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Red Clover Supplementation Alleviates Neurological Deficits in Estrogen Deficient Rats Exposed to Chronic
Neha Goyal1, Rishabh Chaudhary1, Khushboo Aggarwal1
1M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India.
The European Journal of Neuroscience
|June 18, 2025
Summary
Red clover (RC) supplementation effectively alleviates neurological deficits caused by estrogen deficiency and chronic stress in rats. This phytoestrogen shows potential as a natural alternative for managing menopausal-related neurological symptoms.
Area of Science:
- Neuroendocrinology
- Pharmacology
- Phytochemistry
Background:
- Estrogen deficiency post-menopause exacerbates neurological issues like stress, anxiety, depression, and memory loss.
- Conventional hormone replacement therapy (HRT) carries adverse effects, prompting interest in safer alternatives.
- Phytoestrogens, plant-derived compounds mimicking estrogen, offer a promising therapeutic avenue with fewer side effects.
Purpose of the Study:
- To investigate the efficacy of red clover (RC) in mitigating neurological disorders.
- To evaluate RC's effects in an animal model simulating post-menopausal estrogen deficiency and chronic stress.
Main Methods:
- Estrogen deficiency was induced in rats via ovariectomy (OVX).
- Chronic unpredictable mild stress (CUMS) was applied to mimic stress and anxiety.
- Groups received red clover (RC) supplementation, 17-β estradiol (E2), or fluoxetine (Flx) for comparison.
Main Results:
- OVX, CUMS, and combined OVX+CUMS induced significant physiological, neurobehavioral, biochemical, molecular, and histopathological brain changes.
- RC supplementation, E2, and Flx treatments markedly reversed the pathological alterations observed in the hippocampus.
- These treatments restored neurological function toward normal levels in the affected rat groups.
Conclusions:
- Red clover demonstrates significant potential in ameliorating neurological disorders linked to estrogen deficiency.
- RC effectively counteracts the adverse neurological effects of chronic stress in an estrogen-deficient state.
- This study supports red clover as a viable natural therapeutic option for menopausal neurological symptoms.

