Comparative Analyses of Bioavailability, Biotransformation, and Excretion of Nobiletin in Lean and Obese Rats

Abstract

Nobiletin, one of the prevalent polymethoxyflavones in citrus peels, was reported to possess various health benefits. We conducted the excretion study and pharmacokinetics study of nobiletin via oral administration and intravenous injection and 15 day consecutive dosing study using the high fat diet-induced obese rats and their lean counterparts. By comparing the demethylated metabolite profiles in the urine and feces, gut microbiota demonstrated greater biotransformation activity on nobiletin than the host. The absolute oral bioavailability of nobiletin in lean (22.37% ± 4.52%) and obese (18.67% ± 4.80%) rats has a negligible statistically significant difference (P > 0.05). However, a higher extent of demethylated metabolites was found in the feces and plasma of obese rats than lean rats (P < 0.05). Moreover, the consecutive dosing of nobiletin might lead to a higher extent of demethylated metabolites in the plasma and in feces. These results suggested that gut microbiota played important roles in nobiletin metabolism.

Biotransformation and Quantification of Sinensetin and Its Metabolites in Plasma, Urine, and Feces of Rats

“…However, the excretion of Sin in feces conversely showed a significantly higher amount, which is possibly due to the undissolved Sin in corn oil. Based on our present result, it is intriguing to discover that, in general, Sin and its metabolites had higher urinary-to-fecal excretion ratios than nobiletin and its metabolites as previously reported, 18 although Sin contrarily possessed a weaker lipophilic property. While it was also indicated before that the double-sword effect of high lipophilicity on the one hand enhances the membrane permeability of compounds by facilitating their transcellular transport, on the other hand, it aggravates the metabolic clearance and consequently the first-pass metabolism.…”

Pharmacokinetics and Metabolites of 12 Bioactive Polymethoxyflavones in Rat Plasma

“…has been reported. 37 A subsequent study by Zhang et al further showed that the gut microbiota showed stronger biotransformation activity of nobiletin than the host, 38 indicating that the gut microbiota might be another important factor diminishing the absorption of OH-PMFs.…”

The Protective Effects of Sour Orange (Citrus aurantium L.) Polymethoxyflavones on Mice Irradiation-Induced Intestinal Injury

“…Evidence is mounting that the gut microbiota is essential for PMF metabolism and PMFs can shape the microorganism characteristics. Modification of PMFs might be carried out by gut microorganisms, including demethylation, hydroxylation, glycosylation and ring opening [ 35 ]. Meanwhile, PMFs could influence metabolic pathways, for example, the amino acid metabolism pathway.…”