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Effects and mechanisms of ginsenoside Rg1 in alleviating hypothalamic oxidative stress and metabolic dysfunction via
Zhang Huang1, Yiming Zheng1, Zenghui Fan1
1Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Background:
Metabolic diseases, particularly those related to obesity and diabetes, are strongly associated with chronic oxidative stress. The hypothalamus, responsible for energy regulation, becomes susceptible to oxidative damage under high-fat and high-sugar diets. Nrf2, a crucial transcription factor for antioxidant defense, plays a significant role in combating oxidative stress, but its impact on hypothalamic pathways, including tyrosine metabolism, remains unexplored.
Methods:
Obese rats (DIO) were induced using a high-fat diet plus 10% (w/v) fructose-glucose syrup (F-55) in drinking water (HFHFD) and treated with ginsenoside Rg1. We performed RNA sequencing on hypothalamic tissues and conducted GO/KEGG pathway enrichment analysis to identify key differentially expressed pathways. Western blotting and BV2 cell experiments were used for gene validation.
Results:
Rg1 intervention improved body weight gain, glucose tolerance, and significantly reduced hypothalamic oxidative stress levels in DIO rats. Transcriptome analysis showed that Rg1 significantly enriched tyrosine metabolic pathways in the hypothalamus. Further validation showed that Rg1 treatment downregulated the expression of the key enzymes Aldh3a1, Aox3, and Dct. Notably, pharmacological inhibition of Nrf2 in BV2 cells significantly attenuated the regulatory effects of Rg1 on these genes.
Conclusion:
Rg1 ameliorated HFHFD-induced metabolic impairment and was associated with reduced hypothalamic oxidative stress signaling, supporting a potential role of Nrf2-related tyrosine metabolic pathways and suggesting that peripheral Rg1 may modulate hypothalamic circuits via both direct and indirect peripheral-to-central mechanisms, with implications for managing obesity and type 2 diabetes.
