• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.202-210
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• 1997

Protective effect of DA-9601, an extract of Artemisia Herb, against ethanol-induced gastric mucosal injury was evaluated in rats. In the prophylactic study, DA-9601 exhibited total protection (99.4%) against absolute ethanol-induced gastropathy, And the protective effect of DA-9601 lasted up to 2 hours, which was longer than those of other contemporary mucoprotectants. In the treatment study, DA-9601 significantly facilitated the healing of 70% ethanol-induced mucosal damage, which was superior to cetraxate, a commonly used anti-ulcer drug. The mechanisms of mucoprotection of DA-9601 were also assessed. DA-9601 increased the release of prostaglandin E$_2$ from murine neutrophils in a dose-dependent manner in vitro. The cytoprotective effect of DA-9601 against ethanol-induced mucosal damage was significantly diminished by the concommitant injection of N$\omega$-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, i.v.), a non-specific nitric oxide (NO) synthase inhibitor, while it was not affected by preinjection of indomethacin (5 mg/kg, s.c.), a prostaglandins-depletor. And it was found that DA-9601 significantly enhanced adaptive cytoprotective action of 10% ethanol against absolute ethanol (56.9$\pm$6.5 vs 23.0$\pm$3.3 mm$^2$, p<0.05, mean$\pm$SEM), though its exact underlying mechanism remains to be clarified. The present fin[lings demonstrate that DA-9601 exerts gastroprotecticv actions for the stomach against ethanol through several different underlying mechanisms, in which prostanglandins and NO are involved. In conclusion, the results obtained suggest that DA-9601 can be useful both in prevention and treatment of ethanol-induced gastric damage.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.111-121
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• 1996

Antiulcer effects of Artemisia herba extract (DA-9601) were evaluated in various types of experimental gastric ulcer induced in rats. And the effects of DA-9601 on mucus, basal and stimulated gastric acid secretion were also investigated in rats. DA-9601 (12.5∼400 mg/kg, p.o.) prevented the formation of gastric ulcers induced by 60% EtOH in 150 mM HC1, restraint water immersion stress, platelet activating factor (PAF), aspirin in 150 mM HCI with Pylorus-ligation and indomethacin. DA-9601 (4∼400 mg/kg, p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer and significantly stimulated mucus secretion in a dose-dependent manner. DA-9601 (20∼200 mg/kg, i.d.), however, did not inhibit basal gastric acid secretion in pylorus ligated rats and DA-9601 (200 mg/kg, i.d.) failed to influence histamine-, pentagastrin- and carbachol- stimulated gastric acid secretion. These results suggest that DA-9601 has inhibitory action on gastric lesion and ulceration through increasing mucus secretion in the stomach of rats without influencing basal and stimulated gastric acid secretion.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.165-173
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• 1997

This study was conducted to investigate the effect of DA-9601, an extract of Artemisiae Herba, which is known to possess mucoprotective action either by free radical scavenging effect or increase of mucus secretion, against animal models of inflammatory bowel disease (IBD) induced by trinirobenzene sulfonic acid (TNBS) or other noxious agents. Experimental colitis was induced by intracolonic administration of TNBS in 50% ethanol, or 1 ml of 7% acetic acid solution (AA), by subcutaneous injection of indomethacin (INDO) in rats, or by supplementing drinking water with 5% dextran sodium sulfate (DSS) in albino mice. DA-9601 was treated orally for 4 to 7 days. Animals were euthanized 1 day after the last treatment for morphological and biochemical analysises. All the noxious agents including TNBS, AA, INDO and DSS elicited severe colitis. The animals treated with DA-9601 showed a consistent, dose-related reduction in the severity of colitis, grossly and histologically. The reduction was significant (p<0.05) after administration of DA-9601 at dose range of 10 mg/kg or above. In TNBS-induced colitis, the rats receiving DA-9601 showed significantly decreased mucosal myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBA-RS), when compared to control and mesalazine groups. Mucosal proinflammatory cytokine levels were also decreased after DA-9601 treatment. In conclusion, DA-9601 ameliorated macroscopic and histologic scores in experimental colitis either through decreasing oxidative stress or by attenuating cytokines involved in inflammation. DA-9601 could be a promising drug for the therapy of IBD.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.439-448
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• 2021

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4⁺ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GM-CSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ⁺ Th1 cells, IL-4⁺ Th2 cells, IL-9⁺ Th9 cells, IL-17⁺ Th17 cells, and Foxp3⁺ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.354-363
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• 1996

This study was conducted to investigate the repeated dose toxicity of DA-9601, an antiulcer agent of Artemisia app. extract, in rats. DA-9601 was administered orally once a day for 4 weeks to 10 males and 10 females per group at doses of 0(vehicle control), 125, 500 or 2000 mg/kg/day. Throughout the study, no treatment-related deaths and clinical signs were observed. In female rats receiving 125 mg/kg of DA-9601, water consumption increased slightly on day 4, 11 and 25. Hematological examination showed a decrease of MCV and an increase of PLT in male rats at the doses of 500 and 2000 mg/kg groups. Blood biochemistry revealed slight decreases of cholesterol, BUN and Na in male rats and decreases of total bilirubin and creatinine and slight increases of globulin and Cl in female rats. The organ weights at the end of 4 weeks showed slight changes in some organs of treated groups. But, all these changes were not considered to be of toxicological importance, because they did not show dose-response relationship and relevance to gross and microscopic findings. Histopathologically, abnormal treatment-related changes were not observed in any organ and target organs were not detected. On the basis of these results, the NOAEL(no-observed-adverse-effect level) of DA-9601 was estimated to be more than 2000 mg/kg/day under the conditions tested.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.196-196
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• 1996

Artemisia extract powder (DA-9601)의 일반약리 작용을 mice, rat 및 rabbit에서 검토하였다. DA-9601은 rota-rod test에 의한 운동 협조능, 초산 writhing 반응, tail-flick test 및 randall-sellito test를 이용한 진통작용, thiopental sodium의 수면작용, 장관 수송능, carrageenan의 염증, 현수에 의한 근이완작용, 정상체온, strychnine의 경련작용, 수정관, 자궁각 및 Evans blue의 피부혈관 투과성에 별다른 영향을 미치지 않았다. DA-9601은 토끼의 적출회장 운동을 억제하였고 혈압 강하작용과 이뇨작용을 나타내었다

• 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.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.414-419
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• 1997

Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent from Artemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostagiandin $E_2;(PGE_2)$ and prostagiandin F_${1{\alpha}}$$(PGF_{1{\alpha}})$ levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.508-513
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• 1998

The hepatoprotective effect of DA-9601, a quality-controlled extract of artemisisa asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride ($CCI_{4}$) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of Da-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or $CCI_{4}$ (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of Da-9601 reduced the elevation of serum ALT, AST. LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. Da-9601 also prevented APAP- and $CCI_{4}$-induced hepatic glutathione (GSH) depletion and $CCI_{4}$-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.174-183
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• 1996

The general pharmacological properties of Artemisia extract powder (DA-9601) produced from Artemisia asiatica leaves were investigated in mice, rats, guinea pigs and rabbits. DA-9601 at the dose of 800 mg/kg po had no influences on general behaviour, barbital sleeping time and motor coordination of mice. The material at the oral dose of 800 mg/kg did exhibit neither analgesic action nor hypothermic effect. Anticonvulsant action, muscle relaxant action and the effect on intestinal propulsion were not identified at 800 mg/kg po. In the isolated ileum and trachea of guinea pig, the material did not show direct erect and inhibitory action of chemically or electrically stimulated contraction at the concentration of $2\times10^{-5}$g/ml. The sinus rates of atria and contractility of papillary muscle of guinea pig were not influenced by DA-9601 at a dose of $2\times10^{-5}$g/ml. No influences on blood pressure and respiration were observed at 40 mg/kg iv, in rabbits. However, transient decreases in blood pressure of rabbits were observed as given 120 mg/kg in iv route with slight respiratory depression, and slight diuretic effect could be found without any changes in $Na^+$ and $K^+$ excretion.