Sulfonation Disposition of Capsaicin: In Vitro and in Vivo

Capsaicin (CAP), the major pungent component of chili peppers, undergoes sulfation mediated by sulfotransferases (SULTs), an important phase II metabolic pathway influencing its pharmacological properties. In this study, we systematically investigated the sulfation metabolism of CAP and its underlying mechanisms in vitro and in vivo. Five sulfated metabolites were identified in rats with the liver as the primary site. Among them, M3-SO₃ was the most abundant, followed by CAP-SO₃ and M2-SO₃, while M4-SO₃ was the least abundant. SULT1C4 and SULT1E1 mainly catalyzed CAP and M2 sulfation, whereas SULT1C4 was essential for M3 sulfation. In addition, CAP sulfation occurred in multiple brain regions. Unlike the liver, brain metabolism favored M2-SO₃ over M3-SO₃, highlighting distinct central versus peripheral sulfation profiles. Brain microdialysis further confirmed this discrepancy. These findings provide a foundation for exploring the pharmacological roles of CAP and its sulfated metabolites, particularly within the central nervous system.