Neuroprotective Potential of Tamarillo (Cyphomandra betacea) Epicarp Extracts Obtained by Sustainable Extraction Process

Abstract

Tamarillo (Cyphomandra betacea (Cav.) Sendt.), or tree tomato, is a tropical fruit from the Andean region of South America; it is highly rich in vitamins, minerals, and polyphenolic compounds. In this study, extracts from tamarillo epicarp (TE) were obtained by pressurized liquid extraction (PLE), and their in-vitro neuroprotective potential was assessed. A central composite design with response surface methodology was performed to optimize PLE as a function of solvent composition and temperature. Selected response variables were extraction yield, total phenolic content (TPC), total flavonoid content (TFC), total carotenoid content (TCC), antioxidant (ABTS), and anti-inflammatory (LOX) activities, and anti-acetylcholinesterase (AChE) inhibitory capacity. According to the desirability function, the optimal conditions were 100% ethanol and 180°C with a 0.87 desirability value. Next, the anti-butyrylcholinesterase enzyme (BChE), reactive oxygen species (ROS), and reactive nitrogen species (RNS) inhibition as well as cytotoxicity in HK-2, THP-1 monocytes, and SH-5YSY neuroblastoma cell lines were studied for the TE extract obtained under optimized conditions. The optimum TE extract provided the following results: extraction yield (36.25%), TPC (92.09 mg GAE/g extract), TFC (4.4 mg QE/g extract), TCC (107.15 mg CE/g extract), antioxidant capacity (ABTS, IC50 = 6.33 mg/ml extract), LOX (IC50 = 48.3 mg/ml extract), and AChE (IC50 = 97.46 mg/ml extract), and showed no toxicity at concentration up to 120 μg/ml extract for all the tested cell lines. Finally, chemical characterization by liquid chromatography-tandem mass spectrometry (UHPLC-q-TOF-MS/MS) of the optimum TE extract exhibited an important presence of hydroxycinnamic acid derivatives and other phenolic acids as well as quercetin hexoside and rutin, as main metabolites responsible for the observed biological properties. All these results suggested that TE, which represents between 8 and 15% of the total fruit, could become a promising natural by-product with a potential “multitarget” activity against Alzheimer's disease.

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

“…With regard to T33 extract, the hydroxycinnamic acid ethyl caffeate was the main compound, followed by other phenolic acids such as gallic acid and p- coumaric acid (see Table 5 ), as reported by Suárez Montenegro et al ( 18 ).…”

“…Hassan et al ( 41 ) reported antioxidant and AChE inhibition activity of methanolic and aqueous conventional extracts from tamarillo, which showed lower anticholinesterase capacity than our T33 extract. These differences may be attributed to higher total phenolic and flavonoid content in the T33 extract obtained by a PLE procedure ( 18 ).…”

“…Kalanchoe extracts have also been shown to possess a high content of neuroprotective phenolic compounds ( 16 ). Second, epicarp from C. betacea (tamarillo) has been described as a valuable source of vitamins, carotenoids, and polyphenols, among others, with reported antioxidant and anti-inflammatory properties ( 17 , 18 ). Third, cooperage woods, such as those from R. pseudoacacia (acacia) and N. pumilio (lenga), are commonly used during wine production to impart pleasant aroma and sensorial properties.…”

“…Tamarillo peel was removed manually and washed with distilled water and dried at room temperature for 72 h. After that, the peel was grounded, sieved to a particle size between 250 and 500 μm, and vacuum-packed for storage at −18°C. Tamarillo peel extract (T33) was obtained by PLE as previously described by our group ( 18 ). In brief, the extraction was performed using a Dionex accelerated solvent extract (ASE 200, Sunnyvale, CA, USA) operating at 10 MPa.…”

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“…The PLE conditions were optimized using a CCD, as described in Section 2.4 , and by selecting the TPC, AChE and LOX inhibitory activity levels and ROS scavenging capacity as response variables. Since previous studies had demonstrated that the extraction yield is not necessarily connected to the neuroprotective potential of different natural extracts [ 22 , 23 ], this response variable was not considered in the PLE optimization model. Moreover, and considering that phenolic compounds can prevent the development of the AD pathology [ 24 , 25 , 26 ], the TPC was fostered in the optimization process.…”