Liver has enormous capacity to regenerate in the mammalian body. In rodents, only 7–10 days are required to restore following the 70% partial hepatectomy (PHx). And in humans, the remaining liver mass completely regenerates in approximately 3 months [1]. Given the enormous regenerative capacity of the liver, PHx has become the mainstay of curative treatment for patients with hepatocellular carcinoma [2]. Liver regeneration is a flexible and highly orchestrated process with individual variations among patients. Approximately 20% of patients suffer from post-hepatectomy liver failure due to insufficient liver regeneration [3]. Nevertheless, there are limited drugs available to improve recovery after liver surgery, and the protocols are lacking in clinical practice [4]. Therefore, it is urgent to develop strategies to facilitate liver regeneration, which improves the prognosis of patients with PHx in clinical practice.

Oleanolic acid, a naturally pentacyclic triterpenoid compound which has been proved to exhibit diverse pharmacological activities such as anti-inflammatory, anti-tumor, and anti-diabetic effects [[5], [6], [7]]. In particular, its hepatoprotective effects are well known and have been extensively studied. In China, OA has been used as an over-the-counter (OTC) medicine for chronic hepatitis [8]. Extensive evidence has demonstrated the hepatoprotection of OA against several substance-induced liver injury, including acetaminophen, d-galactosamine plus endotoxin, carbon tetrachloride and cholestasis [[9], [10], [11], [12]]. New indications for existing drugs play a key role in clinical practice, and further investigation is needed to determine whether OA can enhance liver regeneration after PHx.

Pregnane X receptor (PXR, NR1I2) belongs to the nuclear receptor superfamily and primarily distributes in the intestine and liver [13]. Our previous study demonstrated that PXR activation induced liver regeneration and enlargement by increasing cell size and promoting hepatocyte proliferation [14]. Moreover, PXR has been reported to interact with Forkhead box O 1 (FOXO1) to repress its target gene expression and accelerate cell cycle progression [15,16]. Notably, FOXO1 can tightly regulate G0/G1 and G1/S phase progression and inhibit the cyclin-dependent kinase inhibitor 1B (CDKN1B) and retinoblastoma-like protein 2 (RBL2), which are some cell cycle suppressors. The PXR signaling pathway has been shown to play a critical role in liver regeneration. However, whether the PXR signaling pathway contributes to liver regeneration after OA treatment remains unknown.

Therefore, the current study aimed to explore the effect of OA on liver regeneration following PHx, and to further investigate the potential mechanisms in vivo and in vitro.