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Evidence-Based Complementary and Alternative Medicine
Volume 2011 (2011), Article ID 380809, 9 pages
Review Article

Dilong: Role in Peripheral Nerve Regeneration

1School of Chinese Medicine, China Medical University, Taichung, Taiwan
2The Pre-Clinical Medicine College, Nanjing University of Traditional Chinese Medicine, Nanjing 210029 Jiangsu, China
3Drexel University, School of Nursing and Health Professions, Department of Physical Therapy and Rehabilitation Sciences, Philadelphia, PA, USA
4School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan
5Graduate Institute of Chinese Medical Science, China Medical University, Taichung 404, Taiwan
6Department of Healthcare Administration, Asia University, Taichung, Taiwan
7Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
8Emergency Department, Taichung Veterans General Hospital, Taiwan
9Orthopaedic Department, Armed Forces General Hospital, Taichung, Taiwan
10Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
11Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan

Received 21 April 2010; Accepted 25 May 2010

Copyright © 2011 Yung-Ming Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Dilong, also known as earthworm, has been widely used in traditional Chinese medicine (TCM) for thousands of years. Schwann cell migration and proliferation are critical for the regeneration of injured nerves and Schwann cells provide an essentially supportive role for neuron regeneration. However, the molecular mechanisms of migration and proliferation induced by dilongs in Schwann cells remain unclear. Here, we discuss the molecular mechanisms that includes (i) migration signaling, MAPKs (mitogen-activated protein kinases), mediated PAs and MMP2/9 pathway; (ii) survival and proliferative signaling, IGF-I (insulin-like growth factor-I)-mediated PI3K/Akt pathways and (iii) cell cycle regulation. Dilong stimulate RSC96 cell proliferation and migration. It can induce phosphorylation of ERK1/2 and p38, but not JNK, and activate the downstream signaling expression of PAs (plasminogen activators) and MMPs (matrix metalloproteinases) in a time-dependent manner. In addition, Dilong stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with chemical inhibitors (U0126 and SB203580), and small interfering ERK1/2 and p38 RNA, resulting in migration and uPA-related signal pathway inhibition. Dilong also induces the phosphorylation of IGF-I-mediated PI3K/Akt pathway, activates protein expression of PCNA (proliferating cell nuclear antigen) and cell cycle regulatory proteins (cyclin D1, cyclin E and cyclin A) in a time-dependent manner. In addition, it accelerates G1-phase progression with earlier S-phase entry and significant numbers of cells entered the S-phase. The siRNA-mediated knockdown of PI3K that significantly reduces PI3K protein expression levels, resulting in Bcl2 survival factor reduction, revealing a marked blockage of G1 to S transition in proliferating cells. These results reveal the unknown RSC96 cell migration and proliferation mechanism induced by dilong, which find use as a new medicine for nerve regeneration.