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  • Curcumin is able to upregulate

    2022-11-30

    Curcumin is able to upregulate the protein level of NGF through cannabinoid receptor CB1, where the activation of Akt pathway probably plays an important part in the CB1-mediated signal transmission [9,10]. This finding suggested that the protection of curcumin in spinal motor neurons of SNI rats is possibly associated with NGF and Akt signaling. NGF, generally secreted by gliocytes or neurons, can also exist as a precursor form pro-NGF, which promotes neuron death instead of survival after its injury in the presence of sortilin (a co-expressed receptor with p75NTR) [[11], [12], [13]]. After the sympathetic neuron CH5183284 sale are axotomized, the cleavage of pro-NGF increased and mature NGF (mNGF) level increased [11]. In the presence of low TrkA, the apoptotic induction of proNGF was enhanced [14], and curcumin is able to upregulate the protein level of TrkA and p75NTR in the substantia nigra of Parkinson’s disease rats [15]. These results showed us the possibility that curcumin exerts its neural protecting effect via upregulating the receptors TrkA and p75NTR and the ligand NGF.
    Materials and methods
    Results
    Discussion In present study, we demonstrated that curcumin protected PC-12 neurons against H2O2-induced apoptosis through upregulation of mature NGF, TrkA and Akt phosphorylation. Suppression of NGF interrupted the protective effect of curcumin on PC-12 neuron cells. Inhibition of PI3K and suppression of Akt attenuated the anti-apoptotic effect of curcumin in vitro. In addition, curcumin protected the rat ventral motor neurons from following SNI, in which NGF and Akt signaling pathways were involved. These findings suggested that NGF and PI3K/Akt signaling may be the key target of curcumin in protecting the neurons from injury. Curcumin, as H-atom donor, exhibits free radical scavenging activity [18,19]. At low superoxide concentrations, curcumin effectively caused superoxide scavenging without itself undergoing any chemical change, but at higher concentrations of superoxide, curcumin inhibited superoxide activity by reacting with it [20]. Curcumin increased the cell viability, intracellular ROS and decreased the apoptosis in BV-2 microglia, indicating the neuroprotective effect against oxidative damage [21,22]. Curcumin inhibited appoptosin-induced apoptosis in SH-SY5Y cells by upregulating the expression of HO-1, reducing the production of intracellular heme and ROS, and preventing the ΔΨm loss [23]. In our in vitro experiment, curcumin significantly reduced the apoptotic PC-12 cells which were exposed to H2O2 for 12 h. Curcumin is a lipophilic molecule and can cross the blood brain barrier (BBB) and, therefore, can attain the functional pharmacological level in brain tissue [[24], [25], [26]]. Due to its immediate metabolism, curcumin is not detectable in the brain after 2 h [24] and therefore it is suggested to be taken on a regular basis in order to reach the optimal therapeutic level in the brain tissue [27]. For this reason, we intraperitoneally injected curcumin for 4 weeks and our results exhibited that curcumin significantly reduced the neuronal cell death rate in rats following SNI. The neurotrophins play crucial roles regulating survival and apoptosis in the developing and injured nervous system [28]. As one of the most important neurotrophins, nerve growth factor, a trophic molecule, is pivotal for survival of sensory and sympathetic neurons [29]. The biological action of NGF is mediated by two NGF-receptors, high affinity receptor TrkA NGFR and low affinity receptor p75NTR, which regulates signaling through TrkA NGFR [30]. The ratio of these two receptors distributed on cell surface decides the effect of NGF [31]. The reduced transport of NGF can lead to nervous cell damage [32]. Injection of NGF significantly reduced cell apoptosis in injured motor neurons [29]. In addition numerous studies have demonstrated that NGF administration can facilitate peripheral nerve growth and restore the functional activity of damaged peripheral neurons in animals [29,[33], [34], [35]]. However, due to intravenously NGF administration caused unwanted side effects in peripheral nerve, the attempts of exogenous NGF administration in human were not encouraging [36]. Therefore, induction of increased production of NGF using safe strategies may be an optimal option.