The Presence of Caffeic Acid in Cerebrospinal Fluid: Evidence That Dietary Polyphenols Can Cross the Blood-Brain Barrier in Humans

Grabska-Kobylecka, Izabela; Kaczmarek-Bak, Justyna; Figlus, Małgorzata; Prymont-Przymińska, Anna; Zwolinska, Anna; Sarniak, Agata; Włodarczyk, Anna; Głąbiński, Andrzej; Nowak, Dariusz

doi:10.3390/nu12051531

Cited by 51 publications

(31 citation statements)

References 56 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a recent study demonstrated the presence of non-endogenous caffeic acid in the human CSF. These studies confirm that plant phenolics can cross the BBB in humans and reach the neurons and microglia [42]. However, the exact mechanisms by which they may permeate the BBB are not fully understood.…”

Section: Discussionmentioning

confidence: 62%

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

et al. 2021

View full text Add to dashboard Cite

Ajuga bracteosa Wall. ex Benth. is an endangered medicinal herb traditionally used against different ailments. The present study aimed to create new insight into the fundamental mechanisms of genetic transformation and the biological activities of this plant. We transformed the A. bracteosa plant with rol genes of Agrobacterium rhizogenes and raised the regenerants from the hairy roots. These transgenic regenerants were screened for in vitro antioxidant activities, a range of in vivo assays, elemental analysis, polyphenol content, and different phytochemicals found through HPLC. Among 18 polyphenolic standards, kaempferol was most abundant in all transgenic lines. Furthermore, transgenic line 3 (ABRL3) showed maximum phenolics and flavonoids content among all tested plant extracts. ABRL3 also demonstrated the highest total antioxidant capacity (8.16 ± 1 μg AAE/mg), total reducing power, (6.60 ± 1.17 μg AAE/mg), DPPH activity (IC50 = 59.5 ± 0.8 μg/mL), hydroxyl ion scavenging (IC50 = 122.5 ± 0.90 μg/mL), and iron-chelating power (IC50 = 154.8 ± 2 μg/mL). Moreover, transformed plant extracts produced significant analgesic, anti-inflammatory, anticoagulant, and antidepressant activities in BALB/c mice models. In conclusion, transgenic regenerants of A. bracteosa pose better antioxidant and pharmacological properties under the effect of rol genes as compared to wild-type plants.

show abstract

Section: Discussionmentioning

confidence: 62%

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Phenolic acids have been shown to modulate different factors associated with the pathogenesis of neurodegenerative diseases, such as systemic inflammation and oxidative stress, and thus indirectly affect cognitive health [ 40 ]. As suggested by the evidence from experimental studies, specific phenolic acids and their metabolites (i.e., caffeic acid, ferulic acid) have been found in cerebrospinal fluid, suggesting that these compounds may cross the blood–brain barrier and thus directly affect brain cells [ 41 , 42 ]. Moreover, new evidence suggests that there is an interaction between dietary polyphenols and gut microbiota and their effect toward the brain [ 43 , 44 ]: it has been determined that gut microbiota composition significantly affects the bioavailability of polyphenols including phenolic acids and consequently may mediate and modulate the effect of dietary polyphenols toward cognitive health [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary Phenolic Acids and Their Major Food Sources Are Associated with Cognitive Status in Older Italian Adults

et al. 2021

View full text Add to dashboard Cite

Background: Life expectancy is increasing along with the rising prevalence of cognitive disorders. Among the factors that may contribute to their prevalence, modifiable risk factors such as diet may be of primary importance. Unarguably, plant-based diets rich in bioactive compounds, such as polyphenols, showed their potential in decreasing risk of neurodegenerative disorders. Therefore, the aim of the present study is to investigate whether exposure to components of plant-based diets, namely phenolic acids, may affect cognitive status in older Italian adults. Methods: The demographic, lifestyle and dietary habits of a sample of individuals living in southern Italy were analyzed. Dietary intake was assessed through food frequency questionnaires (FFQs). Data on the phenolic acids content in foods were estimated using the Phenol-Explorer database. Cognitive status was evaluated using The Short Portable Mental Status Questionnaire. Multivariate logistic regression analyses were used to assess the associations. Results: The mean intake of phenolic acids was 346.6 mg/d. After adjustment for potential confounding factors, individuals in the highest quartile of total phenolic acid intake were less likely to have impaired cognitive status (OR = 0.36 (95% CI: 0.14, 0.92)); similarly, the analysis for subclasses of phenolic acids showed the beneficial effect toward cognitive status of greater intake of hydroxycinnamic acids (OR = 0.35 (95% CI: 0.13, 0.91)). Among individual compounds, only higher intake of caffeic acid was inversely associated with impaired cognitive status (OR = 0.32 (95% CI: 0.11, 0.93)); notably, the association with ferulic acid intake was significant only when adjusting for background characteristics, and not for adherence to the Mediterranean diet. Conclusions: This study revealed that greater intakes of dietary phenolic acids were significantly inversely associated with impaired cognition, emphasizing the possible role of phenolic acids in the prevention of cognitive disorders.

show abstract

“…Additionally, chlorogenic acid was maintained in plasma and entered the CNS following intravenous injection in rats [52]. In a clinical study, individuals who had consumed foods containing caffeic acid showed increased caffeic acids levels in the CNS crossing the blood-brain barrier [53]. However, it remains unclear which bioactive component(s) with anti-microglial activation effects are present in the butanol fraction of EJE.…”

Section: Discussionmentioning

confidence: 99%

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway

Park

Kim

2020

Antioxidants

View full text Add to dashboard Cite

Microglial activation-mediated neuroinflammation influences the development of inflammatory pain. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of aqueous Erythronium japonicum extract (EJE) in microglia activation-mediated inflammatory pain. EJE was found to suppress lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), ionized calcium-binding adapter molecule 1 (IBA-1), and pro-inflammatory cytokines in BV2 microglial cells. In addition, LPS-induced c-Jun NH2 terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation were inhibited by EJE. Intriguingly, EJE also inhibited p65 phosphorylation by activating extracellular signal-regulated kinase-1/2 (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Furthermore, the effects of EJE treatment, such as HO-1 induction and the reduction of NF-ĸB activation, were reversed by ERK1/2 inhibition. In an inflammatory pain mouse model, Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia and foot swelling were alleviated by the oral administration of EJE. Consistent with in vitro results, EJE increased HO-1, while decreasing CFA-induced COX-2, IBA-1, and pro-inflammatory cytokines in the spinal cord. Among the components of EJE, butanol most heavily suppressed LPS-induced microglial activation and increased HO-1 expression. These findings indicate that EJE can alleviate inflammatory pain by inhibiting p38 and JNK and by suppressing NF-ĸB via ERK/Nrf2/HO-1 signaling.

show abstract

The Presence of Caffeic Acid in Cerebrospinal Fluid: Evidence That Dietary Polyphenols Can Cross the Blood-Brain Barrier in Humans

Cited by 51 publications

References 56 publications

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

Dietary Phenolic Acids and Their Major Food Sources Are Associated with Cognitive Status in Older Italian Adults

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway

Contact Info

Product

Resources

About