DHI Increases the Proliferation and Migration of Schwann Cells Through the PI3K/AKT Pathway and the Expression of CXCL12 and GDNF to Promote Facial Nerve Function Repair

• Published in: Neurochemical research Vol. 47; no. 5; pp. 1329 - 1340
• Main Authors: Gao, De-kun, Sun, Lian-hua, Sun, Xia-yu, Yang, Jun, He, Jing-chun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2022; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cardiovascular disease; Cell Biology; Cell migration; Cell Proliferation; Cerebrovascular diseases; Clinical medicine; CXCL12 protein; Diabetes; Drugs, Chinese Herbal; Experiments; Facial nerve; Facial Nerve - metabolism; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Injuries; Medicine; Myelin; Nerve Regeneration; Nerves; Neurochemistry; Neurology; Neurons; Neuroprotection; Neurosciences; Original Paper; Otolaryngology; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Recovery; Regeneration; Repair; Schwann cells; Schwann Cells - metabolism; Vascular diseases; Facial nerve injury; CXCL12; DHI; GDNF; PI3K/AKT pathway
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-022-03532-0

The facial nerve is one of the vulnerable nerves in otolaryngology. Repair and recovery of facial nerve injury have a high priority in clinical practice. The proliferation and migration of Schwann cells are considered of great significance in the process of nerve injury repair. Danhong injection (DHI), as a common drug for cardiovascular and cerebrovascular diseases, has been fully certified in neuroprotection research, but its role in facial nerve injury is still not clear. Our study found that DHI can promote the proliferation and migration of RSC96 cells, a Schwann cell line, and this effect is related to the activation of the PI3K/AKT pathway. LY294002, an inhibitor of PI3K, inhibits the proliferation and migration of RSC96 cells. Further studies have found that DHI can also promote the expression of CXCL12 and GDNF at gene and protein levels, and CXCL12 is, while GDNF is not, PI3K/AKT pathway-dependent. Animal experiments also confirmed that DHI could promote CXCL12 and GDNF expression and promote facial nerve function recovery and myelin regeneration. In conclusion, our in vitro and in vivo experiments demonstrated that DHI could promote the proliferation and migration of Schwann cells through the PI3K/AKT pathway and increase the expression of CXCL12 and GDNF to promote facial nerve function repair.