Zishan Huang ^1,2 Feng Li ¹ Xiaoyu Zheng ¹ Jiarui Zheng ^1,3 Yilei Dong ¹ Ding Zhao ¹ Huanyu Gou ¹ Mingjiang Yao ^1* Jianxun Liu ^1*

• ¹ Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
• ² Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
• ³ Heilongjiang Academy of Chinese Medicine, Harbin, China

• Catalpol promotes neuro-restoration processes that may involve mitochondria, including restoration of its structure and amelioration of dysfunction • The Shh signaling pathway is primarily associated with embryonic development, but may also involve mitochondrial in its effects • Catalpol may promote endogenous neural stem cell proliferation and differentiation, as well as synaptogenesis, through activation of the Shh signaling pathway ABSTRACT Ischemic stroke greatly threatens human life and health. Neuro-restoration is considered to be the critical points in reestablishing neurological function and improving the quality of life of patients.Catalpol is the main active ingredient of the Chinese herbal medicine Dihuang, which has the beneficial efficacy in traditional remedy, is closely related to the mitochondrial morphology and function. In the present study, we investigated whether catalpol has a neurorestorative effect after multiple cerebral infarctions and its underlying mechanisms. After inducing multiple cerebral infarctions in rats by multiple cerebral infarctions (MCI) for 14 days, catalpol alleviated neurological deficits, reduced the degree of brain atrophy, as well as minimize pathological damage in the hippocampus and cortex. In addition, catalpol also promoted hippocampal neurogenesis and synaptogenesis by improving the mitochondrial structure and promoting mitochondrial function, as evidenced by the up-regulation of positive expression of both Recombinant Doublecortin (DCX) and 5-Bromodeoxyuridinc (BrdU), the enhancement of the Total antioxidant capacity(T-AOC), and the increase in the expression of synapse-associated proteins, Synaptophysin (SYP) and post-synaptic density-95 (PSD-95). Finally, we observed that catalpol up-regulated the expression of Sonic hedgehog (Shh) and Glioma-associated homologue-1 (GLI-1), factors related to the Shh signaling pathway. In conclusion, catalpol may regulate mitochondria through activation of the Shh signaling pathway and exert its role in promoting hippocampal neurogenesis and synaptogenesis.