Blood-Brain Barrier Permeability of Asiaticoside, Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

• Published in: Journal of pharmaceutical sciences 2021-02, Vol.110 (2), p.698-706
• Main Authors: Hanapi, Nur Aziah, Mohamad Arshad, Ahmad Saifuddin, Abdullah, Jafri Malin, Tengku Muhammad, Tengku Sifzizul, Yusof, Siti R.
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Central nervous system; Endothelial; In vitro model; Natural products; Permeability
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2020.09.015

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (Papp) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10−6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.