• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.343-350
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• 2008

Oroxylin A is a flavonoid isolated from Scutellaria baicalensis, which is one of the most important medicinal herbs in traditional Korean medicine. In this study, we investigated the psychopharmacological activities of oroxylin A using the open field, rota-rod, balanced wire and plus-maze tests in Spontaneously Hypertensive Rats (SHR) and Wistar Kyoto Rats (WKY). Oroxylin A reduced hyperactivity in SHR (ADHD animal model) although it tended to increase locomotor activity in WKY. Methylphenidate did not reduce hyperactivity. Oroxylin A alleviated impulsive behaviors such as rearing, the percentage of moving time to the central area and the tendency to move into an unstable condition (open area in elevated plus-maze). Methylphenidate also reduced the percentage of staying time in the central area and the tendency to move into an unstable condition. Both oroxylin A and methylphenidate enhanced motor attention in SHR and WKY. Oroxylin A antagonized the muscimol ($GABA_A$ receptor agonist)-induced $Cl^-$current and its action was similar to that of bicuculline ($GABA_A$ receptor antagonist). The effects of oroxylin A may be caused by the antagonism at the $GABA_A$ receptor. Thus, oroxylin A may be a candidate of drug for treatment of ADHD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.4
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• pp.384-389
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• 2014

The purpose of this study is to investigate the modulatory effect of oroxylin A on hydrogen peroxide production in TM4 mouse testis sertoli cells induced by the synthetic analog of double-stranded RNA [polyinosinic-polycytidylic acid]. Hydrogen peroxide production was measured by dihydrorhodamine 123 (DHR) assay. Oroxylin A significantly inhibited the polyinosinic-polycytidylic acid (PIC)-induced production of hydrogen peroxide for 0.5, 2, 12, 18, and 24 hr incubation at the concentrations of 5, 10, 25, and $50{\mu}M$ in TM4 (P < 0.05) in dose dependent manner. These results suggest that oroxylin A has a protective effect against PIC-induced cellular toxicity with its inhibition of hydrogen peroxide production in PIC-induced sertoli cells.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.283-290
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• 2016

Oroxylum indicum has long been used in Asian traditional medicine to prevent and treat respiratory diseases, diabetes, diarrhea and other conditions. Oroxylin A is a flavone that is present in Oroxylum indicum and in Scutellaria baicalensis. Because the root extracts of both plants have been shown to have anti-allergic effects, the authors investigated whether oroxylin A is likely to have beneficial effects on allergic asthma using female Balb/c mice and rat RBL-2H3 mast cells. Antigen-induced degranulation was measured in vitro by measuring b-hexosaminidase activity. A murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of oroxylin A. Sensitization and challenge of ovalbumin induced allergic asthma responses, the accumulations of eosinophils and Th2 cytokine levels in bronchoalveolar lavage fluid and lung tissues. Oroxylin A administration decreased numbers of inflammatory cells, especially eosinophils, and reduced the expression and secretion of Th2 cytokines, including IL-4 and IL-13, in lung tissues and bronchoalveolar lavage fluid. Histologic studies showed oroxylin A reduced inflammatory signs and mucin production in lungs. These findings provide evidence that oroxylin A has potential use as an anti-allergic therapeutic.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.1918-1923
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• 2016

Two baicalein derivatives, baicalin and oroxylin A, were synthesized in this study. These derivatives exhibit diverse biological activities, such as anxiolytic and anticancer activities as well as memory enhancement. In order to synthesize baicalin from aglycon baicalein using Escherichia coli, we utilized a glycosyltransferase that regioselectively transfers glucuronic acid from UDP-glucuronic acid to the 7-hydroxy group of baicalein. To increase baicalin productivity, an araA deletion E. coli mutant, which accumulates UDP-glucuronic acid, was used, and ugd, which converts UDP-glucose to UDP-glucuronic acid, was overexpressed. Using these strategies, approximately $720.3{\mu}M$ baicalin was synthesized from $1,000{\mu}M$ baicalein. Oroxylin A was then synthesized from baicalein. Two O-methyltransferases (OMTs), ROMT-15 and POMT-9, were tested to examine the production of oroxylin A from baicalein. E. coli harboring ROMT-15 and E. coli harboring POMT-9 produced reaction products that had different retention times, indicating that they are methylated at different positions; the structure of the reaction product from POMT-9 was consistent with oroxylin A, whereas that from ROMT-15 was 7-O-methyl baicalein. Using E. coli harboring POMT-9, approximately 50.3 mg/l of oroxylin A ($177{\mu}M$) was synthesized from 54 mg/l baicalein ($200{\mu}M$).

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.83-89
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• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.36-42
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• 2012

Baicalin, a main constituent of the rhizome of Scutellaria baicalensis, is metabolized to baicalein and oroxylin A in the intestine before its absorption. To understand the role of intestinal microflora in the pharmacological activities of baicalin, we investigated its anti-inflammatory effect in mice treated with and without antibiotics. Orally administered baicalin showed the anti-inflammatory effect in mice than intraperitoneally treated one, apart from intraperitoneally administered its metabolites, baicalein and oroxylin A, which potently inhibited LPS-induced inflammation. Of these metabolites, oroxylin A showed more potent anti-inflammatory effect. However, treatment with the mixture of cefadroxil, oxytetracycline and erythromycin (COE) significantly attenuated the anti-inflammatory effect of orally administered baicalin in mice. Treatment with COE also reduced intestinal bacterial fecal ${\beta}$-glucuronidase activity. The metabolic activity of human stools is significantly different between individuals, but neither between ages nor between male and female. Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of $1.427{\pm}0.818$ and $1.025{\pm}0.603$ pmol/min/mg wet weight, respectively. Baicalin and its metabolites also inhibited the expression of pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$, and the activation of NF-${\kappa}B$B in LPS-stimulated peritoneal macrophages. Of them, oroxylin A showed the most potent inhibition. Based on these findings, baicalin may be metabolized to baicalein and oroxylin A by intestinal microflora, which enhance its anti-inflammatory effect by inhibiting NF-${\kappa}B$ activation.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.552-558
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• 2016

Severe complications associated with EV71 infections are a common cause of neonatal death. Lack of effective therapeutic agents for these infections underlines the importance of research for the development of new antiviral compounds. In the present study, the anti-EV71 activity of norwogonin, oroxylin A, and mosloflavone from Scutellaria baicalensis Georgi was evaluated using a cytopathic effect (CPE) reduction method, which demonstrated that all three compounds possessed strong anti-EV71 activity and decreased the formation of visible CPEs. Norwogonin, oroxylin A, and mosloflavone also inhibited virus replication during the initial stage of virus infection, and they inhibited viral VP2 protein expression, thereby inhibiting viral capsid protein synthesis. However, ribavirin has a relatively weaker efficacy compared to the other drugs. Therefore, these findings provide important information that will aid in the utilization of norwogonin, oroxylin A, and mosloflavone for EV71 treatment.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.18-24
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• 1999

Various flavonoid derivatives were previously reported to possess the inhibitory activity on cyclooxygenase/lipoxygenase. And these properties of flavonoids might contribute to their anti-inflammatory activity in vivo. In this study, several polyhydroxylated/methoxylated flavonoid derivatives such as oroxylin A. wogonin, skullcapflavone II, tectorigenin and iristectorigenin A were isolated from the medicinal plants. these compounds were evaluated fro their inhibitory effects on cyclooxygenase/lipoxygenase from the homogenate of human platelets in vitro. It was found that isoflavones including daidzein and tectorigenin possessed the inhibitory activity on cycloooxygenase, although the potency of inhibition was far less than that of indomethacin. In addition, oroxylin A, baicalein and wogonin inhibited 12-lipoxygenase activity without affecting cyclooxygenase, which suggested that 5,6,7- or 5,7,8-trisubstitutions of A-ring of flavone gave favorable results. The IC50 values of oroxylin A and NDGA against 12-lipoxygenase were found to be 100 and 1.5 uM, respectively.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.27-35
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• 2012

Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-$3{\beta}$ signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.

• Natural Product Sciences
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• v.26 no.1
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• pp.1-9
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• 2020

Flavonoids are mainly contained in the vegetables and medicinal herbs. Until now, over 5,000 kinds of flavonoid have been identified and their biological activities have been reported. Among them, we are interested in oroxylin A and spinosin because of their specific structures having bulky group at C-6 of ring A. Oroxylin A is contained in the Scutellaria baicalensis and exhibits cognitive enhancing activity as a GABA_A receptor antagonist, which is different from those of mainly contained in the S. baicalenis, baicalein or wogonin. Spinosin is isolated from Zizyphus jujuba var. spinosa and mainly studied as a hypnotic or anxiolytic agent because of traditional knowledge about its original herb. As far as we know, the cognitive function of spinosin was first identified by our group. In this review, we discuss how such flavonoids exert their pharmacological activities associated with cognitive function based on the receptor binding study and behavioral studies. Traditional knowledge and reverse pharmacology may be addressed in the research field of phytochemical pharmacology and useful to unveil the secret of phytochemicals.