Permeability determination and pharmacokinetic study of nobiletin in rat plasma and brain by validated high-performance liquid chromatography method

In the present study, we are reporting permeability and pharmacokinetics of nobiletin in rat plasma and brain, using a validated reverse phase high performance liquid chromatographic method. Protein precipitation method was used for the extraction of nobiletin and coumarin (IS) from rat plasma and brain tissue. The system was run in isocratic mode with mobile phase consisting of potassium dihydrogen ortho-phosphate (pH 4.5; 0.04 mM) and acetonitrile in ratio of 50:50, v/v. The total chromatographic run time was 9.0 min. The method was proved to be accurate and precise at linearity range of 0.05–10 μg/mL with a correlation coefficient (r) of ≥ 0.994 in rat plasma and ≥ 0.995 in rat brain. The intra- and inter-day precision and accuracy values are found to be within the assay variability limits as per the FDA guidelines. Nobiletin was found stable in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and long term storage in a freezer at − 70 ± 10 °C. Maximum concentrations of nobiletin in both plasma and brain were observed at 1 h after single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were 1.78 and 4.20 μg/mL, respectively. The AUC_0–t in plasma and brain were 7.49 and 20.66 μg·h/mL, respectively. The mean elimination half life (t_1/2) in plasma and brain were 1.80 and 11.42 h, respectively. The Parallel Artificial Membrane Permeability Assay (PAMPA) permeability of nobiletin was found to be high at both pH 4.0 and 7.0.     

Citrus Flavonoids in Fruit and Traditional Chinese Medicinal Food Ingredients in China

Flavonoids-enriched tissues of citrus such as peel, immature fruit and flower are consumed as culinary seasonings, tea ingredients in China for centuries. This HPLC quantitative study on the five citrus flavonoids, naringin, hesperidin, neohesperidin, sinensetin and nobiletin on a wide range of Chinese citrus fruits and several Traditional Chinese Medicinal food ingredients in East China, revealed a great diversity in flavonoid composition. Huyou peel (C. paradisi cv. Changshanhuyou) was found to be the best naringin (3.25%) and neohesperidin (2.76%) source; C. aurantium, a major ingredient of several citrus-related TCM, is also a suitable source of naringin and neohesperidin, and a good juice source for flavanone glycosides; the peel of Wenzhoumiju (C. unshiu) is one of the richest local species in hesperidin (up to 6.25%); Zaoju (C. subcompressa) has the highest content of nobiletin (0.59%), a polymethoxylated flavone. LC-ES-MS analysis of Zanthoxylum genus for flavonoids revealed for the first time the presence of significant amounts (0.74%) of hesperidin in the root of Liangmianzhen (Z. nitidum (Roxb.) DC), a relative of Sichuan pepper, which is a spice widely used in China.     

川陈皮素研究进展

介绍了川陈皮素2种制备方法：植物萃取法和化学合成法,并综述了川陈皮素在医学、食品科学等方面的最新研究进展。     

Nobiletin attenuates palmic acid-induced lipidosis in hepatocytes and regulatory mechanism of lncLSTR

AIM: To observe the effects of nobiletin on palmic acid (PA)-induced lipidosis in hepatocytes and to discuss the regulatory mechanism of lncLSTR. METHODS: AML12 cells were cultured in vitro. The control group, PA group (0.2 mmol/L) and protection group (exposure to nobiletin at 1 mg/L, 5 mg/L, 15 mg/L or 50 mg/L for 2 h, followed by treatment with 0.2 mmol/L PA) were established according to the experimental requirements. The lipid accumulation was morphologically observed by Oil red O staining in the cells. The qPCR was applied to detect mRNA expression, and the protein expression was determined by and Western blot. RESULTS: PA treatment (0.2 mmol/L) induced lipidosis, while 50 mg/L nobiletin pretreatment suppressed the lipidosis. Compared with control group, the mRNA expression of Apoc2 in PA group was significantly down-regulated (P<0.05), but increased by nobiletin pretreatment compared with PA group (P<0.05). The protein expression of Apoc2 in PA group was significantly down-regulated (P<0.05), but increased by nobiletin pretreatment (P<0.05). The expression of lncLSTR in PA group was significantly increased (P<0.05) and that was inhibited by nobiletin pretreatment (P<0.05). A negative correlation between Apoc2 protein and lncLSTR expression in PA group (R²=0.717 9, P<0.01) was observed. A negative correlation between Apoc2 protein and lncLSTR expression in protection group (R²=0.525 3, P<0.05) was also found. CONCLUSION: Nobiletin has anti-lipidosis effect on hepatocytes. The mechanism is partially related to the inhibition of up-regulation of lncLSTR, thus down-regulating Apoc2 expression.