Aspalathus linearis (Rooibos) and Agmatine May Act Synergistically to Beneficially Modulate Intestinal Tight Junction Integrity and Inflammatory Profile

Abstract

In order to promote gastrointestinal health, significant increases in the prevalence of gastrointestinal disorders should be paralleled by similar surges in therapeutics research. Nutraceutical interventions may play a significant role in patient management. The current study aimed to determine the potential of Aspalathus linearis (rooibos) to prevent gastrointestinal dysregulation resulting from high-dose trace-amine (TA) exposure. Considering the substantial female bias in functional gastrointestinal disorders, and the suggested phytoestrogenicity of rooibos, the study design allowed for a comparison between the effects of an ethanol extract of green rooibos and 17β-estradiol (E2). High levels of ρ-tyramine (TYR) and agmatine (AGM), but not β-phenethylamine (PEA) or tryptamine (TRP), resulted in prostaglandin E2 (PGE2) hypersecretion, increased tight-junction protein (TJP; occludin and ZO-1) secretion and (dissimilarly) disrupted the TJP cellular distribution profile. Modulating benefits of rooibos and E2 were TA-specific. Rooibos pre-treatment generally reduced IL-8 secretion across all TA conditions and prevented PGE2 hypersecretion after exposure to both TYR and AGM, but was only able to normalise TJP levels and the distribution profile in AGM-exposed cells. In contrast, E2 pre-treatment prevented only TYR-associated PGE2 hypersecretion and TJP dysregulation. Together, the data suggest that the antioxidant and anti-inflammatory effects of rooibos, rather than phytoestrogenicity, affect benefits illustrated for rooibos.

Translation of preclinical ethnomedicine data in LMICs: the example of rooibos

“…In vervet monkeys, rooibos normalised Firmicutes to Bacteroidetes ratio to rescue high-fat high-sugar diet-induced metabolic dysregulation ( Mangwana, 2020 ), and increased relative abundance of beneficial bacterial species ( Faecalibacterium prausnitzii, Prevotella stercorea and P. copri, Akkermansia muciniphia, Bacteroides intestinalis, Desulfovibrio piger and Bifidobacterium adolescentis ). More recent in vitro studies confirmed increased probiotic microbial growth and favourably modulated secretome trace amine content to promote gut health ( Pretorius et al, 2022 ; Pretorius and Smith, 2022 ). Taken together, changes in the gut microbiome are likely to influence host regulation and homeostasis and as such, the potential benefit conferred by rooibos supplementation necessitates additional robust investigation.…”

“…In fact, rooibos has such high potency that pro-oxidant outcome have been reported for extracted (i.e., concentrated) rooibos when administered in the absence of disease or conditions of oxidative stress ( Joubert et al, 2005 ). Secondly, rooibos constituents quercetin, aspalathin and catechin inhibit lipid peroxidation ( Snijman et al, 2009 ), a mechanism likely responsible for its reported membrane-protective effects of rooibos ( Ulicna et al, 2019 ; Pretorius and Smith, 2022 ). A multitude of studies in cell-free systems and in cell culture have also demonstrated improved antioxidant enzyme activities (particularly for catalase and superoxide dismutase (SOD)) ( Waisundara and Hoon, 2015 ) and mitochondrial bioenergetics ( Mthembu et al, 2021 ).…”

“…The antioxidant capacity of rooibos also links closely to an anti-inflammatory outcome. In this context, data from in vitro models of inflammation associate rooibos administration with improved tight junction protein expression and interaction status to maintain endothelial cellular structure and barrier integrity ( Ku et al, 2015 ; Lee and Bae, 2015 ; Pretorius and Smith, 2022 ), modulation of PGE2 synthesis ( Hedbrant et al, 2022 ), inhibition of basophil activation ( Pedretti and Peter, 2020 ) and an inhibitory effect on concentrations of pro-inflammatory mediators–such as IL-1α, IL-6, IL-8, VCAM-1 and ATF4 gene expression ( Lawal et al, 2019b ), as well as IFN-γ, IL-12, IL-2, IL-17a, TNF-α, IL-8, IL-6, IL-1β and CXCL10 ( Nehme et al, 2023 )–and increased anti-inflammatory cytokine, IL-10 ( Ichiyama et al, 2007 ). In addition, the flavonoid actives aspalathin and nothofagin were reported to prevent the expression of cell adhesion molecules and transendothelial migration of neutrophils in LPS- and high glucose-exposed cells ( Ku et al, 2015 ; Lee and Bae, 2015 ), while other rooibos constituents quercetin, luteolin and chrysoeriol reportedly inhibited antigen- and calcium ionophore-stimulated degranulation in basophils ( Morishita et al, 2019 ).…”