Blood-Brain Barrier Permeability Study of Potential Neuroprotective Compounds Recovered From Plants and Agri-Food by-Products

José David Sánchez-Martínez; Alberto Valdés; Rocio Gallego; Zully Jimena Suárez-Montenegro; Marina Alarcón; Elena Ibañez; Gerardo Alvarez-Rivera; Alejandro Cifuentes

doi:10.3389/fnut.2022.924596

Blood-Brain Barrier Permeability Study of Potential Neuroprotective Compounds Recovered From Plants and Agri-Food by-Products

Front Nutr. 2022 Jun 16:9:924596. doi: 10.3389/fnut.2022.924596. eCollection 2022.

Authors

José David Sánchez-Martínez¹, Alberto Valdés¹, Rocio Gallego¹, Zully Jimena Suárez-Montenegro¹, Marina Alarcón², Elena Ibañez¹, Gerardo Alvarez-Rivera¹, Alejandro Cifuentes¹

Affiliations

¹ Laboratory of Foodomics, Institute of Food Science Research, CIAL, Spanish National Research Council (CSIC) - Universidad Autónoma de Madrid (UAM), Madrid, Spain.
² Area of Food Technology, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, Ciudad Real, Spain.

Abstract

Plants and agri-food by-products represent a wide and renewable source of bioactive compounds with neuroprotective properties. In this research, various green extraction techniques were employed to recover bioactive molecules from Kalanchoe daigremontiana (kalanchoe), epicarp of Cyphomandra betacea (tamarillo), and cooperage woods from Robinia pseudoacacia (acacia) and Nothofagus pumilio (lenga), as well as a reference extract (positive control) from Rosmarinus officinalis L. (rosemary). The neuroprotective capacity of these plant extracts was evaluated in a set of in vitro assays, including enzymatic [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX)] and antioxidant [ABTS, and reactive oxygen and nitrogen species (ROS and RNS)] bioactivity tests. Extracts were also submitted to a parallel artificial membrane permeability assay mimicking the blood-brain barrier (PAMPA-BBB) and to two cell viability assays in HK-2 and SH-SY5Y cell lines. Comprehensive phytochemical profiling based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) analysis showed enriched content of phenolic and terpenoid compounds in the target extracts. Moreover, in vitro bioactivity tests showed promising neuroprotective capacity, particularly for supercritical-fluid extraction (SFE) extract from acacia (ABTS IC₅₀ = 0.11 μg ml^-1; ROS IC₅₀ = 1.56 μg ml^-1; AChE IC₅₀ = 4.23 μg ml^-1; BChE IC₅₀ = 1.20 μg ml^-1; and LOX IC₅₀ = 4.37 μg ml^-1), whereas PAMPA-BBB assays revealed high perfusion capacity of some representative compounds, such as phenolic acids or flavonoids. Regarding cytotoxic assays, tamarillo and rosemary SFE extracts can be considered as non-toxic, acacia SFE extract and lenga pressurized liquid extraction (PLE) extract as mild-cytotoxic, and kalanchoe as highly toxic extracts. The obtained results demonstrate the great potential of the studied biomass extracts to be transformed into valuable food additives, food supplements, or nutraceuticals with promising neuroprotective properties.

Keywords: UHPLC-Q-TOF-MS; agri-food by-products; bioactive compounds; blood-brain barrier; green extraction; neuroprotective.