Identification of nevadensin as an important herb-based constituent inhibiting estragole bioactivation and physiology-based biokinetic modeling of its possible in vivo effect

Levels of Genotoxic and Carcinogenic Ingredients in Plant Food Supplements and Associated Risk Assessment

“…For example, Jeurissen et al [79] demonstrated that a methanolic basil extract was able to adequately inhibit the sulfotransferase catalyzed bioactivation and DNA adduct formation in HepG2 human hepatoma cells exposed to the proximate carcinogen of estragole. The basil compound responsible for the inhibition was subsequently identified as nevadensin [80]. These results indicate that the bioactivation of estragole is likely to be lower when estragole is consumed in the presence of other herbal ingredients compared to the exposure of estragole as a pure compound.…”

Bioactivation of herbal constituents: simple alerts in the complex system

“…For instance, basil (Ocimum basilicum L., Lamiaceae) extract contains estragole which exerts its carcinogenicity through bioactivation pathway catalyzed by CYP enzymes and SULT. However, the study by Jeurissen et al showed that some ingredients in basil extract inhibit the activity of CYP1A2 and SULT, which might weaken the bioactivation potential of estragole [102][103][104]. Therefore, when estragole was utilized along with other ingredients in basil extract, the potential toxicity would be lower.…”

Nevadensin: Isolation, chemistry and bioactivity

“…[ Figure 3: Synthesis of nevadensin [9] Estragole (a natural constituent of several herbs and spices including sweet basil) was found to be responsible for induction of hepatomas in rodent bioassays, an effect ascribed to estragole bioactivation to 1'-sulfooxyestragole (SULT, a proximate carcinogen), resulting in DNA adduct formation. Allhusainy et al [52] established nevadensin as a constituent of basil, able to inhibit DNA adduct formation in rat hepatocytes exposed to the proximate carcinogen 1'-hydroxyestragole and nevadensin. The inhibition of SULT by nevadensin was incorporated into the recently developed physiologically based biokinetic (PBBK) rat and human models for estragole bioactivation and detoxification; the experimental results suggested that co-administration of estragole at a level inducing hepatic tumours in vivo (50 mg/ kg body weight) with nevadensin at a molar ratio of 0.06, representing the ratio of their occurrence in basil, results in almost 100% inhibition of the ultimate carcinogen SULT, when assuming 100% uptake of nevadensin.…”