• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.145-151
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• 2012

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured $in$ $vivo$ phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its $in$ $vivo$ PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.

• Journal of Microbiology and Biotechnology
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• v.9 no.5
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• pp.672-674
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• 1999

Cepacidine A was first identified as a novel antifungal antibiotic which was isolated from the culture broth of Pseudomonas cepacia AF200l. It showed a potent in vitro antifungal activity against various pathogenic fungi, but did not show any activity against bacteria. Recently, the immunosuppressive action of cepacidine A was discovered using an in vitro screening system involving inhibition of the proliferation of murine lymphocytes stimulated by 2 mitogens, and also by in vivo mouse models involving inhibition of delayed type hypersensitivity and SRBC hemagglutination. Cepacidine A showed a significant activity of cellular immunosuppression (ED/sub 50/) at concentration levels of 1-3 ㎎/㎏, i.p.. Unfortunately, the delayed toxicity at a dose of above 3 ㎎/㎏ i.p. was apparent.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.1-10
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• 2020

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

• Archives of Pharmacal Research
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• v.26 no.3
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• pp.192-196
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• 2003

This study describes the synthesis of novel enol esters (3) and triketones (4) as analogues of succinylacetone (SA) (Ed- this abbreviation is introduced here based on your use of it in the body of the paper) and the evaluation on the mouse allogeneic mixed lymphocyte reaction (MLR) and the murine model of antigen-induced paw edema formation for immunosuppressive activity. Enol esters (3a-f) were about 2-4 fold more potent than SA in in vitro activity.

• Archives of Pharmacal Research
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• v.26 no.3
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• pp.197-201
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• 2003

Novel $\beta$-hydroxy propenamides as analogues of the active metabolite of leflunomide (A 771726) were synthesized and evaluated for their inhibitory activity on dihydroorotate dehydrogenase (DHODH) in an investigation into their immunosuppressive activity. Compounds 2a, 3a, and 3h were approximately 4-40 times more potent than leflunomide in their activity while they were-less active than A 771726.

• Archives of Pharmacal Research
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• v.14 no.2
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• pp.147-159
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• 1991

Effects of twenty-one different flavonoids and their related compounds on the phagocytosis of colloidal carbon by macrophages in liver and spleen humoral immune responses against bacterial $\alpha$-amylase and cellular immune responses against oxazolone and dinitrofluorobenzene were studied in vivo and in vitro. It was shown that most of the flavonoids accelerated significantly the phagocytosis, and they suppressed significantly not only humoral and cellular immune responses but also the development of immunological memory after the antigenic stimulation. Especially, malvin was the most active in phagocysis, and disodium cromoglycate and morin were the most active in humoral and cellular immunosuppression, respectively. Daidzuin had the most potent inhibitory activity in the development of memory cells. The structure-activity relationships of the flavonoids in immunosuppression became apparant from these results: 1. The presence of $C_{2-3}$ double bond and $C_4$ Ketone group in C-ring was important for their immunosuppressive activity. 2. Flavonoids with benzene ring at 2 or 3 position in C-ring showed the almost same activities. 3. The opening of C-ring did not affect their immunosuppressive activity. 4. The glycosylated flavonoids at 3 position in C-ring were less less potent than their aglycones. 5. Di-or tri-hydroxylated flavonoids in B-ring were more potent than mono-hydroxylated. 6. Chromanochromanone also had the immunosuppressive activity.

• Korean Journal of Animal Reproduction
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• v.13 no.3
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• pp.179-187
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• 1989

The experiment was carried out to study the profile of uterine specific protein during early pregnancy in sows and to test it's immunosuppressive activity. Uterine protein samples were obtained by flushing the uterine horn on Day 3, 6, 9, 12 and 15 of the estrous cycle and the pregnancy respectively and the protein concentration of each sample was determined. The change of uterine protein was examined by sodium dodecyl sulfate(SDS)-PAGE. The immunosuppressive activity of uterine secretory protein was investigated according to the lymphocyte blastogenesis response to mitogen. The results of this experiment are summarized as follows ; 1. The uterine protein during estrous cycle and early pregnancy was relatively constant up to Day 9, but increased on Day 12. Maxium total protein values were found on Day 15. The concentration of serum proteins were about 82-95 mg during estrous cycle, but decreased to about 70-82 mg during early pregnancy. 2. The proteins components similar electrophoretic patterns(PAGE) that were no differences (band ; a, b, c, d, e, f, g, I) on Days 3, 6 and 9 of the estrous cycle and pregnancy. But there were more 2 bands specifically on Day 12 of the pregnancy and on Day 15 of estrous cycle and showed more 4 bands on Day 15 of early pregnancy. They seemed to be acidoprotein and their average molecular weight were 38,000, 22,300 and 12,600. 3. When uterine protein were added 500$\mu\textrm{g}$/ml, there was no immunosuppresive activity on Day 3 of estrous cycle and lymphocyte blastogenesis was slightly suppressed on Day 3 of pregnancy. The immunosuppressive activity on Day 9 of estrous cycle and pregnancy appeared in 500$\mu\textrm{g}$/ml and 150$\mu\textrm{g}$/ml, respectively the uterine protein on Day 12 and 15 showed immunosuppresive activity, which at the level of 150$\mu\textrm{g}$/ml during non-pregnancy and at the level of 100 to 125$\mu\textrm{g}$/ml during early pregnancy, respectively.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• Advances in Traditional Medicine
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• v.10 no.3
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• pp.150-154
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• 2010

The immunosuppressive activity of the Methanol extract of bark of Madhuca longifolia (Koenig) consisting of a mixture of saponins, flavonoids, tannins, steroids, phenol and glycosides was studied on the immune responses in mice. Methanol extract of Madhuca longifolia (MLL) was administered orally at doses of 50, 100 and 150 mg/kg/day to healthy mice divided into four groups consisting of six animals each. The assessment of immunomodulatory activity was carried out by testing the humoral (antibody titre) and cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs. Furthermore, the effect on hematological parameters as well as relative organ weight was determined. On oral administration MML showed a significant decrease delayed type hypersensitivity (DTH) response whereas the humoral response to sheep RBCs was unaffected. Thus MLL significantly suppressed the cellular immunity by decreasing the footpad thickness response to sheep RBCs in sensitized mice. With a dose of 100 and 150 mg/kg/day the DTH response was $7.66{\pm}2.75$ and $6.41{\pm}1.21$ respectively in comparison to corresponding value of $14.50{\pm}2.38$ for untreated control group. These differences in DTH response were statistically significant (P < 0.05). The study demonstrates that MLL shows preferential suppression of the components of cell-mediated immunity and shows no effect on the humoral immunity.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.341-345
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• 2024

The objective of the study is to estimate the potential of gintonin, as an immune enhancing agent through natural killer cell (NK cell) activity in cyclophosphamide (CY)-induced immunosuppressive animals. Accumulated results reveals that, gintonin attenuated CY-induced immunosuppression and it might modulate NK cell activity to boost the immunity.