• Journal of Microbiology and Biotechnology
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• 제7권4호
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• pp.272-277
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• 1997

In the purification of elaiophylin from a culture of Streptomyces hygroscopicus MCY -846, mono- and di-methyl-elaiophylin were obtained through a O-methylation of the hemiketal hydroxy group of elaiophylin. All the three elaiophylins showed cytotoxicity against several human tumor cell lines and murine cell lines. Elaiophylin and monomethyl-elaiophylin also showed antimicrobial activities against gram-positive bacteria and potent inhibitory effects on the activation of B cells by lipopolysaccharide as well as on the proliferation of mouse splenic lymphocytes stimulated by mitogens but dimethyl-elaiophylin did not. This result indicates that elaiophylin and monomethyl-elaiophylin would be strong immunosuppressants. Furthermore this result revealed an interesting structure-activity relationship suggesting that the lack of symmetry and/or the free OH group at C-11 of elaiophylin might be important in conferring biological activities.

• IMMUNE NETWORK
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• 제11권1호
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• pp.42-49
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• 2011

Background: In this study, we have investigated the effect of Korean red ginseng (KRG) extracts on the production of TNF-${\alpha}$ and IL-8 in human keratinocytes. Also, to examine the antioxidative effect of red ginseng extracts, free radical scavenging activity and superoxide dismutase (SOD) activity in human dermal fibroblasts was measured. Methods: To investigate the effect of KRG in atopic dermatitis, we measured the level of TNF-${\alpha}$ and IL-8 secretion in LPS-stimulated human keratinocytes after the treatment of KRG extracts using enzyme-linked immunosorbent assay. Anti-oxidative activity was investigated by measuring 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and SOD activity. Results: The stimulation of human keratinocytes with KRG extracts shifted the LPS-induced cytokine secretion toward a more immunosuppressive response. KRG dose-dependently decreased TNF-${\alpha}$ and IL-8 production in HaCaT cells and a significant inhibition of TNF-${\alpha}$ was shown when cells were treated with 500 and $1,000{\mu}g/ml$ of KRG extracts. Additionally, KRG extracts showed DPPH radical scavenging and SOD activity in a dose-dependent manner. Particularly, SOD activities of concentrations higher than $60{\mu}g/ml$ of KRG extracts were significantly different in human dermal fibroblast cells. Conclusion: Based on this study, KRG extracts may be a useful immunosuppressive agent in the treatment of atopic dermatitis.

• Preventive Nutrition and Food Science
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• 제8권1호
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• pp.7-12
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• 2003

This study examined the effect of pine needle distillate (Pinus densiflora Sieb. et Zucc) on the immune system and hematological parameters. C57BL/6 male mice weighing 20 ~21 g were divided into 3 groups and intraperitonially injected with either 200 $\mu$L of saline (control), 50% diluted (P50) or 100% pine needle distillate (P100) once a day for 24 days. At the end of the experiment, the mice were anesthetized by ether and peripheral blood was collected from the femoral artery and the spleen was excised. Spleen weight decreased significantly (p<0.001) in the pine needle groups compared to the control group. The blood was used for a complete blood count and flow cytometrical analysis after immunofluorescence staining. The pine needle distillate dose-dependently decreased the CD4$^{＋}$/CD8 sup ＋/ ratio (p <0.05), and showed a tendency to increase the mean FSC (forward scatter) values of the CD8$^{＋}$T cells, while decrease the values of the CD4$^{＋}$T cells. There were no significant differences in WBC, RBC and platelet counts among the three groups, but hemoglobin and hemoglobin-related parameters and platelet volume increased and red blood cell volumes decreased with the administration of the pine needle distillate. These results suggest that the pine needle distillate may have immunosuppressive effects.

• Journal of Ginseng Research
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• 제46권6호
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• pp.711-721
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• 2022

The immune system is one of the most important parts of the human body and immunomodulation is the major function of the immune system. In response to outside pathogens or high inflammation, the immune system is stimulated or suppressed. Thus, identifying effective and potent immunostimulants or immunosuppressants is critical. Ginsenosides are a type of steroid saponin derived from ginseng. Most are harmless to the body and even have tonic effects. In this review, we mainly focus on the immunostimulatory and immunosuppressive roles of two types ginsenosides: the protopanaxadiol (PPD)-type and protopanaxatriol (PPT)-type. PPT-type ginsenosides include Rg1, Rg2, Rh4, Re and notoginsenoside R1, and PPD-type ginsenosides include Rg3, Rh2, Rb1, Rb2, Rc, Rd, compound K (CK) and PPD, which activate the immune responses. In addition, Rg1 and Rg6 belong to PPT-type ginsenosides and together with Rg3, Rb1, Rd, CK show immunosuppressive properties. Current explorations of ginsenosides in immunological areas are in the preliminary stages. Therefore, this review may provide some novel ideas to researchers who study the immunoregulatory roles of ginsenosides.

• 혜화의학회지
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• 제10권1호
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• pp.29-46
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• 2001

In the result of investigating traditional chinese medical literatures to understand definite immunopharmacologic effects of drugs for clearing away heat and detoxicating such as Ampelopsis Radix, Rhapontici Radix, Cremastrae Appendiculatae Tuber, Rhaseoli Radiati Semen, Potentillae Discolohs Herba, Potentillae Chinensis Herba, Chrysanthemi Indici Flos, Lomcerae Caulis, we could reach conclusions as follows: 1. Rhapontici Radix, Chrysanthemi Indici Flos can increase voracity of leukocytes, macrophages and increase to produce IL-2 by splenocytes. 2. Potentillae Chinensis Herba, Chrysanthemi Indici Flos, Lonicerae Caulis can inhibit activities of B lymphocytes and have anti-inflammatory effects. 3. Drugs for clearing away heat and detoxicating almost have antibiotic, anti-inflammatory effects, and so can be applied to many inflammatory immune diseases. 4. Drugs for clearing away heat and detoxicating also have antifebrile, diuretic, detoxicating effects. Above results indicates that Drugs for clearing away heat and detoxicating have immunosuppressive effect, so that can be applied to many inflammatory immune diseases.

• Molecules and Cells
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• 제28권2호
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• pp.125-130
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• 2009

Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological effects of tacrolimus on $CD4^+$ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on $CD4^+$ T cell subsets. Mouse or human $CD4^+$ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of $CD4^+$ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed T cells were examined by quantitative PCR. In the case of conventional $CD4^+$ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division of regulatory $CD4^+$ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules.

• Toxicological Research
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• 제8권2호
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• pp.191-203
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• 1992

The immunosuppressive effects of safrole were studied in female BALB/c mouse. Mice were given 100,200and 400mg safrole/kg daily for 14days and evaluated on day 15. The day 4 immunogloblin-M antibody response to T-dependent antigen, sheep red blood cells (SRBC) was inhibited dose-dependently in all doses studied. In vitro antibody response to polyclonal antigen, lipopolysaccharide (LPS) by spleen cell suspensions from safrole-treated mice were also significantly inhibited. When safrole was treated for 14days to mice, and mitogen-induced proliferation of splenocytes were assayed on day 15, there were significant suppression of responses to B-cell mitogen, LPS and T-cell mitogen concanavalin A(Con A) at a dose of 400mg safrole/kg. Direct addition of safrole on the splenocyte culture also produced a dose dependent suppression on in vitro antibody response to LPS, and mitogen-induced lymphoproliferatin at doses of 100,200,400 and 800${\mu}M$ safrole. The role of metabolic activation in safrole-induced suppression of in vitro antibody response was studied using splenocyte-hepatocyte coculture system. The suppression of in vitro antibody respose to LPS by safrole was not altered when safrole were incubated in the splenocyte-hepatocyte system for 4hr as compared with direct addition of safrole in splenocytes culture. Neither the addition of salicylamide, sulfotransferase inhibitor, nor the addation of inorganic sulfate, sulfation cofactor to the splenocyte-hepatocyte coculture, altered the suppression of antibody response by safrole. These results suggest that the immunosuppression by safrole may not by produced by the reactive metabolites which are mediated in carcinogenesis of safrole.

• Journal of Ginseng Research
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• 제44권4호
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• pp.538-543
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• 2020

Cardiovascular diseases are a rapidly growing epidemic with high morbidity and mortality. There is an urgent need to develop nutraceutical-based therapy with minimum side effects to reduce cardiovascular risk. Panax ginseng occupies a prominent status in herbal medicine for its various therapeutic effects against inflammation, allergy, diabetes, cardiovascular diseases, and even cancer, with positive, beneficial, and restorative effects. The active components found in most P. ginseng varieties are known to include ginsenosides, polysaccharides, peptides, alkaloids, polyacetylene, and phenolic compounds, which are considered to be the main pharmacologically active constituents in ginseng. P. ginseng is an adaptogen. That is, it supports living organisms to maintain optimal homeostasis by exerting effects that counteract physiological changes caused by physical, chemical, or biological stressors. P. ginseng possesses immunomodulatory (including both immunostimulatory and immunosuppressive), neuromodulatory, and cardioprotective effects; suppresses anxiety; and balances vascular tone. P. ginseng has an antihypertensive effect that has been explained by its vasorelaxant action, and paradoxically, it is also known to increase blood pressure by vasoconstriction and help maintain cardiovascular health. Here, we discuss the potential adaptogenic effects of P. ginseng on the cardiovascular system and outline a future research perspective in this area.

• Toxicological Research
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• 제26권3호
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• pp.163-170
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• 2010

Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in transplant surgery and the treatment of several autoimmune diseases. However, major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity and cardiovascular diseases have substantially limited its usage. Although molecular mechanisms underlying these adverse effects are not clearly understood, there is some evidence that suggests involvement of reactive oxygen species (ROS). In parallel, protective effects of various antioxidants have been demonstrated by many research groups. Extensive studies of CsA-induced nephrotoxcity have confirmed that the antioxidants can restore the damaged function and structure of kidney. Subsequently, there have appeared numerous reports to demonstrate the positive antioxidant effects on liver and other organ damages by CsA. It may be timely to review the ideas to envisage the relationship between ROS and the CsA-induced toxicity. This review is comprised of a brief description of the immunosuppressive action and the secondary effects of CsA, and a synopsis of reports regarding the antioxidant treatments against the ROS-linked CsA toxicity. A plethora of recent reports suggest that antioxidants can help reduce many CsA's adverse effects and therefore might help develop more effective CsA treatment regimens.

• Genomics & Informatics
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• 제6권4호
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• pp.227-230
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• 2008

Compounds of polyketide origin possess a wealth of pharmacological effects, including antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive activities. Many of these compounds and their semisynthetic derivatives are used today in the clinic. Most of the gene clusters encoding commercially important drugs have also been cloned and sequenced and their biosynthetic mechanisms studied in great detail. The area of biosynthetic engineering of the enzymes involved in polyketide biosynthesis has recently advanced and been transferred into the industrial arena. In this work, we introduce a computational system to provide the user with a wealth of information that can be utilized for biosynthetic engineering of enzymes involved in post-PKS tailoring steps. Post-PKS tailoring steps are necessary to add functional groups essential for the biological activity and are therefore important in polyketide biosynthesis.