Phytochemicals and Mental Health

The gut-brain axis has mainly been studied in relation to bacteria; commensal fungi have received less attention. Dysbiosis of the gut bacterial microbiota has been linked to depression in children and adolescents, but the mycobiota's contribution has not been examined. In this study by Hao et al. (2023), 145 children and adolescents with depression and 110 age- and gender-matched healthy controls provided feces samples to analyze their fungal microbiome in relation to the gut microbiota and for sequencing mitochondrial internal transcribed spacer 2 (ITS2) rRNA gene. The authors observed that the stool fungal microbiome of depressed children and adolescents had changed taxonomic makeup. However, fungal diversity remained unchanged. The depressed individuals had higher concentrations of important fungi like Apiotrichum and Saccharomyces, but Aspergillus and Xeromyces had much lower concentrations. Notably, the bacterial-fungal interkingdom network was significantly changed in depressed children and teenagers, and mycobiome profiles were connected to various bacterial microbiomes. The cross-sectional design, however, made it impossible to determine if the gut mycobiota and the children and adolescents with depression are causally related. The authors conclude that, in depressed children and adolescents, the gut mycobiome is changed. Fungi are crucial to maintaining the balance of the gut microbiota and may help discover new depression treatment targets. [NPID: Depressive, children, mycobiota, microbiome]

Flavonoids are dietary antioxidant and anti-inflammatory compounds. Previously, Holland et al. demonstrated the links between flavonoids and cognition. In this current study, the authors (2022) explored the links between cognitive performance (episodic memory, global cognition, visuospatial ability, semantic memory, working memory, and perceptual speed) and the dietary intake of flavonoids and flavonol constituents (isorhamnetin, kaempferol, myricetin, quercetin) in a sample of 961 participants of the Rush Memory and Aging Project, a 6.9-year prospective cohort study of adults aged between 60-100 years old. An annual cognitive evaluation was done using 19 standardized tests, while dietary intake was evaluated through a validated semi-quantitative food frequency questionnaire. Analysis of the results revealed that increased dietary intake of flavonols and flavonol constituents decreased the rate of decline in episodic memory, perceptual speed, semantic memory, visuospatial ability, working memory, and global cognition. Furthermore, out of individual flavonol constituents, only quercetin and kaempferol were associated with significant decreases in the rate of cognitive decline. The authors conclude that the dietary consumption of flavonols and flavonol constituents may help reduce the rate of decline in cognitive abilities and global cognition in a population of seniors. [NPID: Flavonols, dietary intake, seniors, global cognition, cognitive domains]

Despite the progress in the understanding of Alzheimer’s disease (AD) pathogenesis and clinical course, advancing AD treatment beyond symptomatic intervention remains lacking. AD is a chronic neurodegenerative disease, characterized by amyloid beta (Aβ) peptide depositions that construct neurofibrillary tangles (NFTs). Recent evidence points to flavonoids as potential dietary interventions for AD treatment owing to their anti-inflammatory, antioxidant, anticholinesterase, and particularly their anti-amyloidogenic properties, where flavonoids were shown to help clear Aβ proteins and inhibit mTOR/autophagy signaling. In this review by Uddin et al. (2020), the authors explore the potential mechanisms behind the beneficial impact of flavonoids on AD and their role as novel therapeutic modalities. [NPID: Alzheimer’s disease, PI3K/Akt signaling, MAPK signaling, mTOR, amyloid plaque, flavonoids, neurofibrillary tangles]

Cerebral injuries cause a cascade of inflammatory events, namely, tissue responses in the form of reactive gliosis and microgliosis, and the secretion of inflammatory substances like cytokines, proteases, reactive oxygen, and nitrogen species. This cascade is thought to play a critical role in post-traumatic systemic and neuroinflammatory states and associated cognitive impairments seen in several neurological disorders. Standard treatment guidelines involve the use of non-steroidal anti-inflammatory drugs (NSAIDs) to control inflammation, however, their poor safety profile makes long term use unlikely. The use of naturally-occurring compounds as therapeutic alternatives is gaining traction due to their feasibility and their wide range of physiological effects. In the holistic practice of Ayurveda, Ashwagandha (Withania somnifera, Winter cherry) is a shrub with notable immunomodulatory properties. Gupta & Kaur (2018) built on their previous in vitro experiments, and aimed to investigate the use of a water extract from the Ashwagandha leaves (ASH-WEX) to treat systemic LPS-induced neuroinflammation and subsequent behavioral complications seen in an in vivo rat model. During the eight weeks of the study, it was observed that oral ASH-WEX administration substantially treated the anxiety-like behavior seen in rats, where treated rats achieved better Elevated Plus Maze test scores. In addition, the treated rats demonstrated significantly lower markers of brain tissue injury, systemic inflammation, and oxidative stress. The authors attribute these findings to identifying several activated pathways related to inflammatory suppression in rats as a result of ASH-WEX treatment (NFκB, P38, and JNK MAPKs). The authors conclude that their study demonstrates pioneering evidence to the anti-neuroinflammatory properties of ASH-WEX against LPS-induced neuroinflammation and its behavioral complications, inferring that Ashwagandha leaves and their contained phytochemicals may present a favorable foundation to develop new anti-neuroinflammatory interventions. [NPID: Anxiety-like behavior, Ashwagandha, inflammatory cytokines, lipopolysaccharide, neuroinflammation, reactive gliosis]

Polyphenols are plant compounds with unique structural elements that have several effects on our well-being and have been shown to help combat obesity, hyperglycemia and hyperlipidemia. Polyphenols are found in many plants, and are a topic of growing interest for their beneficial impact on stress. In this review, Sakakibara & Shimoi (2020) present a summary of the physiological reactions to stress and the biomarkers used to evaluate these reactions in animal studies and human trials. They also look at popular animal models used to measure the efficacy of anti-stress interventions, and discuss the recent findings from investigating the mechanism of action and impact of polyphenols on stress in animal models and human trials. The authors highlight that these recent findings necessitate more studies and human trials to further understand the impact of polyphenols on stress and their possible use as preventative measures against health complications related to stress. [NPID: Stress, polyphenols, plants, animal models, human trials]

Depression is a globally prevalent and crippling disease, afflicting individuals across the world regardless of their age. Although research on depression produced variable results, a common denominator seen in studies is the rise in inflammatory markers and oxidative stress associated with depression, which invariably, were found to be linked to the etiology and onset of depression. In this review by Behl et al. (2022), the authors outline oxidative stress and inflammatory markers seen in depressive disorders and the relationship between them and current treatment interventions. Natural polyphenols were found to have an inhibitory effect on various cell signaling pathways, including oxidative stress and inflammatory pathways, which potentiates polyphenols in preventing and treating depressive disorders. The authors highlight the part polyphenols play in treating depressive disorders, and argue that conducting further work to outline their mechanism of action and identifying their key compounds is necessary to develop innovative interventions to prevent and treat depressive disorders. [NPID: Antidepressants, depression, inflammation, oxidative stress, psychiatric disorders]

In this study, Gan et al. (2019) investigated whether bamboo leaf flavonoids had an impact on depressive symptoms in type 2 diabetic rats, and attempted to understand the mechanism by which flavonoids exerted their antidepressant effects. Male Sprague-Dawley (SD) rats at eight weeks of age were divided into 5 groups: Two control groups including one for the study design, a group which received bamboo leaf flavonoid diluted in solvent, a solvent control group and a final control group of normal rats that received the bamboo leaf flavonoid intervention. Depression was induced in the rats via administration of streptozotocin (STZ), and bamboo leaf flavonoids were administered for 12 weeks. To evaluate depression, the rats underwent Tail Suspension Tests (TST) and Forced Swimming Tests (FST), in addition to evaluating markers of cellular stress, inflammation and brain neurons via Western blotting, enzyme-linked immunosorbent assay (ELISA), and Nissl staining of brain samples, respectively. The authors observed that, compared to control groups, 12 weeks of bamboo leaf flavonoids treatment had improved mobility parameters in TST and FST, healthier brain hippocampal tissue and reduced inflammatory and cellular stress markers in treated rats. In conclusion, the authors state that treatment with bamboo leaf flavonoids helps improve symptoms and signs of depression in diabetic rats, as evident by healthier brain tissue and a reduction in inflammatory markers, and by inhibition of cellular stress pathways in treated rats compared to controls. [NPID: Depression, diabetes mellitus, type 2, flavonoids, hippocampus, rats, animal]

Depression is a prevalent mental health disease that impacts over 350 million individuals across the globe. Current research postulates that dietary choices may protect against depression, with several studies highlighting the benefits of the Mediterranean diet (rich in vegetables and olive oil, and including moderate amounts of protein) on depression. A potential theory as to why the Mediterranean diet exerts these effects is due to boasting elevated levels of polyphenols. Thus, Bayes et al. (2020) conducted this systematic literature review to investigate the impact of polyphenols found in the Mediterranean diet on depression. By searching through several databases (PROQUEST, SCOPUS (Elsevier), MEDLINE (EBSCO), CINAHL, and EMBase, up to 18 February, 2019) and selecting 20 observational and 17 experimental studies that included adults ages 18-80 years and by assessing depression scores in relation to polyphenol intake from several sources (tea, coffee, citrus, nuts, soy, grapes, legumes, and spices), the authors found that 29 studies reported a substantial polyphenol impact on improving symptoms of depression. Furthermore, this review found links between consuming polyphenols and the odds of suffering from depression, in addition to a substantial relationship between consuming polyphenols and a reduction in the symptoms of depression. The authors conclude that their review discovered areas necessitating further studies to fully outline the beneficial part polyphenols may play in treating depressive symptoms in both young and adult male populations. [NPID: Depression, flavonoids, major depressive disorder, mental health, phytochemicals, polyphenols, Mediterranean diet]

Depression is a critical mental health disorder that has a chronic course, and is prone to deterioration if treatment is not administered promptly. Recent literature demonstrated the relationship between the gut microbiome and the brain through the microbiome-gut-brain axis. In this study by Park et al. (2020), the authors investigated the results of flavonoid consumption on depression through evaluating alterations in gut microbiome and symptoms of depression following the administration of flavonoid-rich orange juice to young participants over the course of eight weeks. Depressive symptoms were evaluated via the Center for Epidemiological Studies Depression Scale (CES-D). The results showed that, compared to control participants, the consumption of flavonoid-rich orange juice lead to an increase of the Lachnospiraceae family of the gut microbiome, which relates to higher levels of brain-derived neurotrophic factor (BDNF; a neurotrophin that is involved in the therapeutic response to antidepressants). The authors conclude that these results present gut microbiome alteration using flavonoids as a new approach to treating depression in young adults. [NPID: Lachnospiraceae, depression, flavonoid treatment, microbiota]

Spurred by a lack of sufficient studies investigating the impact of dietary carotenoids on depression, Lin & Shen (2021) conducted their study to explore the links between carotenoids found in diet and the pervasiveness of symptoms of depression. Selecting a population of 4,105 adults from the 2015-2016 United States National Health and Nutrition Examination Survey, the authors evaluated dietary consumption using two 24-h dietary recall interviews, and for symptoms of depression through the nine-item Patient Health Questionnaire (PHQ-9). The analyses revealed a significant decrease of symptoms of depression with intake of beta-cryptoxanthin above 110 ug/1000 Kcal, but no changes were observed with either alpha-carotene, beta-carotene, lycopene, or lutein/zeaxanthin. Thus, the authors conclude that consuming a diet rich in beta-cryptoxanthin may confer protection against symptoms of depression, and that further research is necessary to state informed dietary recommendations. [NPID: Beta-cryptoxanthin, carotenoids, depression, dose-response, NHANES, PHQ-9]

Depression is a grave mental health disorder that elicits several complications, including poor quality of life, behavioral problems, and limitations of activities of daily living, in millions of patients globally. Identifying new therapeutic options to combat depression is an area of continuously growing interest, and more recently, the links between oxidative stress and the onset of depression. Flavonoids are naturally-occurring plant compounds that were found to induce antidepressant-like activity, amongst their several physiological and biochemical effects on the human body. Recent evidence on the use of antioxidant flavonoids as novel dietary interventions to treat symptoms of depression revealed substantial promise of their potential to herald creative antidepressant pharmacotherapeutic agents. In this review by Hritcu et al. (2017), the authors highlight the chemical and pharmacological mechanisms behind the antidepressant activity of flavonoids, and their impact on oxidative stress relative to the pathology of depression. [NPID: Depression, flavonoids, antidepressant, oxidative stress]

Flavonoids, which are biologically active chemicals found in plants, have been shown to have significant physiological functions that benefit our health, however, flavonoids are not readily absorbed in the intestine and require pre-processing through the intestinal gut microbiota. Flavonoids, in turn, influence the gut microbiome population by providing the microbiome with nutrients from their breakdown, and thus help in improving overall gut health. Studies have shown that the onset of mental health disorders such as depression is linked to changes in the gut microbiome that influence the gut-brain axis. Taking this into account, Zhao et al. (2021) present their work on how the relationship between flavonoids and the gut microbiome may be utilized to treat symptoms of depression. [NPID: Bioavailability, depression, flavonoids, intestinal microbiota]