Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice.
OBJECTIVE
To explore whether intestinal microflora plays a role in anti-pruritic activity of baicalin, a main constituent of the rhizome of Scutellaria baicalensis (SB).


METHODS
Baicalin was anaerobically incubated with human fecal microflora, and its metabolites, baicalein and oroxylin A, were isolated. The inhibitory effect of baicalin and its metabolites was accessed in histamine- or compound 48/80-induced scratching behavior in mice.


RESULTS
Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of 40.2+/-26.2 and 1.2+/-1.1 nmol.h(-1).mg(-1) wet weight of human fecal microflora, respectively. Baicalin (20, 50 mg/kg) showed more potent inhibitory effect on histamine-induced scratching behavior when orally administered than intraperitoneally. In contrast, baicalein and oroxylin A had more potent inhibitory effect when the intraperitoneally administered. The anti-scratching behavior activity of oral baicalin and its metabolites was in proportion to their inhibition on histamine-induced increase of vascular permeability with oroxylin A more potent than baicalein and baicalin. In Magnus test using guinea pig ileum, oroxylin A is more potent than baicalein and baicalin in inhibition of histamine-induced contraction. The anti-scratching behavioral effect of oral baicalin was significantly reduced when oral antibiotics were simultaneously administered, whereas the effect of baicalein and oroxylin A were not affected.


CONCLUSIONS
Oral baicalin may be metabolized by intestinal microflora into baicalein and oroxylin A, which ameliorate pruritic reactions through anti-histamine action.
Trinh
Hien-trung
HT
Department of Pharmaceutical Science and Department of Life and Pharmaceutical Sciences, Kyung Hee University, 1 Hoegi, Dongdaemun-ku, Seoul, Korea.
Joh
Eun-ha
EH
Kwak
Ho-young
HY
Baek
Nam-in
NI
Kim
Dong-hyun
DH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000982:Antipruritics / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D005243:Feces / Q000382:microbiology; D044950:Flavanones / Q000032:analysis / Q000627:therapeutic use*; D005419:Flavonoids / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage; D006633:Histamine Antagonists / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D011537:Pruritus / Q000188:drug therapy*; D031364:Scutellaria baicalensis / Q000737:chemistry / Q000378:metabolism; D013307:Streptomycin / Q000008:administration & dosage; D013752:Tetracycline / Q000008:administration & dosage
D000900:Anti-Bacterial Agents; D000982:Antipruritics; D044950:Flavanones; D005419:Flavonoids; D006633:Histamine Antagonists; C038044:baicalin; C006680:baicalein; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D006632:Histamine; D013752:Tetracycline; D013307:Streptomycin
J Pharm Pharmacol. 2005 Dec;57(12):1581-90
16354402
J Pharm Pharmacol. 1998 Oct;50(10):1155-60
9821663
Semin Dermatol. 1995 Dec;14(4):271-6
8679431
Pharm Res. 1999 Oct;16(10):1653-7
10554113
QJM. 1995 Sep;88(9):603-7
7583073
Anesth Analg. 2003 Dec;97(6):1724-1729
14633550
J Pharm Pharmacol. 2000 Dec;52(12):1563-8
11197087
Planta Med. 2003 Jun;69(6):518-22
12865969
Skin Pharmacol Appl Skin Physiol. 2001 Mar-Apr;14(2):87-96
11316967
J Neurosci. 1997 Oct 15;17(20):8003-8
9315918
J Pharm Pharmacol. 2005 Jun;57(6):743-50
15969929
J Ethnopharmacol. 2007 Apr 4;110(3):412-8
17110066
Eur J Pharmacol. 2006 Jan 13;530(1-2):172-8
16359660
Arch Pharm Res. 2002 Apr;25(2):165-9
12009030
Chem Pharm Bull (Tokyo). 1990 Jan;38(1):209-11
2337942
Immunopharmacol Immunotoxicol. 2003 Nov;25(4):585-94
14686800
Pharm Res. 2004 Nov;21(11):2120-6
15587936
Yakugaku Zasshi. 1975 Jan;95(1):108-13
1169297
Planta Med. 2000 Oct;66(7):607-11
11105563
Eur J Pharmacol. 1998 Jun 12;351(1):1-5
9698198
Biol Pharm Bull. 2004 Oct;27(10):1580-3
15467199
Yakugaku Zasshi. 1982 Apr;102(4):388-91
7131255
J Chromatogr A. 2005 Feb 25;1066(1-2):243-7
15794578
Life Sci. 2005 Nov 26;78(2):140-6
16107266
Eur J Pharmacol. 1995 Mar 14;275(3):229-33
7539379
Nihon Yakurigaku Zasshi. 1970;66(2):237-47
5464145
Eur J Pharmacol. 2002 Jul 19;448(2-3):175-83
12144939