Min Wang1, Mingjiang Yao2, Jianxun Liu3, Norio Takagi4, Bin Yang5, Miao Zhang6, Li Xu7, Junguo Ren8, Xiaodi Fan9, Fangze Tian10. 1. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. Electronic address: minbjzyy@163.com. 2. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: ymj_ren@163.com. 3. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: jianxun_liu@163.com. 4. Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. Electronic address: takagino@toyaku.ac.jp. 5. Department of Pathology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: yangbin555@126.com. 6. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: watersmiao@sina.cn. 7. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: xuli1230@sina.com. 8. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: reek2003@163.com. 9. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: xiaodi.1018@163.com. 10. Research Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: tianfangze@163.co.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia, also known as stroke, can stimulate the proliferation and migration of endogenous neural stem cells (NSCS) in subventricular zone of the lateral ventricle and subgranularzone of the dentate gyrus in the adult hippocampus as a defense response to damage. However, the proliferation of endogenous NSCS is insufficient for central nervous system repair. Neurogenesis and anti-neuroinflammation are two important aspects for neuroprotection. Rhizome Ligusticum chuanxiong (LC), the dried rhizomes of Ligusticum striatum DC., has been widely used to treat stroke for over hundreds of years in Traditional Chinese Medicine. PURPOSE: of the study: Previous reports on pharmacological mechanism of LC mainly focus on the cerebral blood flow and thrombolysis. We aim to explore whether LC provides neuroprotective effect by increasing neurogenesis and inhibiting the IL-1β, TNF-α and expressions of glial fibrillary acidic protein. MATERIALS AND METHODS: LC extract was delivered to microsphere-embolized (ME) cerebral ischemia Wister rats to examine its neuroprotection. Body weight, neurological scores, hematoxylin-eosin staining (HE), TUNEL assay were conducted for neurological damage. Neurogenesis was evaluated by assessing the expression of Doublecortin (DCX) and neurogenic differentiation1 (NeuroD1) through immunofluorescence staining. Western blot performed to measure the protein levels of growth associated protein-43(GAP-43), glial fibrillary acidic protein (GFAP). IL-1β and TNF-α was detected by Elisa. RESULTS: LC alleviated pathomorphological change and apoptosis of neurons in the hippocampus caused by ME surgery. Furthermore, LC significantly increased the DCX in the DG of adult rat hippocampus at 14 days after surgery. A significant upregulation of GAP-43 compared to the ME after LC was administered. Besides, LC decreased pro-inflammatory cytokine (IL-1β, TNF-α) and protein level of GFAP. CONCLUSION: The finding suggested that LC had the ability to protect neurons by promoting the endogenous proliferation of neuroblast and production of neural differentiation factor in rats after ischemia injury. Meanwhile, LC can anti-neuroinflammation, which is important for the treatment of neuron injury. Accordingly, LC perhaps a promising medicine for neuron damage therapy after cerebral ischemia.
ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia, also known as stroke, can stimulate the proliferation and migration of endogenous neural stem cells (NSCS) in subventricular zone of the lateral ventricle and subgranularzone of the dentate gyrus in the adult hippocampus as a defense response to damage. However, the proliferation of endogenous NSCS is insufficient for central nervous system repair. Neurogenesis and anti-neuroinflammation are two important aspects for neuroprotection. Rhizome Ligusticum chuanxiong (LC), the dried rhizomes of Ligusticum striatum DC., has been widely used to treat stroke for over hundreds of years in Traditional Chinese Medicine. PURPOSE: of the study: Previous reports on pharmacological mechanism of LC mainly focus on the cerebral blood flow and thrombolysis. We aim to explore whether LC provides neuroprotective effect by increasing neurogenesis and inhibiting the IL-1β, TNF-α and expressions of glial fibrillary acidic protein. MATERIALS AND METHODS:LC extract was delivered to microsphere-embolized (ME) cerebral ischemia Wister rats to examine its neuroprotection. Body weight, neurological scores, hematoxylin-eosin staining (HE), TUNEL assay were conducted for neurological damage. Neurogenesis was evaluated by assessing the expression of Doublecortin (DCX) and neurogenic differentiation1 (NeuroD1) through immunofluorescence staining. Western blot performed to measure the protein levels of growth associated protein-43(GAP-43), glial fibrillary acidic protein (GFAP). IL-1β and TNF-α was detected by Elisa. RESULTS:LC alleviated pathomorphological change and apoptosis of neurons in the hippocampus caused by ME surgery. Furthermore, LC significantly increased the DCX in the DG of adult rat hippocampus at 14 days after surgery. A significant upregulation of GAP-43 compared to the ME after LC was administered. Besides, LC decreased pro-inflammatory cytokine (IL-1β, TNF-α) and protein level of GFAP. CONCLUSION: The finding suggested that LC had the ability to protect neurons by promoting the endogenous proliferation of neuroblast and production of neural differentiation factor in rats after ischemia injury. Meanwhile, LC can anti-neuroinflammation, which is important for the treatment of neuron injury. Accordingly, LC perhaps a promising medicine for neuron damage therapy after cerebral ischemia.
Authors: Lin Zhao; Li Dong Ding; Zi Hao Xia; Peng Sheng; Meng Meng Shen; Zhong Ming Cai; Bing Chun Yan Journal: Front Pharmacol Date: 2022-03-23 Impact factor: 5.810