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4-Hydroxychalcone attenuates hyperaldosteronism, inflammation, and renal injury in cryptochrome-null mice
Qi Qu1, Bingguang Dai1, Bo Yang1
1Department of Cardiovascular Surgery, The Fourth People's Hospital of Jinan City, Jinan 250031, China.
Abstract:
In the present study, we aimed to investigate the preventive effects of 4-hydroxychalcone (4HCH) on resistant hypertension. We used cryptochrome-null mice, which characteristically show high plasma aldosterone levels, inflammation, and renal injury. The cryptochrome-null mice received high-salt treatment and were treated orally with 4HCH 10 mg/kg, 4HCH 20 mg/kg, and 4HCH 40 mg/kg, respectively. The salt administration in cryptochrome-null mice is able to induce an increase in systolic pressure which is associated with hyperaldosteronism, inflammation, and kidney injury. Treatment with 40 mg/kg 4HCH reduced systolic hypertension, serum IL-1β, and TNF-α levels and suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and renal injury. The impact of 4HCH on the hyperaldosteronism, inflammation, and kidney injury provides new insights for future development of therapeutic strategies in resistant hypertension.
Insights
4-hydroxychalcone (4HCH) shows promise in preventing resistant hypertension. It reduced high blood pressure, inflammation, and kidney damage in a mouse model, offering potential therapeutic insights.
Area of Science:
- Biomedical Science
- Pharmacology
- Nephrology
Background:
- Resistant hypertension is characterized by high blood pressure unresponsive to standard treatments.
- Cryptochrome-null mice exhibit hyperaldosteronism, inflammation, and renal injury, mimicking aspects of resistant hypertension.
- High-salt intake exacerbates these conditions in susceptible models.
Purpose of the Study:
- To investigate the preventive effects of 4-hydroxychalcone (4HCH) on resistant hypertension.
- To evaluate 4HCH's impact on hyperaldosteronism, inflammation, and kidney injury in a relevant preclinical model.
Main Methods:
- Cryptochrome-null mice were subjected to high-salt treatment to induce hypertension.
- Mice were orally administered varying doses of 4-hydroxychalcone (4HCH): 10, 20, and 40 mg/kg.
- Systolic blood pressure, serum inflammatory markers (IL-1β, TNF-α), NF-κB activation, and renal histology were assessed.
Main Results:
- High-salt administration increased systolic pressure, aldosterone levels, inflammation, and renal injury in cryptochrome-null mice.
- Treatment with 40 mg/kg 4HCH significantly reduced systolic hypertension.
- 4HCH administration suppressed serum IL-1β and TNF-α levels, inhibited NF-κB activation, and mitigated renal injury.
Conclusions:
- 4-hydroxychalcone demonstrates significant preventive effects against salt-induced resistant hypertension in a preclinical model.
- 4HCH ameliorates hyperaldosteronism, inflammation, and kidney damage, suggesting a therapeutic potential.
- These findings provide a basis for developing novel therapeutic strategies targeting resistant hypertension.
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