PMID- 38243958 OWN - NLM STAT- Publisher LR - 20240120 IS - 1875-5402 (Electronic) IS - 1386-2073 (Linking) DP - 2024 Jan 11 TI - Use of Network Pharmacology and Experiment Validation to Uncover the Mechanism of Jianshen Lishui Prescription in the Treatment of Intracerebral Hemorrhage. LID - 10.2174/0113862073256436231031100059 [doi] AB - BACKGROUND: As a Chinese medicinal formula, the Jianshen Lishui prescription has been clinically proven to be effective in treating intracerebral hemorrhage (ICH). Yet, the mechanisms involved are unknown. METHODS: (1) Network pharmacology analysis: It involved the screening of active components in the Jianshen Lishui prescription, identification of potential targets for these components, and the screening of ICH-related targets. Common targets for both disease and drug were identified. Protein- protein interaction networks were constructed, followed by further screening of core targets. Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis were performed on these core targets. Finally, molecular docking verification was carried out using the active components and core targets. (2) Experimental verification: It was conducted using a rat model of intracerebral hemorrhage. This involved observing neurological deficit scores in the rats and measuring cerebral water content. The effects of Jianshen Lishui prescription on the neurological function, cerebral water content, and brain tissue core targets were observed through HE staining, Western blot and qPCR. RESULTS: (1) In this study, 29 common targets were obtained by intersecting 256 potential drug targets and 642 genes associated with ICH. 9 core targets were obtained by employing the protein- protein interaction (PPI) construction system to screen more specific targets. In addition, the findings revealed that the molecular mechanism of Jianshen Lishui prescription in treating ICH was mainly related to cancer signaling pathways and signal transduction pathways, based on the results of GO and KEGG enrichment analysis. Molecular docking results showed that the active constituent of Jianshen Lishui prescription mannitol has the highest binding activity with KRAS, luteolin, and Poria sterol with AR, INS1 and KRAS, cerebrosterol with GNB1, INS and ESR1, and sitosterol with AR, INS1 and KRAS. (2) Animal experiments verified that Jianshen Lishui prescription significantly alleviated encephaledema and improved nerve functions of the rat model of ICH. And INS1 expression levels were upregulated and the expression levels of AR, KRAS, PTGS2, and ESR1 were down-regulated by the prescription. CONCLUSION: Jianshen Lishui prescription protects the nerve function of ICH patients by inhibiting inflammation and reducing cerebral edema. This study provides more supportive evidences for the clinical use of traditional Chinese prescriptions in ICH treatment. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Yuguang, Gao AU - Yuguang G AUID- ORCID: 0000-0003-1704-6235 AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. FAU - Deqing, Huang AU - Deqing H AUID- ORCID: 0000-0001-7763-0359 AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. FAU - Jie, Zhong AU - Jie Z AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. FAU - Yujuan, Ma AU - Yujuan M AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. FAU - Kan, Yang AU - Kan Y AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. FAU - Yuxiong, Liao AU - Yuxiong L AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. FAU - Qiong, Zhu AU - Qiong Z AD - Guangxi University of Chinese Medicine, China. FAU - Qiqi, Liu AU - Qiqi L AD - Neurology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine, China. LA - eng PT - Journal Article DEP - 20240111 PL - United Arab Emirates TA - Comb Chem High Throughput Screen JT - Combinatorial chemistry & high throughput screening JID - 9810948 SB - IM OTO - NOTNLM OT - Jianshen lishui prescription OT - experimental evaluation. OT - intracerebral hemorrhage OT - mechanism of action OT - molecular docking OT - network pharmacology EDAT- 2024/01/20 21:41 MHDA- 2024/01/20 21:41 CRDT- 2024/01/20 10:14 PHST- 2023/06/13 00:00 [received] PHST- 2023/09/19 00:00 [revised] PHST- 2023/09/25 00:00 [accepted] PHST- 2024/01/20 21:41 [medline] PHST- 2024/01/20 21:41 [pubmed] PHST- 2024/01/20 10:14 [entrez] AID - CCHTS-EPUB-137257 [pii] AID - 10.2174/0113862073256436231031100059 [doi] PST - aheadofprint SO - Comb Chem High Throughput Screen. 2024 Jan 11. doi: 10.2174/0113862073256436231031100059.