Traditional medicine and herbal remedies are gaining popularity worldwide, comprising a significant portion of healthcare research, advancements, and market demand. Growing scientific evidence supports their substantial efficacy as pharmaceutical ingredients and dietary supplements in preventive healthcare. When developing pharmaceuticals, it is crucial to ensure that ingredients are free from side effects and toxicity in order to prioritize safety. Geckos, known as shou gong, are a diverse group of lizards that are widely utilized for treating various diseases in Korean Medicine. This study was conducted to assess the potential acute toxicity of a water extract Gekko gecko by a single oral dose in Sprague-Dawley rats. Twenty rats of each sex were randomly assigned to four groups (5 rats each). Test articles were administrated once by oral gavage to rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg body weight. Mortality, changes of body weight, and clinical signs of gross observation were monitored for 14 days after dosing. At the end of a 14-day observation period, all animals were sacrificed and complete macroscopic and hematological examinations were performed. There was no dead animal or test article-related effect on clinical signs, body weight, or gross finding. Other specific changes were not found between control and treated groups in hematology. Results showed no adverse effect at a dose of 500, 1,000, or 2,000 mg/kg in rats. The minimal lethal dose was considered to be over 2,000 mg/kg body weight in rats.

The aim of this study was to investigate the hypoglycemic effects of saengshik in Sprague-Dawley (SD) rats and to explore the potential of three commercially available saengshik products (BS, LS, WS) as an alternative diabetic meal. Blood glucose levels were measured at 30, 60, 90, 120, and 150 minutes after the ingestion of experimental materials. In experiment 1, the amount of experimental materials remained the same. We measured blood glucose-related biomarkers as the area under the blood glucose response curve (AUC), glycemic index (GI), maximum concentration (Cmax), and time to reach maximum concentration (Tmax). AUC and Cmax of the experimental group showed significant differences compared to the control group, while GI and Tmax did not show significant differences among the groups but were lower in the experimental group compared to the control group. In experiment 2, carbohydrates were adjusted to the same amount. We measured blood glucose-related biomarkers in the same manner as Experiment 1 and obtained similar results. These hypoglycemic effects appear to be attributed to phytochemicals and dietary fiber found in whole, unrefined grains. These results suggest that saengshik exerts hypoglycemic effects by modulation of glucose-related biomarkers.

This study examined the subacute oral toxicity of Dendropanax morbiferus H.Lév leaves hot-water extracts (DMWE) using male and female Spargue-Dawley rats. Rats were orally administered the DMWE at dose levels of 0, 250, 500, 1,000, and 2,000 mg/kg body weight (BW) for four weeks. For experimental period, clinical signs and the number of deaths were examined, and feed intake and BW of all experimental animals were measured once a week for four weeks. At the end of the experiment, blood samples were collected from all rats, and all animals were euthanized and autopsies were performed to collect major organs. No dead animals were found during the experimental period. In addition, no differences were found between control and DMWE-treated groups in feed intakes, BW changes, organ weights, clinical signs, hematological parameters, and serum biochemical parameters. The results of this study provided evidence that oral administration of DMWE at the dose of 2,000 mg/kg BW is safe in rats and may not exert severe toxic effects.

The surfactant, 2-{2-[2-(4-nonylphenoxy)ethoxy]ethoxy}ethan-1-ol, is used in detergents, pesticides, cosmetics, and disinfectants. Since it is found in products that can be inhaled, we evaluated its toxicity to humans upon exposure. A total of 18 rats were exposed to nasal inhalation for 4 hr to determine the acute inhalation toxicity of 2-{2-[2-(4-nonylphenoxy) ethoxy]ethoxy}ethan-1-ol; the exposure concentrations were 5.0, 1.0, and 0.5 mg/L, with three males and three females at each concentration. After the end of the exposure, mortality, general symptoms, and weight changes were observed for 14 days, and autopsy findings were confirmed. The actual concentrations of the test substance in the chamber during the exposure were measured as 3.29, 1.03, and 0.52 mg/L, respectively. The delivered dose was 552.72, 173.04, and 87.36 mg/kg/day for males, and 829.08, 259.56, and 131.04 mg/kg/day for females. As a result of the test in the OECD Test Guideline 436, all animals exposed to a concentration of 3.29 mg/L died; three males and one female died out of six exposed to the 1.0 mg/L concentration. In addition, one died out of six males exposed to a 0.5 mg/L concentration. As a result, 2-{2-[2-(4-nonylphenoxy)ethoxy]ethoxy}ethan-1-ol was considered to be Globally Harmonized System of Classification and Labelling of Chemicals Category 2 (> 0.5–1 mg/L).

The purpose of this study was to investigate the effects of extract mixture of C. wilfordii and P. umbrosa (IPLUS-CWPU) on bone growth in 4-week old young male SD rats. To confirm the effect of IPLUS-CWPU, we measured the length of bone growth plate, the ratio of proliferative zone to the length of growth plate and the expression level of insulin-like growth factor, IGF-1. The IPLUS-CWPU treatment shows a significant increase of tibial and femoral growth plate and the ratio of proliferative zone in growth plate. Especially, the length increased by 13.9% and 25.3% in the tibia and femur, respectively, in the high-dose group compared to the normal group. Moreover, the expression of IGF-1 gene in liver was upregulated in IPLUS-CWPU treated groups. These results indicated that IPLUS-CWPU administration could increase the proliferative zone of bone growth plate in early developmental stage by upregulation of IGF-1 gene.

This study investigated the preventive effect of Dendropanax morbifera leaf extracts (DMLEs) drew out with water, 30, 50 and 70% ethanol against alcohol-induced hepatotoxicity in vitro and vivo. The 3-(4,5-dimethylthiazol-2-yl)-2,5-dipenyltetrazolium bromide (MTT) assay was performed to assess cytotoxic activity of DMLEs, and the half-maximal inhibitory concentration (IC50) ranged between 1.11 and 2.08 mg/mL on Hep3B cells. In preventing ethanol-induced-hepatotoxicity on Hep3B cells, 30 and 50% ethanol DMLEs were significantly effective compared to the 5% ethanol treatment control. In addition, the 30% ethanol DMLE was orally provided to rats 30 min prior to the administration of ethanol (3 mL/kg body weight). At 1, 3 and 5 h after ethanol treatment, the plasma levels of ethanol and acetaldehyde were determined. The 30% ethanol DMLE effectively decreased the plasma ethanol levels during 5 h but increased the plasma acetaldehyde levels until 3 h and then significantly decreased at 5 h, as compared to the control. These results indicate that the 30% ethanol DMLE possesses a potent preventive effect against ethanol-induced liver toxicity in Sprague-Dawley rats.

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.

Abeliophyllum distichum Nakai is a deciduous shrub of a flowering plant in Oleaceae. It is an important plant resource and consists of only one species in the entire world. A. distichum Nakai is well known an edible, medicinal herb in its habitat districts, but the toxicological evaluation for the safe use of its extract is still insufficient. The study characterized the toxicity of an Abeliophyllum distichum Nakai ethanol extract in Sprague-Dawley (SD) rats and determined the safe dosage levels in a 13 weeks toxicity study. Abeliophyllum distichum Nakai ethanol extract was orally administered once daily for 2 weeks at 0, 500, 1,000 and 2,000 mg/kg/day to male and female SD rats. while recording the clinical signs of toxicity, body weight, food intake/consumption, eye test and urine analysis. Only the total protein frequency in the urine of male SD rats (p<0.05), the right ovary of the 500 mg/kg group (p<0.01) and the right adrenal gland of the 1,000 mg/kg group (p<0.05) in the female rats showed statistically significant changes. But no toxic effects were noted from repeated-dose administration of the Abeliophyllum distichum Nakai ethanol extract in the SD rats during the observation period. The post-mortem examinations showed no test substance-mediated changes. The hematological analysis and clinical blood chemistry data demonstrated no toxic effects from repeated-dose administration of Abeliophyllum distichum Nakai ethanol extract in the SD rats during the observation period. Based on these results, this data suggests that a dose of 1,000 mg/kg/day is a highest treatment to administer when conducting a further 13 weeks toxicity study.

Excessive body weight gain during the growth period of early life may predispose individuals towards obesity and metabolic disorder in later life. We investigated the possibility of using the food efficiency ratio as an early indicator for predicting susceptibility to diet-induced obesity and insulin resistance. Four-week-old, prepubertal, male Sprague Dawley rats were divided into obesity-prone and obesity-resistant groups based on food efficiency ratio values after five days on a high-fat diet. Metabolic parameters measured after 2, 6, and 10 weeks, and specific phenotypes were compared with each group. Obesityprone rats had higher increases in body weight and fat mass compared to obesity-resistant rats over the study period. Obesity-prone rats became glucose intolerant early in this study and remained so throughout the experimental period, with increases in fat weight and leptin levels occurring first, followed by increases in insulin level. Gluconeogenesis and insulin resistance significantly increased in obesity-prone groups in which activities of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were increased and glucokinase activity decreased. Higher food efficiency ratio at an early age was closely correlated with body fat accumulation, hyperleptinemia, and hyperinsulinemia of middle and elderly age. We suggest a high food efficiency ratio in prepubertal subjects may be a useful predictor of future obesity and insulin resistance.

The antiobesity effect of commercial kochujang and fermented wheat grains in Sprague-Dawley (SD) rats was studied. The experiment was consisted of 6 groups. Normal, high fat diet (HFD), HFD+raw wheat grains, HFD+first fermented wheat grains (FFWG, with Aspergillus oryzae) HFD+final fermented wheat grains (FiFWG, fermented more for 30~40 days), and HFD+ commercial kochujang. The results showed that final body weight, weight gain, food efficiency ratio, and adipose tissue weight were markedly decreased by the commercial kochujang and the fermented wheat grains, whereas non-fermented raw wheat grains had no such effect. Lipid contents such as total lipid, total triglyceride and total cholesterol decreased in the serum and organs of liver and adipose tissues by the commercial kochujang and the fermented wheat grains as well. These results also indicated that fermented wheat grains exhibited more suppressive effects on high fat induced-obesity than raw wheat grains. Increased fermentation time and adding the red pepper powder resulted in increased the anti-obesity effect. Especially, commercial kochujang showed higher antiobestic effects than fermented wheat grains. These in vivo findings suggested that well-fermented end products of the wheat grains and red pepper powder in kochujang could be useful in the prevention of obesity.

Renal dysplasia is a developmental disorder of the renal parenchyma involving anomalous differentiation. It is characterized by persistent metanephric ducts surrounded by primitive mesenchyme, fetal or immature glomeruli, fetal or immature tubules, interstitial fibrosis, and dysontogenic metaplasia involving tissues such as cartilage. Renal dysplasia has been rarely reported in rats. Here, we observed a small left kidney in a rat used in a short-term repeat toxicity study. The rat showed no clinical signs throughout the study. All parameters, including those reflecting kidney functions, were normal upon hematological examination and urinalysis. Grossly, the kidney was small (5 × 8 mm) and its surface appeared normal. Histological examination revealed that the cortex and medulla were poorly demarcated and contained immature/atrophic glomeruli, immature renal tubules, and mesenchymal cells. The cortex contained immature glomeruli, atrophic glomeruli with cystic dilatation of Bowman’s capsular space, and some atypical tubules. Primitive metanephric tubules in the medulla were larger in diameter than normal collecting ducts, lined by a tall columnar epithelium with pale cytoplasm and basal nucleus, and surrounded by loose mesenchymal cells. Occasional tubules contained pale eosinophilic homogenous material in the lumen. Thus, this was diagnosed as a case of renal dysplasia on the basis of histologic features and is the first reported case of renal dysplasia in Sprague Dawley rats.

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.

오늘날 현대인들의 식생활방식 중 과다한 열량의 영양소 섭취로 인하여 초래되는 비만의 유발 원인 중의 하나로 알려진 고지혈증(hyperlipidemia)에 대한 예방효과가 있는 것으로 알려진 전통방식으로 제조된 고추장의 생리활성 기능성 효과를 분석하고자 하였다. 이 연구에서는 실험동물로서 Sprague-Dawley(SD)-Rat에 대해서 고추장 추출물의 건강증진 효과에 대해서 실험동물을 사용하여 직접 확인하고 시도하였다. 실험군은 실험동물용 일반사료만을 먹인 음성대조군 그룹(N-group)과 일반사료와 고추장 추출물을 동시에 먹인 시험그룹(K-group) 그리고 양성대조군으로 고콜레스테롤 사료만을 먹인 그룹(H-group)으로 구분하여 5주간 사육하면서 건강증진효과의 발현에 대해서 분석하 였다. 3그룹의 실험동물을 5주간의 사육 후 해부했을 때 H-group의 모든 동물(100%)에서 공통적으로 심한 지방간 (fatty liver) 소견이 관찰되었으나, N-group이나 K-group의 어떠한 동물에서도 지방간 소견은 관찰되지 않았다. 한편, 실험동물의 혈장성분에 대한 혈액생화학적 성적의 비교에서는 고지혈증의 예방에 유익한 성분으로 알려진 HDL의 경우, 고추장 추출물 투여 그룹(25±8.43 ㎎/㎗)은 H-group(22.6±4.16) 보다 다소간 상승된 수치를 보였으나, 특히 고지혈 증을 악화시키는 원인으로 알려진 LDL 경우에는 H-group (55.8± 44.8 ㎎/㎗)이 고추장 추출물 투여 그룹(8.6±1.52 ㎎/㎗)과 음성대조군인 N-group(9.8±2.39)의 성적보다도 유의적으로 높은 수치를 나타냈다. 결과적으로 이 연구에서 SD-Rat에 투여했던 고추장 추출물은 실험동물에서 건강기능 개선효과의 하나인 저지방혈증 효과를 발현한 것으로 사료되었다.

Amoxicillin, a well-known antibiotic, has a broad spectrum against gram-negative and gram-positive bacteria. This experiment was conducted in order to investigate the effect of micronized and non-micronized amoxicillin prepared using different comminution techniques on change in blood concentration of rats. Forty adult male Sprague Dawley rats (6~7 weeks of age, body weight 128.3 ± 10.7 g) were randomly allocated to two treatment groups: micronized amoxicillin (MA) group treated with micronized amoxicillin trihydrate powder (particle size, over 90% of 10 μm), non-micronized amoxicillin (NMA) group treated with non-micronized amoxicillin trihydrate powder (particle size, over 70% of 100 μm), given 480 mg/kg body weight once daily for four days. The results showed a significant increase in serum concentration in the MA group on days 3 and 4, compared to the NMA group (P<0.05). In particular, serum concentration of the MA group on day 4 was increased almost two times that of the NMA group. The results indicate that due to the increase of the drug’s oral bioavailability, higher serum concentration would be achieved with the micronized amoxicillin trihydrate than with the non-micronized drug.

SD-rat에 대조구(Control), 고 콜레스테롤(HC), 3.5% 펙틴-가수분해 효소(Viscozyme L)로 처리된 토마토 케이크(ETC) 를 각각 4주 간 급이하였다. 첫 일주일에는 HC-급이군의 체증 증가가 151.7%로 유의적 증가를 보였지만(p<0.05), ETC- 급이군의 경우는 115.4%를 보였다. Control- 및 ETC-급이군의 사료 효율은 각각 0.236±0.041 및 0.447±0.030으로 HC-급 이군의 경우(0.355±0.034)에 비하여 유의적인 차이를 보였다(p<0.05). ETC-급이군의 신장 및 부고환의 지방체는 각각 0.303 및 0.274 g 씩 감소하였다. HC-와 ETC-급이군 간의 혈청 콜레스테롤, 트리글리세라이드, HDL- 및 LDL-콜레스테 롤 수치의 유의적인 차이는 보이지 않았다. ETC-급이군의 경우 2주 급이시 ABTS radicals로 평가한 총 항산화 활성은 약 1.1배 높았으며, 2 및 4주간 급이시 glutathione peroxidase 활성은 각각 2.5 및 1.3배 높게 나타났다.

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.

Cordyceps militaris (CM) has been used as a traditional folk medicine to strengthen the immune system and regain energy in Far East Asian countries. Some of men have been suffered from the insufficient secretion of testosterone causing by physical factors, social and psychological factors. Testosterone is an essential steroid hormone controlling male reproductive function. Alternative medicines in plants, fungi, and insects have been studied to enhance sexuality. Cordyceps species including Cordyceps sinensis and C. militaris has been used as for the enhancement of sexual function for hundreds of years. In the present study, we determined the effect of fruiting bodies of C. militaris which cultured on bee drone medium (DCM) on testosterone concentration in Sprague-Dawley rats. Eighteen rats per group were housed to regular diet or diet supplemented with DCM for 4 weeks. Serum was collected from 6 rats per group. Results showed that changes of the body weight, food and water intake of the rats were not observed in this study. However, DCM significantly stimulated testosterone production (p < 0.05) compared to the control. Hence, it suggests that fruiting bodies of C. militaris grown on the bee drone medium might be developed as a complementary medicine to improve sexual hormones.