title: Protocatechuic Acid from Alpinia oxyphylla Induces Schwann Cell Migration via ERK1/2, JNK and p38 Activation.
abstract: Alpinia oxyphylla MIQ (Alpinate Oxyphyllae Fructus, AOF) is an important traditional Chinese medicinal herb whose fruits is widely used to prepare tonics and is used as an aphrodisiac, anti salivary, anti diuretic and nerve-protective agent. Protocatechuic acid (PCA), a simple phenolic compound was isolated from the kernels of AOF. This study investigated the role of PCA in promoting neural regeneration and the underlying molecular mechanisms. Nerve regeneration is a complex physiological response that takes place after injury. Schwann cells play a crucial role in the endogenous repair of peripheral nerves due to their ability to proliferate and migrate. The role of PCA in Schwann cell migration was determined by assessing the induced migration potential of RSC96 Schwann cells. PCA induced changes in the expression of proteins of three MAPK pathways, as determined using Western blot analysis. In order to determine the roles of MAPK (ERK1/2, JNK, and p38) pathways in PCA-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production, the expression of several MAPK-associated proteins was analyzed after siRNA-mediated inhibition assays. Treatment with PCA-induced ERK1/2, JNK, and p38 phosphorylation that activated the downstream expression of PAs and MMPs. PCA-stimulated ERK1/2, JNK and p38 phosphorylation was attenuated by individual pretreatment with siRNAs or MAPK inhibitors (U0126, SP600125, and SB203580), resulting in the inhibition of migration and the uPA-related signal pathway. Taken together, our data suggest that PCA extract regulate the MAPK (ERK1/2, JNK, and p38)/PA (uPA, tPA)/MMP (MMP2, MMP9) mediated regeneration and migration signaling pathways in Schwann cells. Therefore, PCA plays a major role in Schwann cell migration and the regeneration of damaged peripheral nerve.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Da-Tong
authors.initials: DT
authors.lastname: Ju
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Chinese Medicine Department, China Medical University, Beigang Hospital, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Catherine Reena
authors.initials: CR
authors.lastname: Paul
authors.affiliation: Laboratory of Exercise Biochemistry, TPEC, Taipei, Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore, India.
authors.forename: Vijaya Padma
authors.initials: VP
authors.lastname: Viswanadha
authors.affiliation: Orthopaedic Department, Armed Forces General Hospital, Taichung, Taiwan.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yueh-Sheng
authors.initials: YS
authors.lastname: Chen
authors.affiliation: 1PT Biotechnology Co., Ltd., Taichung, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Chang
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.|Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D062385:Hydroxybenzoates / Q000302:isolation & purification* / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics*; D051381:Rats; D012583:Schwann Cells / Q000502:physiology*
chemical_list: D004365:Drugs, Chinese Herbal; D062385:Hydroxybenzoates; C009091:protocatechuic acid
keywords: Alpinia oxyphylla MIQ; Fruit Extract; Nerve Regeneration; Protocatechuic Acid; Schwann Cell Migration