Components of Banisteriopsis caapi, a Plant Used in the Preparation of the Psychoactive Ayahuasca, Induce Anti-Inflammatory Effects in Microglial Cells

Abstract

Banisteriopsis caapi is used to prepare the psychoactive beverage ayahuasca, and both have therapeutic potential for the treatment of many central nervous system (CNS) conditions. This study aimed to isolate new bioactive compounds from B. caapi extract and evaluate their biological activity, and that of the known β-carboline components of the plant (harmine, harmaline, and tetrahydroharmine), in BV-2 microglial cells, the in vivo activation of which is implicated in the physiopathology of CNS disorders. B. caapi extract was fractionated using semipreparative liquid chromatography (HPLC-DAD) and the exact masses ([M + H]⁺m/z) of the compounds in the 5 isolated fractions were determined by high-resolution LC-MS/MS: F1 (174.0918 and 233.1289), F2 (353.1722), F3 (304.3001), F4 (188.1081), and F5 (205.0785). Harmine (75.5-302 µM) significantly decreased cell viability after 2 h of treatment and increased the number of necrotic cells and production of reactive oxygen species at equal or lower concentrations after 24 h. F4 did not impact viability but was also cytotoxic after 24 h. Most treatments reduced proinflammatory cytokine production (IL-2, IL-6, IL-17, and/or TNF), especially harmaline and F5 at 2.5 µM and higher concentrations, tetrahydroharmine (9.3 µM and higher), and F5 (10.7 µM and higher). The results suggest that the compounds found in B. caapi extract have anti-inflammatory potential that could be explored for the development of treatments for neurodegenerative diseases.

Keywords: BV-2 microglial cells; Banisteriopsis caapi; ayahuasca; cytokines; reactive oxygen species; ß-carbolines.

Figure 1

Structures of the main β-carbolines found in Banisteriopsis caapi.

Figure 2

HPLC-DAD chromatogram of a Banisteriopsis caapi methanolic extract, at 230 nm. Putative identification of procyanidin and epicatechin (Samoylenko et al., 2010) and harmalinic acid (Hashimoto, 1975). m/z refers to the protonated ion ([M + H]⁺) in the UHPLC-TripleTOF 5600+. THH: tetrahydroharmine.

Figure 3

Viability of BV-2 cells treated at different concentrations for 2 h with Banisteriopsis caapi extract (BC, (A)), the isolated fractions F1 to F5 (B–F), and β-carbolines (G–I). Values are presented as mean ± SEM (n = 3, except for control, n = 6). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to cells with no treatment (control).

Figure 4

Cell count (left) and ROS production (right) after 24 h in BV-2 cells treated with Banisteriopsis caapi extract fractions F2 (A,B) and F4 (C,D) and harmine (E,F). Values are presented as mean ± SEM (n = 4–5); * p < 0.05, ** p < 0.01, *** p < 0.001 compared to cells with no treatment (control). Viable + early apoptotic and necrotic cells in all treatments is equal to 100%.