia model to simulate sleep apnea and 6-OHD (6-hydroxy-dopamine) model simulates restless syndrome.

[0067] Sleep Deprived Model: In this model, the animals (Table 1) were subjected to 24 hours of sleep deprivation using the multiple platform method [See: Colavlto et al. Front. Syst. Neurosci., Volume 7 - 2013}. Each rat was placed on a small platform inside a water tank-like swim apparatus, with the water level kept 4 cm below the platform and bright light was shone for 6 hours to ensure animals in Table 1 were sleep deprived, hr this method, the rats were able to move within the tank and jump from one platform to another. The principle behind this method was that when the rats became sleepy and drowsy, they would fall into the water due to muscle relaxation, and upon falling, they would quickly wake up. Each group of animals were treated with respective doses as in Table I for 1 month before subjecting to sleep deprivation. And all the animals in the respective groups were tested for behavioural parameters and assayed for molecular markers for a period of 12 hours, the rationale behind to understand if the groups treated with compounds showed beneficial effects against control (untreated). As evident from Fig. 1 & Fig. 2, groups that have been treated with Compounds and subjected to sleep deprivation had a comparatively better sleep to those untreated control group (Table 2).Table 2: Groups of animals and respective Sleep Time from Model 1 (All the values were expressed in Mean ± SEM (11=6).. *P<0.05, **P<0.01)

[0068] Open Field Test (OFT): In another test of behavioural parameters of rats from different groups (Table I) post sleep deprivation as in previous paragraph. In this model, the rats (Table 1) were subjected to 24 hours of sleep deprivation The OFT was used to evaluate locomotion in rats and thereby animal behaviour in response to sleep deprivation, In a quiet environment, the rat was placed in the centre of the bottom surface of the open field reaction box (50 cm3x 50 cm ’ x 45 cm3), video recording and timing were perfonned at the same time, and the rat was allowed to move freely in the box for 5 min. The bottom plane of the open field reaction chamber is divided into nine areas, including the centre, perimeter, and comers. The time that the rat passed through each area within 5 min was then recorded and analyzed using a video-tracking system (Shanghai Xinruan Information Technology Co. Ltd., China). A rat placed in a bare, open chamber will initially stay near the walls and avoid the centre. Normal animals typically acclimatize to the chamber and eventually explore the comer areas. More sleep deprived animals spend significantly more time in the open area as they take time to figure out the safe comers of the box. The movement of the animal’s activity in the respective groups is monitored using a camera placed above the open field. Computer software measures the time spent in the centre compared to the periphery [See: Natalia et al. Interdiscip Toxicol. 2013; Vol. 6(3): 126-135}. Figs. 3 & 4 represents total box, which encompasses both the central area and the peripheral (outer) areas of the chamber the entire open field or arena where the rodent is placed. Figs. 5 & 6 refers to the central area of the open field. Typically, this area is defined by an inner square or circle within the total box, often located away from the walls. The amount of time spent in the centre box is often used as an indicator of rodents that are significantly sleep deprived over the rodents that are in the periphery. It is evident from (Figs 3-6) and Table 3, that rats in Groups 2-7 spend lesser time in the centre compared to periphery indicating the groups pre-treated with Compounds had a positive effect on sleepmanagement. Infact, rodents in Group 4 and 7, that have been subjected to higher concentration of pre-treatment spends at least 50 folds lesser time at the Center (Figs. 5 & 6).Table 3: Groups of animals and respective Time spent in the Box (All the values were expressed in Mean ±SEM (h=6). *P<0.05, **P<0.01, when compared to control group)

[0069] Urination and Defecation: Sleep-depriving environments increases nocturnal urine volume (UV). The sleep deprived group showed increase in number of counts in urination as well as defecation, which was reduced in pre-treated groups [See: Claudia Chaperon. Biol. Res. Nurs. 2010 Jan;l l(3):236-44]. Animals were put into metabolic cages and the urination and defecation count was measured for 12 hours. The volume of urine and the number of defecated pallets were measured and given counts. It is evident that groups pretreated with Compounds had relatively or significantly lower count of urination or defecation (Fig. 7, Fig. 8) suggesting the Compounds had positive effect in sleep management. It is clear that higher concentration of Fisetin showed pronounced 76 folds and 73 folds lesser urination and defecation counts compared to the control groups (Fig. 7, Fig. 8).

[0070] Melatonin Levels: One of the important biomarkers that signals positive effect in sleep management is the level of Melatonin. Melatonin is referred to as a sleep hormone. Melatonin supplementations have sleep-promoting effects and sleep qualityimproves when the circadian system is aligned with rhythmic circulating melatonin. Melatonin synthesis and secretion is regulated by the suprachiasmatic nucleus (SCN). The hormone, in turn, modulates the SCN and peripheral clocks throughout the body, acting as a marker of circadian rhythm. To synthesise melatonin, pineal cells first convert tryptophan in the blood into serotonin through hydroxylation and decarboxylation. N-acetyltransferase transforms serotonin into N-acelyl serotonin, which is subsequently methylated by hydroxyl indole-O-methyltransferase to form melatonin. It is evident that groups pre-treated with Compounds showed at least 10-to- 75 -fold increase in Melatonin levels compared to control group. In fact, Fisetin groups showed slightly better effects than Resveratrol treated groups (Fig. 9). It is clear that highest concentration of Fisetin and Resveratrol provided 39 and 30 folds increase in melatonin levels compared to the control. Based on the behavioural and molecular markers assessment from the Sleep Deprived Model, highest concentrations of Fisetin (50 mg / kg, p.o.), Resveratrol (90 mg / kg, p.o.) and combinations (50 mg / kg, p.o. + 90 mg / kg, p.o.) were selected for subsequent studies.

[0071] Chronic Intermittent hypoxia (CIH) model: In another model. Chronic Intermittent hypoxia (CIH) model to simulate sleep apnea was assessed. Further, the group of animals selected for this model are shown in Table 4. The normal oxygen provided to rodents is 21% O2, 24 hours per day. For induction of Intermittent hypoxia: 7% O2 for 60 s, alternating with 20% O2 for 60 s, 8 hours per day, 8 weeks. In this model, concentration of Compounds including combination was optimized from response in Sleep Deprivation Model (Para. 005). CIH was induced for the first 4 w eeks, followed by treatment w ith effective dose of Compounds for the next 4 weeks, n = 6 , as in Table 4. hi this model a total of of 24 Wistar rats were randomly divided into four groups as shown below' in Table 4. Long-term CIH induces sleep deprivation. The chronic lack of oxygen can disrupt the balance of neurotransmitters in the brain, leading to changes in mood regulation and sleep.Table 4: Groups for the Study

[0072] The elevated plus maze is widely used behavioural assay for rodents and it has been validated to assess CIH. Under conditions of sleep deprivation or anxiety, the number of entries in open arm increases. The basic measure is the animal preference for dark, enclosed places over bright, exposed places. The drug treatment reduces the anti-anxiety or sleep deprivation behaviour thus limiting their entries to the open arm of the [See: Gozal et al. JNeurosci. 2001 Apr 1 ;21(7):2442-50,' Huan Tang et al. Sleep Biol. Rhythms. 2023 Jim 3;21(4):439-446]. It is evident from Figs. 10 and 11, that the groups treated with Compounds either showed lesser entries in open arm or time spent in the open arm compared to the control group suggesting the treatment with Compounds showed positive effect in sleep management in a model that simulates sleep apnea. Fisetin treated groups spent 33 folds lesser entries (36 folds lesser time), resveratrol groups spent 39 folds lesser entries (41 folds lesser time) and combinations showed groups spent 71 folds lesser entries (65 folds lesser time) in open arms compared to the control, suggesting combinations had greater effect compared to the individual over the control groups.

[0073] Brain Derived Neurotrophic Factor (BDNF) : One of another key biomarkers to validate the role of sleep is BDNF. There is a connection between BDNF and insomnia and sleep deprivation (SD). Blood was withdrawn from rats and serum was separated to measure BDNF levels. The chronic stress leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase [See: Schmitt, Karen et al. BDNF in sleep, insomnia, andsleep deprivation. "Annals of medicine 48.1-2 (2016): 42-51]. It has been reported on how BDNF affects working memory in sleep deprivation subjects [See: Ning et al. Sleep Med. 2024 Jun: 1 18:1-8], also BDNF) has an important role in cognitive function and has been linked to clinical insomnia recently [See: Fan et al. Sleep, Volume 42, Issue 1, January 2019], It is evident (Fig. 12) Compounds showed at least 10 to 75 fold increase in BDNF levels compared to the control group. It must be noted the combination showed 55-fold increase compared to the control group, whereas Fisetin treated group showed 22 fold increase and Resveratrol treated group showed 33 fold increase in BDNF levels compared to the control. This data can have significance to those subjects having issues with cognition, memory, learning, learning, and attention that are associated with sleep.

[0074] Melatonin Levels: One of the important biomarkers that signals positive effect in sleep management is the level of Melatonin. Blood was withdrawn from rats and serum was separated to measure melatonin levels. Melatonin is referred to as a sleep hormone. Melatonin supplementations have sleep-promoting effects and sleep quality improves when the circadian system is aligned with rhythmic circulating melatonin. Melatonin synthesis and secretion is regulated by the suprachiasmatic nucleus (SCN). The hormone, in turn, modulates the SCN and peripheral clocks throughout the body, acting as a marker of circadian rhythm. To synthesise melatonin, pineal cells first convert tryptophan in the blood into serotonin through hydroxylation and decarboxylation. N-acetyltransferase transforms serotonin into N-acetyl serotonin, which is subsequently methylated by hydroxyl indole-O-methyltransferase to form melatonin. It is evident from Fig. 13 that Compounds treated groups showed at least 25 to 150 fold increase in Melatonin levels compared to control groups. It must be noted the combination showed 150-fold increase compared to the control group, whereas Fisetin treated group showed 50 fold increase and Resveratrol treated group showed 25 fold increase (Fig. 13).

[0075] NADPH Oxidase (NOX4): NADPH oxidase 4 is an enzyme that in humans is encoded by the N0X4 gene, and is a member of the NOX family of NADPH oxidases. NOX4 generates reactive oxygen species (ROS), plays a key role in oxidative stress, which can influence various physiological processes, including sleep. NOX4 potentially influences circadian rhythms. Mechanistically, oxidative stress is provoked by chronic sleep deprivation (SD), and it has been shown that NOX4 expression was increased in the retina of 4-month SD mice group [See: Tang el al. Chronic SleepDeprivation Impairs Visual Functions via Oxidative Damage in Mice, The American Journal of Pathology, 194(2), 307-320], Here, we looked at the expression levels of NOX-4, measured from serum separated from blood withdrawn from rats. It is evident (Fig. 14) that Fisetin, Resveratrol and the combination showed decreases expression levels of NOX-4 by 33%, 20%, and 40% respectively.

[0076] 6-OHD (6-hydroxy-dopamine ) induced restless syndrome: 6-OHDA (6- hydroxy-dopamine) induced restless syndrome refers to a condition in animal models, typically rodents, where researchers induce a state resembling restless legs syndrome by injecting 6-OHDA into the brain, which selectively destroys dopamine-producing neurons, leading to a significant decrease in dopamine levels [See: Zhurakovskaya et al. Sleep-State Dependent Alterations in Brain Functional Connectivity under Urethane Anesthesia in a Rat Model of Early-Stage Parkinson ’s Disease, eNeuro 2019;6\. . Each group of animals were treated with respective doses as in Table 4 for 1 month before subjecting to sleep deprivation using 6-OHD. Lidocaine was applied to the scalp and to the surface of the skull. 6-OHDA (10 pg / 4 pl, n = 20) or vehicle was infused into the right striatum (coordinates from bregma: AP: +1.0. L: -2.7, DV: -5.0) at a flow rate of 0.5 pl / min. The needle was retained in position for 4 minutes after the infusion to prevent backflow. A single dose of buprenorphine (0.02 mg / kg, s.c.) was given to relieve any postoperative pain. After surgery, the animals were kept in individual stainless-steel cages for 3 days to allow recovery and were subsequently returned in groups of two for behavioral assessment and quantification of molecular markers.

[0077] Open Field Test (OFT) in Restless Leg Syndrome: The OFT was used to evaluate locomotion in mice and thereby animal behaviour in response to sleep deprivation, In a quiet environment, the rat was placed in the canter of the bottom surface of the open field reaction box (50 cm3x 50 cm3x 45 cm3), video recording and timing were performed at the same time, and the rat was allowed to move freely in the box for 5 min. The bottom plane of the open field reaction chamber is divided into nine areas, including the center, perimeter, and corners. The time that the rat passed through each area within 5 min was then recorded and analyzed using a video-tracking system (Shanghai Xinruan Information Technology Co. Ltd., China). A rodent placed in a bare, open chamber will initially stay near the walls and avoid the centre. Normal animals typically acclimatize to the chamber and eventually explore the comer areas. More sleep deprived animals spend significantly less time in the open area and moretime near the walis. The movement of the animal’s activity in the respective groups is monitored using a camera placed above the open field. Computer software measures the time spent in the centre compared to the periphery. It is evident from Total box and Center box (Fig. 15, Fig. 16), groups treated with Fisetin, Resveratrol or the combinations spent lesser time at the Center compared to the control 50 times, 75 times and 83 times respectively. Clearly suggesting that animals that are pre-treated with Compounds showed better toleration to 6-OHD ( 6-hydroxy-dopamine ) induced restless syndrome.

[0078] Urination and Defecation: Sleep-depriving environments increases nocturnal urine volume (UV). The sleep deprived group showed increase in number of counts in urination as well as defecation, which was reduced in pre-treated groups [See: Claudia Chaperon. Biol. Res. Nurs. 2010 Jan: 11(3):236-44\. It is evident (Fig. 17) that Fisetin treated groups showed 60% and 73% lesser urination and defecation count, Resveratrol treated groups showed 68% and 73% lesser urination and defecation count, whereas the combination showed 80% and 89% lesser urination and defecation count. The combination group showed pronounced effect.

[0079] Melatonin Levels: One of the important biomarkers that signals positive effect in sleep management is the level of Melatonin. Blood was withdrawn from rats and serum was separated to measure melatonin levels. Melatonin is referred to as a sleep hormone. Melatonin supplementations have sleep-promoting effects and sleep quality improves when the circadian system is aligned with rhythmic circulating melatonin. Melatonin synthesis and secretion is regulated by the suprachiasmatic nucleus (SCN). The hormone, in turn, modulates the SCN and peripheral clocks throughout the body, acting as a marker of circadian rhythm. To synthesise melatonin, pineal cells first convert tryptophan in the blood into serotonin through hydroxylation and decarboxylation. N-acetyltransferase transforms serotonin into N-acetyl serotonin, w'hich is subsequently methylated by hydroxyl indole-O-methyltransferase to form melatonin. It must be noted the combination showed 240-fold increase compared to the control group, whereas Fisetin treated group showed 140 fold increase and Resveratrol treated group showed 125 fold increase (Fig. 18).

[0080] Gamma-Aminobutyric Acid (GABA): Neurotransmitters GABA and adenosine in the ventrolateral preoptic (VLP) nucleus inhibit the ascending activity during sleep , resulting in a transition from NREM sleep to REM sleep cycles. Based on the dynamic interactions of neurotransmitters, GABA appears to be an essentialneurotransmiter that modulates sleep. Therefore, understanding the role of the GABAergic system on sleep is necessary7for developing a better insomnia treatment. GABA is involved in normal brain functions, including cognition, memory, and learning. It is the primary inhibitory neurotransmitter in the brain and counterbalances the excitatory' neurotransmiter glutamate. GABAergic neurons are primarily located in the basal forebrain and the anterior hypothalamus. They are essential in modulating sleep by releasing a high level of GABA during sleep to inhibit cells that stimulate arousal functions. Targeting the GABAergic system thus is a promising approach to novel drug development for treating insomnia [See: Varinthra et al. The role of the GABAergic system on insomnia, Tzu Chi Medical Journal 36.2 (2024): 103-109], It is evident (Fig. 19) the expression levels of Fisetin treated groups increased by 100 folds, Resveratrol treated groups by 43 folds, and the combination groups by 171 folds. This clearly suggests that the combination showed synergistic effect in increasing GABA levels and showed pronounced insignificance caused by sleep deprivation. . This data can have significance to those subjects having issues with cognition, memory, learning, learning, and attention that are associated with sleep.

[0081] To summarize, overall studies across different models mimicking different sleep disorders such as insomnia, sleep apnea and restless leg syndrome, capturing both behavioural parameters such as OFD, EPM and assessment of biological markers (BDNF, Melatonin and GABA) revealed that combinations overall provided positive sleep management effects. In particular, CIH model mimicking sleep apnea showed 150 folds increase in Melatonin levels, 55 fold increase in BDNF levels, and 71 folds lesser entry (65 folds lesser time) in Elevated Plus Maze for the combinations. Similarly, 6-OHD (6-hydroxy-dopamine) induced restless syndrome showed 240 folds increase in Melatonin levels, 171 fold increase in GABA levels, and 83 folds lesser time in the center on OFT test for the combinations.

[0082] Formulations

[0083] Tables 5-11 provide illustrative examples of nutraceutical formulationsTable 5: Tablet_ _

[0084] Other modifications and variations of the invention will be apparent to those skilled in the art from the foregoing disclosure and teachings. Thus, while only certain embodiments of the invention have been specifically described herein, it will be apparent that numerous modifications may be made thereto without departing from the spirit and scope of the invention.

Claims

We claim,1 . A composition comprising Fisetm, Resveratrol or combinations thereof.

2. The composition as claimed in claim 1, wherein the composition is formulated with pharmaceutically, nutraceutically, cosmeceutically acceptable excipients, adjuvants, diluents or carriers, and administered orally in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, lotions, and eatables.

3. A composition comprising Fssetin or Resveratrol either alone or in combinations thereof for use in management of sleep in a subject, wherein the composition improves sleep in the said subject.

4. The composition as claimed in claim 3, wherein the management of sleep arises in conditions selected from the group consisting of sleep apnea, restless legs syndrome.. (RLS), narcolepsy, circadian rhythm sleep disorders (CRSDs), parasomnia, anxiety, mental disorders, and Insomnia.

5. The composition as claimed in claim 3, wherein the management of sleep is associated with improvement in the behavioral parameters and modulatory effects on the subject.

6. The composition as claimed in claim 5, wherein the behavioral parameters is selected from the group consisting of memory, learning, and attention that are associated with sleep.

7. The composition as claimed in claim 5, wherein the behavioral parameters are assessed from the group consisting of Open Field Test (OFT), Elevated Plus Maze (EPZ), Urination, and Defecation.

8. The composition as claimed in claim 5, wherein the modulatory effect on biological markers is to improve sleep in the said subject.

9. The composition as claimed in claim 5, wherein the biological markers is selected from the group consisting of Melatonin, Brain Derived Neurotrophic Factor (BDNF), NADPH Oxidase NOX-4, and Gamma-Aminobutyric Acid (GABA).

10. The composition for use as in claim 3, wherein the subject is a mammal.

11. The composition for use as in claim 3, wherein the composition is formulated with pharmaceutically, nutraceutically, cosmeceutically acceptable excipients, adjuvants, diluents or carriers, and administered orally in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, lotions, and eatables.

12. A composition comprising Fisetia or Resveratrol either alone or in combinations thereof for use in improving cognitive functions in a subject.

13. The composition as claimed in claim 12, wherein the cognitive functions is selected from the group consisting of memory, focus, attention, and learning.

14. The composition as claimed in claim 12, wherein the subject is cognitively impaired due to sleep deprivation.

15. The composition as claimed in claim 12, wherein improvement in cognitive functions is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF) and Gamma-Aminobutyric Acid (GABA).

16. The composition as claimed in claim 12, wherein the subject is a mammal.

17. A composition comprising Fisetin or Resveratrol either alone or in combinations thereof for use in improving mood in a subject.

18. The composition as claimed in claim 17, wherein improvement of mood arises in conditions selected from the group consisting of stress, anxiety, depression, and trauma.

19. . The composition as claimed in claim 17, wherein the subject is sleep deprived.

20. The composition as claimed in claim 17, wherein improvement of mood is brought about by increasing the levels of Brain Derived Neurotrophic Factor (BDNF), Gamma- Aminobutyric Acid (GABA), and decreasing NADPH Oxidase NOX-4.

21. The composition as claimed in claim 17, wherein the subject is a mammal.

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