The Potential Role and Mechanism of Rhizoma Coptidis Extract and its Bioactive Compounds in Prevention of Diabetic Encephalopathy: Targeting Sodium Ion and Channels

Cao, Ning; Shou, Zhangxuan; Wang, Mimi; Wu, You; Wang, Xuefeng

doi:10.3389/fphar.2025.1542015

ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1542015

The Potential Role and Mechanism of Rhizoma Coptidis Extract and its Bioactive Compounds in Prevention of Diabetic Encephalopathy: Targeting Sodium Ion and Channels

Provisionally accepted

Ning Cao

Zhangxuan Shou

Mimi Wang

You Wu

Xuefeng Wang ^*

Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China

The final, formatted version of the article will be published soon.

Rhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application value in the prevention of diabetic encephalopathy (DE).However, its efficacy and underlying mechanism in DE-prevention have not been elucidated. The purpose of the study is to investigate the preventive effect of RC on DE, focusing on the target through the method of network pharmacology and molecular docking. Four-week-old, male C57BL/6 mice were randomly allocated to six groups: control, model, metformin (200 mg/kg), RCL (0.75 g/kg), RCM (1.5 g/kg), RCH (3 g/kg) groups. The DE-model mice were induced by the streptozocin combined with high-fat diet. Besides, neuroprotective effect of RC was determined in vivo and in vitro.Network pharmacology analysis was used to screen the potential mechanism of RC.After that, the mechanism of action of RC was explored by molecular docking prediction and Western-blot analysis. An analysis of DE patients was conducted to validate from another perspective. The results showed that the cognitive state of DE model mice was improved and neuronal injury was ameliorated after RC administration. RC active compounds, berberine and coptisine, could ameliorate HT22 injury induced by high glucose. Network pharmacology result show voltage-gated sodium channels subtypes (Nav1.1, Nav1.2 and Nav1.6) may be the targets for RC prevention of DE.Then, western blot showed that RC significantly up-regulated Nav1.1 and Nav1.2, while Nav1.6 was not. In addition, serum sodium was related to cognitive status of DE patients, which can be used as a diagnostic index for mild and moderate-severe DE. RC has potential to be a functional food or adjuvant drug for the DE prevention, and Nav1.1 and Nav1.2 are promising DE intervention targets.

Keywords: Rhizoma Coptidis, Diabetic encephalopathy, voltage-gated sodium channels, Serum sodium, Berberine, Coptisine

Received: 09 Dec 2024; Accepted: 18 Feb 2025.

Copyright: © 2025 Cao, Shou, Wang, Wu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xuefeng Wang, Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China

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