Protective Effects of Nongxiang‐Type Tieguanyin on the Liver of D‐Galactose‐Induced Aging C57BL /6 Mice via the NF ‐ κB Signaling Pathway

ABSTRACT This research aimed to investigate the hepatoprotective and anti‐senescence effects of Nongxiang‐type Tieguanyin (Tgy‐N) on D‐galactose (D‐gal)‐induced aging C57BL/6 mice and to elucidate the underlying mechanisms. The chemical composition of Tgy‐N was characterized by colorimetric assays and HPLC. An aging mouse model was established by daily intraperitoneal injection of D‐gal (200 mg/kg) for 8 weeks, with simultaneous intragastric administration of Tgy‐N at 110 or 550 mg/kg/day. Behavioral tests, serum biochemical analyses, hepatic oxidative stress markers, histopathological examination, transcriptomic profiling, and western blotting were performed. The anti‐senescence effect was further validated in Nutlin‐3a‐induced senescent AML12 and HepG2 cells. Tgy‐N contained abundant tea polyphenols (286.91 mg/g) and catechins (137.89 mg/g). HPLC analysis with authentic external standards revealed that the absolute contents of EGCG, catechin, catechin gallate, gallic acid, and epigallocatechin in Tgy‐N extract were 7.96, 5.79, 4.06, 1.67, and 4.91 mg/g, respectively. In vivo, Tgy‐N significantly improved exercise endurance and energy metabolism, reduced the hepatosomatic index, attenuated hepatic oxidative stress (elevated SOD and GSH, reduced MDA), and decreased serum ALT and AST levels. Histologically, Tgy‐N ameliorated hepatic lobule disorganization, reduced fibrosis, decreased SA‐β‐gal‐positive areas, downregulated P16/P21/P53, and upregulated Sirt1. Transcriptomic and western blot analyses revealed that Tgy‐N suppressed the NF‐κB signaling pathway by reducing phosphorylation of IKKα/β and p65. Cellular experiments confirmed that Tgy‐N reduced p16/p21 expression and SA‐β‐gal‐positive cell numbers in Nutlin‐3a‐induced senescent hepatocytes. Tgy‐N protects against D‐gal‐induced hepatic senescence through oxidative stress mitigation and NF‐κB pathway inhibition, supporting its potential as a natural functional food for liver health.