Timosaponin alleviates oxidative stress in rats with high fat diet-induced obesity via activating Nrf2/HO-1 and inhibiting the NF-κB pathway

Anemarrhena asphodeloides originated from the rhizome of Liliaceae Anemarrhena asphodeloides. One of the active pharmacological components of Anemarrhena asphodeloides is timosaponin (TSA), which reduces blood lipids and shows antioxidation and anti-inflammatory effects, but its mechanism is unclear. The objective of this study was to investigate the effect of TSA on oxidative stress induced by a long-term high-fat diet in obese rats. Body weight and the obesity index of the rats were measured during the experiment. Total antioxidant capacity (T-AOC), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were used to detect oxidative stress indexes in serum and liver tissue. To observe the effect of TSA on the liver and adipose tissue of rats with oxidative stress, hematoxylin & eosin (H&E) staining was used. The p-NF-κB, NAD(P)H: quinone oxidoreductase 1 (NQO-1), Heme oxygenase 1 (HO-1), and Nrf2 in Nrf2/HO-1 and NF-κB pathways were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. TSA was found to improve oxidative stress in obese rats by reducing MDA levels and increasing T-AOC and GSH-Px levels. Histological examination revealed that TSA effectively attenuated liver damage and improved obesity in rats. TSA was found to down-regulate the protein level of p-NF-κB and up-regulate the protein level of Nrf2/HO-1. These results suggested that TSA could effectively block inflammation and dyslipidemia in obese rats, thus improving oxidative stress, and its mechanism could be related to the Nrf2/HO-1 and NF-κB pathways.