Yinchen Wuling Powder Exerts Therapeutic Effects on Jaundice by Regulating Mitochondrial Biogenesis via the AMP-activated Protein kinase/Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha/Transcription Factor A, Mitochondrial Signaling Pathway

Objective: Jaundice, a prevalent clinical condition associated with liver dysfunction, is characterized by elevated bilirubin levels and can lead to severe complications if untreated. Traditional Chinese medicine (TCM) has been utilized in the treatment of jaundice for centuries, with Yinchen Wuling powder (YCWLP) being one of the most notable herbal formulations. This study aimed to investigate the therapeutic effects of YCWLP in jaundice, focusing on its regulation of mitochondrial energy metabolism via the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/transcription factor A, mitochondrial (TFAM) signaling pathway. Materials and Methods: An α-naphthyl isothiocyanate (ANIT)-induced jaundice mouse model was established. The mice were subsequently administered YCWLP orally. The impact of YCWLP on bilirubin metabolism was assessed by analyzing the levels of serum biochemical markers. Moreover, transmission electron microscopy was employed to observe mitochondria morphology. Nontargeted metabolomics of liver tissues, network pharmacology, quantitative real-time polymerase chain reaction, and western blot analyses were conducted on the molecular targets of YCWLP. In addition, a hyperbilirubinemia cell model was established using bilirubin/probenecid-treated HepG2 cells. Finally, these model cells were treated with YCWLP to further evaluate its regulatory effect on bilirubin metabolism. Results: Network pharmacology and metabolomics analyses indicated that the AMPK/PGC-1α/TFAM pathway’s plays a critical role in the onset and progression of jaundice by modulating mitochondrial function and energy metabolism. YCWLP administration significantly activated AMPK, which sequentially upregulated the expression of PGC-1α and TFAM. These alterations were associated with reduced reactive oxygen species production, restoration of mitochondrial membrane potential, as well as a significant decrease in intracellular total and indirect bilirubin levels. Finally, YCWLP exerted anti-jaundice effects through the enhancement of mitochondrial energy metabolism, mediated by the activation of the AMPK/PGC-1α/TFAM signaling pathway. This mechanism not only lowered bilirubin levels but also improved overall hepatic function. Conclusions: Our findings collectively highlight the potential of YCWLP as a therapeutic agent for the treatment of jaundice and related hepatic disorders, providing a scientific reference for its use in TCM.