Gut Bacteria and Anxiety

One of the main factors that can influence the mood of an individual is the health of the gut. In particular, the variety of bacteria within the gut can have a significant impact on mental health. In turn, both diet and exercise are able to affect the type and numbers of bacteria inhabiting the gut. Generally, exercise and a good diet improve the bacterial profile of the gut, whereas a lack of exercise and a poor diet can detrimentally affect the profile. For example, studies investigating the effects of diet and exercise on mice have shown that specific bacterial abundances are directly related to the anxious behaviour displayed by the animals and that these were improved with a normal diet but worsened by a high fat diet. The authors also found that exercise could improve the health of the gut, but these improvements did not occur when a high fat diet was consumed, suggesting that although exercise is beneficial, a high fat diet may be dominant in shaping gut health when compared to physical activity. 

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Kang, S. S., Jeraldo, P. R., Kurti, A., Miller, M. E. B., Cook, M. D., Whitlock, K., Goldenfeld, N., Woods, J. A., White, B. A., Chia, N. and Fryer, J. D. 2014. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Molecular Neurodegeneration. 9(1): 1-12
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Serotonin and Anxiety

Serotonin is a neurotransmitter found in humans and animals that is synthesised from the amino acid tryptophan. It is often considered that the function of serotonin is to induce a sense of well being and contentment. However, within the brain of both humans and animals, neurotransmitters perform dual roles, and this is testament to the efficiency of the brain in that it can do more with less, in effect reducing its requirement to synthesise additional types of neurotransmitters. For example, serotonin released from the dorsal raphe nucleus has been shown to enhance fear and anxiety that ultimately activates anxious and fearful behaviour through multiple regulated pathways. This may explain the anxious feelings encountered by some when they take drugs designed to increase serotonin release. The take home message from this is that the complexity of the brain must always be considered when dealing with neurotransmitters as often there are multiple and conflicting pathways for every neurotransmitter. 

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Marcinkiewcz, C. A., Mazzone, C. M., D’Agostino, G., Halladay, L. R., Hardaway, J. A., DiBerto, J. F., Navarro, M., Burnham, N., Cristano, C., Dorrier, C., Tipton, G. J., Ramakrishnan, C., Kozicz, T., Deisseroth, K., Thiele, T. E., McElliott, Z. A., Holmes, A., Heister, L. K. and Kash, T. L. 2016. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature. 537(7618): 97-101
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Vanillic Acid as An Antidepressant: Mechanisms

Vanillic acid is a polyphenolic substance found in plants. Vanillic acid is an oxidised form of vanilla, and is characterised by a similar creamy flavour. The neuroprotective effects of vanillic acid have been evidenced and a number of studies have investigated the mechanisms by which this may occur. For example, in one study the antioxidative and anti-inflammatory effects of vanillic acid were investigated with respect to cell signalling. Some evidence suggests that via antioxidant and anti-inflammatory effects, vanillic acid can affect mood through increases in the mTOR cellular signal, which is a common target of pharmaceutical antidepressants. Therefore evidence from this study suggests that the mechanisms of vanillic acid in treating depression may reflect those of more mainstream alternatives. This provides more evidence that plants provide phytochemicals to the diet that are able to significantly improve health, and in many cases their mechanisms are the same as pharmaceutical drugs used to treat the same conditions. 

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Chuang, H. W., Wei, I. H., Lin, F. Y., Li, C. T., Chen, K. T., Tsai, M. H. and Huang, C. C. 2020. Roles of Akt and ERK in mTOR-Dependent Antidepressant Effects of Vanillic Acid. ACS omega. 5(7): 3709-3716
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Therapeutics of Vanillic Acid

Vanillic acid is a polyphenolic phytochemical. Like all polyphenols, vanillic acid is derived from benzoic acid through enzymatic reactions in plant cells. In cuisine, vanillic acid is used as a flavour enhancer and preservative, and this latter role is possible because polyphenols are antioxidants and this is a necessary characteristic of certain food preservatives. Vanillic acid is found in a wide range of foods including whole grains, herbs, fruits, green tea, juices, beers and wine and is therefore fairly common in the typical diet. Therapeutic doses of vanillic acid have been shown to have antioxidant, anti-inflammatory, immuno-stimulating, neuroprotective, hepatoprotective, cardioprotective, and antiapoptotic properties. One particular role for vanillic acid is as a neuroprotective agent. This may relate to its antioxidant and anti-inflammatory effects, as both inflammation and oxidation are highly damaging to the integrity of neurones. Consuming foods containing vanillic acid may therefore aid mental health and wellbeing. 

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Sharma, N., Tiwari, N., Vyas, M., Khurana, N., Muthuraman, A. and Utreja, P. 2020. An overview of the therapeutic effects of vanillic acid. Plant Archives. 20(2): 3053-3059
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Fats, Lipids and Mood

The brain contains large amounts of lipids, which are located particularly in the cell membranes of neurones. The lipid in the diet can directly influence the fat in the brain, and it has been shown for example that diets high in omega-3 fatty acids can increase the omega-3 fat content of the brain significantly. This diet to brain connection is important because the localised fats and lipids in the cell membranes play a significant role in determining the number and function of proteins on the surface of the cell membranes. These proteins are pivotal in the signal cascades that occur in the brain when neurones fire as they act as enzymes, transporters and receptors. A poor diet can disrupt the normal lipid content of the brain, and if the diet is particularly deficient in important lipids. there is the possibility that brain function will be significantly detrimentally affected. As well as omega-3 fats, glycerolipids, glycerophospholipids, and sphingolipids have all been evidenced to be able to significantly affect brain function. 

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Müller, C. P., Reichel, M., Mühle, C., Rhein, C., Gulbins, E. and Kornhuber, J. 2015. Brain membrane lipids in major depression and anxiety disorders. Biochimica et Biophysica Acta (BBA)- Molecular and Cell Biology of Lipids. 1851(8): 1052-1065
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Vanillic Acid Against Mood Disorders?

Vanillic acid is a polyphenolic compound that is found in a range of edible plants and herbs such as the trunk bark of Amburana cearensis and in the roots of Angelica sinensis. Evidence suggests that vanillic acid has antioxidant and anti-inflammatory effects. As both inflammation and oxidation are characteristic metabolic changes associated with anxiety and depression, studies have investigated vanillic acid for its mood elevating properties. For example, one study administered vanillic acid ro rats and exposed them to experimental stress. The vanillic acid was significantly beneficial at improving sensory motor signs and at decreasing anxious behaviour. These results suggest that vanillic acid is able to regulate the central nervous system and cause changes to mood, possibly through its antioxidant or anti-inflammatory effects. Vanillic acid may also explain the mood elevating effects of Angelica sinensis, that have been reported in other studies that have evaluated the roots of the plant. 

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Khoshnam, S. E., Farbood, Y., Moghaddam, H. F., Sarkaki, A., Badavi, M. and Khorsandi, L. 2018. Vanillic acid attenuates cerebral hyperemia, blood-brain barrier disruption and anxiety-like behaviors in rats following transient bilateral common carotid occlusion and reperfusion. Metabolic Brain Disease. 33(3): 785-793
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Chinese Angelica (Angelica sinsensis) Against Anxiety

Chinese angelica (Angelica sinensis) is one variety of Asian angelica species. Common names for the plant include Dong Quai. Chinese angelia contains a volatile oil called ligustilide, which is believed to have sedative properties. This sedative activity suggests that ligustilide is able to affect the central nervous system. Other evidence suggests that ligustilide is able to relax smooth muscle, which may contribute to its sedative properties. Chinese angelia has been researched for its relaxing effects by testing it on animal models of anxious behaviour. Administration of Chinese angelica to mice reduced stress induced hypothermia, and reduced the display of anxious behaviour in the animals. In comparison to diazepam, a mainstream pharmaceutical anxiolytic drug, Chinese angela showed similar anxiolytic properties on the mice. Chinese angelica may therefore be a possible treatment for anxiety. 

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Chen, S. W., Min, L., Li, W. J., Kong, W. X., Li, J. F. and Zhang, Y. J. 2004. The effects of angelica essential oil in three murine tests of anxiety. Pharmacology Biochemistry and Behavior. 79(2): 377-382
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Chinese Herbal Formula Xiao Yao San Against Depression?

The Chinese herbal formula Xiao Yao San is a combination of herbs that includes bupleurum root, Chinese angelica root, white peony root, poria, bighead atractylodes rhizome, ginger, prepared licorice root, menthol and peppermint. The formula is used in traditional Chinese medicine as a treatment for mood disorders. Evidence suggests that the formula may possess significant antidepressant effects and that in combination with mainstream pharmaceutical antidepressants, may provide significant relief from low mood. In some cases Xiao Yao San may be superior to mainstream antidepressant drugs for the treatment of depression. Nutritionally, this is not surprising, as plants contain a large number of chemicals that have been shown to possess mood elevating properties. When taken in combination, these chemicals may provide significant mental health benefits particularly with regard to anxiety and depression.  

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Zhang, Y., Han, M., Liu, Z., Wang, J., He, Q. and Liu, J. 2012. Chinese herbal formula xiao yao san for treatment of depression: a systematic review of randomized controlled trials. Evidence-Based Complementary and Alternative Medicine. Article ID 931636
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Zizyphi fructus as A Sedative

Zizyphi fructus is the fruit of the Ziziphus jujube tree. The fruit is used in traditional Chinese medicine to treat a number of ailments including chronic bronchitis, consumption and blood disorders, or as an analeptic, expectorant, sedative and taste modifier. The sedative activity of the fruit is interesting because it suggests that components within the fruit are able to interact with the central nervous system. The main phytochemicals in the fruit have been shown to include sugars, triterpenoids, saponins, flavonoids and ethyl fructofuranoside. It is possible that one or all of these components is responsible for the sedative effects. However, it is much more likely that the active ingredients found within the fruit that are responsible for these effects are alkaloids. These include daechu alkaloid-A, daechu alkaloid-B (lysicamine) and daechu alkaloid-E (nornuciferine). Alkaloid fractions of the fruit have been shown to induce sedation in mice as tested by measurements of barbiturate-induced sleeping time. 

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Han, B. H. and Park, M. H. 1987. Sedative activity and its active components of Zizyphi fructus. Archives of Pharmacal Research. 10(4): 208
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Ziziphus jujube as an Antidepressant

Ziziphus jujube is a flowering plant that belongs to the Rhamnacaea or buckthorn family of trees. The plant is often called red date or Chinese Date and it produces a small fruit that resembles an apple. The dried seeds of the fruit of the plant are called Ziziphi spinosae and they are known to possess a wide range of phytochemicals including the saponin jujuboside, the flavone glycoside spinosin, as well as various alkaloids, flavonoids (including rutin) and fatty oils. The seeds of Zizyphus jujube are thought to possess medicinal properties on account of the phytochemicals they possess and this may include mood elevating effects. In experimental animal models, animals exposed to stressful conditions such as the forced swimming test, following administration of Ziziphi spinosae, show significantly lower levels of depressive-like behaviour compared to control animals. This effect is accompanied by an increase in the quantity of neurotransmitters in the brain including the mood elevating chemical serotonin. 

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Wang, Y., Huang, M., Lu, X., Wei, R. and Xu, J. 2017. Ziziphi spinosae lily powder suspension in the treatment of depression-like behaviuor in rats. Complementary and Alternative Medicine. 17:238
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