Biodistribution and pharmacokinetic evaluation of Korean Red Ginseng components using radioisotopes in a rat model.

Background: Although many studies have evaluated the efficacy and pharmacokinetics of Korean Red Ginseng (KRG) components (Rg1, Rb1, Rg3, Rd, etc.), few have examined the in vivo pharmacokinetics of the radiolabeled components. This study investigated the pharmacokinetics of ginsenosides and their metabolite compound K (CK), 20(s)-protopanaxadiol (PPD), and 20(s)-protopanaxatriol (PPT) using radioisotopes in rat oral administration. Methods: Sprague-Dawley rats were dosed orally once with 10 mg/kg of the tritium(3H) radiolabeled samples, and then the blood was collected from the tail vein after 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 96, and 168 h. Radioactivity in the organs, feces, urine, and carcass was determined using a liquid scintillation counter (LSC) and a bio-imaging analyzer system (BAS). Results and conclusion: After oral administration, as the 3H-labeled ginsenosides were converted to metabolites, Cmax and half-life increased, and Tmax decreased. Interestingly, Rb1 and CK showed similar values, and after a single oral administration of components, the cumulative excretion ratio of urine and feces was 88.9%-92.4%. Although most KRG components were excreted within 96-168 h of administration, small amounts of components were detected in almost all tissues and mainly distributed to the liver except for the digestive tract when observed through autoradiography. This study demonstrated that KRG components were distributed to various organs in the rats. Further studies could be conducted to prove the bioavailability and transmission of KRG components to confirm the mechanism of KRG efficacy.

Long-term evaluation of safety and biological effects of Korean Red Ginseng (Panax Ginseng): a long-term in vivo study.

BACKGROUND: Although Korean Red Ginseng (KRG) is safe, this finding was only evaluated in 3-mo-long studies. Its safety was verified through a 6-mo KRG administration clinical study, but long-term studies beyond 6 mo are insufficient. This study investigated the safety and efficacy of 12-mo KRG administration. METHODS: In this study, 300 mg/kg of KRG was administered to male and female Sprague Dawley rats for 4, 8, and 12 mo to evaluate its efficacy and safety. Clinical signs, including pathological examination and haematological analyses, were observed. Flow cytometric analyses were utilised to analyse spleen and thymus immune cell counts after 12 mo. Proteomic analysis of the sera was performed using a nanospray-interfaced mass spectrometer with an 11-plex Tandem Mass Tag (TMT) labelling system. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis and PANTHER. Data are available via ProteomeXchange with identifier PXD032036. RESULTS: No significant body and organ weight changes were observed, and haematological and serum biochemical analyses did not show clinical significance. The effectiveness of long-term KRG administration was confirmed through increased immune cell distribution and activity. Changes in proteins correlated with viral infection reduction were confirmed through proteomic analysis. CONCLUSION: The results suggested that 12-mo KRG intake is safe, improves immune system activity, and reduces viral infections with no significant changes in toxicological aspects.

Safety of red ginseng and herb extract complex (RHC) in menopausal women: A randomized, double-blind, placebo-controlled trial.

Background: Various treatments are used to relieve menopausal symptoms for women. However, herbal substances are frequently used as complementary and alternative therapies as other treatments can increase ovarian and breast cancer risk. While the herbal substances' therapeutic effect is essential, the safety of their use is considered more important. This study aims to confirm the safety of red ginseng and herb extract complex (RHC), which are used to relieve menopausal symptoms. Methods: This randomized, double-blind, placebo-controlled clinical study recruited and divided 120 women experiencing menopausal symptoms into the RHC and placebo groups (60 women per group). Subjects were administered with 2 g RHC or placebo daily for 12 wk. Adverse reactions, female hormonal changes, and uterine thickness were observed and recorded on wk 0, 6, and 12. Hematologic and blood chemistry tests were also conducted. Results: The reactions of the subjects who received RHC or placebo at least once were analyzed. A total of six adverse reactions occurred in the RHC group, while nine occurred in the placebo group; common reactions observed in both groups were genital, subcutaneous tissue, and vascular disorders. However, there was no statistically significant difference between the administration groups (p = 0.5695), and no severe adverse reactions occurred in both groups. Conclusion: This study confirms the safety of daily intake of 2 g of RHC for 12 wk by menopausal women.

Effects of red ginseng oil(KGC11o) on testosterone-propionate-induced benign prostatic hyperplasia.

Background: Benign prostatic hyperplasia (BPH) is a disease characterized by abnormal proliferation of the prostate, which occurs frequently in middle-aged men. In this study, we report the effect of red ginseng oil (KGC11o) on BPH. Methods: The BPH-induced Sprague-Dawley rats were divided into seven groups: control, BPH, KGC11o 25, 50, 100, 200, and finasteride groups. KGC11o and finasteride were administered for 8 weeks. The BPH biomarkers, DHT, 5AR1, and 5AR2, androgen receptor, prostate-specific antigen (PSA), Bax, Bcl-2, and TGF-ß were determined in the serum and prostate tissue. The cell viability after KGC11o treatment was determined using BPH-1 cells, and, androgen receptor, Bax, Bcl-2, and TGF-ß were confirmed by western blotting. Results: In the in vivo study, administration of KGC11o reduced prostate weight by 18%, suppressed DHT (up to 22%) and 5AR2 (up to 12%) levels from administration of 100 mg/kg KGC11o (P < 0.05). PSA was significantly downregulated dose-dependently from at the concentration of 50 mg/kg KGC11o (P < 0.05). BPH-1 cell viability significantly reduced through the treatment with KGC11o. In vitro and vivo, AR, Bcl-2 TGF-ß levels reduced significantly but Bax was increased (P < 0.05). Conclusion: These results suggest that KGC11o may inhibit the development of BPH by significantly reducing the levels of BPH biomarkers via 5ARI, anti-androgenic effect, and anti-proliferation effect, serving as a potential functional food for treating BPH.

Subacute oral toxicity and bacterial mutagenicity of a mixture of Puerariae radix and Hizikia fusiforme extracts.

The study aims to identify the safety profile of a mixed extract (KGC-02-PS) from two traditional medicinal herbs, Puerariae radix and Hizikia fusiforme. In a subacute oral toxicity study, KGC-02-PS was administered orally for 28 days by gavage to Sprague Dawley rats (both sexes) at a daily dose of 0, 500, 1000, and 2000 mg/kg body weight. Bodyweight, food consumption, and clinical signs were monitored during the experimental period. After administering the final dose, this study conducted hematology, serum biochemistry, and pathological evaluations. In addition, the study performed a bacterial reverse mutation test with varying concentrations of KGC-02-PS (312.5 µg - 5,000 µg/plate) following OECD guideline No. 471, before testing five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) in the presence or absence of metabolic activation. The preclinical evaluation of KGC-02-PS's subacute oral toxicity yielded no associated toxicological effects or any changes in clinical signs, body weight, and food consumption. Moreover, examining KGC-02-PS's hematological and serum biochemical characteristics and pathology yielded no toxicological changes in terms of organ weight measurements and gross or histopathological findings. KGC-02-PS neither increased the number of revertant colonies in all bacterial strains used in the bacterial reverse mutation test, nor did it induce genotoxicity related to bacterial reverse mutations under the study's conditions. Also, KGC-02-PS's no-observed-adverse-effect level was greater than 2000 mg/kg.

Immuno-enhancement effects of Korean Red Ginseng in healthy adults: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Most clinical studies of immune responses activated by Korean Red Ginseng (KRG) have been conducted exclusively in patients. However, there is still a lack of clinical research on immune-boosting benefits of KRG for healthy persons. This study aims to confirm how KRG boosts the immune system of healthy subjects. METHODS: A total of 100 healthy adult subjects were randomly divided into two groups that took either a 2 g KRG tablet or a placebo per day for 8 weeks. The primary efficacy evaluation variables included changes in T cells, B cells, and white blood cells (WBCs) before and after eight weeks of KRG ingestion. Cytokines (TNF-α, INF-γ, IL-2 and IL-4), WBC differential count, and incidence of colds were measured in the secondary efficacy evaluation variables. Safety evaluation variables were used to identify changes in laboratory test results that incorporated adverse reactions, vital signs, hematological tests, blood chemistry tests, and urinalysis. RESULTS: Compared to the placebo group, the KRG intake group showed a significant increase in the number of T cells (CD3) and its subtypes (CD4 and CD8), B cells, and the WBC count before and after eight weeks of the intake. There were no clinically significant adverse reactions or other notable results in the safety evaluation factors observed. CONCLUSION: This study has proven through its eight-week intake test and subsequent analysis that KRG boosts the immune system through an increase in T cells, B cells, and WBCs, and that it is safe according to the study's safety evaluation.

A Systems Biological Approach to Understanding the Mechanisms Underlying the Therapeutic Potential of Red Ginseng Supplements against Metabolic Diseases.

Red ginseng has been widely used in health-promoting supplements in Asia and is becoming increasingly popular in Western countries. However, its therapeutic mechanisms against most diseases have not been clearly elucidated. The aim of the present study was to provide the biological mechanisms of red ginseng against various metabolic diseases. We used a systems biological approach to comprehensively identify the component-target and target-pathway networks in order to explore the mechanisms underlying the therapeutic potential of red ginseng against metabolic diseases. Of the 23 components of red ginseng with target, 5 components were linked with 37 target molecules. Systematic analysis of the constructed networks revealed that these 37 targets were mainly involved in 9 signaling pathways relating to immune cell differentiation and vascular health. These results successfully explained the mechanisms underlying the efficiency of red ginseng for metabolic diseases, such as menopausal symptoms in women, blood circulation, diabetes mellitus, and hyperlipidemia.

13-Week repeated oral dose toxicity study on mixture of Korean red ginseng and deer antler extract in Sprague-Dawley rats.

Owing to an increase in the consumption of herbal products as supplementary diets or functional foods, their safety has become an important issue. Repeated oral administration to rats for 13-week was performed to evaluate the potential toxicity of a mixture of Korean red ginseng and deer antler extract, the most popular traditional herbal ingredients. Three test groups for the mixture of Korean red ginseng and deer antler extract were administered at 500, 1000, and 2000 mg/kg/day in addition to a control group (water for injection). 10 male and 10 female rats were included in each group, and we evaluated the clinical, clinicopathological, and histopathological changes in the rats. One male rat in the test group at 1000 mg/kg/day died; however, it was considered a spontaneous death unrelated to the administration of the test substance. No test substance-related toxic effects were noted in rats in terms of body weight, food consumption, ophthalmological findings, urinalysis, hematological parameters, blood biochemical parameters, organ weights, gross postmortem findings, and histopathological findings. The present results suggest that the no observed adverse effect level of the mixture of Korean red ginseng and deer antler extract was greater than 2000 mg/kg/day in all rats after repeated oral administration for 13-week under the present study conditions.

Proteomic studies of putative molecular signatures for biological effects by Korean Red Ginseng.

BACKGROUND: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. METHODS: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. RESULTS: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. CONCLUSION: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.

Subacute Oral Toxicity and Bacterial Mutagenicity Study of a Mixture of Korean Red Ginseng (Panax ginseng C.A. Meyer) and Salvia plebeia R. Br. Extracts.

As various populations are rapidly becoming an aging society worldwide and interest in health issues has increased, demand for functional foods including herbal products has increased markedly to maintain a healthy state which has led to safety issues about their intake as an inevitable result. The objective of this study was to identify the safety profile of a Korean red ginseng and Salvia plebeia R. Br. extract mixture (KGC-03-PS) which is a valuable ingredient that can be used as a functional food. In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of KGC-03-PS were evaluated. Sprague Dawley rats were administered KGC-03-PS orally for 28 days by gavage. Daily KGC-03-PS dose concentrations were 0, 500, 1,000, or 2,000 mg/kg body weight (bw) per day. Bacterial reverse mutation test with KGC-03-PS dose levels ranging from 312.5 to 5,000 µg/plate was carried out by OECD test guideline No. 471. Five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2) were tested in the presence or absence of metabolic activation by plate incorporation method. There were no toxicological effects related with test substance in the clinical evaluation of subacute oral toxicity test including clinical signs, body weight, and food consumption. Moreover, no toxicological changes related to KGC-03-PS were observed in the hematological and serum biochemical characteristics as well as in the pathological examinations, which included organ weight measurements and in the gross- or histopathological findings. KGC-03-PS did not induce an increase in the number of revertant colonies in all bacterial strains of the bacterial reverse mutation test. The no-observed-adverse-effect level of KGC-03-PS is greater than 2,000 mg/kg bw/day, and KGC-03-PS did not induce genotoxicity related to bacterial reverse mutations under the conditions used in this study.

Nonsaponin fraction of Korean Red Ginseng attenuates cytokine production via inhibition of TLR4 expression.

BACKGROUND: Ginsenosides of Korean Red Ginseng extracts (RGE) and its saponin components suppress secretion of inflammasome-mediating cytokines, whereas the nonsaponin fraction (NS) of RGE oppositely stimulates cytokine secretion. Although direct exposure of NS to macrophages in mice induces cytokine production, oral administration of NS has not been studied in inflammasome-related disease in animal models. METHODS: Mice were fed RGE or NS for 7 days and then developed peritonitis. Peritoneal cytokines were measured, and peritoneal exudate cells (PECs) were collected to assay expression levels of a set of toll-like receptors (TLRs) and cytokines in response to NS ingestion. In addition, the role of intestinal bacteria in NS-fed mice was assessed. The effect of preexposure to NS in bone marrow-derived macrophages (BMDMs) on cytokine production was further confirmed. RESULTS: NS ingestion attenuated secretion of peritoneal cytokines resulting from peritonitis. In addition, the isolated PECs from NS-fed mice presented lower TLR transcription levels than PECs from control diet-fed mice. BMDMs treated with NS showed downregulation of TLR4 mRNA and protein expression, which was mediated by the TLR4-MyD88-NFκB signal pathway. BMDMs pretreated with NS produced less cytokines in response to TLR4 ligands. CONCLUSION: NS administration directly inhibits TLR4 expression in inflammatory cells such as macrophages, thereby reducing secretion of cytokines during peritonitis.

Red ginseng monograph.

Ginseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.

Systemic and Local Anaphylaxis is Not Induced by Korean Red Ginseng Mixture in Guinea Pigs.

Currently, injuries to customers due to health functional foods are annually increasing. To evaluate the antigenicity of Korean red ginseng mixture (KRGM), we tested for systemic anaphylactic shock and passive cutaneous anaphylaxis in guinea pigs. Based on a comparison of measured body weights, there were no changes in body weight for the KRGM treatment group compared with the control group. In the ovalbumin treated group, however, there was a statistically significant decrease in body weight. For the active systemic anaphylaxis test, after the induction, there were no symptoms that suggested anaphylactic shock in the control and KRGM treatment group. In the ovalbumin treated group, there were symptoms that suggested severe anaphylaxis, and those symptoms included restlessness, piloerection, tremor, rubbing or licking the nose, sneezing, coughing, hyperpnea, dyspnea, staggering gait, jumping, gasping and writhing, convulsion, side position and Cheyne-stokes respiration. All animals died within thirty minutes in the ovalbumin treated group. For the passive cutaneous anaphylaxis test in guinea pigs sensitized to KRGM, each anti-serum was diluted in a stepwise manner. This was followed by an intravenous injection of a mixture of KRGM and Evans blue. The results of the test showed that all the responses were negative in the control and the low-dose and high-dose administration groups. However, in the ovalbumin treated group, all the responses were positive. Based on the above results, there were no anaphylactic responses for up to 12 times the amount of human intake of KRGM in Hartley Guinea-pigs. The results suggest that KRGM is safe as measured by the systemic and local antigenicity in guinea pigs.

Subacute oral toxicity and bacterial mutagenicity study of Korean Red Ginseng oil.

BACKGROUND: Red ginseng oil (RGO) is produced by supercritical CO2 extraction of secondary products derived from Korean Red Ginseng extract. As the use of RGO has increased, product safety concerns have become more important. METHODS: In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of RGO were evaluated. Sprague-Dawley rats were orally administered with RGO for 28 d by gavage. Daily RGO dose concentrations were 0 mg/kg body weight (bw), 500 mg/kg bw, 1,000 mg/kg bw, or 2,000 mg/kg bw per day. Bacterial reverse mutation tests included five bacterial strains (Escherichia coli WP2 and Salmonella typhimurium TA98, TA100, TA1535, and TA1537), which were used in the presence or absence of metabolic activation. The plated incorporation method for mutation test was used with RGO concentrations ranging from 312.5 µg to 5,000 µg per plate. RESULTS: The subacute oral toxicity test results did not reveal any marked changes in clinical characteristics. There were no toxicological changes related to RGO administration in hematological and serum biochemical characteristics in either control or treatment animals. Furthermore, no gross or histopathological changes related to RGO treatment were observed. The bacterial reverse mutation test results did not reveal, at any RGO concentration level and in all bacterial strains, any increase in the number of revertant colonies in the RGO treatment group compared to that in the negative control group. CONCLUSION: The no-observed-adverse-effect level of RGO is greater than 2,000 mg/kg bw and RGO did not induce genotoxicity related to bacterial reverse mutations.

The world ginseng market and the ginseng (Korea).

Ginseng is being distributed in 35 countries around the world and there are differences by each country in the distribution volume and amount. However, since there is no accurate statistics on production and distribution amount by each country, it is very difficult to predict the world ginseng market. Ginseng trading companies and governments are in desperate need of comprehensive data that shows the world ginseng market status for sales and marketing. For that reason, this study will look into the approximate size of the world ginseng market based on recent ginseng distribution amount by each country and production by major ginseng producing nations. In addition, the review sets an opportunity to check the status of ginseng (Korea) in the world and presents future direction by examining recent history of ginseng development in Korea, which is one of the world's largest ginseng distributers. Since ginseng is cultivated in limited areas due to its growth characteristics, ginseng distributing countries can be divided based on whether they grow it domestically or not. In general, four countries including South Korea, China, Canada, and the US are the biggest producers and their total production of fresh ginseng is approximately 79,769 tons which is more than 99% of 80,080 tons, the total ginseng production around the world. Ginseng is distributed to different countries in various forms such as fresh ginseng, dried ginseng, boiled and dried ginseng (Taekuksam), red ginseng and the related products, etc. and is consumed as food, dietary supplements, functional food, medical supplies, etc. Also, the world ginseng market including ginseng root and the processed products, is estimated to be worth $2,084 million. In particular, the size of the Korean market is $1,140 million which makes Korea the largest distributer in the world. Since the interests in alternative medicine and healthy food is increasing globally, the consumer market of ginseng with many features and the processed products are expected to expand continuously.

Red ginseng root extract mixed with Torilus fructus and Corni fructus improves facial wrinkles and increases type I procollagen synthesis in human skin: a randomized, double-blind, placebo-controlled study.

Red ginseng contains many bioactive constituents, including various ginsenosides that are believed to have antioxidant, immunostimulatory, and anti-aging activities. Yet, no controlled human study has explored its effects on photoaged skin. This study determined whether long-term intake of a red ginseng extract-containing Torilus fructus and Corni fructus mixture reduces facial wrinkles and increases collagen synthesis in human skin. Healthy female volunteers over 40 years of age were randomized in a double-blind fashion to receive either red ginseng extract-containing herbal mixture at 3 g/day or placebo for 24 weeks. Facial wrinkles, elasticity, epidermal water content, erythema, and pigmentation were measured objectively. Facial skin samples were taken before and after treatment, and real-time polymerase chain reaction and immunohistochemical analyses were undertaken for expression of type I procollagen, matrix metalloproteinase (MMP)-9, and fibrillin-1, which are wrinkle-related biochemical markers. A total of 82 subjects completed the study. Facial wrinkles were significantly improved, type I procollagen gene and protein expression was increased, MMP-9 gene induction was prevented, and fibrillin-1 fiber length was elongated only in the treatment group. No changes were seen in the facial elasticity, epidermal water content, facial erythema and pigmentation, and epidermal thickness in either group. Thus a red ginseng extract-containing Torilus fructus and Corni fructus mixture improves facial wrinkles, a clinical sign of photoaging, and this improvement is associated with biochemical and histological evidence of increased collagen synthesis in the dermis. These results substantiate the alleged beneficial effects of red ginseng on photoaging and support its use as an effective "beauty food."

Effect of ginseng mixture on osteoporosis in ovariectomized rats.

In this study, the authors have characterized the effect of HER-S (red ginseng, Angelicae gigantis Radix, Phyllostachys folium, and soybean extracts) on osteoporosis-associated phenomena in ovariectomized (OVX) rats by measuring body weights and bone histomorphometries in control, sham, OVX, OVX(beta-estradiol-treated), and OVX(HER-S-treated) rats. Light microscopic analyses showed a porous or eroded appearance on the femoral trabecular bone surface in OVX rats, whereas the femoral trabecular bone surfaces of the other groups (control, sham, OVX(17beta-estradiol-treated), and OVX(HER-S-treated) rats) were composed of fine particles. The femoral trabecular bone area and number were decreased in OVX rats, but these reductions were significantly prevented by the administration of HER-S for 7 weeks, similar to estrogen. In the blood biochemistry results, serum phosphorus, calcium, T(3), and T(4) remained unchanged, but blood estrogen levels were significantly increased in HER-S-treated rats, which suggests that estrogen is related to the mechanism of the HER-S-induced antiosteoporosis function in OVX rats.

Physiological Functionality and Enzyme Activity of Biomass from Pichia anomala Grown on Ginseng-Steaming Effluent.

A novel biomass was prepared from Pichia anomala KCCM 11473, which grew well in ginseng-steaming effluent (GSE), and its physiological functionalities and enzyme activities were determined. When the strain was cultured in the GSE (pH 6.0) at 30℃ for 48 h, 1.6 mg of biomass per ml-cultures was produced. The cell-free extract of the biomass showed high antihypertensive angiotensin I-converting enzyme inhibitory activity of 72.0% and anticholesteromia HMG-CoA reductase inhibitory activity of 46.5%. The cell-free extract also showed 13.0 U per ml and 8.5 U per ml of neutral protease activity and alkaline protease, respectively.

Phellinone, a new furanone derivative from the Phellinus linteus KT&G PL-2.

Phellinone, a new furanone derivative, has been isolated from the stem-cooked rice culture broth of Phellinus linteus KT&GPL-2. Phellinone was purified by consecutive solvent partition, silica gel, preparative TLC and preparative HPLC. The structure of phellinone was assigned as a furanone derivative on the basis of various spectroscopic analyses, including Mass and NMR spectroscopies. Its molecular weight and formula were found to be 248 and C15H20O3, respectively, and showed antimicrobial activity against Bacillus subtilis IAM 1090.

Characterization and biological activities of recombinant human plasminogen kringle 1-3 produced in Escherichia coli.

Angiogenesis, the formation of new capillaries from preexisting blood vessels, is involved in many pathological conditions, for example, tumorigenesis, diabetic retinopathy, and rheumatoid arthritis. Angiostatin, which contains the kringle 1-4 domains of plasminogen, is known to be a potent inhibitor of angiogenesis and a strong suppressor of various solid tumors. In this study, we expressed recombinant protein containing the kringle 1-3 domains of human plasminogen in Escherichia coli and investigated its biological activities. The protein was successfully refolded from inclusion bodies and purified at a 30% overall yield, as a single peak by HPLC. The purified recombinant protein had biochemical properties that were similar to those of the native form, which included molecular size, lysine-binding capacity, and immunoreactivity with a specific antibody. The recombinant protein was also found to strongly inhibit the proliferation of bovine capillary endothelial cells in vitro, and the formation of new capillaries on chick embryos. In addition, it suppressed the growth of primary Lewis lung carcinoma and B16 melanoma in an in vivo mouse model. Our findings suggest that the recombinant kringle 1-3 domains in a prokaryote expression system have anti-angiogenic activities, which may be useful in clinical and basic research in the field of angiogenesis.