Geissoschizoline, a promising alkaloid for Alzheimer's disease: Inhibition of human cholinesterases, anti-inflammatory effects and molecular docking.

Due to the lack of effective pharmacotherapy options to treats Alzheimer's disease, new strategies have been approached in the search for multi-target molecules as therapeutic options. In this work, four indole alkaloids, geissoschizoline, geissoschizone, geissospermine, and 3',4',5',6'-tetradehydrogeissospermine were isolated from Geissospermum vellosii (Pao pereira) and evaluated for their anticholinesterase activities. While geissospermine inhibited only butyrylcholinesterase (BChE), the other alkaloids behaved as non-selective inhibitors of acetylcholinesterase (AChE) and BChE. In cell viability tests, only geissoschizoline was not cytotoxic. Therefore, geissoschizoline actions were also evaluated in human cholinesterases, where it was twice as potent inhibitor of hBChE (IC50 = 10.21 ± 0.01 µM) than hAChE (IC50 = 20.40 ± 0.93 µM). On enzyme kinetic studies, geissoschizoline presented a mixed-type inhibition mechanism for both enzymes. Molecular docking studies pointed interactions of geissoschizoline with active site and peripheral anionic site of hAChE and hBChE, indicating a dual site inhibitor profile. Moreover, geissoschizoline also played a promising anti-inflammatory role, reducing microglial release of NO and TNF-α at a concentration (1 µM) ten and twenty times lower than the IC50 values of hBChE and hAChE inhibition, respectively. These actions give geissoschizoline a strong neuroprotective character. In addition, the ability to inhibit hAChE and hBChE, with approximate inhibitory potencies, accredits this alkaloid for therapeutic use in the moderate to severe phase of AD. Thus, geissoschizoline emerges as a possible multi-target prototype that can be very useful in preventing neurodegeneration and restore neurotransmission.

Pereirina: o primeiro alcaloide isolado no Brasil? / Was pereirina the first alkaloid isolated in Brazil?

O artigo descreve a história da pereirina, um alcaloide extraído das cascas da Geissospermum vellosii Allemão, uma espécie de planta brasileira da família Apocynaceae, conhecida popularmente como Pau-pereira. A classificação botânica desta espécie e o emprego da pereirina na medicina popular foram as razões que acirraram a disputa entre os farmacêuticos brasileiros e estrangeiros pela glória de sua descoberta no Brasil do século XIX. Neste estudo constatou-se que a glória desta descoberta é do farmacêutico brasileiro Ezequiel Corrêa dos Santos e desta maneira, a pereirina é o primeiro alcaloide isolado no Brasil. As cascas do Pau-pereira foram, durante dois séculos, um importante remédio no combate a diversas doenças, devido às propriedades terapêuticas dos alcaloides presentes nas cascas da espécie e atualmente pesquisas estão sendo realizadas para comprovação científica de sua eficácia no combate a doenças virais como Aids, herpes e hepatite C.

This article describes the history of pereirina, an alkaloid extracted from Geissospermum vellosii Allemão barks, a Brazilian plant of Apocynaceae's family, popularly known as "pau-pereira". The botanical classification of this species and the use of pereirina in popular medicine were reasons for controversies and irritated disputes for the glory of the discovery among Brazilians and foreigners pharmacists. For two centuries, the pau-pereira's barks were important remedy to combat various diseases, because the therapeutic properties of alkaloids present in the barks of the species. The currently researches are being carried out for scientific proof of its effectiveness in combating viral diseases such as AIDS, herpes and hepatitis C.