Safety Assessment of Phytochemicals Derived from the Globalized South African Rooibos Tea (Aspalathus linearis) through Interaction with CYP, PXR, and P-gp

Abstract

Rooibos tea (Aspalathus linearis) is a well-known South African herbal tea enjoyed worldwide. Limited reports indicate the potential of rooibos tea to alter the activity of certain cytochrome P450 (CYP450) isozymes. In this study, the phytochemical investigation of MeOH extract of A. linearis (leaves and stems) resulted in the isolation and characterization of 11 phenolic compounds. The MeOH extract exhibited significant inhibition of the major human CYP450 isozymes (CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19). The strongest inhibition was observed by the extract for CYP3A4 (IC 50 1.7 ± 0.1 μg/mL) followed by CYP2C19 (IC 50 4.0 ± 0.3 μg/mL). Among the tested phytochemicals, the most potent inhibitors were isovitexin on CYP3A4 (IC 50 3.4 ± 0.2 μM), vitexin on CYP2C9 (IC 50 8.0 ± 0.2 μM), and thermopsoside on CYP2C19 (IC 50 9.5 ± 0.2 μM). The two major, structurally related compounds aspalathin and nothofagin exhibited a moderate pregnane-X receptor (PXR) activation, which was associated with increased mRNA expression of CYP3A4 and CYP1A2, respectively. These results indicate that a high intake of nutraceuticals containing rooibos extracts may pose a risk of herb−drug interactions when consumed concomitantly with clinical drugs that are substrates of CYP enzymes.

Impact of Cold versus Hot Brewing on the Phenolic Profile and Antioxidant Capacity of Rooibos (Aspalathus linearis) Herbal Tea

“…Thereafter, mass and retention time alignment and filter-by-frequency (features not present in at least one treatment in 100% of replications were discarded) were applied. However, when multiple annotations were possible, we selected those phenolic compounds previously identified in rooibos [30,31,32,33,34,35]. To achieve a higher degree of confidence in annotation, pooled samples were further analyzed in tandem mass spectrometry, using the previously reported conditions and a data-dependent MS/MS approach in place of the MS-only SCAN.…”

Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp

“…Finally, earlier studies from our group [14,42] and others [32,43,44] have noted that dietary phytochemicals can exhibit dualfunctional behaviors concerning the modulation of xenobiotic metabolism and transport. In other words, phytochemicals may act as agonists for nuclear receptors like CAR, PXR, and AhR while also functioning as catalytic inhibitors for post-translationally matured proteins like CYPs and P-gp.…”

Plants Used for the Traditional Management of Cancer in the Eastern Cape Province of South Africa: A Review of Ethnobotanical Surveys, Ethnopharmacological Studies and Active Phytochemicals

“…Literature surveys have shown that extracts from A. linearis have been reported to inhibit cell proliferation, thereby interfere with the growth of cancerous cells in the skin [ 56 ]. Furthermore, compounds (aspalathin and nothofagin) isolated from the methanol extract of A. linearis have also been reported to exhibit anticancer activity [ 57 ].…”