Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats

Abstract

Isoteoline is a compound of aporphine structure derived from the alkaloid glaucine. Previous studies with isoteoline have shown antagonistic activity at 5-HT(2C) serotonergic receptors. We have investigated whether isoteoline interacts with 5-HT(1B) receptors. An isolation-induced social behavioural deficit test in mice was used as a model of stimulation of these receptors. The deficit in the behaviour of isolated mice in this experimental procedure was reported to be sensitive to 5-HT(1B)-receptor stimulation, since agonists at these receptors are capable of reversing it. In our study, we used N-(3-trifluoromethylphenyl)piperazine (TFMPP) (2 mg kg(-1)) as a reference agonist at these receptor sites. TFMPP completely restored the normal behaviour of the isolated mice. Its effect was prevented by propranolol (4 mg kg(-1)), a beta-adrenergic receptor antagonist with a high affinity for 5-HT(1B) receptors, which was inactive by itself. When isoteoline was given before TFMPP, it did not prevent the effect of the latter. Given alone at doses of 0.25, 1, 4 or 8 mg kg(-1), isoteoline showed an effect of its own to normalize the behaviour of isolated mice. The effect of isoteoline (1 mg kg(-1), i.p.) was antagonized by pretreatment with propranolol, indicating that it was mediated through stimulation of 5-HT(1B) receptors. Repeated treatment with isoteoline (1 mg kg(-1), 2 x 3 days, i.p.) produced tolerance to its effect and significantly attenuated the effect of TFMPP, when animals were tested 16 h after the last injection. In conclusion, the results provided functional evidence of agonist-like activity of isoteoline at the 5-HT(1B) receptors.

Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

“…Following both types of administration, the levels of free fisetin in serum declined rapidly while the levels of sulfated/glucuronidated fisetin increased. Following oral administration at 50 mg/kg, the serum concentration of fisetin sulfates/glucuronides was maintained at *10 lM for [24 h. These results are in sharp contrast to those obtained for 5 OH and 7 OH flavone [80] and baicalein [48] where the levels of free and conjugated flavonoid never exceeded 1 lM following oral administration. When tested in an assay for antioxidant activity, the fisetin sulfates/glucuronides showed somewhat reduced but still significant activity as compared to free fisetin [80].…”

Biotransformation, a Promising Technology for Anti-cancer Drug Development

“…Recent research has reported that baicalin and wogonoside are insoluble in water and hard to be absorbed. However, it is found that baicalein and wogonin are the metabolites of baicalin and wogonoside respectively and can easily be absorbed by digestive tract and its bioavailability is also better than baicalin and wogonoside (Che et al, 2001;Lai et al, 2003). In addition, more scholars found that baicalein and wogonin show strong anti-cancer activities on different kind of cancers cells, such as ovarian, ESCC, bladder, oral, colon, pancreatic, breast, bronchial, colorectal, glioma, lung, cervical cancer cells and the activities are better than baicalin (Zhao et al, 2010;Lan et al, 2011;Huang et al, 2012;Cheng et al, 2012;Zhang et al, 2013;Yang et al, 2013) .…”

Cellular Membrane Protection Against Reactive Oxygen Species by Terminalia Arjuna and Its Active Component Baicalein

“…Earlier pharmacokinetic studies of baicalein in rats have shown that plasma levels of baicalein are low in cases of oral administration as compared to intravenous administration [15]. It is also known that baicalein is absorbed faster and to a greater extent in the intestine [16]. In the rat jejunal loop model, baicalein has also been shown to be readily absorbed [17].…”