• The Korea Journal of Herbology
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• v.34 no.3
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• pp.31-36
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• 2019

Objectives : In this animal study, we performed the single oral dose toxicity test of Standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30% ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying approximate lethal dose (ALD). Methods : According to OECD guidelines for the testing of chemicals section 4 health effects test No. 420 acute oral toxicity study - fixed dose procedure (17 December 2001), single oral dose toxicity test was performed. Animals were divided into two groups: Group 1, vehicle-treated rats (Control); Group 2, SCP 5000 mg/kg treated rats. SCP is composed of two medicinal herbs: Cornus officinalis Sieb. et Zucc. (650 g) and Psoralea corylifolia L. (350 g) in 30% ethanol. SCP was once orally administered to female and male SD rats at dose levels of 5000 mg/kg. Animals were monitored on the mortality, clinical signs, body weight changes and necropsy findings for 14 days. Results : After single oral treatment of SCP, we could not find any mortality up to 5000 mg/kg. Compared with the control group, there were also no significant differences in clinical sign, weight change, weight gain and gross abnormalities in SCP 5000 mg/kg-treated group. Conclusions : Taken together, these results suggest that the ALD of SCP in both female and male SD rats were considered as over 5000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• Parasites, Hosts and Diseases
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• v.61 no.3
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• pp.282-291
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• 2023

Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t_1/2 was 0.97 h, T_max was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED₅₀) and ED₉₀ values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89-treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

• Natural Product Sciences
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• v.12 no.4
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• pp.247-253
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• 2006

The antitumor activity of crude saponin mixture obtained from Luffa tuberosa (Roxb.) (Fam; Cucurbitaceae) hairy roots (CSLT) in mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC-bearing mice receiving 150 and $300{\mu}g/kg$ body weight, (i.p) of CSLT have shown a dose dependent elevation in tumor-tree survival and a highest number of survivors were observed after administration of CSLT $(300{\mu}g/kg)$, which was considered as an optimum dose for its antineoplastic action. The mean survival time (MST) for this dose was approximately $47.1{\pm}0.74d$, when compared with $19.0{\pm}0.36d$ of untreated control. Administration of $300{\mu}g/kg$ CSLT resulted in 130% long-term increased survival time. The measurement of body weight, tumor volume, packed cell volume, viable and non-viable count indicated the efficacy of CSLT in tumor-bearing mice, there was a significant recovery in hematological profiles, and there was depletion in lipid peroxidation levels, and the antioxidant enzyme activities such as GSH, SOD and CAT were restored to near the normal levels. The CSLT was found to be devoid of conspicuous short-term toxicity in the mice when animals were intraperitoneally injected with 250, 500, 750 and $1000{\mu}g/kg$ bodyweight. The treated mice showed conspicuous toxic symptoms only at a dose of $1500{\mu}g/kg$. Mortality of the animals was monitored up to 14 d post drug treatment, $1/7^{th}$ of the $LD_{50}$ dose has been considered for the optimal antineoplastic activity.

• Advances in Traditional Medicine
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• v.7 no.4
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• pp.418-425
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• 2007

The study was to evaluate the antihyperglycemic activity of Biophytum sensitivum (L.) DC in different extracts. Albino Wistar rats with alloxan hydrate induced diabetes were divided into 7 groups of 6 each. Both aqueous and methanolic extract of Biophytum sensitivum were prepared and given individually at different doses to different batches of rats (both normal and diabetic rats) after an overnight fast. Methanolic extract at the dose of 200 mg/kg body weight showed maximum blood glucose lowering effect in diabetic rats. The same dosages did not produce any hypoglycemic activity in normal rats. The antihyperglycemic activity of Biophytum sensitivum was compared with a standard drug Glibenclamide, an oral hypoglycemic agent. The above results suggest that maximum hypoglycemic effect was found only with a dose of up to 200 mg/kg b.w. of methanolic extract which is therefore the optimum dose for hypoglycemia and was used in all the experiments of the present study.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.89-94
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• 2001

The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

• Natural Product Sciences
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• v.11 no.3
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• pp.155-159
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• 2005

The aqueous extract of Coscinium fenestratum was studied for its antioxidant status in STZ-nicotinamide induced type 2 diabetic rats at two dose levels of 250 mg/kg and 500 mg/kg. At the end of the experimental period, diabetic rats treated with aqueous extract at both dose levels showed a significant increase in the levels of enzymatic antioxidants such as glutathione peroxidase, glutathione synthetase, peroxidase, superoxide dismutase and catalase as compared to the untreated control. Similarly, a significant increase was also observed in the levels of the non enzymatic antioxidants ceruloplasmin, ascorbic acid and tocopherol. The results suggest that the aqueous stem extract of C. fenestratum prevents type 2 diabetes mellitus induced oxidative stress.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.111-115
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• 2009

The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.

• Advances in Traditional Medicine
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• v.4 no.3
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• pp.197-209
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• 2004

The study was aimed at evaluating the antioxidant and antimicrobial activities of methanol extract of Caesalpinia bonducella leaves (MECB) (Family: Caesalpiniaceae). The effect of MECB on antioxidant activity, reducing power, free radical scavenging (DPPH radical, nitric oxide radical, superoxide anion radical, hydroxyl radical and hydrogen peroxide radical scavenging), total phenolic content and antimicrobial activities were studied. The antioxidant activity of MECB increased in a dose dependent manner. About 50, 100, 250 and 500 g of MECB showed 53.4, 61.2, 69.1 and 76.2 % inhibition respectively on peroxidation of linoleic acid emulsion. Like antioxidant activity, the effect of MECB on reducing power increased in a dose dependent manner. The free radical scavenging activity of MECB was determined by DPPH radical scavenging method. The potency of this activity was increased with increased amount of extract. MECB was found to inhibit the nitric oxide radicals generated from sodium nitroprusside $(IC_{50}\;=\;102.8\;g/ml)$ whereas the $IC_{50}$ value of curcumin was 20.4 g/ml. Moreover, the MECB was found to scavenge the superoxide generated by photoreduction of Riboflavin. MECB was also found to inhibit the hydroxyl radical generated by Fenton reaction, where the $IC_{50}$ value is 104.17 g/ml compared with catechin 5 g/ml, which indicates the antioxidant activity of MECB. The MECB capable of scavenging hydrogen peroxide in a concentration-dependent manner. The amounts of total phenolic compounds were also determined. Antimicrobial activities of MECB were carried out using disc diffusion methods with five Gram positive, four Gram negative and four fungal species. The results obtained in the present study indicate that MECB leaves are potential source of natural antioxidant and antimicrobial agents.

• Advances in Traditional Medicine
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• v.7 no.3
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• pp.244-253
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• 2007

The present study was carried out to investigate the antihyperglycemic, antihyperlipidemic and antioxidant effect of chloroform and methanol extract of whole plant of Ichnocarpus frutescens (CEIF and MEIF) in streptozotocin (STZ)-induced diabetic rats. Administration of CEIF and MEIF orally at the dose of 200 mg/kg and 400 mg/kg body weight resulted in significant (P<0.01) reduction in blood glucose levels. The body weights were significantly (P<0.001) reduced in STZ-induced diabetic rats when compared to normal rats while the extracts significantly (P<0.01) prevented the decrease in body weight in the CEIF and MEIF treated rats. The study was further undertaken to evaluate the antioxidant and antihyperlipidemic potential of CEIF and MEIF in STZ-induced diabetic rats. The increased levels of lipid peroxidation in the liver tissues of diabetic rats were significantly reverted back to normal levels and a significant increase in activity of antioxidant enzymes such as superoxide dismutase, catalase and the level of reduced glutathione in the liver of diabetic rats after the treatment with CEIF and MEIF was noticed. These results clearly indicate that CEIF and MEIF exhibit significant antihyperglycemic, antihyperlipidemic and in vivo antioxidant activity in STZ-induced diabetic rats and the results were found to be in a dose dependent manner.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.915-918
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• 2004

By bioassay-guided separation, an already known saponin, Pulsatilla saponin D was isolated from the root of Pulsatilla koreana Nakai as a antitumor component when evaluated by in vivo antitumor activity as well as in vitro cytotoxic activity test. It showed potent inhibition rate of tumor growth (IR, 82％) at the dose of 6.4 mg/kg on the BDF1 mice bearing LLC cells.