Research on Unwind+ ingredients

Unwind+

Magnolia bark (Magnolia officinalis)

Magnolia bark in Unwind+ by We Know Health

Magnolia Bark has been used in traditional Chinese medicine for over 1000 years to treat conditions such as acute pain, depression, stress, anxiety and nervous disorders. It is native to the mountains and valleys of China. 

Whilst there have been more than 250 compounds isolated from Magnolia Bark, the most significant active constituents appear to be honokiol, magnolol and related compounds.

Stress, anxiety and sleep

Honokiol and magnolol have many complex actions, however both seem to act in part via GABAA  (gamma-aminobutyric acid) receptor modulation (1). Honokiol also appears to stimulate increased production of GABA via glutamic acid decarboxylase (GAD) enzyme upregulation (2). The GABA system is critical component for mind relaxationa and sleep. Both magnolol (3) and honokiol (4) have been shown to induce non-REM sleep in animal models.

In two double blinded, placebo controlled human studies of a proprietary formula of Magnolia Officinalis and Phellodendron amurense, there were reduced levels of transient anxiety (5) and night time cortisol (6) with the Magnolia Bark product.  Interestingly, dihydrohonokiol from Magnolia Bark had significant anti-anxiety effects but did not exhibit withdrawal effects when compared with diazepam in an animal study (7). Honokiol in Magnolia Bark appears to inhibit catecholamine release (e.g. adrenaline/epinephrine) from adrenal glands in a bovine model and this effect increased with higher doses (8).

Depression

The mixture of magnolol and honokiol from Magnolia Bark reduced stress induced changes in rat brains, showing potent antidepressant-like effects (9). This was shown again in another trial with mice, demonstrating significant increases in serotonin (10).

Pain and inflammation

4′-O-methylhonokiol in Magnolia Bark has demonstrated the ability to activate the cannabinoid analgesic system via the CB2 receptor and additionally inhibit the COX2 system, both of which create a degree of analgesia (11). A combination of magnolol and honokiol alleviated inflammatory pain in a mice model (12) and in a separate third degree burns trial honokiol demonstrated reductions in various inflammatory cytokines therefore promoting analgesia (13). There are numerous other trials investigating different compounds from Magnolia Bark in inflammation that are beyond this page.

Cancer

Honokiol is the subject of a large number of animal and now human trials in cancer patients with potentially promising results. This is outside the scope of this page and we make no claims whatsoever about the ability to treat or manage cancer. For those interested, here is a 2020 review with hundreds of references (14).

Dosing

For Unwind+, we chose a potent 400mg of 10:1 concentrated extract (derived from 4000mg of Magnolia Officinalis) per two capsule dose supplying all the naturally occurring active ingredients such as magnolol, honokiol and 4′-O-methylhonokiol rather than just standardizing for a single ingredient.


Lemon balm (Melissa officinalis)

Lemon balm in Unwind+ by We Know Health

Lemon balm is a perennial herb of the mint family that has been used for centuries in traditional medicine to remedy anxiety and insomnia, digestive issues, headaches, infections such as herpes, and in skin care regimes.

Lemon balm contains a number of interesting active ingredients, most notably ursolic acid, oleanolic acid and rosmarinic acid (known to inhibit GABA transaminase (15)), and antioxidant/anti-inflammatory flavonoids such as apigenin and luteolin (16).

Anxiety, stress and sleep

A proprietary lemon balm extract given twice a day to humans for 15 days showed reductions in anxiety and insomnia (17). Similar results of anxiolysis were found in two mice studies (18,19). These effects are likely related to the ability of lemon balm to inhibit GABA transaminase (normally this enzyme breaks down GABA), promoting more of the inhibitory neurotransmitter GABA in nerve synapses. A systematic review of 10 randomised controlled trials published in 2021 showed a statistically significant improvement in anxiety and depressive symptoms with the use of lemon balm (20).

A randomised, double blind, placebo controlled trial of 98 people investigated the combination of valerian and lemon balm. There was a statistically significant improvement in the quality of sleep in the valerian/lemon balm group with no difference in serious adverse effects versus placebo (21).

Nootropic and neuroprotective properties

Lemon balm has also been investigated for its potential interactions with the acetylcholine/muscarinic/nicotinic system. In a trial of 20 healthy people there were notable improvements after one ingestion in the speed of memory tasks and visual information processing at higher doses (22). Neuroprotective effects have been demonstrated in a hypoxia induced neuronal death model (23) as well as a MDMA (‘Ecstasy’) induced neuronal death model (24).

Dosing

Unwind+ has 60mg of a very potent 40:1 extract (derived from 2400mg of melissa officinalis) per standard two capsule dose. Lemon balm can become stimulating at very high doses in some people owing to its rosmarinic acid content, so it was important for us to understand where this inflection point may be. Our goal was to supply as much as we could of active ingredients without causing stimulation.


Passionflower (Passiflora incarnata)

Passionflower in Unwind+ by We Know Health

Passionflower was originally native to the Americas, where it has been used traditionally to remedy anxiety, insomnia, gastrointestinal issues and seizures. It is complex and contains a number of active ingredients including flavonoids such as isovitexin, vitexin, apigenin, luteolin and quercetin, as well as alkaloids such as harmine, harmaline and harmalol. It also contains a benzoflavone moiety which some believe contributes to its central nervous system effects. 

Anxiety, stress and sleep

Passionflower has been shown to modulate the GABA system in various ways including acting as a re-uptake inhibitor (25) - keeping more ‘relaxing/inhibitory’ GABA available in nerve synapses. Due in part to these effects, Passionflower has been demonstrated via a systematic review of nine clinical trials in humans to have anti-anxiety effects “comparable to drugs such as oxazepam or midazolam” without any significant adverse effects like memory loss (26). These trials stretched across a number of contexts including using passionflower as a pre-medication before surgery. A direct comparison to oxazepam for those with generalised anxiety disorder was studied and found that Passionflower had similar efficacy but had less adverse effects. In particular oxazepam impaired work performance more than Passionflower (27).

Passionflower has also been trialed in those with insomnia. In a double-blind randomized placebo-controlled study, 110 participants consumed a passionflower extract at night for 2 weeks whilst various objective measurements were taken including polysomnography (a type of ‘sleep study’). Total sleep time was significantly increased versus placebo with passionflower (28). Whilst less scientifically dosed, a passionflower tea has also been studied for sleep and demonstrated subjective sleep benefits (29). A combination of herbs including passionflower was directly compared to zolpidem (a prescription drug for insomnia) and was found to be safe and of comparable efficacy (30). 

Dosing

Like Lemon Balm, we have sourced a highly potent 20:1 extract of passionflower (derived from 2400mg of Passionflower Incarnata per two capsule dose). This provides a higher dose than in studies and most products available to promote the desired effect, given we did not discover any significant safety concerns. We also believe that Passionflower’s mechanisms work synergistically with the other ingredients in Unwind+.


Ziziphus spinosa (Zizyphus jujuba var. spinosa, semen ziziphi spinosae, chinese date, jujube)

Ziziphus in Unwind+ by We Know Health

Ziziphus seeds have been used in traditional Chinese medicine for centuries to calm the mind and spirit and specifically have been used as part of a concoction called Suan Zao Ren to treat insomnia.

Ziziphus (referring to the seeds, not the fruit) contains many active ingredients but the saponins such as jujubosides and flavonoids such as spinosin appear to be responsible for its main effects. 

Anxiety, stress and sleep

The jujubosides have been shown to increase the expression and activation of the GABAA receptor (31, 32). Ziziphus has also been shown to modulate the 5-HT (serotonin) receptors involved in anxiolysis (33). Sanjoinine A, another saponin in Ziziphus, was found to upregulate the glutamic acid decarboxylase (GAD) enzyme and to augment pentobarbital-induced sleeping behaviour (34). GAD is the enzyme that catalyses the production of GABA from glutamate. Spinosin, another key ingredient of Ziziphus, has been shown to increase slow wave sleep (deep sleep), total sleep time and sleep latency. The study proposed this was due to modulation of 5-HT1A receptors (35).

In a randomised, placebo-controlled, cross-over trial of people with insomnia, there was a significant increase in both quality and quantity of sleep with Ziziphus (36).

Cognitive enhancement and neuroprotection

In the animal domain, there have been numerous trials suggesting positive brain effects including on memory, hippocampal plasticity and neuroprotection (37, 38, 39). Antioxidant, anti-inflammatory and potentially enhanced cholinergic transmission have been implicated for these effects. Specific discussion of these trials is outside the scope of this page. Hopefully in the future there will be further studies in humans examining these effects.

Dosing

Since Ziziphus effects are mostly demonstrated at high doses by weight which cannot practically fit into a small number of capsules, we sourced a 30:1 concentrated extract. There are multiple active ingredients contributing to the desired effects so we didn’t look for the extract to be standardised to any single ingredient. Standard two capsule dosing of Unwind+ is derived from approximately 7.2g of dry seed, ensuring sufficient potency. As Ziziphus promotes REM sleep we felt much higher doses along with the other ingredients could cause excessively vivid dreams in some people.

 

Taurine (L-taurine, 2-aminoethanesulfonic acid)

Taurine in Unwind+ by We Know Health

Taurine is a critically important amino sulfonic acid compound with neural inhibitory (relaxing) effects as well as antioxidant effects. Taurine is found in many organs of the body but particularly in tissues containing ‘excitable’ cells such as the heart and brain, as well as the retinas. Some Taurine can be produced by the human body in health but this may be impaired in illness, stressful states and ageing. For optimal levels it can be obtained in a diet high in certain seafoods and meats and/or in supplemental form. As Taurine is only found in animal derived products (41), vegans will consume no Taurine in their diet and have been shown to have lower plasma and urine levels (42). The average meat containing diet is thought to supply around 40-90mg of Taurine per day (43,44).

Taurine is often misinterpreted to be a compound that provides an energy boost like guarana and caffeine because it is included in many energy drinks. In fact, Taurine is used in this context to provide a gentle relaxation effect to offset the jitteriness from excessive caffeine.

Optimal central nervous system function

Taurine sits alongside GABA and glycine as a major ‘inhibitory’ neurotransmitter with widespread effects including weak agonism at GABAA  and GABAB receptors (45,46), anti-anxiety effects in animals by activating glycine receptors (47) and increased glutamic acid decarboxylase (GAD) expression in taurine fed mice (48) leading to higher GABA levels and increased seizure threshold. Taurine administration in mice, who like humans can synthesize Taurine, is thought to reduce age-related changes in the GABAergic system (49).

Whilst a long way from humans, an interesting study in fruit flies demonstrated reductions in sleep with caffeine and inversely enhancement of sleep time with Taurine (50).

Taurine has also been suggested as a novel agent to consider in those with depression after promising animal studies, particularly in diabetics (51,52,53).

Cardiovascular health

In a human randomized, double-blinded, placebo controlled trial, Taurine administration was shown to reduce blood pressure in pre-hypertensive individuals (54) due to improvement in vascular function. In animal studies Taurine has shown to have free radical scavenging and cardiac protective effects (55) as well as limitation of atherosclerosis (56).

In humans there are small trials suggestive of improvements in cardiac function with Taurine administration (57,58). Further large scale research is required to clarify.

Liver disease

Taurine has also been trialed for its antioxidant effects in liver disease in both animals and humans. Evidence is mounting regarding liver protective effects in a number of liver disease states such as chronic hepatitis, alcoholism, non-alcoholic fatty liver disease and iron overload (59,60,61,62).

Dosing

We have included 500mg of vegan Taurine in a standard dose of Unwind+. This is significantly more than most people consume per day whilst still being safe support for the brain’s relaxation pathways in combination with the potent herbal extracts present in Unwind+.

Unwind+™ - We Know Health
Unwind+™ - We Know Health
Unwind+™ - We Know Health
Ingredients Unwind+ by We Know Health
Unwind+™ - We Know Health
Unwind+™ - We Know Health
Unwind+™ - We Know Health
Ingredients Unwind+ by We Know Health

Unwind+™

$59.99 AUD
By We Know Health
Minus Plus

Unwind+™ is a calming, science-based formula designed to promote mind relaxation, reduce time to fall asleep, enhance sleep quality, and promote refreshing sleep. Created by expert Steven Musca, Unwind+™ is formulated to help you unwind at the end of the day, reduce racing thoughts, and drift off to sleep peacefully in our modern world.

Our formula is expertly crafted to optimize your brain's GABA levels, leaving you feeling more refreshed and less hungover without messing with your circadian rhythm. Say goodbye to feeling 'wired but tired' and staring at the ceiling with Unwind+™.

At We Know Health, we are pioneering clean, transparent supplement labelling in Australia, so you can trust that what you see is what you get. Experience the benefits of Unwind+™, as traditionally used in Chinese medicine, and start enjoying a more peaceful, restful sleep today.

REFERENCES

  1. Woodbury A, Yu SP, Wei L, García P. Neuro-modulating effects of honokiol: a review. Front Neurol. 2013 Sep 11;4:130. doi: 10.3389/fneur.2013.00130.
  2. Ku TH, Lee YJ, Wang SJ, Fan CH, Tien LT. Effect of honokiol on activity of GAD(65) and GAD(67) in the cortex and hippocampus of mice. Phytomedicine. 2011 Oct 15;18(13):1126-9. doi: 10.1016/j.phymed.2011.03.007.1
  3. Chen CR, Zhou XZ, Luo YJ, Huang ZL, Urade Y, Qu WM. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABA(A) receptor in mice. Neuropharmacology. 2012 Nov;63(6):1191-9. doi: 10.1016/j.neuropharm.2012.06.031.
  4. Qu WM, Yue XF, Sun Y, Fan K, Chen CR, Hou YP, Urade Y, Huang ZL. Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice. Br J Pharmacol. 2012 Oct;167(3):587-98. doi: 10.1111/j.1476-5381.2012.02010.x.
  5. Kalman, D.S., Feldman, S., Feldman, R. et al. Effect of a proprietary Magnolia and Phellodendronextract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial. Nutr J 7, 11 (2008). https://doi.org/10.1186/1475-2891-7-11.
  6. Garrison R, Chambliss WG. Effect of a proprietary Magnolia and Phellodendron extract on weight management: a pilot, double-blind, placebo-controlled clinical trial. Altern Ther Health Med. 2006 Jan-Feb;12(1):50-4.
  7. Kuribara H, Kishi E, Maruyama Y. Does dihydrohonokiol, a potent anxiolytic compound, result in the development of benzodiazepine-like side effects? J Pharm Pharmacol. 2000 Aug;52(8):1017-22. doi: 10.1211/0022357001774741.
  8. Tachikawa E, Takahashi M, Kashimoto T. Effects of extract and ingredients isolated from Magnolia obovata thunberg on catecholamine secretion from bovine adrenal chromaffin cells. Biochem Pharmacol. 2000 Aug 1;60(3):433-40. doi: 10.1016/s0006-2952(00)00343-9.
  9. Xu Q, Yi LT, Pan Y, Wang X, Li YC, Li JM, Wang CP, Kong LD. Antidepressant-like effects of the mixture of honokiol and magnolol from the barks of Magnolia officinalis in stressed rodents. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Apr 1;32(3):715-25. doi: 10.1016/j.pnpbp.2007.11.020.
  10. Yi LT, Xu Q, Li YC, Yang L, Kong LD. Antidepressant-like synergism of extracts from magnolia bark and ginger rhizome alone and in combination in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Jun 15;33(4):616-24. doi: 10.1016/j.pnpbp.2009.03.001.
  11. Chicca A, Gachet MS, Petrucci V, Schuehly W, Charles RP, Gertsch J. 4'-O-methylhonokiol increases levels of 2-arachidonoyl glycerol in mouse brain via selective inhibition of its COX-2-mediated oxygenation. J Neuroinflammation. 2015 May 13;12:89. doi: 10.1186/s12974-015-0307-7.
  12. Lin YR, Chen HH, Ko CH, Chan MH. Effects of honokiol and magnolol on acute and inflammatory pain models in mice. Life Sci. 2007 Sep 8;81(13):1071-8. doi: 10.1016/j.lfs.2007.08.014. Epub 2007 Aug 19.
  13. Khalid S, Khan A, Shal B, Ali H, Kim YS, Khan S. Suppression of TRPV1 and P2Y nociceptors by honokiol isolated from Magnolia officinalis in 3rd degree burn mice by inhibiting inflammatory mediators. Biomed Pharmacother. 2019 Jun;114:108777. doi: 10.1016/j.biopha.2019.108777. Epub 2019 Mar 27.
  14. Ong CP, Lee WL, Tang YQ, Yap WH. Honokiol: A Review of Its Anticancer Potential and Mechanisms. Cancers (Basel). 2019 Dec 22;12(1):48. doi: 10.3390/cancers12010048.
  15. Awad R, Muhammad A, Durst T, Trudeau VL, Arnason JT. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother Res. 2009 Aug;23(8):1075-81. doi: 10.1002/ptr.2712.
  16. Patora J, Klimek B. Flavonoids from lemon balm (Melissa officinalis L., Lamiaceae). Acta Pol Pharm. 2002 Mar-Apr;59(2):139-43.
  17. Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Med J Nutrition Metab. 2011 Dec;4(3):211-218. doi: 10.1007/s12349-010-0045-4. Epub 2010 Dec 17.
  18. Ibarra A, Feuillere N, Roller M, Lesburgere E, Beracochea D. Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice. Phytomedicine. 2010 May;17(6):397-403. doi: 10.1016/j.phymed.2010.01.012. Epub 2010 Feb 18.
  19. Taiwo AE, Leite FB, Lucena GM, Barros M, Silveira D, Silva MV, Ferreira VM. Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender. Indian J Pharmacol. 2012 Mar;44(2):189-92. doi: 10.4103/0253-7613.93846.
  20. Ghazizadeh J, Sadigh-Eteghad S, Marx W, Fakhari A, Hamedeyazdan S, Torbati M, Taheri-Tarighi S, Araj-Khodaei M, Mirghafourvand M. The effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials: A systematic review and meta-analysis. Phytother Res. 2021 Dec;35(12):6690-6705. doi: 10.1002/ptr.7252.
  21. A. Cerny, K. Schmid, Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double-blind, placebo-controlled, multicentre study), Fitoterapia, Volume 70, Issue 3, 1999, Pages 221-228, ISSN 0367-326X, https://doi.org/10.1016/S0367-326X(99)00018-0.
  22. Kennedy DO, Wake G, Savelev S, Tildesley NT, Perry EK, Wesnes KA, Scholey AB. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology. 2003 Oct;28(10):1871-81. doi:10.1038/sj.npp.1300230.
  23. Bayat M, Azami Tameh A, Hossein Ghahremani M, Akbari M, Mehr SE, Khanavi M, Hassanzadeh G. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo. Daru. 2012 Oct 3;20(1):42. doi: 10.1186/2008-2231-20-42.
  24. Hassanzadeh G, Pasbakhsh P, Akbari M, Shokri S, Ghahremani M, Amin G, Kashani I, Azami Tameh A. Neuroprotective properties of melissa officinalis L. Extract against ecstasy-induced neurotoxicity. Cell J. 2011 Spring;13(1):25-30. Epub 2011 Apr 21.
  25. Appel K, Rose T, Fiebich B, Kammler T, Hoffmann C, Weiss G. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytother Res. 2011 Jun;25(6):838-43. doi: 10.1002/ptr.3352. Epub 2010 Nov 19.
  26. Janda K, Wojtkowska K, Jakubczyk K, Antoniewicz J, Skonieczna-Żydecka K. Passiflora incarnata in Neuropsychiatric Disorders-A Systematic Review. Nutrients. 2020 Dec 19;12(12):3894. doi: 10.3390/nu12123894.
  27. Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001 Oct;26(5):363-7. doi: 10.1046/j.1365-2710.2001.00367.x.
  28. Lee J, Jung HY, Lee SI, Choi JH, Kim SG. Effects of Passiflora incarnata Linnaeus on polysomnographic sleep parameters in subjects with insomnia disorder: a double-blind randomized placebo-controlled study. Int Clin Psychopharmacol. 2020 Jan;35(1):29-35. doi: 10.1097/YIC.0000000000000291.
  29. Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality. Phytother Res. 2011 Aug;25(8):1153-9. doi: 10.1002/ptr.3400. Epub 2011 Feb 3.
  30. Maroo N, Hazra A, Das T. Efficacy and safety of a polyherbal sedative-hypnotic formulation NSF-3 in primary insomnia in comparison to zolpidem: a randomized controlled trial. Indian J Pharmacol. 2013 Jan-Feb;45(1):34-9. doi: 10.4103/0253-7613.106432.
  31. Song P, Zhang Y, Ma G, Zhang Y, Zhou A, Xie J. Gastrointestinal Absorption and Metabolic Dynamics of Jujuboside A, A Saponin Derived from the Seed of Ziziphus jujuba. J Agric Food Chem. 2017 Sep 27;65(38):8331-8339. doi: 10.1021/acs.jafc.7b02748. Epub 2017 Sep 18.
  32. You ZL, Xia Q, Liang FR, Tang YJ, Xu CL, Huang J, Zhao L, Zhang WZ, He JJ. Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons. J Ethnopharmacol. 2010 Mar 24;128(2):419-23. doi: 10.1016/j.jep.2010.01.034. Epub 2010 Jan 18.
  33. Chen L, Zhang X, Hu C, Zhang Y, Zhang L, Kan J, Li B, Du J. Regulation of GABAA and 5-HT Receptors Involved in Anxiolytic Mechanisms of Jujube Seed: A System Biology Study Assisted by UPLC-Q-TOF/MS and RT-qPCR Method. Front Pharmacol. 2020 Oct 15;11:01320. doi: 10.3389/fphar.2020.01320.
  34. Ma Y, Han H, Eun JS, Kim HC, Hong JT, Oh KW. Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems. Biol Pharm Bull. 2007 Sep;30(9):1748-53. doi: 10.1248/bpb.30.1748. Erratum in: Biol Pharm Bull. 2007 Dec;30(12):2412. Kim, Hyung-Chun [corrected to Kim, Hyoung Chun].
  35. L.-E. Wang, X.-Y. Cui, S.-Y. Cui, J.-X. Cao, J. Zhang, Y.-H. Zhang, Q.-Y. Zhang, Y.-J. Bai, Y.-Y. Zhao. Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT1A receptors, Phytomedicine, Volume 17, Issue 6, 2010, Pages 404-409, ISSN 0944-7113, https://doi.org/10.1016/j.phymed.2010.01.014.
  36. Shergis JL, Hyde A, Meaklim H, Varma P, Da Costa C, Jackson ML. Medicinal seeds Ziziphus spinosa for insomnia: A randomized, placebo-controlled, cross-over, feasibility clinical trial. Complement Ther Med. 2021 Mar;57:102657. doi: 10.1016/j.ctim.2020.102657. Epub 2020 Dec 29.
  37. Lee Y, Jeon SJ, Lee HE, Jung IH, Jo YW, Lee S, Cheong JH, Jang DS, Ryu JH. Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice. Pharmacol Biochem Behav. 2016 Jun;145:9-16. doi: 10.1016/j.pbb.2016.03.007. Epub 2016 Mar 17.
  38. Lee HE, Lee SY, Kim JS, Park SJ, Kim JM, Lee YW, Jung JM, Kim DH, Shin BY, Jang DS, Kang SS, Ryu JH. Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice. Biomol Ther (Seoul). 2013 Jul 30;21(4):299-306. doi: 10.4062/biomolther.2013.043.
  39. Djeuzong E, Kandeda AK, Djiogue S, Stéphanie L, Nguedia D, Ngueguim F, Djientcheu JP, Kouamouo J, Dimo T. Antiamnesic and Neuroprotective Effects of an Aqueous Extract of Ziziphus jujuba Mill. (Rhamnaceae) on Scopolamine-Induced Cognitive Impairments in Rats. Evid Based Complement Alternat Med. 2021 Aug 10;2021:5577163. doi: 10.1155/2021/5577163.
  40. Hwang IK, Yoo KY, Yoo DY, Choi JH, Lee CH, Kang IJ, Kwon DY, Kim YS, Kim DW, Won MH. Zizyphus enhances cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus in middle-aged mice. J Med Food. 2011 Mar;14(3):195-200. doi: 10.1089/jmf.2010.1123.
  41. Laidlaw SA, Grosvenor M, Kopple JD. The taurine content of common foodstuffs. JPEN J Parenter Enteral Nutr. 1990 Mar-Apr;14(2):183-8. doi: 10.1177/0148607190014002183. Erratum in: JPEN J Parenter Enteral Nutr 1990 Jul-Aug;14(4):380.
  42. Laidlaw SA, Shultz TD, Cecchino JT, Kopple JD. Plasma and urine taurine levels in vegans. Am J Clin Nutr. 1988 Apr;47(4):660-3. doi: 10.1093/ajcn/47.4.660.
  43. Park JY, You JS, Chang KJ. Dietary taurine intake, nutrients intake, dietary habits and life stress by depression in Korean female college students: a case-control study. J Biomed Sci. 2010 Aug 24;17 Suppl 1(Suppl 1):S40. doi: 10.1186/1423-0127-17-S1-S40.
  44. Rana SK, Sanders TA. Taurine concentrations in the diet, plasma, urine and breast milk of vegans compared with omnivores. Br J Nutr. 1986 Jul;56(1):17-27. doi: 10.1079/bjn19860082.
  45. Bureau MH, Olsen RW. Taurine acts on a subclass of GABAA receptors in mammalian brain in vitro. Eur J Pharmacol. 1991 May 25;207(1):9-16. doi: 10.1016/s0922-4106(05)80031-8.
  46. Kontro P, Oja SS. Interactions of taurine with GABAB binding sites in mouse brain. Neuropharmacology. 1990 Mar;29(3):243-7. doi: 10.1016/0028-3908(90)90008-f.
  47. Zhang CG, Kim SJ. Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo. Ann Nutr Metab. 2007;51(4):379-86. doi: 10.1159/000107687. Epub 2007 Aug 29.
  48. L’Amoreaux, W.J., Marsillo, A. & El Idrissi, A. Pharmacological characterization of GABAA receptors in taurine-fed mice. J Biomed Sci 17 (Suppl 1), S14 (2010). https://doi.org/10.1186/1423-0127-17-S1-S14.
  49. El Idrissi A, Shen CH, L'amoreaux WJ. Neuroprotective role of taurine during aging. Amino Acids. 2013 Oct;45(4):735-50. doi: 10.1007/s00726-013-1544-7. Epub 2013 Aug 21. Erratum in: Amino Acids. 2014 Jan;46(1):123.
  50. Fang Ju Lin, Michael M Pierce, Amita Sehgal, Tianyi Wu, Daniel C Skipper & Radhika Chabba (2010) Effect of taurine and caffeine on sleep–wake activity in Drosophila melanogaster, Nature and Science of Sleep, 2:, 221-231, DOI: 10.2147/NSS.S13034.
  51. Caletti G, Olguins DB, Pedrollo EF, Barros HM, Gomez R. Antidepressant effect of taurine in diabetic rats. Amino Acids. 2012 Oct;43(4):1525-33. doi: 10.1007/s00726-012-1226-x.
  52. Yang P, Li X, Ni J, Tian J, Jing F, Qu C, Lin L, Zhang H. Alterations of amino Acid level in depressed rat brain. Korean J Physiol Pharmacol. 2014 Oct;18(5):371-6. doi: 10.4196/kjpp.2014.18.5.371. Epub 2014 Oct 17.
  53. Caletti G, Almeida FB, Agnes G, Nin MS, Barros HM, Gomez R. Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats. Behav Brain Res. 2015 Apr 15;283:11-5. doi: 10.1016/j.bbr.2015.01.018. Epub 2015 Jan 19.
  54. Sun, Q., Wang, B., Li, Y., Sun, F., Li, P., Xia, W., Zhou, X., Li, Q., Wang, X., Chen, J. and Zeng, X., 2016. Taurine supplementation lowers blood pressure and improves vascular function in prehypertension: randomized, double-blind, placebo-controlled study. Hypertension, 67(3), pp.541-549.
  55. Hanna J, Chahine R, Aftimos G, Nader M, Mounayar A, Esseily F, Chamat S. Protective effect of taurine against free radicals damage in the rat myocardium. Exp Toxicol Pathol. 2004 Dec;56(3):189-94. doi: 10.1016/j.etp.2004.08.004.
  56. Murakami S. Taurine and atherosclerosis. Amino Acids. 2014 Jan;46(1):73-80. doi: 10.1007/s00726-012-1432-6. Epub 2012 Dec 8.
  57. Azuma J, Sawamura A, Awata N, Ohta H, Hamaguchi T, Harada H, Takihara K, Hasegawa H, Yamagami T, Ishiyama T, et al. Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. Clin Cardiol. 1985 May;8(5):276-82. doi: 10.1002/clc.4960080507.
  58. Jeejeebhoy F, Keith M, Freeman M, Barr A, McCall M, Kurian R, Mazer D, Errett L. Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction. Am Heart J. 2002 Jun;143(6):1092-100. doi: 10.1067/mhj.2002.121927.
  59. Zhang Z, Liu D, Yi B, Liao Z, Tang L, Yin D, He M. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model. Mol Med Rep. 2014 Nov;10(5):2255-62. doi: 10.3892/mmr.2014.2544. Epub 2014 Sep 5.
  60. Hsieh YL, Yeh YH, Lee YT, Huang CY. Effect of taurine in chronic alcoholic patients. Food Funct. 2014 Jul 25;5(7):1529-35. doi: 10.1039/c3fo60597c.
  61. Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, Wei Y, Jiang H, Orlicky DJ, Petersen DR, Pagliassotti MJ, Maclean KN. Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1710-22. doi: 10.1152/ajpregu.00677.2010. Epub 2011 Sep 28.
  62. Hu YH, Lin CL, Huang YW, Liu PE, Hwang DF. Dietary amino acid taurine ameliorates liver injury in chronic hepatitis patients. Amino Acids. 2008 Aug;35(2):469-73. doi: 10.1007/s00726-007-0565-5. Epub 2007 Aug 10.