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

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.