Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite)

Abstract

Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7.5 µg/mL) induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

Nutritive and Bioactive Properties of Mesquite (Prosopis pallida) Flour and Its Technological Performance in Breadmaking

“…Nevertheless, it also did not show hepatotoxicity in the primary cell culture (non-tumor cells; PLP2) applied in this study, revealing no toxicity up to the maximum concentration studied (GI 50 at >400 µg/mL). The results about the cytotoxic activity of P. pallida or P. alba pod flour extracts are scarce in literature; however, some authors showed that P. juliflora leave extracts caused a significant reduction in cell viability in various human cancer cell lines [42][43][44]. Tables A1-A4 given in Appendix A, compile the full results of the analysis of variance for the effects of white wheat flour type, mesquite flour substitution level, and their interaction, as well as the mean and standard errors of the technological quality properties for the main effects.…”

Identification of a Novel Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase: In Vitro and In Silico Studies

“…According to the protocol established by Pitanga et al [ 48 ] and Silva et al [ 49 ], glial cells were obtained from the beheading of the animals, followed by the removal of the brain hemispheres aseptically. The meninges and blood vessels were removed from each cortex, and then the material was mechanically dissociated and filtered through a sterile membrane (75 mm).…”

Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence

“…TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase LC3II expression and increase GFP-LC3 cells number [64] ABTS, 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid; DMSO, dymethylsulfoxide; DPPH, 1,1-diphenyl-2-picrylhydrazyl; IBC, inhibitory bactericidal concentration; IC50, inhibitory concentration providing 50% of inhibition; LPS, lypopolyssacharide; MIC, minimum inhibitory contentration; RSA, radical scavenging activity.…”

“…Moreover, alkaloids extract and fractions stimulated caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. The stimulation of autophagy was stated after 4 h, characterized by a reduction in P62 protein level, increase in LC3II expression and decline in the number of GFP-LC3 cells [64].…”