wogonin and flavone

Wogonin and baicalein are bioactive flavones in the popular Chinese herbal remedy Huang-Qin (Scutellaria baicalensis Georgi). These specialized flavones lack a 4'-hydroxyl group on the B ring (4'-deoxyflavones) and induce apoptosis in a wide spectrum of human tumor cells in vitro and inhibit tumor growth in vivo in different mouse tumor models. Root-specific flavones (RSFs) from Scutellaria have a variety of reported additional beneficial effects including antioxidant and antiviral properties. We describe the characterization of a new pathway for the synthesis of these compounds, in which pinocembrin (a 4'-deoxyflavanone) serves as a key intermediate. Although two genes encoding flavone synthase II (FNSII) are expressed in the roots of S. baicalensis, FNSII-1 has broad specificity for flavanones as substrates, whereas FNSII-2 is specific for pinocembrin. FNSII-2 is responsible for the synthesis of 4'-deoxyRSFs, such as chrysin and wogonin, wogonoside, baicalein, and baicalin, which are synthesized from chrysin. A gene encoding a cinnamic acid-specific coenzyme A ligase (SbCLL-7), which is highly expressed in roots, is required for the synthesis of RSFs by FNSII-2, as demonstrated by gene silencing. A specific isoform of chalcone synthase (SbCHS-2) that is highly expressed in roots producing RSFs is also required for the synthesis of chrysin. Our studies reveal a recently evolved pathway for biosynthesis of specific, bioactive 4'-deoxyflavones in the roots of S. baicalensis.

Topics: Acyltransferases; Animals; Antioxidants; Apoptosis; Biosynthetic Pathways; Cell Line, Tumor; Cytochrome P-450 Enzyme System; Flavanones; Flavones; Flavonoids; Gene Expression Regulation, Plant; Humans; Mice; Plant Extracts; Plants, Medicinal; Scutellaria baicalensis

Exploration for inhibitors against expression of IgE receptor (Fc epsilonRI) on human mast cell, a significant trigger to acute and chronic allergic symptoms, disclosed epigallocatechin gallate (EGCG), epicatechin gallate, and gallocatechin gallate as active principles. Additionally, the anthocyanidin, delphinidin, and the flavone, tricetinidin, possessing a pyrogallol function were also revealed to suppress expression of Fc epsilonRI. Structure-activity relationship analysis among catechins, anthocyanidins, and flavones revealed the pyrogallol moiety to be crucial for biological potency. Furthermore, EGCG was clarified to reduce generation of gamma-chain subunit to suppress expression of Fc epsilonRI on human mast cells.

Topics: Anthocyanins; Anti-Allergic Agents; Catechin; Cell Line; Flavones; Flavonoids; Gene Expression; Humans; Hypersensitivity; Mast Cells; Receptors, IgE

The involvement of genes in flavones biosynthesis was investigated in different organs and suspension cells obtained from Scutellaria baicalensis. Three full-length cDNAs encoding phenylalanine ammonia-lyase isoforms (SbPAL1, SbPAL2, and SbAPL3) and one gene encoding cinnamate 4-hydroxylase (SbC4H) from S. baicalensis were isolated using rapid amplification of cDNA ends (RACE)-PCR. These cDNAs were used together with previously-isolated clones for 4-coumaroyl CoA ligase (4CL) and chalcone synthase (CHS) to show the expression level in different organs of S. baicalensis. These genes were upregulated in suspension cells of S. baicalensis with biotic/abiotic stress factors. The baicalin and baicalein contents in roots were 22 and 107 times higher than those in flowers, respectively. The treatment of suspension cells with methyl jasmonate (MeJa) enhanced the major flavones in S. baicalensis. Cumulatively, the results of this study should advance ability to biosynthesize important and useful medicinal compounds from a variety of plant species.

Topics: Amino Acid Sequence; Chromatography, High Pressure Liquid; Cloning, Molecular; Flavanones; Flavones; Flavonoids; Gene Expression Regulation, Plant; Genes, Plant; Molecular Sequence Data; Organ Specificity; Phenylalanine Ammonia-Lyase; Scutellaria baicalensis; Sequence Alignment; Sequence Analysis, DNA; Time Factors; Trans-Cinnamate 4-Monooxygenase

The hot water and 70% ethanol extracts of dried mad-dog skullcap (Scutellaria lateriflora) both bound to the 5-HT(7) receptor, with 87.2 +/- 6.2% and 56.7 +/- 1.3% inhibition of [(3)H]-LSD binding to the receptor at 100 microg/mL, respectively. The on-line analysis of a 70% ethanol extract by HPLC-UV/MS resulted in the identification of five flavones (1-5). Fractionation of the ethanol extract resulted in the isolation of three flavone-glucuronides (6-8) and a flavanone-glucuronide (9), including one new compound, lateriflorin (5,6,-dihydroxy-7-glucuronyloxy-2'-methoxyflavone) (8). The structure of 8 was determined by NMR ((1)H NMR, (13)C NMR, and NOESY experiments) and MS analysis. From the results obtained in the testing of the pure compounds, it is evident that the activity on the 5-HT(7) receptor is at least partly due to the presence of flavonoids. Scutellarin and ikonnikoside I showed the highest inhibition of [(3)H]-LSD binding with IC(50) values of 63.4 and 135.1 microM, respectively.

Topics: Cells, Cultured; Flavones; Flavonoids; Humans; Inhibitory Concentration 50; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plants, Medicinal; Receptors, Serotonin; Scutellaria; Serotonin Antagonists; Vermont

Wogonin (5,7-dihydroxy-8-methoxyflavone), isolated from Scutellaria radix, was previously reported to inhibit the expression and activity of the enzyme cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated cells of a mouse macrophage cell line, RAW 264.7. Here, in order to find in vivo effects, inhibition by wogonin of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxygenase-2 expression and anti-inflammatory activity in vivo were investigated. When applied topically to the dorsal skin of mice, wogonin at doses of 50-200 microg/site/treatment (total of five treatments in 3 days) inhibited cyclooxygenase-2 expression and prostaglandin E2 production induced by multiple treatments with TPA. At 200 microg/site/treatment, wogonin caused a 55.3% reduction of prostaglandin E2 production on the dorsal skin compared with an increased production in the TPA-treated control group. The same compound significantly inhibited mouse ear edema induced by TPA in both preventive (58.1% inhibition) as well as curative treatment (31.3% inhibition) schedules at 200 microg/ear/treatment. Inhibition of neutrophil infiltration was also observed. Therefore, wogonin may be beneficial for cyclooxygenase-2-related skin disorders.

Topics: Animals; Antioxidants; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Edema; Flavanones; Flavones; Flavonoids; Gene Expression; Isoenzymes; Magnoliopsida; Male; Mice; Mice, Inbred ICR; Plant Extracts; Prostaglandin-Endoperoxide Synthases; Skin Diseases; Tetradecanoylphorbol Acetate