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PM · Lens · Study on the Mechanism of Berberine Based on PI3K/mTOR/Autophagy Pathway to Ameliorate Sepsis-associated Encephalopathy Injury

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Article · Volume 22, Issue 3 · pp. 1181–1187

Study on the Mechanism of Berberine Based on PI3K/mTOR/Autophagy Pathway to Ameliorate Sepsis-associated Encephalopathy Injury

Yu Li1, Wei Du2, Shijun Tang3, Yuan-Jia Yue4, Xing Rong4, Hongxiang Wang4, Dugujia Gaerma5, Lin Jiang4

  1. 1Department of Health Care Centers, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.
  2. 2Department of Intensive Care Medicine, Zhejiang Qiushi Cardiovascular Disease Hospital, Hangzhou, Zhejiang, China.
  3. 3MA (10 mg/kg/d) for 1 day, after which samples were taken. HE Staining Sections were placed in 4% paraformaldehyde fixative for 48 h, rinsed under running water for 8 h and then placed in 75% ethanol for overnight dehydration, followed by gradient dehydration, transparency and embedding in dipping wax on the next day. The embedded paraffin blocks were cut into 5 μm sections using a slicer. Haematoxylin staining time was 5 min, eosin staining time was 5 s, followed by dehydration, transparency and neutral gum sealing. Nissl Staining Paraformaldehyde fixed sections, sections were dipped into the toluidine blue stain, the staining vat was placed in a thermostat under 60°C invasion of staining for 30 min, 95%.
  4. 4Department of Pharmacy, Xinjiang Medical University Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, China.
  5. 5Department of Pharmacy, Urumqi Friendship Hospital, Urumqi, Xinjiang, China Pharmacognosy Magazine.

Abstract

Background: Sepsis-associated encephalopathy (SAE) is a major cause of high mortality, and no specific therapeutic drugs are currently available. Berberine has been well-documented for its neuroprotective effects, but its mechanism of action remains unclear. Objectives: Use of network pharmacology to study the mechanism of action of berberine (BER) in the treatment of sepsisassociated encephalopathy (SAE). Materials and Methods: Application of network pharmacology to predict the signalling pathway of BER in the treatment of SAE. The mouse model of SAE was constructed, and determination of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-10 (IL-10) was done by enzyme-linked immunosorbent assay (ELISA). The effects of BER on neuronal damage in SAE mice were examined by haematoxylin-eosin (HE) staining and Nissl staining. Transmission electron microscopy was used to observe neuronal autophagy formation, and Western blot analysis was employed to explore the mechanism of action. Results: Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, BER is most likely to treat SAE via the phosphatidylinositol-3 kinase (PI3K)-Akt pathway. TNF-α, IL-1β, IL-6 and IL-10 levels were significantly lower in the BER group than in the SAE group, and the opposite trend was shown in the 3MA group. HE staining and Nissl staining BER were found to significantly reduce SAE injury; terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and transmission electron microscopy visualised under the microscope that the injured cells were shrunken and apoptosis occurred. Western blotting experiments revealed that PI3K, mammalian target of rapamycin (mTOR), matrix metalloprotein-9 (MMP-9) and p62 were reduced in the BER group as compared to the SAE group; Beclin1 and light chain 3 (LC3) were elevated; the opposite trend was shown in the 3MA group. Conclusion: This study predicted the mechanism of action of BER acting on the PI3K/mTOR signalling pathway for the treatment of SAE and linked more potential therapeutic targets.

Keywords: Network pharmacology; PI3K/mTOR; autophagy; sepsis-associated encephalopathy; berberine

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