Enhanced hepatic exposure and toxicity from concurrent administration of coumarin and bakuchiol in psoralea corylifolia L. under LPS-induced immune stress.

Ethnopharmacological Relevance: Psoralea corylifolia L., known as "Bu Gu Zhi" in traditional Chinese medicine, is widely used for its antioxidant and anti-inflammatory properties. It is traditionally employed to treat conditions such as vitiligo, osteoporosis, and various skin diseases. Despite its therapeutic benefits, there are safety concerns due to reports of liver injury associated with its use, especially under conditions of immune stress.

Aim Of The Study: This study aimed to investigate the hepatotoxic effects of coumarin and bakuchiol-the key bioactive components of Psoralea corylifolia L.-under lipopolysaccharide (LPS)-induced immune stress in mice.

Materials And Methods: Mouse models were used to evaluate liver injury. coumarin (139.91 mg/kg), bakuchiol (280.00 mg/kg), and LPS (6.00 mg/kg) were administered individually and in combination. Liver toxicity was assessed through histopathological examinations and liver enzyme assays. Transcriptomic analyses were performed to identify dysregulated genes and pathways. Pharmacokinetic studies measured hepatic exposure, and molecular dynamics simulations examined intermolecular interactions between the compounds.

Results: While coumarin and bakuchiol alone did not induce significant liver toxicity at the administered doses, their concurrent administration under immune stress significantly exacerbated liver injury. This was evidenced by pronounced histopathological changes and elevated liver enzyme levels. Transcriptomic analysis revealed dysregulation of genes related to inflammation, oxidative stress, and metabolic processes, with significant overlap in affected pathways, suggesting shared mechanisms underlying the enhanced liver injury. Pharmacokinetic studies demonstrated increased hepatic exposure during co-administration, with coumarin enhancing the solubility and absorption of bakuchiol. Molecular dynamics simulations supported these findings by illustrating enhanced intermolecular interactions between the two compounds.

Conclusions: The study demonstrates that co-administration of coumarin and bakuchiol under immune stress conditions exacerbates hepatotoxicity, highlighting potential risks associated with the use of Psoralea corylifolia L. in individuals with underlying inflammation. These findings emphasize the need for cautious therapeutic use and consideration of immune status when prescribing this traditional medicine, as well as the development of safer combination strategies.