Artemisia annua (AA) is a well-known as a source of antimalarial drug (artemisinin), which also has been traditionally used as an antipyretic and hemostatic agent in Korea and China. In preclinical effective study, a water extract of Artemisia annua (WEAA) ameliorated weight gain and hepatic lipid accumulation in high-fat diet-fed mice. The plasma levels of triglyceride, AST, and ALT were reduced in the WEAA-treated group. Based on these results, the safety of WEAA as a functional ingredient for liver health was evaluated in this repeated dose oral toxicity study before the clinical trial. Sprague- Dawley (SD) rats were treated by gavage with 20 times (1,000 mg/kg) more than the effective dose for 13 weeks. All rats had survived at the end of the study, and there were no changes indicating obviously abnormal clinical sign and behavior. The treatment of WEAA were also observed no obvious toxicities in the body weights, urine, hematological, serum biochemical, ophthalmic and histopathological examinations. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) of WEAA in SD rats was estimated to be 1,000 mg/kg. In conclusion, WEAA could be used as a safe functional ingredient for the improvement of liver health in individuals with hepatic diseases including nonalcoholic steatohepatitis.

본 연구는 Spragye-Dawely 계통의 암컷 랫드에서 종합 비타민의 반복경구투여 독성평가와 대식세포 Raw 264.7 세포의 NO 및 TNF-α assay를 통한 면역 활성을 평가하기 위해서 실시하였다. 종합비타민을 대식세포의 활성능을 측정하기 위해 Raw 264.7 세포에서 NO와 TNF-α의 생성을 측정하였다. 종합비타민을 대식세포에 24시간 처리한 결과 대조군과 비교 시 NO와 TNF-α가 유의적으로 상승하였다. 이 결과 종합비타민이 대식세포인 Raw 264.7 세포를 활성화시키는 것으로 사료된다. 또한 랫드에서 종합비타민의 독성평가를 위하여 랫드에 종합비타민을 0.24 g/ kg, 1 g/kg 그리고 2 g/kg을 4주 동안 경구투여를 하였다. 종합비타민의 안전성을 확인하기 위해 다음과 같은 관찰 및 검사를 하였다. 검사항목으로는 체중과 사료 섭취량, 임상증상, 혈청생화학적 검사를 관찰한 결과 대조군과 투여군을 비교 시 유의적인 변화가 나타나지 않았다. 따라서 종합비타민은 생리대사에 무해하며 면역증강의 효과를 나타내는 것으로 사료된다.

This study was designed to evaluate a repeated oral dose toxicity and immunomodulating activity of Pulsatilla koreana and Artemisiae annuae in Sprague-Dawley rats. The female rats were treated with Pulsatilla koreana and Artemisiae annuae of control group, low group (0.5 ml/kg), medium group (1 ml/kg), high group (2 ml/ kg) for distilled water, intragastrically for 4 weeks, respectively. To ensure the safety of Pulsatilla koreana and Artemisiae annuae such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. Hematological results were the increase of neutrophils, lymphocytes and monocytes in the high dose group of Pulsatilla koreana. The increase immune cells in the high dose group of Pulsatilla koreana might immunomodulating activity. No significant differences in body weight, feed intake, serum biochemical analysis and histopathological between control and fed group were found. In conclusion, Pulsatilla koreana and Artemisiae annuae is physiologically safe and improve immunomodulating activity.

This study was conducted in order to investigate repeated-dose toxicities of Magnolia ovobata ethanol extract (MEE). MEE was administered orally to male and female Sprague Dawley rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg for four weeks. Repeated administration of MEE did not induce abnormalities in general signs, body weight gain, feed and water consumption, necropsy findings, or organ weights. In addition, no abnormality was observed in hematological analyses; red blood cells and their indices, white blood cells, platelets, and coagulation times. In male rats, BUN and creatinine showed an increase at doses of 2,000 mg/kg and 500-1,000 mg/kg, respectively, while in female rats, lactate dehydrogenase and creatine phosphokinase showed a decrease at 2,000 mg/kg, the upper-limit dose of repeated-dose toxicity studies. However, there were no dose-dependent increases or gender-relationship. In addition, other parameters of the hepatic and muscular toxicities as well as energy and lipid metabolism were not affected. In microscopic examination, no considerable pathological findings were observed. The results indicate the safety of oral administration of MEE to the upper-limit dose.

Four-week repeated-dose toxicity of Misaengtang (MST) was evaluated according to Toxicity Test Guideline of Korea Food and Drug Administration using 6-week-old Sprague-Dawley rats. Based on the results of preliminary single-dose toxicity study, confirming safety up to an upper-limit dose, MST was dissolved in drinking water and orally administered at doses of 500, 1,000, or 2,000 mg/kg for 28 days. All doses including the upper-limit limited dose (2,000 mg/kg) of MST did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology and blood biochemistry. Rather, high doses (1,000-2,000 mg/kg) of MST reduced the serum levels of alanine transaminase, aspartate transaminase, creatinine phosphokinase, lactate dehydrogenase and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Both maximum-tolerable dose and no-observed-adverse-effect level were not determined. The results indicate that long-term intake of high-dose MST might not induce general adverse-effects.

죽상경화증(arteriosclerosis)의 예방과 치료를 목적으로 조성된 새로운 한방처방인 WK-38을 웅성과 자성 랫트에 13주간 반복 투여하여 독성을 평가하였다. WK-38은 대황(大黃, Rhei Rhizoma), 후박(厚朴, Magonoliae Cortx), 목단피(牧丹皮, Moutan Cortex Radicis)의 복합물로 구성되었다. 실험동물에게 5 mg/kg, 50 mg/kg 또는 500 mg/kg을 경구로 투여하였다. 투여기간 동안 사망, 일반증상, 섭이량, 섭수량, 및 체중증가 등을 관찰하였다. 투여된 WK-38 모든 용량에서 사망하는 개체는 없었다. 시험기간 동안 체중의 지속적인 증가가 관찰되었으며 통계학적으로 유의적인 차이는 나타나지 않았다. 안검사 및 뇨검사에서 모든 투척군에서 대조군과 비교하여 시험물질 투여에 기인한 유의성 있는 변화는 관찰되지 않았다. WK-38 투여는 혈액학적 검사 및 혈액 생화학적 검사 결과 시험물질에 의한 독성학적 변화로는 판단되는 지표는 없었다. 이상의 결과에 근거하여 본 시험 조건하의 WK-38의 랫트에 대한 13주 반복 경구투여 시험에서는 독성학적 변화가 관찰되지 않았다. 따라서 무독성량은 500 mg/kg을 상회하는 것으로 판단된다.

Background: Cassia tora L., an annual or perennial plant of the Fabaceae family, is traditional medicine with various biological activities, including anti-constipation and, anti-inflammation. Chemical compounds such as anthraquinone glycoside and naphthalene derivatives have been isolated from this plant. Cassia tora L. is a common contaminant of agricultural commodities, but is toxic to cattle and poultry. Methods and Results: To investigate the potential toxicity, Cassia tora L. aqueous extract (CO) was administered orally to rats for 26 weeks at 0 (control), 300, 1,500 and 3,000㎎/㎏/day (n = 10 for male rats for each dose). The positive control comprised animals orally administered anthraquinone 100㎎/㎏/day. There was no treatment-related mortality. An increase in the kidney weight was observed at 3,000㎎/㎏/day of CO and anthraquinone 100㎎/㎏/day. Macrophage infiltration in the colon was observed at CO 1,500 and 3,000㎎/㎏/day and anthraquinone 100㎎/㎏/day, but there were no significant toxicological changes in the incidence and severity of the finding. Conclusions: The oral no-observed-adverse-effect level (NOAEL) of CO was 3,000㎎/㎏/day in male rats and no target organs were identified. In addition, 300㎎/㎏ was found to be the no-observed-effect level (NOEL) for systemic toxicity under the conditions of the study.

The object of this study was to obtain single oral dose toxicity of Arisaema Rhizome (Arisaema amurense f. serratum (Nakai) Kitag) aqueous extracts. Arisaema Rhizome (Chunnamsong in Korean) is one of the most important folk remedy plants used in Asia. In the study, a 28-day rat oral gavage study has been conducted with the extracts from Arisaema Rhizome at dose of 1,250, 2,500 and 5,000 ㎎/㎏/day. The following endpoints were evaluated: clinical observations, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it was estimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female rats are 5000 ㎎/㎏/day of the water-extracts from Arisaema Rhizome.

Pharmacological studies and clinical practices have indicated that Radix Astragali, a dried root of Astragalusmembranaceus possesses a lot of biological activities, including antioxidant, hepatoprotective, anti-diabetic, tonic, diuretic,antimicrobial, antiviral, and immunological activities. These biological activities approved by the modern pharmacologicalstudies are mainly due to the constituents of Astragalus membranaceus including polysaccharides, saponins, flavonoids,amino acids, and trace elements. In resent, the main constituents in the root part showing a lot of biological activities hasbeen isolated also from the aboveground parts such as leaves and sprouts in our laboratory. However, the safety evaluationfor the aboveground parts of Astragalus membranaceus should be checked before expanding their application as one of food.In the study, a 90-day rat oral gavage study has been conducted with the extracts from Astragalus membranaceus-above-ground parts at doses of 1000, 3000, and 5000㎎/㎏/day. The following endpoints were evaluated: clinical observations, bodyweight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it wasestimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female ratsare 5000㎎/㎏/day of the water-extracts from Astragalus membranaceus-aboveground parts.

This study was performed to investigate the four-week repeated-dose toxicity of the crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1), a lactic acid bacterium isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. There were no test-article-related deaths or abnormal clinical signs in both the male and female rats during the observation period. Furthermore, no differences in the body weight changes, food intake and water consumption levels of the control and treatment groups were found. The hematological parameters, serum biochemical analysis results, histopathological examination results and all other findings also showed no significant or dose-dependent changes. There were also no changes in the organ weights upon the administration of the crude antifungal compounds produced by Lb. plantarum AF1. These results suggest that the oral administration of the crude antifungal compounds produced by Lb. plantarum AF1 had no adverse effects up to a dosage level of 2,000 mg/kg in both male and female rats.