Influence of mefenamic acid on the intestinal absorption and metabolism of three bioactive flavones in Radix Scutellariae and potential pharmacological impact

Figures & data

Figure 1. Chemical structures of baicalein (B), wogonin (W), oroxylin A (OA), mefenamic acid (MEF) and 3,7-dihydroxyflavone (IS).

Figure 2. Representative mass spectra of glucuronic acid and sulfate conjugates of B/W/OA in Caco-2 samples from apical to basolateral transport study. BG (445/269): Baicalein-7-O-glucuronide; BS (349/269): Baicalein-O-sulfate; WG (459/283): Wogonin-7-O-glucuronide; WS (363/283): Wogonin-O-sulfate; OAG (459/283): Oroxylin A-7-O-glucuronide; OAS (363/283): Oroxylin A-O-sulfate.

Figure 3. Cumulative amount of B, W and OA at the receiver side as a function of time during absorption transport in Caco-2 cell monolayer model.

Table 1. Effect of MEF on the absorption (P_app) and metabolism (% of metabolism) of B/W/OA (10 μM) in the Caco-2 monolayer model (n = 3).

	Loading compounds
	B	B + MEF	W	W + MEF	OA	OA + MEF
Papp (×10^−6cm/sec)	1.69 ± 0.89	5.24 ± 0.27***	1.57 ± 0.10	6.08 ± 0.19***	3.09 ± 0.70	4.13 ± 0.38
% of metabolism	72.75 ± 2.44	21.11 ± 0.69***	73.27 ± 3.25	17.90 ± 5.55***	89.84 ± 2.99	45.44 ± 3.38***

***p < 0.001.

Figure 4. Efflux transport of glucuronides and sulfates of B, W and OA at the apical and basolateral sides during absorption in the Caco-2 cell monolayer model.

Table 2. Effect of RS, MEF and co-administration on the production of PGE₂ in rat (n = 3).

	PGE2 concentration (pg/ml)
Time post MEF dosing (h)	RS	MEF	MIX
4	494.37 ± 11.75	73.13 ± 3.03	49.04 ± 2.03
6	285.28 ± 5.20	24.68 ± 2.51	29.31 ± 1.11
8	68.18 ± 2.65	6.88 ± 0.45	16.42 ± 0.71