• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.243-247
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• 2011

Rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, has been shown to be anti-inflammatory. In the present study, a possible interaction between rutaecarpine and caffeine was investigated in male Sprague Dawley rats. Twenty four hr after the oral pretreatment with rutaecarpine at 80 mg/kg for three consecutive days, rats were treated intravenously with 10 mg/kg of caffeine. Compared with control rats, the pharmacokinetic parameters of caffeine in rutaecarpine-pretreated rats were significantly changed, possibly due to the rapid metabolism. The production of three metabolites of caffeine (i.e., paraxanthine, theobromine and theophylline) was also significantly changed in rats pretreated with rutaecarpine. The present results suggest that oral rutaecarpine would change the intravenous pharmacokinetic characteristics of caffeine.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.215-218
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• 2008

To investigate the possible interaction between rutaecarpine and phenobarbital in rats, phenobarbital in saline at 80 mg/kg was given ip to male SD rats for 3 consecutive days. Saline was given to control animals. One day after phenobarbital pre-treatment, rutaecarpine at 16 mg/kg was administered through penile vein. Blood was collected and analyzed by using HPLC. The pharmacokinetic parameters were determined with the non-compartmental model. Pre-treatment with phenobarbital significantly altered the pharmacokinetic profiles of rutaecarpine and its metabolite, 10-hydroxyrutaecarpine. The AUC of rutaecarpine was reduced to approximately 50% of control and the plasma half-life of rutaecarpine was significantly shortened when compared with control. In addition, the Cmax of 10-hydroxyrutaecarpine was increased approximately 160% of control. The AUC and the plasma half-life of 10-hydroxyrutaecarpine were decreased to 76.9% of control and to 82.7 min from 175.9 min, respectively. The results suggested that phenobarbital might accelerate the metabolism of rutaecarpine, thereby changing the pharmacokinetic parameters of rutaecarpine in male SD rats.

• Proceedings of the PSK Conference
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• pp.127.2-128
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• 2003

Rutaecarpine is an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa. In addition to its traditional use in treatment of gastrointestinal disorders, rutaecarpine has recently been characterized to have anti-inflammatory activity through cyclooxygenase-2 inhibition. More recently, to develop rutaecarpine as an anti-inflammatory agent, total synthesis of rutaecarpine has successfully been established in our group. (omitted)

• Toxicological Research
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• v.24 no.3
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• pp.195-199
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• 2008

It has been reported that hepatic microsomal cytochrome P450(CYP) 2E1 is responsible for the metabolism of chlorzoxazone(CZX) to 6-hydroxychlorzoxazone. The present study was undertaken to assess the possible interaction of rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, with CZX. Male Spraque-Dawley rats were administered with 80 mg/kg/day of oral rutaecarpine for three consecutive days. Twenty four hr after the pre-treatment with rutaecarpine, the rats were treated with 20 mg/kg of intravenous CZX. Rat hepatic microsomes isolated from rutaecarpine-treated rats showed greater(50% increase) activity of p-nitrophenol hydroxylase(a marker of CYP2E1) when compared with the control rats. Compared with control rats, the AUC of CZX was significantly smaller(84% decrease) possibly due to significantly faster CL(646% increase) in rats pretreated with rutaecarpine. This could be, at least partially, due to induction of CYP2E1 by rutaecarpine.

• Natural Product Sciences
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• v.20 no.4
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• pp.262-268
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• 2014

Rutaecarpine is one of the major alkaloids present in the fruits of Evodia rutaecarpa. In this study, rutaecarpine was evaluated, both in vitro and in vivo, for its hepatoprotective properties against thioacetamide (TAA)-induced hepatic fibrosis. The results showed that rutaecarpine inhibited TAA-induced cytotoxicity, reduced the expression of the fibrogenic cytokine transforming growth factor ${\beta}1$ ($TGF-{\beta}1$), and induced the expression of bcl-2. To evaluate its in vivo effects, animal models with TAA-induced hepatic fibrosis were utilized. Levels of liver tissue injury-associated enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were monitored. $TGF-{\beta}1$ and the ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) were measured as markers of the protective effects on hepatic fibrosis. The AST and ALT levels in blood were greatly enhanced by TAA and completely blunted by rutaecarpine. Rutaecarpine led to the down-regulation of $TGF-{\beta}$ and Bax mRNA expression, as well as the up-regulation of Bcl-2 and $Bcl-X_L$ mRNA levels. In conclusion, rutaecarpine inhibited TAA-induced hepatic fibrosis and apoptosis by inducing the expression of Bcl-2 while blocking $TGF-{\beta}1$ in our TAA-intoxicated model.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.175-178
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• 2004

Rutaecarpine is one of quinazolinocarboline alkaloids found in Evodia rutaecarpa, a Rutaceous plant and it has shown various biological effects including antiinflammation. However, the effect of rutaecarpine on nervous system was not reported yet. In this study we investigated the general pharmacology of rutaecalpine on the central nervous system. Rutaecapine (4O and 400 mg/kg) did not change chemoshock induced by pentylenetetrazole. However, oral administration of rutaecarpine altered motor coordination examined by rotarod test, pentobarbital-induced sleeping time and acetic acid-induced writhing syndrome in mice at the doses of 40 and 400 mg/kg. Rutaecarpine also induced hypothermia in mice at both doses. The results suggest that rutaecapine possesses neuromodulating activities on central nervous system in addition to the various biological effects on the Periphery.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.487-491
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• 2012

The aim of this study was to investigate the inhibitory effects of rutaecarpine on DNA strand breaks and apoptosis induced by hydrogen peroxide ($H_2O_2$) in murine Hepa-1c1c7 cells. Oxidative DNA damage was estimated by nuclear condensation assessment, fluorescence-activated cell sorting analysis, and Comet assay. Rutaecarpine inhibited cell death induced by $500{\mu}M$ $H_2O_2$, as assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Treatment with rutaecarpine reduced the number of DNA strand breaks induced by $H_2O_2$, as assessed by DAPI staining and Comet assay, and increased quinone reductase, phosphatidylinositol 3-kinase, and pAkt protein levels, as assessed by western blotting.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.293-297
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• 2006

The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin $E_2$ synthesis from lipopolysaccharide-treated RAW 264.7 cells at $1-10{\mu}M$. Evodiamine inhibited cyclooxygenase-2 induction and NF-kB activation, while rutaecarpine did not. On the other hand, goshuyuamide II inhibited 5-lipoxygenase from RBL-1 cells $(IC_{50}=6.6{\mu}M)$, resulting in the reduced synthesis of leukotrienes. However, these three compounds were not inhibitory against inducible nitric oxide synthase-mediated nitric oxide production from RAW cells up to $50{\mu}M$. These pharmacological properties may provide the additional scientific rationale for anti-inflammatory use of the fruits of E. rutaecarpa.

• Natural Product Sciences
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• v.5 no.2
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• pp.65-69
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• 1999

By bioassay guided fractionation followed by chromatographic separation of the MeOH extract from the fruit of Evodia rutaecarpa (Juss.) Benth. (Rutaceae), a new cyclooxygenase-2 inhibitor was isolated and identified as an alkaloid, rutaecarpine. Other alkaloids such as evodiamine and dehydroevodiamine together with limonoids were also isolated and characterized.

• Proceedings of the Korean Society of Toxicology Conference
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• pp.170-170
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• 2005