Buyang huanwu decoction promotes remyelination via miR-760-3p/GPR17 axis after intracerebral hemorrhage

Yang Wang; Zhe Yu; Menghan Cheng; En Hu; Qiuju Yan; Fei Zheng; Xiaohang Guo; Wei Zhang; Haigang Li; Zhilin Li; Wenxin Zhu; Yao Wu; Tao Tang; Teng Li

doi:10.1016/j.jep.2024.118126

Buyang huanwu decoction promotes remyelination via miR-760-3p/GPR17 axis after intracerebral hemorrhage

J Ethnopharmacol. 2024 Jun 28:328:118126. doi: 10.1016/j.jep.2024.118126. Epub 2024 Mar 30.

Authors

Yang Wang¹, Zhe Yu², Menghan Cheng², En Hu¹, Qiuju Yan², Fei Zheng³, Xiaohang Guo⁴, Wei Zhang³, Haigang Li⁵, Zhilin Li², Wenxin Zhu², Yao Wu², Tao Tang¹, Teng Li⁶

Affiliations

¹ Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Xiangya Hospital, Central South University, Jiangxi, Nanchang, PR China.
² Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
³ The College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, PR China.
⁴ School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, PR China.
⁵ Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, Hunan, PR China.
⁶ Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Xiangya Hospital, Central South University, Jiangxi, Nanchang, PR China. Electronic address: litengxiangya@csu.edu.cn.

PMID: 38556140
DOI: 10.1016/j.jep.2024.118126

Abstract

Ethnopharmacological relevance: The repairment of myelin sheaths is crucial for mitigating neurological impairments of intracerebral hemorrhage (ICH). However, the current research on remyelination processes in ICH remains limited. A representative traditional Chinese medicine, Buyang Huanwu decoction (BYHWD), shows a promising therapeutic strategy for ICH treatment.

Aim of the study: To investigate the pro-remyelination effects of BYHWD on ICH and explore the underlying mechanisms.

Materials and methods: The collagenase-induced mice ICH model was created for investigation. BYHWD's protective effects were assessed by behavioral tests and histological staining. Transmission electron microscopy was used for displaying the structure of myelin sheaths. The remyelination and oligodendrocyte differentiation were evaluated by the expressions of myelin proteolipid protein (PLP), myelin basic protein (MBP), MBP/TAU, Olig2/CC1, and PDGFRα/proliferating cell nuclear antigen (PCNA) through RT-qPCR and immunofluorescence. Transcriptomics integrated with disease database analysis and experiments in vivo and in vitro revealed the microRNA-related underlying mechanisms.

Results: Here, we reported that BYHWD promoted the neurological function of ICH mice and improved remyelination by increasing PLP, MBP, and TAU, as well as restoring myelin structure. Besides, we showed that BYHWD promoted remyelination by boosting the differentiation of PDGFRα⁺ oligodendrocyte precursor cells into olig2⁺/CC1⁺ oligodendrocytes. Additionally, we demonstrated that the remyelination effects of BYHWD worked by inhibiting G protein-coupled receptor 17 (GPR17). miRNA sequencing integrated with miRNA database prediction screened potential miRNAs targeting GPR17. By applying immunofluorescence, RNA in situ hybridization and dual luciferase reporter gene assay, we confirmed that BYHWD suppressed GPR17 and improved remyelination by increasing miR-760-3p.

Conclusions: BYHWD improves remyelination and neurological function in ICH mice by targeting miR-760-3p to inhibit GPR17. This study may shed light on the orchestration of remyelination mechanisms after ICH, thus providing novel insights for developing innovative prescriptions with brain-protective properties.

Keywords: Buyang huanwu decoction; G-protein coupled receptor 17; Intracerebral hemorrhage; Oligodendrocyte; Remyelination; microRNA.

MeSH terms

Animals
Cerebral Hemorrhage / drug therapy
Cerebral Hemorrhage / metabolism
Drugs, Chinese Herbal* / pharmacology
Drugs, Chinese Herbal* / therapeutic use
Mice
MicroRNAs* / genetics
Nerve Tissue Proteins
Receptor, Platelet-Derived Growth Factor alpha
Receptors, G-Protein-Coupled / genetics
Remyelination*

Substances

buyang huanwu
Receptor, Platelet-Derived Growth Factor alpha
Drugs, Chinese Herbal
Receptors, G-Protein-Coupled
MicroRNAs
GPR17 protein, mouse
Nerve Tissue Proteins