Formononetin Ameliorates Cognitive Disorder via PGC-1α Pathway in Neuroinflammation Conditions in High-Fat Diet-Induced Mice
Abstract
Background: Alzheimer’s disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer’s disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-β generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer’s disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer’s disease with Formononetin. Objective: The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. Methods: Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). Results: We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. Conclusion: Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.
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Preclinical studies show constituents from red clover can be useful in healing neuroinflammation and reasoning disorders encouraged by a high-fat diet in mice.
“It has been revealed from Preclinical studies that constituents gotten from this estrogenic plant can be useful in healing neuroinflammation and reasoning disorders encouraged by a diet rich in fat in mice [90]”
From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [90]
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From plant to brain: flavonoids in the management of obesity-associated cognitive dysfunction
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- Authors
- Fu, X., Qin, T., Yu, J., Jiao, J., Ma, Z., Fu, Q., Deng, X., & Ma, S.
- Affiliations
- China Pharmaceutical University (CN)
- Corresponding author
- Ma, Shiping
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2019-12-09
- Volume
- 18
- Issue
- 7
- Pages
- 566-577
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2966642078
- Cited by
- 42
- References
- 61
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 7 · 2020: 3
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81703735, 81573701)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- formononetin, Alzheimer's disease, neuroinflammation, PGC-1α, high-fat diet, cognitive decline, tau hyperphosphorylation, NF-κB signaling, Nrf2/HO-1 pathway, hippocampus, isoflavones, red clover, metformin, learning and memory impairment, inflammatory cytokines
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Anti-Inflammatory Agents, Hippocampus, Inflammation, Isoflavones, Male, Mice, Inbred ICR, tau Proteins, Nootropic Agents, Diet, High-Fat, Cognitive Dysfunction
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