Abstract
Aim:
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.
Conclusion:
Oral baicalin may be metabolized by intestinal microflora into baicalein and oroxylin A, which ameliorate pruritic reactions through anti-histamine action.
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References
Hagermark O . Itch mediators. Semin Dermatol 1955; 14: 271–6.
Lerner EA . “Itch: mechanisms and management of pruritis,” Berhard J, editor. New York: McGraw-Hill, 1944. p 23–5.
Schmeiz M, Schmidt R, Bickel A, Handerker HO, Torebjork HE . Specific C-receptors for itch in human skin. J Neurosci 1997; 17: 8003–8.
Raiford DS . Pruritus of chronic chlestasis. QJM 1995; 88: 603–7.
Kuraishi Y, Nagasawa T, Hayashi K, Satoh M . Scratching behavior induced by pruritogenic but not algesiogenic agents in mice. Eur J Pharmacol 1995; 275: 229–33.
Zhu YP . “Chinese Materia Medica.” Australia: Harwood academic publichers; 1998. p127–35.
Wu S, Sun A, Liu R . Separation and purification of baicalin and wogonoside from the Chinese medicinal plant Scutellaria baicalensis Georgi by high-speed counter-current chromatography. J Chromatogr A 2005; 1066: 243–7.
Chou TC, Chang LP, Li CY, Wong CS, Yang SP . The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia. Anesth Analq 2003; 17: 1724–9.
Jang SI, Kim HJ, Hwang KM, Jekal SJ, Pae HO, Choi BM, et al. Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice. Immunopharmacol Immunotoxicol 2003; 25: 585–94.
Kim DH, Cho KH, Moon SK, Kim YS, Kim DH, Choi JS, et al. Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite. J Pharm Pharmacol 2005; 57: 1581–90.
Akao T, Kawabata K, Yanagisawa E . Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J Pharm Pharmacol 2000; 52: 1563–8.
Yim JS, Kim YS, Moon SK, Cho KH, Bae HS, Kim JJ, et al. Metabolic activities of ginsenoside Rb1, baicalin, glycyrrhizin and geniposide to their bioactive compounds by human intestinal microflora. Biol Pharm Bull 2004; 27: 1580–3.
Abe K, Inoue O, Yumioka E . Biliary excretion of metabolites of baicalin and baicalein in rats. Chem Pharm Bull 1990; 38: 209–11.
Akao T, Dakashita Y, Hanada M, Goto H, Shimada Y, Terasawa K . Enteric excretion of baicalein, a flavone of Scutellariae Radix, via glucuronidation in rat: involvement of multidrug resistance-associated protein 2. Pharm Res 2004; 21: 2120–6.
Lu T, Song J, Huang F, Deng Y, Xie L, Wang G, et al. Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats. J Ethnopharmacol 2007; 110: 412–8.
Xing J, Chen XY, Zhong DF . Absorption and enterohepatic circulation of baicalin in rats. Life Sci 2005; 78: 140–6.
Xing J, Chen XY, Sun YM, Luan Y, Zhong DF . Interaction of baicalin and baicalein with antibiotics in the gastrointestinal tract. J Pharm Pharmacol 2005; 57: 743–50.
Takido M, Aimi M, Takahashi S, Yamamouchi S, Torii H, Dohi S . Studies on the constituents in the water extracts of crude drugs. I. On the roots of Scutellaria baicalensis Georgi (Wōgon) (1). Yakugaku Zasshi 1975; 95: 108–13.
Tomimori T, Miyaichi Y, Kizu H . On the flavonoid constituents from the roots of Scutellaria baicalensis Georgi. I. Yakugaku Zasshi 1982; 102: 388–91.
Lee DK, Kim YS, Ko CN, Cho KH, Bae HS, Lee KS, et al. Fecal metabolic activities of herbal components to bioactive compounds. Arch Pharm Res 2003; 25: 165–9.
Sugimoto Y, Umakoshi K, Nojiri N, Kamei C . Effects of histamine H1 receptor antagonists on compound 48/80-induced scratching behavior in mice. Eur J Pharmacol 1998; 351: 1–5.
Choo MK, Park EK, Han MJ, Kim DH . Antiallergic activity of ginseng and its ginsenosides. Planta Med 2003; 69: 518–522
Liaw J, Gau YY, Chao YC . Effect of baicalin on tracheal permeability in ovalbumin (OA)-sensitized guinea pigs. Pharm Res 1999; 16: 1653–7.
Koda A, Nagai H, Wada H . Pharmacological actions of baicalin and baicalein. 2. On passive anaphylaxis. Nippon Yakurigaku Zasshi 1970; 66: 237–47.
Taniguchi C, Homma M, Takano O, Hirano T, Oka K, Aoyagi Y, et al. Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction. Planta Med 2000; 66: 607–611.
Kobashi K, Akao T . Relation of intestinal bacteria to pharmacological effects of glycosides. Bioscience Microflora 1997; 16: 1–7.
Akao T, Kida H, Kanaoka M, Hattori M, Kobashi K . Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol 1998; 50: 1155–60.
Inagaki N, Nagao M, Kawasaki H, Kim JF, Nagai H . Scratching behavior in various strains of mice. Skin Pharmacol Appl Skin Physiol. 2001; 14: 87–96.
Ui H, Andoh T, Lee JB, Nojima H, Kuraishi Y . Potent pruritogenic action of tryptase mediated by PAR-2 receptor and its involvement in anti-pruritic effect of nafamostat mesilate in mice. Eur J Pharmacol 2006; 530: 172–8.
Inagaki N, Igeta K, Kim JF, Nagao M, Shiraishi N, Nakamura N, et al. Involvement of unique mechanisms in the induction of scratching behavior in BALB/c mice by compound 48/80. Eur J Pharmacol 2002; 448: 175–83.
Acknowledgements
This study was financially supported by the research fund of Korean Food and Drug Administration (2009).
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Trinh, Ht., Joh, Eh., Kwak, Hy. et al. Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice. Acta Pharmacol Sin 31, 718–724 (2010). https://doi.org/10.1038/aps.2010.42
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DOI: https://doi.org/10.1038/aps.2010.42
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