Effects of Korean red ginseng on T-cell repopulation after autologous hematopoietic stem cell transplantation in childhood cancer patients.

Background: Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. Methods: This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. Results: All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4+ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4+ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28- subset was ameliorated. Conclusions: These findings suggest that KRG promotes the repopulation of CD4+ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.

Characteristics of Korean ginseng varieties of Gumpoong, Sunun, Sunpoong, Sunone, Cheongsun, and Sunhyang.

BACKGROUND: Ginseng (Panax ginseng Meyer) is an important medicinal herbs in Asia. However, ginseng varieties are less developed. METHOD: To developed ginseng varieties, a pure line selection method was applied in this study. RESULTS: Gumpoong was testing of 4-yr-old specimens in 2002, the proportions of the below-ground roots that were rusty colored for Gumpoong was 1.29 in Daejeon and 1.45 in Eumseong, whereas the proportions for its yellow berry variant were 2.60 and 2.45 in the two regions, respectively. Thus the Gumpoong was resistant to root rust. Sunpoong has a high yielding property. Its average root weight is 70.6 g for 6-yr-old roots. Its yield is 2.9 kg/1.62m(2) and the rate of heaven- and earth-grade product is 20.9%, which is very high compared to 9.4% for Yunpoong. Sunone is resistance to root rot and the survival rate of 4-yr-old roots was 44.4% in 1997, whereas that of the violet-stem variant landrace was 21.7%. Sunhyang has content of arginyl-fructosyl-glucose (AFG), which produces the unique scent of red ginseng, is 95.1 µmol/g and greater than the 30.8 µmol/g of Chunpoong in 6-yr-old plants. Sunun and Cheongsun are being nurtured to protect genetic resources. CONCLUSION: Developed ginsneg varieties will be used as the basis for the protection of genetic resources and breeding.

Safety Analysis of Panax Ginseng in Randomized Clinical Trials: A Systematic Review.

Background:Panax ginseng C.A. Meyer is one of the most frequently used herbs in the world. The roots of Panax ginseng have been used as a traditional tonic and medicine for thousands of years in Korea and China. Today, ginseng root is used as a dietary supplement and complementary medicine and for adjuvant therapeutics worldwide. The efficacy of ginseng has been studied in a wide range of basic research and clinical studies. However, it has been reported that the results from clinical studies are conflicting, and they depend on the parameters of the protocol design including the conditions of the participants and the types of ginseng used such as red ginseng, white ginseng, fermented ginseng and cultured ginseng. [...].

Metabolomic approach for discrimination of processed ginseng genus (Panax ginseng and Panax quinquefolius) using UPLC-QTOF MS.

Discriminating between two herbal medicines (Panax ginseng and Panax quinquefolius), with similar chemical and physical properties but different therapeutic effects, is a very serious and difficult problem. Differentiation between two processed ginseng genera is even more difficult because the characteristics of their appearance are very similar. An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS)-based metabolomic technique was applied for the metabolite profiling of 40 processed P. ginseng and processed P. quinquefolius. Currently known biomarkers such as ginsenoside Rf and F11 have been used for the analysis using the UPLC-photodiode array detector. However, this method was not able to fully discriminate between the two processed ginseng genera. Thus, an optimized UPLC-QTOF-based metabolic profiling method was adapted for the analysis and evaluation of two processed ginseng genera. As a result, all known biomarkers were identified by the proposed metabolomics, and additional potential biomarkers were extracted from the huge amounts of global analysis data. Therefore, it is expected that such metabolomics techniques would be widely applied to the ginseng research field.

Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography.

A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides.

Antimetastatic effect of nobiletin through the down-regulation of CXC chemokine receptor type 4 and matrix metallopeptidase-9.

CONTEXT: Nobiletin is one of the citrus bioflavonoids and can be found in citrus fruits such as lemons, oranges, tangerines, and grapefruits. The most studied properties of nobiletin are its anti-inflammatory and anticancer activities. OBJECTIVE: The exact mechanisms of how nobiletin inhibits tumor metastasis and invasion are still not fully understood. In this study, we screened various natural compounds to down-modulate the CXC chemokine receptor-4 (CXCR4) and matrix metallopeptidase-9 (MMP-9). MATERIALS AND METHODS: The effect of nobiletin on the constitutive expressions of CXCR4 and MMP-9, MMP-9 enzymatic activity, associated nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation, and tumor cell invasion in human breast cancer cells was investigated. CXCR4 and MMP-9 expression were evaluated via reverse transcription polymerase chain reaction (RT-PCR) and western blotting. NF-κB activation was also evaluated by electrophoretic mobility shift assay (EMSA). In addition, the antimetastatic effects of nobiletin were determined by gelatin zymography and invasion assay. RESULTS: Nobiletin down-regulated both the constitutive expressions of CXCR4 and MMP-9 in human breast cancer cells with IC(50) values of 32 and 24 µM, respectively. Nobiletin also suppressed MMP-9 enzymatic activity and tumor cell invasion under noncytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the nobiletin-induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the down-regulation of CXCR4 and MMP-9 were at the transcriptional level, as indicated by the down-regulation of mRNA expression and the suppression of the constitutive NF-κB and MAPKs activation. DISCUSSION AND CONCLUSION: Our results indicate, for the first time, that nobiletin is a novel blocker of CXCR4 and MMP-9 expressions and thus has the potential to suppress metastasis of breast cancer.

The hydrolyzed products of iridoid glycoside with ß-glucosidase treatment exert anti-proliferative effects through suppression of STAT3 activation and STAT3-regulated gene products in several human cancer cells.

CONTEXT: Iridoids belong to a group of monoterpene compounds with cyclopentane ring and found as mostly the glycoside forms in nature. They act primarily as the defense substances and found in various medicinal plants. OBJECTIVE: Although many iridoids exhibit anti-inflammatory and anticancer activities, their molecular targets/pathways are not fully understood. Here, the antiproliferative effect of the hydrolyzed-iridoid product (H-iridoid) form through the STAT3 signaling pathways on tumor cells was investigated. MATERIALS AND METHODS: H-iridoids were obtained from five iridoid glycosides with ß-glucosidase treatment. The effects of several H-iridoids on cell viability and cell proliferation in tumor cells were measured by the MTT assay. The phosphorylation levels of STAT3, its regulatory molecules, and apoptosis by H-geniposide treatment in DU145 cells were investigated by immunoblots and flow cytometry. RESULTS: No single iridoid glycoside exerted any cytotoxicity in the tumor cells, whereas H-iridoids had significant cytotoxic, antiproliferative, and STAT3 inhibitory effects and revealed different potencies depending on their chemical structures. Among the H-iridoids tested, H-geniposide inhibited constitutive STAT3 activation through inhibiting upstream JAK1 and c-Src. Consistent with STAT3 inactivation, H-geniposide downregulated the expressions of Bcl-2, Bcl-xL, survivin, and cyclin D1; this correlated with the accumulation of cells in the sub-G1 phase of the cell cycle and the induction of apoptosis. DISCUSSION AND CONCLUSIONS: Our results indicate that the hydrolysis of the glycosidic bond from iridoid glycoside is required for exhibiting cytotoxicity in tumor cells. H-geniposide is the most potent agent and a novel blocker of STAT3 activation in DU145 cells.

Inhibitory Potencies of Several Iridoids on Cyclooxygenase-1, Cyclooxygnase-2 Enzymes Activities, Tumor Necrosis factor-α and Nitric Oxide Production In Vitro.

To verify the anti-inflammatory potency of iridoids, seven iridoid glucosides (aucubin, catalpol, gentiopicroside, swertiamarin, geniposide, geniposidic acid and loganin) and an iridoid aglycone (genipin) were investigated with in vitro testing model systems based on inhibition of cyclooxygenase (COX)-1/-2 enzymes, the tumor necrosis factor-α (TNF-α) formation and nitric oxide (NO) production. The hydrolyzed-iridoid products (H-iridoid) with ß-gludosidase treatment only showed inhibitory activities, and revealed different potencies, depending on their chemical structures. Without the ß-gludosidase treatment, no single iridoid glycoside exhibited any activities. The aglycone form (genipin) also did not show inhibitory activities. To compare anti-inflammatory potency, the inhibitory concentrations (IC(50)) in each testing system were measured. The hydrolyzed-aucubin product (H-aucubin) with ß-gludosidase treatment showed a moderate inhibition on COX-2 with IC(50) of 8.83 µM, but much less inhibition (IC(50), 68.9 µM) on COX-1 was noted. Of the other H-iridoid products, the H-loganin and the H-geniposide exhibited higher inhibitory effects on COX-1, revealing IC(50) values of 3.55 and 5.37 µM, respectively. In the case of TNF-α assay, four H-iridoid products: H-aucubin, H-catalpol, H-geniposide and H-loganin suppressed the TNF-α formation with IC(50) values of 11.2, 33.3, 58.2 and 154.6 µM, respectively. But other H-iridoid products manifested no significant activity. Additional experiments on NO production were conducted. We observed that only the H-aucubin exhibited a significant suppression with IC(50) value of 14.1 µM. Genipin, an agycone form, showed no inhibitory effects on all testing models, implying the hydrolysis of the glycosidic bond of iridoid glycoside is a pre-requisite step to produce various biological activities.

A Milestone in Codifying the Wisdom of Traditional Oriental Medicine: TCM, Kampo, TKM, TVM-WHO International Standard Terminologies on Traditional Medicine in the Western Pacific Region.

The WHO published a dictionary-type book entitled 'WHO International Standard Terminologies on Traditional Medicine in the Western Pacific Region' which has a total of 3259 technical terms which have been commonly used in traditional Chinese (TCM), Japanese (Kampo), Korean (TKM) and Vietnamese (TVM) medicines. In this comprehensive guide, each term has the English expression, the original Chinese character and a concise English definition. The book covers 3106 terms from basic theories, diagnostics, diseases, various therapeutics including acupuncture and moxibustion and even the English wording of 153 titles which are considered the most important traditional medical classics published in these four countries. A prominent feature of the compilation is the codification format that assigns numbers in hundred decimal units for each category of the section. This type of coding system provides the flexibility for adding more terminologies in the future and is useful for constructing a database for the retrieval of various published scientific articles. Overall, the usage of these standard terminologies is highly desirable to deliver accurate meanings, and ultimately to avoid a variety of expressions for a single term in different scientific manuscripts on Oriental medicine.

Elucidation of anti-inflammatory potencies of Eucommia ulmoides bark and Plantago asiatica seeds.

This study elucidated possible mechanisms for the different anti-inflammatory potencies exhibited by the water extracts of Eucommia ulmoides bark and Plantago asiatica seeds, which contain various iridoids. Water extracts of both herbal materials were tested in vitro with a battery of assay models: lipopolysaccharide-induced thromboxane B(2) for cyclooxygenase-1 (COX-1), prostaglandin E(2) for cyclooxygenase-2 (COX-2), the translocation of nuclear factor-kappaB (NF-kappaB), and tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) production in RAW 264.7 cells. The contents of the iridoid glycosides, aucubin (AU), catalpol (CA), and geniposide (GE), were quantified by high-performance liquid chromatography (HPLC). Neither E. ulmoides nor P. asiatica suppressed the COX-1 enzyme. P. asiatica significantly inhibited COX-2 (concentration required for 50% inhibition [IC(50)] = 8.61 (microg/mL), TNFalpha (IC(50) = 9.63 (microg/mL), and NO (IC(50) = 8.65 (microg/mL) production. P. asiatica blocked the translocation of NF-kappaB from the cytosol to the nucleus. E. ulmoides suppressed only the COX-2 enzyme (IC(50) = 9.92 (microg/mL). The results of the HPLC analysis revealed that P. asiatica contained three iridoid glycosides, AU, CA, and GE. E. ulmoides contained CA and GE, but no AU was detected. The difference in the anti-inflammatory potencies of E. ulmoides and P. asiatica appears to be dependent on the presence of AU. Considering the IC(50) values, both herbal extracts exhibit modest and less potent anti-inflammatory activities than common synthetic non-steroidal anti-inflammatory drugs.

The practice of Korean medicine: an overview of clinical trials in acupuncture.

Acupuncture, one of the Oriental medical therapeutic techniques that can be traced back at least 2500 years, is growing in popularity all over the world. Korea has continued to develop its own unique tradition of medicine throughout its long history, and has formed different types of acupuncture methods. The purpose of this review is to summarize clinical case studies in acupuncture and related therapies, such as acupressure, electric acupuncture, auricular acupuncture and moxibustion in Korea. A survey of Korean journals revealed that a total of 124 studies were published from 1983 to 2001. Results obtained from the survey showed that most clinical studies using acupuncture, electric acupuncture, moxibustion and other traditional therapies could alleviate a relatively broad range of medical problems. However, it should be emphasized that almost all clinical case studies published in various local journals did not follow the 'good clinical practice' with respect to regulatory aspects. Since they were not conducted using the randomized double-blinded controls with a large sample size, all the results should be considered as therapeutic indications. This review is an attempt to show the scope of acupuncture in our country and the kind of diseases, after many years of clinical experience, that were deemed valid targets for clinical trials.

An Overview of Traditional Chinese Herbal Formulae and a Proposal of a New Code System for Expressing the Formula Titles.

Traditional Chinese herbal therapy can be characterized by the use of a large number of multi-herb formulae. To provide modern and Western scientists without knowledge of Chinese literature and cultural background easy access to information, a database with a total of 11 810 traditional Chinese herbal formulae was constructed. All the information was then translated into understandable scientific terms in English. While coining the formula titles in English, we discovered some principles governing the naming of titles by using computer analysis. In addition, we observed that about 92% of the formulae are in the range of single-herb formulae to thirteen-herb formulae. Most large number-herb formulae are formulated by combining pre-existing smaller number-herb formulae. The King herbs () with major therapeutic activity in a multi-herb formula were identified by the formulation concept using two parameters: the herbal dose and the herbal drug property (the degree of toxicity). Based on such analytical data, we established an English code system representing all formula titles written in ideographic Chinese characters: an array of important key words such as 'Herbal name in Latin + Efficacy (Target organs) + Preparation form + Number of herbs.' By searching the English version of the database with any of the above key words, a variety of information on the status of traditional Chinese herbal therapy can be accessed.

Inhibition of sortase, a bacterial surface protein anchoring transpeptidase, by beta-sitosterol-3-O-glucopyranoside from Fritillaria verticillata.

A glucosylsterol, beta-sitosterol-3-O-glucopyranoside, has been isolated as an active principle with sortase inhibitory effect from the bulbs of Fritillaria verticillata by bioassay-guided chromatographic fractionation. The isolate was a potent inhibitor of sortase, with an IC(50) value of 18.3 microg/ml and had antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Micrococcus leuteus with MIC values of 50, 200, and 400 microg/ml, respectively, indicating that this compound is a possible candidate for the development of a bacterial sortase inhibitor. In addition, sitosterol was found to be inactive upon sortase and bacterial cell growth. These results suggest that the inhibitory potency of beta-sitosterol-3-O-glucopyranoside is sensitively dependent upon the glucopyranoside side chain moiety.

Inhibition of the bacterial surface protein anchoring transpeptidase sortase by medicinal plants.

Inhibition by medicinal plant extracts of a recombinant sortase was evaluated for antibacterial drug discovery. The coding region of sortase, a transpeptidase that cleaves surface proteins of gram-positive bacteria, was amplified by PCR from the chromosome of Staphylococcus aureus ATCC 6538p with the exception of an N-terminal membrane anchor sequence, expressed in Escherichia coli, and purified by metal chelate affinity chromatography. The purified sortase had maximum activity at pH 7.5 and was stable at 20-45 degrees C for the cleavage of a synthetic fluorophore substrate. The enzyme inhibitory activity in medicinal plants was also evaluated for antibacterial drug discovery. Among 80 medicinal plants tested, Cocculus trilobus, Fritillaria verticillata, Liriope platyphylla, and Rhus verniciflua had strong inhibitory activity. The extract with the greatest activity was the ethyl acetate fraction derived from the rhizome of Cocculus trilobus (IC50 = 1.52 microg/ml).