Guattegaumerine Protects Primary Cultured Cortical Neurons Against Oxidative Stress Injury Induced by Hydrogen Peroxide Concomitant with Serum Deprivation

Abstract

Guattegaumerine is a natural product with characteristics of being lipophilic and reaching high concentration in the brain, but its function in the central nervous system has not yet been observed. This study was designed to evaluate the neuroprotective effects of guattegaumerine on rat primary cultured cortical neurons. Following a 24-h exposure of the cells to combined serum-starvation and hydrogen peroxide, a significant augment in neuron damage as determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release were observed. Preincubation of guattegaumerine dramatically improved the cell viability and inhibited LDH release. Preincubation of guattegaumerine also dramatically inhibited malondialhehyde (MDA) production and elevated the decreased total antioxidative capacity in cells caused by the combined injury. Results of flow cytometry and immunohistochemistry showed that pre-addition of guattegaumerine interrupted the apoptosis of the neurons, reversed the up regulation of the pro-apoptotic gene (Bax) and the down regulation of the anti-apoptotic gene (Bcl-2). Furthermore, guattegaumerine suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by either H(2)O(2) or KCl in Ca(2+)-containing extracellular solutions, and high concentration of 2.5 microM guattegaumerine also suppressed the increase of [Ca(2+)](i) induced by H(2)O(2) in Ca(2+)-free solution. These observations suggested that guattegaumerine may possess potential protection against oxidative stress injury, which might be beneficial for neurons.

Natural compounds from traditional medicinal herbs in the treatment of cerebral ischemia/reperfusion injury

“…As a result, effects of herb components on Ca 2+ overload induced by ischemic reperfusion have been studied extensively. Some herb components, for example, guattegaumerine (bisbenzylisoquinoline alkaloid from Guatteria gaumeri) [43] and TSG [22] , are found to reduce ischemia induced Ca 2+ overload in neurons. However, the exact mechanisms have not been elucidated in most studies.…”

Alkaloids

“…416 This paradigm was shown further with dauricine (CS 1.234), which at a dose of 84 mg/kg lessened neuronal apoptosis of rodent models of stroke. could explain the survival of cortical neurons exposed to H 2 O 2 with a marked decrease in malofialdehyse (MDA), increase in the levels of anti-apoptotic protein (Bcl-2), and reduction in pro-apoptotic Bcl-2-associated X protein (Bax), at a dose of 2.5 μM.…”