1 Anti-inflammatory effect and protection of rat neural stem cells
The ratio of pro-apoptotic and anti-apoptotic proteins in the Bcl-2 protein family determines whether cells undergo apoptosis after being stimulated by apoptotic signals. When the Bcl-2/Bax value decreases, Bax forms a homodimer to induce cell apoptosis; when the Bcl-2/Bax value increases, Bax and Bcl-2 form a heterodimer to achieve Bcl-2 inhibition of cell death. Apoptotic function. Zhu Ning et al. found in rat experiments that under the stimulation of Aβ1-42-mediated inflammatory response in neural stem cells, the expression levels of Bcl-2 and Bax were the highest in each group, while the Bcl-2/Bax value was the highest in each group. lowest. After Hup A pretreated microglia, liquid chip detection showed that the secretion of inflammatory factors was reduced, and at the same time, the Bcl-2/Bax value was significantly higher than that of the Aβ group, which inhibited the apoptosis of neural stem cells. The results of Western blotting and flow cytometry both suggested that Hup A could inhibit the apoptosis of neural stem cells.
2 Against the neurotoxicity of organophosphates
The main mechanism of Huperzine A High against organophosphate poisoning is: the reversible combination of Hup A with acetylcholinesterase in advance of administration, thus preventing the irreversible combination of organophosphorus compounds and acetylcholinesterase. Compared with other reversible cholinesterase inhibitors such as pyridostigmine bromide, Hup A has two advantages: On the one hand, Huperzine A High can pass through the blood-brain barrier, thereby protecting the acetylcholinesterase in the brain . On the other hand, butyrylcholinesterase and carboxylesterase may be endogenous organophosphate scavengers, Hup A can selectively inhibit plasma erythrocyte acetylcholinesterase, but has no inhibitory effect on butyrylcholinesterase, So the selectivity of Hup A is helpful for the prevention of organophosphate poisoning.
3 Fight against glutamate toxicity
Glutamate is an agonist of N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are stimulated to increase the influx of calcium ions into neurons, and excessive calcium ions can lead to cell death . Huperzine A High can reduce the toxicity of glutamate to nerve cells and increase the cell survival rate, especially for mature neuron cells, because there are more NMDA receptors in mature neuron cells. The mechanism of anti-glutamate may be that after the NMDA receptor is stimulated, Hup A blocks somewhere downstream of its signal transduction channel, thereby preventing cell death caused by glutamate. In addition, the protective effect of Hup A on nerve cells may also be Involvement mediated by glutamate receptors.
4 Fights Oxidative Stress
Huperzine A High protects neuronal cells against the toxicity of β-amyloid production and increases the production of superoxide dismutase (SOD). Rat primary cortical cells cultured in vitro were incubated under the condition of Aβ25-35 (the 25th to 35th amino acid residues of β-amyloid protein fragments), and the apoptosis of the cells could be observed, the viability of the cells decreased significantly, and the morphology of neurons Alteration and its DNA fragmentation. Pre-administration of Hup A can significantly improve cell survival and prevent nuclear fragmentation. The mechanism is that Hup A inhibits the formation of reactive oxygen species (ROS reactive oxygen species) and the activity of caspase-3 enzyme.
5 Inhibition of neurotoxicity of NO
Studies have shown that NO can inhibit the growth of human neuroblastoma SK-N-SH line cells and induce cell apoptosis. Huperzine A High, ginkgolides A and B can block the apoptosis and growth inhibition of sodium nitroprusside (NO donor) on SK-N-SH cells. In addition, Hup A and ginkgolides A and B can also inhibit the production of NO in mouse glial cells and the production of NO in human and mouse astrocytes.