Depression is a worldwide public health problem that affects millions of people every year. Due to recent reports that depressed individuals have an altered gut microbiome composition, there is speculation that treatments that influence microorganisms in the gut could potentially lead to alleviation of depressive symptoms. Apple cider vinegar has been studied extensively for its health-promoting properties and benefits. Apple cider vinegar’s main ingredient is the short chain fatty acid, acetic acid. Short chain fatty acids have been shown to improve mood state and depressive symptoms, as well as amplify the effect of prebiotics in restoring the gut microbiome. This experimental design study examined the effects of ingesting 2 tbsp. apple cider vinegar (1 g acetic acid) twice daily with a meal on the levels of urinary metabolites in 14 college students compared to a control group of 11 college students that took one vinegar supplement tablet (0.015 g of acetic acid) daily for 28 days. All participants were healthy, normal to underactive (< 300 minutes of moderate exercise a week), and free of chronic or acute illnesses. Urinary metabolite analysis revealed a significant production of enzymes involved in the hexosamine pathway in the liquid vinegar group compared to baseline levels. However, anticipation of an alteration in tryptophan metabolites, a possible consequence of altered metabolism of gut microflora, was not observed. These data suggest that apple cider vinegar might be a potential treatment for depression through the production of hexosamine pathway enzymes.

Sphingosine-1-phosphate receptors (S1PRs) and their signaling pathways play an important role in mediating vascular health and function. Upon ligand mediated activation, S1PRs 1-5 couple with diverse heterotrimeric G-protein subunits (Gαi, Gαq/11, Gα12/13), initiating multimodal downstream signaling pathways which result in various physiological outcomes in the vasculature, including cell proliferation and migration, barrier integrity preservation or loss, contraction, and inflammation. Specifically, S1PR2 activation has been linked to endothelial activation, barrier integrity loss, and inflammation, whereas S1PR1 activation contributes to barrier integrity preservation, vasodilation, and anti-inflammatory properties. Although the role of S1PRs during pathophysiological conditions such as acute ischemic stroke is under current investigation, the complete S1PR expression profile in the cerebrovasculature following acute ischemic injury has not yet been investigated. Therefore, the present study was aimed to characterize the expression profiles of S1PRs 1-5 in human brain microvascular endothelial cells (HBMECs) and human brain vascular smooth muscle cells (HBVSMCs) following 3h hypoxia plus glucose deprivation (HGD; in vitro ischemic injury) exposure. At the mRNA level, we observed expression of S1PRs 1-5 in HBVSMCs and S1PRs 1-4 in HBMECs. Under basal conditions, we employed real-time RT-PCR and observed that mRNA levels of S1PR1 were highest in expression followed by S1PR3 then S1PR2 in HBMECs. On the other hand, S1PR3 mRNA was the highest followed by S1PR2 then S1PR1 in HBVSMCs. In HBMECs, HGD exposure increased S1PR1 mRNA and protein levels, but decreased S1PR1 mRNA in HBVSMCs. Similarly, HGD induced increased S1PR3 mRNA in HBMECs and decreased S1PR3 mRNA in HBVSMCs. For S1PR2, HGD did not alter mRNA or protein expression in HBMECs but increased mRNA levels in HBVSMCs. These data suggest that acute exposure to HGD appears to differentially regulate expression of S1PRs in HBMECs and HBVSMCs. The differential expression in S1PRs both basally and following HGD exposure may suggest distinct signaling mechanisms at play within the two cerebrovascular cell types, implicating these receptors as potential therapeutic targets following ischemic injury.