In vitro and in vivo anti-inflammatory, antibacterial and pharmacokinetic properties of baicalein

Baicalein is a bioactive flavone originally isolated from the roots of Scutellaria baicalensis, Scutellariala teriflora and Oroxylum indicum. The in vitro and in vivo anti-inflammatory and antibacterial properties of baicalein and pharmacokinetics after its single intramuscular administration were studied in Wistar rats. The in vitro anti-inflammatory activity of baicalein (10, 50 and 100 µM) was tested for its ability to inhibit the COX-2 enzyme by measuring PGE2 levels and determination of nitric oxide (NO) production in lipopolysaccharide (LPS) treated RAW 264.7 macrophage cells, in which baicalein was found to have significant inhibition of NO and PGE2 production in RAW 264.7 macrophage cells as compared with the LPS control group. The in vivo anti-inflammatory activity of baicalein (200 mg/kg) was assessed using the carrageenan-induced rat paw oedema model, following intramuscular injection. A significant percentage of inhibition of oedema volume was observed when compared with the carrageenan control group. In vitro and in vivo antibacterial activities of baicalein were determined by the micro broth dilution technique and neutropenic rat thigh infection model, wherein baicalein did not show any antibacterial property. Concentrations of baicalein were determined in rat plasma by high performance liquid chromatography (HPLC) after a single intramuscular administration at a dose of 200 mg/kg body weight, in which the mean peak plasma drug concentration (Cmax) of 0.77 ± 0.02 μg/mL was achieved at 0.08 h. The mean elimination half-life (t½β), the apparent volume of distribution (Vd(area)), total body clearance (Cl(B)) and mean residence time (MRT) were observed as 0.63 ± 0.06 h, 601.03 ± 28.18 L/kg, 677.39 ± 35.36 L/h/kg and 0.76 ± 0.06 h, respectively. Conclusively, in the present study, baicalein did not show in vitro or in vivo antibacterial property, but proved to have good anti-inflammatory activity. The available anti-inflammatory drugs have proved to have side effects in veterinary and human therapeutics. In this situation, baicalein may become an effective alternative to non-steroidal anti-inflammatory drugs and should also be studied in target animal species. Further research should be carried out to improve the solubility and bioavailability of baicalein through injectable routes.
Baikalein je bioaktivni flavon izvorno izoliran iz korijena biljaka Scutellaria baicalensis, Scutellariala teriflora i Oroxylum indicum. U ovom su radu istraživana in vitro i in vivo protuupalna i antibakterijska svojstva baikaleina te farmakokinetika nakon njegove pojedinačne intramuskularne primjene u wistar štakora. In vitro protuupalno djelovanje baikaleina (10, 50 i 100 µM) analizirano je s obzirom na sposobnost inhibicije enzima COX-2 mjerenjem razine PGE2 i određivanjem proizvodnje dušikova oksida (NO) u makrofagnim stanicama RAW 264,7 tretiranim lipopolisaharidom (LPS). Ustanovljeno je da baikalein znakovito inhibira proizvodnju NO i PGE2 u makrofagnim stanicama RAW 264,7 u usporedbi s LPS kontrolnom skupinom. In vivo protuupalno djelovanje baikaleina (200 mg/ kg) procijenjeno je pomoću modela za mjerenje edema šape nakon intramuskularne injekcije karagenana, te je uočena znakovita inhibicija volumena edema u usporedbi s kontrolnom skupinom. In vitro i in vivo antibakterijsko djelovanje baikaleina određeno je metodom razrjeđivanja mikrobujona te modelom infekcije bedra neutropeničnog štakora, pri čemu baikalein nije pokazao antibakterijska svojstva. Koncentracije baikaleina utvrđene su u plazmi štakora tekućinskom kromatografijom visoke djelotvornosti (HPLC) nakon pojedinačne intramuskularne primjene u dozi od 200 mg/kg tjelesne mase u kojoj je prosječna vršna koncentracija lijeka (Cmax) bila 0,77 ± 0,02 μg/mL, a postignuta je za 0,08 h. Prosječan poluživot eliminacije (t½β) bio je 0,63 ± 0,06 h, providni volumen distribucije (Vd(površina)) 601,03 ± 28,18 L/kg, ukupni tjelesni klirens (Cl(B)) 677.39 ± 35.36 L/h/kg, a prosječno vrijeme zadržavanja (MRT) 0,76 ± 0,06 h. Zaključeno je da u ovom istraživanju baikalein nije pokazao in vitro i in vivo antibakterijska svojstva, ali je pokazao dobro protuupalno djelovanje. S obzirom na to da dostupni protuupalni lijekovi imaju nuspojave u liječenju ljudi i životinja, baikalein bi mogao biti učinkovita alternativa nesteroidnim protuupalnim lijekovima te bi ga trebalo istražiti i kod ciljanih životinjskih vrsta. Potrebna su daljnja istraživanja kojima bi se poboljšala topljivost i bioraspoloživost baikaleina injekcijskom primjenom.