ABSTRACT
The search for flavonoids with novel therapeutic effects has been intense. Wogonin, as a naturally existing monoflavonoid, has been shown to have therapeutic potential in vitro and in vivo. Methods for its extraction from herbs and its chemical synthesis have been developed. Pharmacokinetic studies have shown a rapid tissue distribution and prolonged plasma elimination phase of wogonin. It has been shown experimentally that wogonin exerts anti‐oxidant activity, which may, in part, underlie its antiinflammatory, anti‐cancer, antiviral and neuroprotective actions. The recent discovery of its anxiolytic activity suggests a new mechanism of action, involving interaction with the benzodiazepine (BZD) binding site of the GABAA receptor and modulation of this receptor activity. Although the safety record of wogonin is remarkable and voluminous literature about its pharmacological effects is available, it has not been used in Western medicine in the form of a pure chemical. In this article we review its therapeutic effects, its sources and pharmacokinetic profile to highlight its therapeutic potential.
Keywords: Antiinflammatory drugs, Antioxidants, Anxiolytics, Flavonoids, Huang Qin, Neuroprotectives, Scutellaria baicalensis, Wogonin
Full Text
The Full Text of this article is available as a PDF (95.3 KB).
REFERENCES
- 1. Allan J, Robinson R. J Chem Soc 1924. ;2192–2194. [Google Scholar]
- 2. Chang WS, Lee YJ, Lu FJ, Chiang HC. Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res 1993;13:2165–2170. [PubMed] [Google Scholar]
- 3. Chang YL, Shen JJ, Wung BS, Cheng JJ, Wang L. Chinese herbal remedy wogonin inhibits monocyte chemotactic protein‐1 gene expression in human endothelial cells. Mol Pharmacol 2001;60:507–513. [PubMed] [Google Scholar]
- 4. Chen YC, Shen SC, Chen LG, Lee TJ, Yang LL. Wogonin, baicalin and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase‐2 gene expressions induced by nitric oxide synthase inhibitors, lipopolysaccharide. Biochem Pharmacol 2001;61:1417–1427. [DOI] [PubMed] [Google Scholar]
- 5. Chen YC, Shen SC, Lee WR, et al. Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK‐HEP‐1. Arch Toxicol 2002;76:351–359. [DOI] [PubMed] [Google Scholar]
- 6. Chi YS, Cheon BS, Kim HP. Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase‐2 and the induction of inducible nitric oxide synthase in lipopolysaccharide‐treated RAW 264.7 cells. Biochem Pharmacol 2001;61:1195–1203. [DOI] [PubMed] [Google Scholar]
- 7. Chi YS, Lim H, Park H, Kim HP. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: In vivo regulation of inflammation‐associated gene expression. Biochem Pharmacol 2003;66:1271–1278. [DOI] [PubMed] [Google Scholar]
- 8. Cho J, Lee HK. Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells. Eur J Pharmacol 2004;485:105–110. [DOI] [PubMed] [Google Scholar]
- 9. Chou CJ. Rivularin, a new flavone from Scutellaria rivularis J Taiwan Pharm Assoc 1978;30:36–43. [Google Scholar]
- 10. Dhar DN. The chemistry of chalcones and related compounds. New York : John Wiley & Sons, 1981. ;5–9. [Google Scholar]
- 11. Du Y, Chen XY, Yang HY, Zhong DF. Determination of wogonin in rat plasma by liquid chromatography‐tandem mass spectrometry. Yao Xue Xue Bao 2002;37:362–366 (in Chinese). [PubMed] [Google Scholar]
- 12. Gao Z, Huang K, Xu H. Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide‐induced oxidative stress in HS‐SY5Y cells. Pharmacol Res 2001;43:173–178. [DOI] [PubMed] [Google Scholar]
- 13. Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999;1472:643–650. [DOI] [PubMed] [Google Scholar]
- 14. Heller W, Forkmann G. Biosynthesis of flavonoids In: Harborne JB, Ed. The flavonoids, advances in research since 1986. London : Chapman & Hall, 1993. [Google Scholar]
- 15. Herrmann K. Flavonols and flavones in food plants: A review. J Food Technol 1976;11:433–448. [Google Scholar]
- 16. Hsu HY. Oriental materia medica: A concise guide. Long Beach , CA : Oriental Healing Arts Institute, 1986;448–450. [Google Scholar]
- 17. Huang HC, Hsieh LM, Chen HW, Lin YS, Chen JS. Effects of baicalein and esculetin on transduction signals and growth factors expression in T‐lymphoid leukemia cells. Eur J Pharmacol 1994;268:73–78. [DOI] [PubMed] [Google Scholar]
- 18. Huang RL, Chen CC, Huang HL, et al. Anti‐hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis Planta Med 2000;66:694–698. [DOI] [PubMed] [Google Scholar]
- 19. Huang WH, Chien PY, Yang CH, Lee AR. Novel synthesis of flavonoids of Scutellaria baicalensis Georgi. Chem Pharm Bull (Tokyo) 2003;51:339–340. [DOI] [PubMed] [Google Scholar]
- 20. Huen MS, Hui KM, Leung JW, et al. Naturally occurring 2'‐hydroxyl‐substituted flavonoids as high‐affinity benzodiazepine site ligands. Biochem Pharmacol 2003;66:2397–2407. [DOI] [PubMed] [Google Scholar]
- 21. Huen MS, Leung JW, Ng W, et al. 5,7‐Dihydroxy‐6‐methoxyflavone, a benzodiazepine site ligand isolated from Scutellaria baicalensis Georgi, with selective antagonistic properties. Biochem Pharmacol 2003;66:125–132. [DOI] [PubMed] [Google Scholar]
- 22. Hui KM, Huen MS, Wang HY, et al. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem Pharmacol 2002;64:1415–1424. [DOI] [PubMed] [Google Scholar]
- 23. Hui KM, Wang XH, Xue H. Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site. Planta Med 2000;66:91–93. [DOI] [PubMed] [Google Scholar]
- 24. Ikemoto S, Sugimura K, Yoshida N, et al. Antitumor effects of Scutellariae radix and its components baicalein, baicalin and wogonin on bladder cancer cell lines. Urology 2000;55:951–955. [DOI] [PubMed] [Google Scholar]
- 25. Inagaki I, Hisada S, Shima K. Studies on the constituents of Anodendron affine Durce. I. Isolation of wogonin, dambonitol, sucrose and some other components from stems. Yakugaku Zasshi 1971;91:1133–1136. [DOI] [PubMed] [Google Scholar]
- 26. Kaptchuk TJ. The web that has no weaver: Understanding chinese medicine. New York : Congdon and Weed, 1983. [Google Scholar]
- 27. Kefford JF, Chandler BV, Eds. The chemical constituents of citrus fruits. New York : Academic Press, 1970. [Google Scholar]
- 28. Kim BR, Kim DH, Park R, et al. Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Planta Med 2001;67:396–399. [DOI] [PubMed] [Google Scholar]
- 29. Kim H, Kim YS, Kim SY, Suk K. The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci Lett 2001;309:67–71. [DOI] [PubMed] [Google Scholar]
- 30. Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure‐activity relationships. Biochem Pharmacol 1999;58:759–765. [DOI] [PubMed] [Google Scholar]
- 31. Lai MY, Hsiu SL, Chen CC, Hou YC, Chao Leem, PD. Urinary pharmacokinetics of baicalein, wogonin and their glycosides after oral administration of Scutellariae radix in humans. Biol Pharm Bull 2003;26:78–83. [DOI] [PubMed] [Google Scholar]
- 32. Lee H, Kim YO, Kim H, et al. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J 2003;17:1943–1944. [DOI] [PubMed] [Google Scholar]
- 33. Lee WR, Shen SC, Lin HY, Hou WC, Yang LL, Chen YC. Wogonin and fisetin induce apoptosis in human promyeloleukemic cells, accompanied by a decrease of reactive oxygen species, activation of caspase 3 and Ca2+‐dependent endonuclease. Biochem Pharmacol 2002;63:225–236. [DOI] [PubMed] [Google Scholar]
- 34. Liu XF, Liu ML, Iyanagi T, Legesse K, Lee TD, Chen SA. Inhibition of rat liver NAD(P)H: quinone acceptor oxidoreductase (DT‐diaphorase) by flavonoids isolated from the Chinese herb Scutellariae radix (Huang Qin). Mol Pharmacol 1990;37:911–915. [PubMed] [Google Scholar]
- 35. Ma SC, Du J, But PP, et al. Antiviral Chinese medicinal herbs against respiratory syncytial virus. J Ethnopharmacol 2002;79:205–211. [DOI] [PubMed] [Google Scholar]
- 36. Shen SC, Lee WR, Lin HY, et al. In vitro and in vivo inhibitory activities of rutin, wogonin and quercetin on lipopolysaccharide‐induced nitric oxide and prostaglandin E2 production. Eur J Pharmacol 2002;446:187–194. [DOI] [PubMed] [Google Scholar]
- 37. Shieh DE, Liu LT, Lin CC. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res 2000;20:2861–2865. [PubMed] [Google Scholar]
- 38. Son D, Lee P, Lee J, Kim H, Kim SY. Neuroprotective effect of wogonin in hippocampal slice culture exposed to oxygen and glucose deprivation. Eur J Pharmacol 2004;493:99–102. [DOI] [PubMed] [Google Scholar]
- 39. Timberlake CF, Henry BS. Plant pigments as natural food colours. Endeavour 1986;10:31–36. [DOI] [PubMed] [Google Scholar]
- 40. Tomimori T, Miyaichi Y, Imoto Y, Kizu H, Namba T. Studies on the constituents of Scutellaria species. V. On the flavanoid constituents of Ban Zhi Lian, the whole herb of Scutellaria rivularis Wall (1). Shoyakugaku Zasshi 1984;38:249–252. [Google Scholar]
- 41. Tsai TH, Chou CJ, Tsai TR, Chen CF. Determination of wogonin in rat plasma by liquid chromatography and its pharmacokinetic application. Planta Med 1996;62:263–266. [DOI] [PubMed] [Google Scholar]
- 42. Ueng YF, Shyu CC, Liu TY, et al. Protective effects of baicalein, wogonin against benzo[a]pyrene‐ and aflatoxin B(1)‐induced genotoxicities. Biochem Pharmacol 2001;62:1653–1660. [DOI] [PubMed] [Google Scholar]
- 43. van Loon IM. The golden root: Clinical applications of Scutellaria baicalensis Georgi flavonoids as modulators of the inflammatory response. Alt Med Rev 1998. ;472–480. [Google Scholar]
- 44. Wagner H, Farkas L. Synthesis of flavonoids In: Harborne JB, Mabry TJ, Mabry H, Eds. The flavonoids. New York : Academic Press, 1975. ;127–213. [Google Scholar]
- 45. Wakabayashi I. Inhibitory effects of baicalein and wogonin on lipopolysaccharide‐induced nitric oxide production in macrophages. Pharmacol Toxicol 1999;84:288–291. [DOI] [PubMed] [Google Scholar]
- 46. Zanoli P and Avallone R and Baraldi M. Behavioral characterization of the flavonoids apigenin and chrysin. Fitoterapia 2000;71:S117–S123. [DOI] [PubMed] [Google Scholar]
- 47. Zuo F and Zhou ZM and Zhang, Q et al. Pharmacokinetic study on the multi‐constituents of Huangqin‐Tang decoction in rats. Biol Pharm Bull 2003;26:911–919. [DOI] [PubMed] [Google Scholar]