exceeding 5000 mg/kg BW. In the 28-day sub-chronic toxicity assay, SD male/female mice received PHI at 5000, 15000, and 25,000 mg/kg BW. Across all dose groups, no adverse effects were observed in clinical signs, organ to weight ratio, body weight, food and water consumption, and biochemical parameters. Additionally, histopathological examination revealed normal organ status. To further explore hepatic functional response, antioxidant indices and key drug-metabolizing enzymes were quantified in rat liver. PHI significantly enhanced hepatic antioxidant capacity, reflected by increased SOD and GSH levels and reduced MDA content. Moreover, PHI markedly suppressed the transcription level and protein expression of PXR and its downstream enzyme CYP3A1, suggesting a modulatory effect on xenobiotic metabolism. Collectively, these findings demonstrate that PHI exhibits a wide margin of oral safety and exerts beneficial regulatory effects on hepatic antioxidant function. This systematic evaluation provides essential evidence supporting the potential use of PHI as a safe antiviral and antioxidant agent in veterinary clinical application.
Qian et al. (2026) studied this question.