Alpinia oxyphylla Miq

Latin Name:

Alpinia oxyphylla Miq.

PinYin Name:

yizhiren

Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration | BMC Complementary and Alternative Medicine | Full Text

SRC:https://bmccomplementalternmed.biomedcentral.com/articles/10.1186/s12906-017-1695-2 Schematic model of the survival and proliferative effects of AOF extract on RSC96 Schwann cell. Stimulation of Schwann cell with AOF extract activate IGF-I signaling, leading to upregulation of the PI3K/Akt pathway and activation of the cell cycle regulatory proteins cyclin D1, E and A, resulting in the survival and proliferation of RSC96 Schwann cell
Neurotrophic factors, including IGFs, are a set of growth factors that influence the growth and regeneration of neurons [21-25]. According to recent reports, IGF-1 plays an important role in cell survival and Schwann cell proliferation [4, 26]. Regenerating peripheral nerves show high IGF-1 expression in their advancing growth cone. The IGF-1 expression activates the PI3K/Akt signaling pathway and is associated with the proliferation of Schwann cells and regeneration of peripheral nerves [27-32].
AOF extract also induced cell proliferation via activating the PI3K/Akt signaling pathway in RSC96 cells. The PI3K signaling induced by IGF-1 attenuates Schwann cell apoptosis by caspase activation and is also known to facilitate the transition of cell cycle from the G1 to S phase [31, 33]. Inhibition of PI3K effectively inhibits the IGF-1-induced anti-apoptotic and neuro-protective effects, and exhibits the significant role of PI3K in the induced survival of Schwann cells [29, 30]. Bioactive compounds that induce the up-regulation of IGF-1 can potentially activate the PI3K/Akt signaling and lead to modulating the expression of regulatory proteins (Bcl-2, p-Bad, PCNA and cyclins) to favor Schwann cell survival and proliferation during nerve regeneration. We show a beneficial effect in the up-regulation of the IGF-1-related survival pathway and the stimulation of cell proliferation in cultured RSC96 cells following AOF treatment.
Cell proliferation is regulated at various levels, and the G1/S cell cycle transition is one of the most important requirements for DNA replication and mitosis.
Progression through the G1 phase into the S phase requires cyclin D and cyclin E activity; whereas, Cyclin A activity is required for the DNA replication of S phase and mitosis initiation [34-36]. Our current results showed that the G1/S transition of cell cycle progression was induced by AOF extract treatment (Fig. 3b). The time course study revealed that the AOF extract treatment is effective in cyclin A up-regulation, subsequent promotion of DNA replication and the increasing cell number in the S phase, which eventually results in cell proliferation. However, the expressions of cyclin D1 and cyclin E did not show any significant change. In certain cells, such as hematopoietic cells, the IGF expression acts as an inhibitor of cell death [37, 38]. However, IGF-1 has also been shown to stimulate cell cycle progression via G1 or the G0/G1 transition in cultured fibroblasts and mammary epithelial cells [39-41]. We also provide data demonstrating that the cell cycle is driven by cyclins with corresponding changes in IGF-1 levels. AOF-induced alterations of the cell cycle in RSC96 cells may serve as critical determinants for nerve cell proliferation and IGF-1-related cell survival. Despite the fact that we cannot exclude other minor candidates involved in the related pathways, we clearly showed that certain proteins of the IGF-1-related signal pathway were up-regulated following AOF extract treatment.
Systematic survey on literatures shows that over 80 chemical constituents which were identified from A. oxyphylla including diarylheptanoids, flavonoids, polyphenols, sesquiterpenes, steroids, volatile oil and their glycosides, etc. [42-48]. Emerging studies evaluated that the abundance of nine secondary metabolites differentially concentrated in seeds and fruit capsules of A. oxyphylla, including sesquiterpenes (e.g., nootkatone), diarylheptanoids (e.g., oxyphyllacinol and yakuchinone A and B) and flavonoids (e.g., chrysin, izalpinin, tectochrysin, kaempferide and apigenin-4′,7-dimethylether) [49, 50]. Protocatechuic acid (PCA), one of the major metabolite of complex polyphenols, which has been identified in the kernels of AOF [9, 51, 52], it also has been reported that PCA process positive effect on antioxidant, anti-inflammatory, and antiapoptosis [8-11, 53]. Our recent studies revealed that PCA promoted RSC96 Schwann cells regeneration and migration by activating ERK1/2, JNK1/2 and p38 MAPK pathways [54]. It also been reported that PCA effectively promoted RSC96 cell survival and proliferation by activating IGF-IR-PI3K-Akt signaling [55]. The protective effects associated with the chemical constituents of PCA correlates with the pharmacological activities of AOF as defined in the present study.