Ethylmethylhydroxypyridine Succinate Limits Inflammatory-Degenerative Changes in the Hypothalamus and Corrects Disturbances in the Circadian Rhythm of Corticosterone Secretion in Aged Rats

Jun 2, 2026Bulletin of experimental biology and medicine

Ethylmethylhydroxypyridine Succinate Reduces Inflammation and Aging Damage in the Brain's Control Center and Restores Daily Corticosterone Rhythm in Old Rats

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Abstract

A 14-day treatment with ethylmethylhydroxypyridine succinate at 100 mg/kg reduced inflammatory cytokines in the hypothalamus of aged rats.

Chronic low-grade inflammation in the hypothalamus is linked to aging.
The treatment decreased levels of inflammatory cytokines IL-1β and TNFα.
Increased expression of anti-inflammatory cytokines TGF-β1 and IL-10 was observed.
Upregulation of growth factors VEGF and BDNF was noted, indicating enhanced cellular support.
Markers of mitochondrial and synaptic growth showed improved levels after treatment.
Reduced circulating corticosterone levels were associated with the treatment effects.

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Aging is associated with chronic low-grade inflammation in the hypothalamus, hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and disruption of circadian rhythms of glucocorticoid secretion. Using the immunoblotting method, we found that a course of ethylmethylhydroxypyridine succinate (100 mg/kg, daily intraperitoneal injections for 14 days) reduced the level of inflammatory cytokines (IL-1β, TNFα) in the hypothalamus of aged (18-month-old) rats and upregulated the expression of anti-inflammatory cytokines (TGF-β1 and IL-10), growth factors (VEGF and BDNF), markers of mitochondriogenesis (PGC-1α, NDUFV2, SDHA, cyt c1, and COX2) and synaptogenesis (SYP), succinate receptor SUCNR1, and insulin receptor INSRβ. These molecular changes were associated with reduced circulating corticosterone levels, as determined by ELISA. Our findings demonstrate the normalizing effect of succinate/SUCNR1 signaling on the circadian activity of the HPA axis during aging.

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Ethylmethylhydroxypyridine Succinate Limits Inflammatory-Degenerative Changes in the Hypothalamus and Corrects Disturbances in the Circadian Rhythm of Corticosterone Secretion in Aged Rats

Abstract

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