Luteolin and luteolin-7-O-glucoside were isolated from the ethanolic extract of Dendranthema morifolium Ramat Tzvel. The structures of these analytes were identified by nuclear magnetic resonance ((1)H and (13)C NMR) and mass spectrometry. Ethanolic and water extracts contained luteolin-7-O-glucoside at 4.19 and 6.56%, respectively. However, the level of luteolin was only 0.19% in the ethanolic extract, and luteolin was not detected in the water extract. To examine the pharmacokinetics and bioavailability of luteolin and luteolin-7-O-glucoside in rats, parallel studies of luteolin (10 mg/kg, iv; and 100 mg/kg, po) and luteolin-7-O-glucoside (10 mg/kg, iv; and 1 g/kg, po) were conducted. The analytes were detected by high-performance liquid chromatography coupled with a photodiode array detector. A phenyl-hexyl (150 × 4.6 mm iv; 5.0 μm) column was used to separate the analytes from the biological samples. The pharmacokinetic data demonstrate that the areas under the concentration curves (AUCs) of luteolin were 261 ± 33 and 611 ± 89 (min μg/mL) after luteolin administration (10 mg/kg, iv; and 100 mg/kg, po, respectively). The oral bioavailability of luteolin was 26 ± 6%. The AUCs of luteolin-7-O-glucoside were 229 ± 15 and 2109 ± 350 (min μg/mL) after administration of luteolin-7-O-glucoside (10 mg/kg, iv; and 1 g/kg, po, respectively). The oral bioavailability of luteolin-7-O-glucoside was approximately 10 ± 2%. In the group that received luteolin-7-O-glucoside orally, a biotransformed luteolin product was detected, but this product was not detected in the group that received luteolin-7-O-glucoside intravenously. The biotransformation ratio of luteolin to luteolin-7-O-glucoside (the AUC ratio of metabolite/parent compound) was approximately 48.78 ± 0.12%. These results demonstrate that luteolin-7-O-glucoside is primarily hydrolyzed to luteolin in the gastrointestinal tract and then absorbed into the systemic circulation.

Isolation of Luteolin and Luteolin-7-O-glucoside from Dendranthema morifolium Ramat Tzvel and Their Pharmacokinetics in Rats.

Flavonoid p-coumaroylglucosides and 8-hydroxyflavone allosylglucosides in some labiatae

Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders.

Acacetin (5,7-dihydroxy-4′-methoxyflavone), a constituent of flavone naturally present in plants, has anti-cancer and anti-inflammatory activities. Neuroinflammation is thought to be one of the major pathological mechanisms responsible for Parkinson’s disease (PD), and has been a primary target in the development of treatment for PD. In the present study, we evaluated the neuroprotective effect of acacetin in PD induced by 1-methyl-4-phenylpyridine (MPP+)/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined the related pathways in vitro and in vivo. In primary mesencephalic culture, acacetin protected dopaminergic (DA) cells and inhibited production of inflammatory factors such as nitric oxide, prostaglandin E2, and tumor necrosis factor-α against MPP+-induced toxicity in a dose-dependent manner. Then, we confirmed the effect of acacetin (10 mg/kg/d for 3 d, per os (p.o.)) in a mouse model of PD induced by MPTP (30 mg/kg/d for 5 d, intraperitoneally (i.p.)). In the behavioral test (pole test), the acacetin-treated mice showed decreased time of turning and locomotor activity, which were longer in MPTP-only treated mice. In addition, the acacetin-treated group inhibited degeneration of DA neurons and depletion of dopamine level induced by MPTP toxicity in the substantia nigra and striatum of the brain. Moreover, the acacetin-treated group inhibited microglia activation, accompanied by production of inducible nitric oxide synthases and cyclooxygenase-2. These results suggest that acacetin can protect DA neurons against the neurotoxicity involved in PD via its anti-inflammatory action.

A. Chatterjee

Papers

Acacetin 7-O-β-d-galactopyranoside from Chrysanthemum indicum