The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels

IntroductionRhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application in the prevention of diabetic encephalopathy (DE). However, its efficacy and underlying mechanism in DE prevention have not been elucidated yet. The objective of the current stu...

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Main Authors: Ning Cao, Zhangxuan Shou, Mimi Wang, You Wu, Xuefeng Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1542015/full
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author Ning Cao
Zhangxuan Shou
Mimi Wang
You Wu
Xuefeng Wang
author_facet Ning Cao
Zhangxuan Shou
Mimi Wang
You Wu
Xuefeng Wang
author_sort Ning Cao
collection DOAJ
description IntroductionRhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application in the prevention of diabetic encephalopathy (DE). However, its efficacy and underlying mechanism in DE prevention have not been elucidated yet. The objective of the current study is to investigate the preventive effect of RC on DE, thereby focusing on the target through the method of network pharmacology and molecular docking.MethodsSixty 4-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), and RCH (3 g/kg). The DE-model mice were induced by streptozocin combined with a high-fat diet. In addition, the neuroprotective effect of RC was determined both in vivo and in vitro. Network pharmacology analysis was used to screen the potential mechanism of RC. Thereafter, the underlying mechanism of action of RC was explored by molecular docking prediction and Western blot analysis. An analysis of patients with DE was performed to validate it from another perspective.ResultsThe results showed that the cognitive state of DE model mice was improved and neuronal injury was ameliorated after RC administration. Active compounds in RC, berberine and coptisine, were found to ameliorate HT22 injury induced by high glucose. Network pharmacology results suggest that voltage-gated sodium channel subtypes (Nav1.1, Nav1.2, and Nav1.6) may be the targets for RC prevention of DE. Furthermore, the Western blot analysis revealed that RC significantly upregulated Nav1.1 and Nav1.2, while Nav1.6 could not. In addition, serum sodium was related to the cognitive status of DE patients, which can be used as a diagnostic index for mild and moderate–severe DE.DiscussionRC has the potential to be a functional food or adjuvant drug for DE prevention, and Nav1.1 and Nav1.2 are promising DE intervention targets.
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spelling doaj-art-0550b4d1059d4fc7a9b37b660b87406f2025-08-20T02:53:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15420151542015The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channelsNing Cao0Zhangxuan Shou1Mimi Wang2You Wu3Xuefeng Wang4Pharmacy Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaPharmacy Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaPharmacy Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaPharmacy Department, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaIntroductionRhizoma Coptidis (RC) is an edible and medicinal herb with anti-hyperglycemia, which has potential application in the prevention of diabetic encephalopathy (DE). However, its efficacy and underlying mechanism in DE prevention have not been elucidated yet. The objective of the current study is to investigate the preventive effect of RC on DE, thereby focusing on the target through the method of network pharmacology and molecular docking.MethodsSixty 4-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), and RCH (3 g/kg). The DE-model mice were induced by streptozocin combined with a high-fat diet. In addition, the neuroprotective effect of RC was determined both in vivo and in vitro. Network pharmacology analysis was used to screen the potential mechanism of RC. Thereafter, the underlying mechanism of action of RC was explored by molecular docking prediction and Western blot analysis. An analysis of patients with DE was performed to validate it from another perspective.ResultsThe results showed that the cognitive state of DE model mice was improved and neuronal injury was ameliorated after RC administration. Active compounds in RC, berberine and coptisine, were found to ameliorate HT22 injury induced by high glucose. Network pharmacology results suggest that voltage-gated sodium channel subtypes (Nav1.1, Nav1.2, and Nav1.6) may be the targets for RC prevention of DE. Furthermore, the Western blot analysis revealed that RC significantly upregulated Nav1.1 and Nav1.2, while Nav1.6 could not. In addition, serum sodium was related to the cognitive status of DE patients, which can be used as a diagnostic index for mild and moderate–severe DE.DiscussionRC has the potential to be a functional food or adjuvant drug for DE prevention, and Nav1.1 and Nav1.2 are promising DE intervention targets.https://www.frontiersin.org/articles/10.3389/fphar.2025.1542015/fullRhizoma Coptidisdiabetic encephalopathyvoltage-gated sodium channelsserum sodiumberberinecoptisine
spellingShingle Ning Cao
Zhangxuan Shou
Mimi Wang
You Wu
Xuefeng Wang
The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels
Frontiers in Pharmacology
Rhizoma Coptidis
diabetic encephalopathy
voltage-gated sodium channels
serum sodium
berberine
coptisine
title The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels
title_full The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels
title_fullStr The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels
title_full_unstemmed The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels
title_short The potential role and mechanism of Rhizoma Coptidis in prevention of diabetic encephalopathy: targeting sodium ion and channels
title_sort potential role and mechanism of rhizoma coptidis in prevention of diabetic encephalopathy targeting sodium ion and channels
topic Rhizoma Coptidis
diabetic encephalopathy
voltage-gated sodium channels
serum sodium
berberine
coptisine
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1542015/full
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