Multi-targeted action of rooibos may protect against ischaemic stroke-induced neurological deficit and endothelial dysfunction

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 1), p.118822, Article 118822
• Main Authors: Pretorius, L., Ross, K.S., Smith, C.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Aspalathus - chemistry; Disease Models, Animal; Endothelium, Vascular - drug effects; GreenOxithin; Ischemic Stroke - drug therapy; Ischemic Stroke - prevention & control; Larval zebrafish; NeuroD1; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Plant Extracts - pharmacology; Tight junction proteins; Vascular health; Zebrafish; ZO-1
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118822

Indigenous use communities in the Western Cape (South Africa) where Aspalathus linearis (Brum.f) R.Dahlgren - or rooibos - grows naturally, has a long history of using rooibos for medicinal purposes. Apart from its well-known antioxidant effect, the Cederberg community in particular has been using rooibos as a treatment for high blood pressure. Given the detrimental effects of high blood pressure on endothelial cells, rooibos may either directly or indirectly affect vascular health. This, together with more recent reports of neuroprotective effects, may position rooibos as complementary medicine in related vascular conditions such as ischaemic stroke. The study aimed to evaluate the potential benefit of acute administration of unfermented rooibos, on vascular health in a larval zebrafish model of stroke. Stroke was induced via 24-h ponatinib exposure, in the presence or absence of an aqueous solution of an ethanolic extract of unfermented Rooibos (GreenOxithin™). The magnitude of stroke was assessed by monitoring larval locomotion and thrombus formation. In terms of specific mechanisms probed, changes in redox status (MDA and TEAC), neurological markers (TH and NeuroD1) and endothelial health (tight/adhesion junction protein expression) were assessed. Rooibos treatment limited thrombus formation and prevented stroke-induced deficits on larval motility. In terms of redox status, rooibos treatment prevented lipid peroxidation 3 days after initial stroke induction, reducing the need for significant upregulation of endogenous antioxidant mechanisms. Stroke-induced changes in neuronal (NeuroD1 and TH) protein expression were normalized in the presence of rooibos, suggesting a neuroprotective role. In terms of tight junction proteins, stroke-related decreases in ZO-1 expression were again prevented by rooibos treatment. In addition, rooibos treatment may beneficially modulate levels of claudin-5 and VE-cadherin, to indirectly limit stroke-associated vascular dysfunction. Taken together, activity data and physiological assessments suggest that unfermented rooibos may indeed have benefit in the context of stroke, via action at multiple targets. Thus, current data further our understanding of the mechanisms of actions of rooibos and warrant future research to confirm sufficient bioavailability of rooibos in target tissues, in mammalian systems. [Display omitted] •Ponatinib-induced thrombus formation was prevented in the presence of rooibos.•Stroke-associated decrea