Network Pharmacology-Guided Evaluation of Ginger and Cornelian Cherry Extracts Against Depression and Metabolic Dysfunction in Estrogen-Deficient Chronic Stressed Rats
Year: 2025
Type: article
Abstract: This study investigated the therapeutic effects of water extracts from Zingiber officinale Roscoe (ginger) and Cornus officinalis Siebold and Zucc. fruits (COF) water extracts on depression-like behavior and metabolic dysfunction in estrogen-deficient rats exposed to chronic mild stress (CMS). Network pharmacology analysis identified three bioactive compounds in ginger and four in COF, with 11 overlapping targets linked to both depression and metabolic pathways, primarily involving NR3C1, HTR2A, MAOA, and SLC6A4 genes associated with hypothalamic–pituitary–adrenal (HPA) axis regulation and neurotransmitter modulation. Ovariectomized rats received 200 mg/kg/day of ginger or COF extracts for 7 weeks, with a 4-week CMS protocol initiated at week 3. Both extracts significantly improved depression-like behaviors, memory performance, glucose tolerance, lipid profiles, and bone mineral density, normalized HPA axis markers (corticosterone and ACTH), and increased hippocampal serotonin and dopamine levels. Ginger demonstrated greater efficacy in improving memory and metabolic outcomes compared to COF. Molecular docking further validated these findings, revealing strong and stable interactions between key phytochemicals—such as hydroxygenkwanin and telocinobufagin—and target proteins MAOA, HTR2A, and NR3C1, supporting their mechanistic role in stress and mood regulation. These results support supplementing ginger and COF extracts as promising botanical interventions for estrogen-deficiency-related mood and metabolic disorders, with potential clinical application at a human-equivalent dose of 1.5 g/day.
DOI: 10.3390/ijms26104829
Authors: Nara Lee, Ting Zhang, Hanbin Joe, Sunmin Park
Institution: Hoseo University
Language: English
Subfield: Complementary and alternative medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G530975197, G8538481910
OpenAlex ID: W4410500463
