• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1569-1572
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• 2009

The pharmacokinetics of decursin and decursinol angelate (D/DA) were investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The levels of D/DA and metabolized decursinol in the blood following oral and intravenous administrations declined according to first-order kinetics, with $T_{1/2}$ values of 56.67, 58.01, and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretions of D/DA in bile duct-cannulated rats was $36.10{\pm}2.9%$, $25.35{\pm}3.8%$, and $34.20{\pm}3.2%$, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.37-44
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• 1998

This study was performed to examine the effects of DA-9601, a novel antiulcer agent extracted from Artemisiae Herba, on radiation colitis in the rat. Female Wistar rats received a 30 Gy dose of irradiation to the 2 cm of distal colon in length using an intrarectal applicator system. 30 mg/tg or 100 mg/kg of DA- 9601 was administered orally 30 min before and 4 h after radiation on day 1. And the same dose of DA-9601 was given to the animals twice a day from day 2 to 14. As a reference control, sucralfate suspension (100 or 300 mg/head) was given as an enema based on the same treatment schedule of DA-9601. Body weight change and the frequency of diarrhea were recorded during the observation period as markers of radiationinduced injury, All animals were sacrificed on day 15 for evaluation of macro- and microscopic findings and mucosal myeloperoxidase (MPO) activity. Radiated animals showed diarrhea, mucosal redness and histologic changes characterized by edema and eosinophilic infiltration of the periglandular lamina propria with loss of colonic epithelium. Radiation also significantly increased mucosal MfO activity of affected colon f\\\\\\\\`<0.05). However, most of these changes were completely protected by oral administration with DA-9601. DA-9601 reduced radiation-induced histologic alteration significantly in a dose-related manner (P<0.05). In addition, mucosal MPO activity in rats receiving high dose of DA-9601 decreased significantly when compared with that in radiated control. High dose of sucralfate (300 mg/head) alleviated radiation-induced histologic lesion, but failed to reach statistical significance. The results of this study suggest that DA-9601 can be useful for the prevention of acute clinical symptoms of radiation proctocolitis and that decrease of mucosal MPO by DA-9601 plays a role in its protective mechanism(s), at least in part.

• Journal of Nutrition and Health
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• v.39 no.3
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• pp.225-235
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• 2006

Although it has traditionally known that deer antler and medicinal herbs extract contain some functional components for health promotion, the nutritional significance remains to be elucidated. This study examined the efficacy of deer antler extract (DA) , medicinal herbs extract (MH) and their mixture (DAMH) on serum IGF-I, bone growth with growing rats in vivo and splenocyte proliferation with spleen cells in vitro. Three week-old young female rats (Sprague-Dawley) were divided into 4 groups and then fed basal diet (AIN-93G) or experimental diets containing DA, MH, DAMH, respectively, for 7 weeks. We collected blood, liver, kidney, spleen, femur and tibia from rats. There was no significant difference in weight gain, but food intake increased in DA- and MH-fed groups. There were no signs of liver and kidney damage in the DA, MH and DAMH-fed groups compared to basal diet group. In femur and tibia, wet weights: breaking forces and bone minerals (Ca, Mg and Zn) were significantly higher in the DA-fed group than in the other groups. Serum alkaline phosphatase (ALP) , bone-specific alkaline phosphatase (BALP) activities were significantly lower in the DA, MH, DAMH-fed groups than in basal diet group. Also, serum insulin-like growth factor-I (IGF-I) concentrations were significantly increased in DA-fed group compared to the other groups. Therefore DA was shown to have an activity of bone growth promotion by increasing the IGF-I, a major bone growth factor. The deer antler extract showed an enhanced immune action on the primary cultured-cells from spleen of rats, representing that splenocytes were proliferated by lipopolysaccharide (LPS), but not by concanavalin A (Con A). These results indicate that deer antler extract has beneficial effects on bone growth via IGF-I and on splenocyte activation.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.489-496
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• 2000

This study was conducted to investigate the effects of streptozotocin-induced (STZ) diabetes on insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBPs), and IGF-I carrier proteins in serum, liver, and kidney. The levels of total and free IGF-I were measured by radioimmunoassay (RIA). The patterns of IGFBPs were determined by western ligand blotting (WLB) analysis. The profiles of IGF-I carrier proteins in serum were determined by column chromatography. The levels of total and free IGF-I in serum were lower in STZ-induced diabetic rat than normal rat (p<0.01). Similarly, the levels of total IGF-I in liver was lowered in STZ-induced diabetic rats. On the other hand, the levels of total IGF-I in kidney were increased in STZ-induced diabetic rats compared with normal rats (p<0.01). In serum and liver from STZ-induced diabetic rats, the amount of IGFBP-3 was decreased and the amount of IGFBP-2 was increased compared with normal rats. There was a not difference in amount of IGFBP-4 in serum between STZ-induced diabetic rats and normal rats. The serums of normal rats have higher 150kDa carrier proteins than in STZ-induced diabetic rats, whereas, most of 50kDa carrier proteins were found in STZ-induced diabetic rats. These results demonstrate that in STZ-induced diabetic rats, IGF-I/IGFBPs system that included functional bioactivity was changed in serum as well as tissues, and these changes may play an important role in pathogenesis of diabetes.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.354-360
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• 1999

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034,$ 7-carboxymethyloxy-3^{l}, 4^{l},$ 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD : two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3~3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 gm/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

• Archives of Pharmacal Research
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• v.23 no.5
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• pp.471-476
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• 2000

DA-8159, a new phosphodiesterase 5 inhibitor, was assessed for its erectogenic potential by a penile erection test in rats, the relaxation of isolated rabbit corpus cavernosum (CC), and estimation of the intracavernous pressure (ICP) in the anesthetized dog. Oral administration of DA-8159 (0.3 to 1 ${\mu}g/kg$ ) increased the number of erections in rats with increasing dosage, with the highest penile erection index at 10 ${\mu}g/kg$ DA-8159 induced the relaxation of phenylephrine (PHE)-induced contractions in the rabbit CC and decreased the $IC_{50}$ of the nitric oxide donor sodium nitroprusside (SNP) in a dose-dependent fashion. In pentobarbital-anesthetized dogs, the intravenous administration of DA-8159 (1~300 ${\mu}g/kg$ ) potentiated the increase in ICP induced by the intracavernosal SNP in a dose-related manner. These findings suggest that DA-8159 has significant therapeutic potential in the treatment of erectile dysfunction.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.183-192
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• 2018

Post-traumatic stress disorder (PTSD) is a trauma-induced psychiatric disorder characterized by impaired fear extermination, hyperarousal, anxiety, depression, and amnesic symptoms that may involve the release of monoamines in the fear circuit. The present study measured several anxiety-related behavioral responses to examine the effects of berberine (BER) on symptoms of anxiety in rats after single prolonged stress (SPS) exposure, and to determine if BER reversed the dopamine (DA) dysfunction. Rats received BER (10, 20, or 30 mg/kg, intraperitoneally, once daily) for 14 days after SPS exposure. BER administration significantly increased the time spent in the open arms and reduced grooming behavior during the elevated plus maze test, and increased the time spent in the central zone and the number of central zone crossings in the open field test. BER restored neurochemical abnormalities and the SPS-induced decrease in DA tissue levels in the hippocampus and striatum. The increased DA concentration during BER treatment may partly be attributed to mRNA expression of tyrosine hydroxylase and the DA transporter in the hippocampus, while BER exerted no significant effects on vesicular monoamine transporter mRNA expression in the hippocampus of rats with PTSD. These results suggest that BER had anxiolytic-like effects on behavioral and biochemical measures associated with anxiety. These findings support a role for reduced anxiety altered DAergic transmission and reduced anxiety in rats with PTSD. Thus, BER may be a useful agent to treat or alleviate psychiatric disorders like those observed in patients with PTSD.

• Biomolecules & Therapeutics
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• v.2 no.1
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• pp.82-93
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• 1994

DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of Fl fetuses, as well as growth, behaviour and mating performance of Fl offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in Fl offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and Fl offspring are 0.1 mg/kg/day and NOEL for Fl fetuses is 0.3 mg/kg/day.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.124-124
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• 1998

Portal hypertensive gastropathy (PHG) is part of a complex syndrome which occurs as a complication of chronic liver disease and portal hypertension. The gastric mucosa in these patients shows typical congestion of ‘mosaic-like’ pattern and vulnerable to various noxious agents such as NSAIDs and ethanol. We previously reported that DA-9601, a quality-controlled extract from Artemisia asiatica, exhibits cytoprotection against various gastritis models. In the present study we investigated the effect of DA-9601 on ethanol-induced gastric damage in PHG rats. Experimental PHG was produced by CBD ligation in SD rats. DA-9601 was orally administered at a dose of 30 mg/kg or 100 mg/kg daily for 2 weeks.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.9-19
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• 1993

DA-125, a new anthracycline antibiotic, showed antitumor activity against animal tumors and human tumors. Therefore we studied the cardiotoxic potential of DA-125 in hamsters and rats as a part of safety research, and compared it with that of doxorubicin(DXR). In acute cardiotoxicity test model used hamsters DA-125 was administered intravenously at a dose of 6, 9, 12 mg/kg, and DXR at 3 mg/kg was given. The electrocardiogram(ECG) of hamsters was recorded for 30 minutes after administration. The DA-125 caused slight ECG alterations at a dose of 6 mg/kg. At a dose of 12 mg/kg DA-125 induced moderate to remarkable changes in ECG like decrease of heart rate, widening of PR interval and 07 interval, and A-V block in 3 out of 5 animals. The severity of ECG alteration at 12 mg/kg of DA-125 was similar to that at 3mg/kg of DXR and these changes caused by DA-125 and DXR recovered within 10 minutes after injection. In chronic cardiotoxicity test model used rats, DA-125 was administered intravenously once a week for three weeks at a dose of 6, 9mg/kg and DXR was given at a dose of 6mg/kg. Electrocardiogram was recorded every week from the start of administration to 2 weeks after the last administration and the animals were sacrificed for histological heart examination at 1 week or 2 weeks after the last administration. DA-125 did not cause any abnormal changes in ECG and in histological heart examination due to administration, but DXR caused widening of ST segment, QRS complex, and QT interval from 1 week after administration and these changes were continued to necropsy. These alterations in ECG were accompanied by cardiac histological lesions such as vacuolation in myocardiac cells, interstitial edema and necrosis of myocytes. These results suggest that DA-125 is less cardiotoxic than DXR.