Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration.

This study investigates the molecular mechanisms by which Alpiniae oxyphyllae fructus (AOF) promotes neuron regeneration. A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of AOF extract (0-200 mg/ml). We investigated the role of MAPK (ERK1/2, JNK and p38) pathways for AOF-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in RSC96 Schwann cells. The results showed that AOF increased the expressions of uPA, tPA, MMP-9, and MAPKs in vivo. In vitro, our results show that treatment with AOF extract induces ERK1/2, JNK, and p38 phosphorylation to activate the downstream PAs and MMPs signaling expression. AOF-stimulated ERK1/2, JNK, and p38 phosphorylation attenuated by individual pretreatment with siRNAs or inhibitors (U0126, SP600125 and SB203580), resulting in migration and uPA-related signal pathway inhibition. Taken together our data suggests the MAPKs (ERK1/2, JNK and p38), PAs (uPA, tPA), MMP (MMP2, MMP9) regenerative and migration signaling pathway of Schwann cells regulated by AOF extract might play a major role in Schwann cell migration and damaged peripheral nerve regeneration.

Citation

Yung-Ming Chang, Chi-Xin Ye, Tsung-Jung Ho, Te-Neng Tsai, Ping-Ling Chiu, Chin-Chuan Tsai, Yueh-Min Lin, Chia-Hua Kuo, Fuu-Jen Tsai, Chang-Hai Tsai, Chih-Yang Huang. Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration. The International journal of artificial organs. 2014 May;37(5):402-13

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PMID: 24811302

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