Evidence map›Paper›PMID 40970090›Full record

ArticleFrontiers in cell and developmental biology2025

Mechanism of Huaiqihuang (HQH) against cyclophosphamide (CYP)-induced hippocampal neurotoxicity based on network pharmacology, molecular docking and experimental verification.

Yueming Zhang, Fengwei Huang, Jinghui Zhai, Jingmeng Sun, Boyu Li, Sixi Zhang

Abstract read
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Article in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yueming ZhangDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, China.
Fengwei HuangDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, China.
Jinghui ZhaiDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, China.
Jingmeng SunDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, China.
Boyu LiSecond Clinical Medical College, Harbin Medical University, Harbin, China.
Sixi ZhangDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Cyclophosphamide (CYP) is widely used for the treatment of cancer and autoimmune diseases. However, neurotoxicity accompanied with application of CYP seriously affects the final clinical outcome. Huaiqihuang (HQH) is a Chinese herbal complex with immunomodulatory effect and widely used for treating various diseases. The present research was conducted to evaluate the protective effect of HQH against CYP-induced neurotoxicity and to elucidate the underlying mechanisms. Methods: Sprague-Dawley rats were randomly divided into four groups (10 per group): the CYP-only group (single dose of 200 mg/kg), low- and high-dose HQH + CYP groups (pretreatment with 3 or 6 g/kg HQH for 5 days), and control (saline) group. Histopathological analysis and behavioral tests was used to evaluate the therapeutic effects of HQH on CYP-induced neurotoxicity. Network pharmacology, molecular docking, and Western blot were employed to assess the anti-neurotoxicity mechanisms. Results: Both doses of HQH restored histopathological aberrations, oxidative stress and inflammation caused by CYP in rats. Behavioral tests showed that HQH pretreatment improved motor coordination and balance in CYP-treated rats. Network pharmacology identified core targets including HSP90AA1, TP53, MAPK1, AKT1, RELA, TNF. Molecular docking revealed that TNF, HSP90AA1, TP53, and MAPK1 had strong binding affinities with CYP. Experimental validation using Western blot confirmed that HQH significantly decreased the protein expression of TNF, HSP90AA1, TP53, and MAPK1 in hippocampal tissues. Conclusion: HQH mitigates CYP-induced hippocampal neurotoxicity by decreasing oxidative stress, and inflammation, with HSP90AA1 being a key target, providing a novel therapeutic strategy for chemotherapy-associated cognitive impairment.

Indexed as

cyclophosphamideHuaiqihuangmolecular dockingnetwork pharmacologyneurotoxicity

Identifiers

PMID40970090
PMCPMC12440942

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