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. 2025 Aug:189:118342.
doi: 10.1016/j.biopha.2025.118342. Epub 2025 Jul 12.

Oral apigenin prevents obesity-related muscular atrophy, but not obesity itself, in middle-aged rats fed a high-calorie diet

Josimar Macedo de Castro  1 , Alanis da Silva Melo  1 , Beatriz Lima Silveira  1 , Igor Antônio Souza Martins  1 , Maielli Martins Marçal  1 , Tenille Dal Bosco  1 , Melina Belén Keingeski  2 , Elisa Carolina Lange de Oliveira  2 , Mario Reis Alvares-da-Silva  2 , Patrick Türck  3 , Alex Sander da Rosa Araujo  3 , Layane Ramos Ayres  4 , Lucas Stahlhöfer Kowalewski  4 , Mariana Kras Borges Russo  4 , Mauricio Krause  4 , Dirson João Stein  1 , Iraci L S Torres  5
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Free article

Oral apigenin prevents obesity-related muscular atrophy, but not obesity itself, in middle-aged rats fed a high-calorie diet

Josimar Macedo de Castro et al. Biomed Pharmacother. 2025 Aug.
Free article

Abstract

Obesity constitutes a growing global health concern, affecting individuals during the aging process. Flavonoids that increase tissue NAD+ levels, such as apigenin (Api), are proposed for the treatment of obesity and age-related diseases. Thus, this study aimed to provide initial preclinical evidence of Api in this setting using middle-aged rats induced to obesity by a high-calorie diet (HCD). Forty-seven 15-month-old male Wistar rats were assigned to five groups: standard diet (SD) or HCD, each with (Api at 50 mg/kg) or without treatment (vehicle), plus vehicle control group. Obesity induction and therapeutic intervention were conducted concurrently for 88 days. Biometric, cardiac, adiposity, muscular, and blood biochemical parameters were analyzed. Eighty-eight days post HCD rats had hyperglycemia, hypertriglyceridemia, increased visceral and subcutaneous fat, and heart hypertrophy, indicating obesity and related disorders (p < 0.05 for all). The gastrocnemius of these rats exhibits reduced mass, smaller myocytes, and fibrosis (p < 0.05), indicating sarcopenia, likely caused or worsened by obesity. In parallel, preemptive Api treatment failed to prevent obesity and did not affect key adipose tissue browning genes, cardiac oxidative stress markers, or sirtuin and CD38 levels. However, it mitigated muscle loss and hypotrophy, in addition to elevating p70S6K levels in HCD-fed rats (p < 0.05 for both). These preclinical results suggest that although Api may not prevent some HCD-induced disturbances, it may attenuate age- and obesity-related atrophy via p70S6K anabolic signaling in middle-aged rats. To support clinical translation, particularly in sarcopenia subtypes, further mechanistic and therapeutic investigations on Api are required to elucidate its effects on skeletal muscle.

Keywords: Aging; Apigenin; Flavonoids; High-calorie diet; Middle-aged rats; Obesity; Skeletal muscle.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Iraci L. S. Torres reports financial support was provided by National Council for Scientific and Technological Development and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGS. Dirson Joao Stein reports financial support was provided by National Council for Scientific and Technological Development. Josimar Macedo de Castro reports financial support was provided by Coordination of Higher Education Personnel Improvement. Iraci L.S. Torres reports financial support was provided by Clinics Hospital of Porto Alegre. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.