Boswellia carteri Birdw. Resin Extract Induces Phase-I Cytochrome P-450 Enzyme Gene Expressions in Human Hepatocarcinoma (Hep G2) Cells: In vitro and in silico Studies

Sahar S Alghamdi,1– 3 Hussah N Albahlal,1 Raghad Saleh Alajmi,1 Amani Alsharidah,4 Aljawharah Almogren,2 Rasha Suliman,5 Zeyad I Alehaideb1– 3 1King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia; 2King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; 3Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia; 4King Saud University (KSU), Riyadh, Saudi Arabia; 5Fatima College for Health Sciences, Abu Dhabi, United Arab EmiratesCorrespondence: Sahar S Alghamdi, Email [email protected]: Boswellia carteri (B. carteri) resin is widely recognized for its anti-inflammatory, wound-healing, and immunomodulatory properties. This study examines the ability of its aqueous extracts to modulate the expression of key cytochrome P450 (CYP) enzymes—CYP1A2, CYP2B6, and CYP3A4—in Hep G2 cells, emphasizing pharmacokinetic and toxicological implications.Methods: Aqueous extracts were evaluated for endotoxin contamination and cytotoxicity to ensure suitability for in vitro experimentation. PCR analysis was employed to quantify CYP enzyme gene expression. Computational tools, including Protox-II, Swiss ADME, and molecular docking, were used to assess pharmacokinetics, CYP interactions, and biological targets. Competitive binding assays were performed to investigate the involvement of the constitutive androstane receptor (CAR) in CYP induction.Results: The results suggest that several metabolites, particularly ursodeoxycholic acid and beta-sitosterol, show potential interactions with CYP enzymes, with ursodeoxycholic acid demonstrating the highest probability of biological effects on CYP and a strong binding affinity to the Constitutive Androstane Receptor (CAR). Moreover, a receptor competitive binding assay suggested that the primary mechanism of CYP 2B6 and 3A4 induction is through activation of the CAR receptor although additional confirmatory studies are necessary.Discussion: The observed CYP enzyme induction through CAR receptor activation aligns with USFDA guidelines for CYP studies. However, the hepatotoxic potential of ursodeoxycholic acid and the associated toxicity risks of other metabolites underscore the need for caution. The findings highlight the potential for herb–drug interactions, particularly with pharmaceuticals metabolized by CYP enzymes.Conclusion: In conclusion, there is a potential for interactions between B. carteri resins and pharmaceuticals metabolized by CYP enzymes; thus, we advise caution to consumers, patients, and healthcare providers regarding their concomitant use. Although our findings provide valuable insights, further in vivo studies are essential to validate the modulatory effects of B. carteri on CYP gene expression. Keywords: Boswellia carteri, cytochrome P-450 enzymes, nuclear receptors, natural products, oleo-gum resin