Anti-aging Effects of Angelica keiskei Leaf Extract on Skeletal Muscle: Associations with NF-κB p65 and PGC-1α in a D-galactose Model

Abstract

Aging-associated skeletal muscle dysfunction is highly interlinked to chronic inflammation and mitochondrial dysregulation, with the suppression of PGC-1α representing a key molecular event. The use of natural phytochemicals to prevent aging-related pathological conditions has received increasing attention, including Angelica keiskei. This study examined the effects of A. keiskei leaf extract on skeletal muscle in a D-galactose (D-gal)-induced aging rat model, focusing on NF-κB p65 protein levels and PGC-1α-associated mitochondrial regulatory markers. Male rats were administered D-gal to induce accelerated aging and subsequently treated with A. keiskei extract. NF-κB p65 levels were assessed by ELISA, while the mRNA expression of Ppargc1a and its target gene Tfam, and mitochondrial antioxidants (Sod2, Txn1, and Prdx1) in skeletal muscle tissue was quantified using real-time quantitative PCR. Administration of D-gal markedly increased NF-κB p65 protein levels, reduced the Ppargc1a and Tfam expression, and inhibited the mRNA expression of Sod2, Txn1, and Prdx1, suggesting that inflammation impairs mitochondrial biogenesis and antioxidant defenses. Treatment with A. keiskei extract reduced NF-κB p65 protein levels, restored Ppargc1a mRNA expression, and partially restored antioxidant-related gene expression. These data indicate that A. keiskei extract attenuates the molecular characteristics of skeletal muscle aging through the suppression of inflammaging and the preservation of the PGC-1α-dependent mitochondrial regulatory pathways. This study collectively provides preliminary preclinical evidence that A. keiskei leaf extract may attenuate selected molecular and functional features of D-gal-induced skeletal muscle aging through changes consistent with reduced inflammatory signaling and preservation of PGC-1α-associated mitochondrial regulation.