Antibodies specific for Candida mannan can enhance host resistance against candidiasis

Yongmoon Han 대한약학회 1997 大韓藥學會 總會 및 學術大會 Vol.1997 No.1

Immunoactivity of Ginsenosides Re and Rg1 that Enhances Resistance of Mice Against Experimental Disseminated Candidiasis

Yongmoon Han,Byung-Seok Jin,Sung-Kwon Ko,이주희 한국생약학회 2004 Natural Product Sciences Vol.10 No.3

In this study, an immunoactivity of panaxtriol ginsenosides Re and Rg1 against infection due to Candida albicans was investigated. The ginsenosides were extracted from Red Ginseng with 85% ethanol and heat-treatment and were analyzed by HPLC on water-acetonitrile as a mobile phase. The HPLC analysis revealed that the extract contained ginsenosides Re and Rg1, which were eluted as a combined peak. By agar diffusion susceptibility, the mixture of Re and Rg1 had no growth-inhibitory activity on C. albicans yeast cells. However, in animal tests BALB/c mice given the mixture of Re and Rg1 intraperitoneally (i.p.) before intravenous (i.v.) infection with live C. albicans yeast cells had longer mean survival times (MST) than MST of control mice groups that received only buffer solution instead of Re and Rg1. In experiments 60% of the ginsenosides-treated mice survived the entire duration of the 50-day observation. The Re and Rg1 mixture induced production of nitric oxide when interacted with RAW 264.7 macrophage cell line. In addition, the mixture caused morphological change of the macrophages. These data indicate that immunostimulation by the Re and Rg1 may be responsible for the protection of mice against disseminated candidiasis.

Isolation of Ginkgolides and the Effect of These Components on Inflammation in Mice Induced by Complete Freund's Adjuvant

Han Yongmoon,Lee Soonhyun 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.2

Chlorogenic Acid의 면역보조제 효과

한용문(Yongmoon Han) 대한약학회 2010 약학회지 Vol.54 No.6

We have been focussing on discovery of natural compounds that have immunoregulatory activities for many years. In the present study, we investigated if chlorogenic acid (CRA), a polyphenolic compound, has an immunoadjuvant activity. Prior to examining the immunoadjuvant activity, effect of CRA on proliferation of T- or B-lymphocyte was determined. Results showed that CRA enhanced the proliferation of those lymphocytes in dose-dependant manner (P<0.05), and the proliferation enhancement by CRA was appeared to be more effective to B-cells than to T-cells. Based on these observations, it was tested with bovine serum albumin (BSA) and Candida albicans cell wall (CACW) as antigenic sources if CRA has an immunoadjuvant activity. In experiments, BSA alone or a mixture of BSA plus CRA was injected intraperitoneally to mice (BALB/c strain). For a negative control, mice were given only diluent (DPBS) by the same route. In other experiment, CACW was tested by the same way as did with BSA. Three weeks after the first immunization these animals were boosted. Antisera collected from the mice one week after the booster were analyzed by ELISA. Results displayed that the induction of anti-BSA antibody was increased in mice that received the mixture of BSA and CRA as compared to anti-BSA induction in BSA only-given mice groups (P<0.05). In case of CACW, a similar observation as did with BSA was made, resulting in that there was app. 40% increased production of the anti-CACW antiserum from the combination (CACW plus CRA)-received mice as compared to antiserum induction from CACW alone-given animals. Taken all together, these data indicate that CRA has an ability of enhancing antibody production regardless of nature of antigenic sources. Presumably, activation of B-cell proliferation by CRA may plays an important role in the immunoadjuvant activity of the polyphenolic compound.

HT-29 암세포 이종이식으로 유발된 종양에 대한 18β-Glycyrrhetinic Acid의 치료효과

한용문(Yongmoon Han),김정현(Jeonghyeon Kim) 대한약학회 2015 약학회지 Vol.59 No.4

In the present study, we determined the effect of 18β-glycyrrhetinic acid (18β-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that 18β-GA induced cell death in HT-29. The cytotoxicity was enhanced as the 18β-GA treatment was prolonged. In case of 72 hrs treatment, LD50 of 18β-GA was approximately 90 μM, and the efficacy at 100 μM of 18β-GA appeared to be equivalent to that of doxorubicin at 1 μM. Based on the in vitro data, we tested the anti-tumor effect of 18β-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 (3×106 cells/mouse) to mice and the mice were treated intraperitoneally with 18β-GA (50 μg/time/mouse) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the 18β-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that 18β-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

Platycodin D 길경성분의 면역보조효과

한용문(Yongmoon Han) 대한약학회 2015 약학회지 Vol.59 No.4

In vaccine development, the major points may be induction of effective and increased levels of antibody production. This is especially the case when the antigenic sources are carbohydrates. For many years, thus, we have researched various types of formulations such as liposomal and conjugate vaccines. However, the fastidious formulation process and high costs are a problem. For this reason, there is currently a focus on utilizing immunoadjuvants. In this present study, we tested if platycodin D (PLD) from Platycodon Radix have immunoadjuvant activity against the cell wall of Candida albicans (CACW). The resulting data showed that in the murine model of antibody production, CACW combined with PLD [CACW/PLD/IFA] increased the production of antibodies specific to C. albicans when compared to the antibody production by [CACW/IFA]-induction, which was used as a negative control (P<0.05). In the case of [CACW/PLD/IFA], the antibody production was 1.4 times as that of the CFA. In addition, formulations containing either had a prolonged antibody inducing activity maintaining the initial titers of antibody as compared to the CFA formula. Cytokine profiling with the antisera displayed that the PLD produced both Th1 and Th2 immunoresponses, but Th1 dominant was much greater (P<0.05). Furthermore, [CACW/PLD/IFA] formula enhanced resistance of mice against disseminated candidiasis, whereas the CFA had no such effect. In conclusion, PLD has an immunologic activity, which is protective against the disease. Thus, PLD can be a goof candidate for a new immunoadjuvant in development of the fungal vaccine.

F4 인삼배당체의 면역 보조 효과

한용문(Yongmoon Han) 대한약학회 2016 약학회지 Vol.60 No.5

There have been many attempts to treat candidal infections by immunological approaches. One attempt is to find a certain adjuvant that induces a protective antibody in host. Previously, we have reported that MAb B6.1, specific for β-1,2 mannotriose located on the Candida albicans cell wall (CACW), protects mice against disseminated candidiasis and vaginal infection. However, the isolation of such an epitope is very costly and requires tremendous amount of time. Thus, this led us to find a simple way to obtain a compound that induces protective antibody. For this purpose, we focused on the discovery of immuoadjuvants capable of inducing protective antibodies. In the present study, we tested whether ginsenoside F4 from Red Ginseng has immunoadjuvant activity against fungal infection. Data displayed that a formulae of CACW combined with F4 (CACW/F4) enhanced production of anti-C. albicans antibody in mice. Analyses by IgG isotyping showed that the formulae suppressed IgG1 (Th2-immunity polarized) but enhanced IgG2b (Th1-immunity polarized), thus resulting in a Th1 immune response. This effect was assessed in a murine model of disseminated candidiasis due to C. albicans. The assesment displayed that the formulae enhanced resistance of mice against the candidiasis, whereas CACW alone was not protective. Overall, F4 has immunoadjuvant activity that provokes the induction of protective antibody in mice through a possible mechanism that enhances Th1 immunity in mice.

전신성 캔디다증에 대한 RK1 인삼배당체의 면역보조 효능

한용문(Yongmoon Han),유정임(Zheong-Imm Rhew) 대한약학회 2017 약학회지 Vol.61 No.4

We have previously shown that the antibody, specific for β-1,2 mannotriose on the Candida albicans cell wall (CACW), is protective against disseminated candidiasis and vaginal infection. Nevertheless, the isolation of such epitope requires tremendous amount of time, which is very costly. This led us to find a simple way to obtain an immuoadjuvant capa-ble of inducing protective antibodies. Thus, in the present study, for the discovery of such adjuvant, we examined gin-senoside RK1 against Candida albicans-caused infections. Our data displayed that a formulae of CACW (C. albicans cell wall) combined with RK1 [CACW/RK1] enhanced production of anti-C. albicans antibody in mice. Analyses by IgG-isotyping showed that the formulae suppressed IgG1 (Th2-immune polarized) but enhanced IgG2a (Th1-immune polarized), thus resulting in a Th1 immunity. This effectiveness of RK1 was assessed in the murine model of disseminated candidiasis caused by C. albicans. The assessment indicated that the formulae with RK1 enhanced resistance of mice against the can-didiasis, whereas [CACW] alone was not protective. Overall, RK1 has immunoregulatory activity that provokes the pro-duction of protective antibody in mice through enhancing Th1 immunity.

Candida albicans 기인성 뇌감염에 대한 로즈마리 정유의 항진균효과

한용문(Yongmoon Han),유정임(Zheong Imm Rhew) 대한약학회 2018 약학회지 Vol.62 No.3

Recently, the number of cases of fungal brain infections has been rising caused by Candida albicans. In this present study, we determined effect of rosemary essential oil (REO) against fungal brain infection due to C. albicans. In experiments, REO extract contained of α-pinene, β-pinene, 1,8-cineole, camphor, and verbenone as main essential oils as analyzed by GC-MS. The REO inhibited C. albicans growth under in-vitro condition. This antifungal activity was dose dependent. Thus, REO was then assessed in the animal model of brain infection. BALB/c mice were pre-treated intraperitoneally with anti-CD4 mAb. Forty-eight hours later, the mice were infected intravenously with C. albicans (Day 1) and these animals received REO every other day for 3 times (Day 1, 3, & 5). At Day 12, their brains were harvested and CFU (colony forming units) values in the brains were measured. Results showed that REO treatment reduced CFU values up to approx. 65% when compared to CFU values of control mice (P < 0.01). Similarly, the REO treatment improved whirling motion in mice, which served as an indicator for the presence of a brain infection. Amphotericin B, a positive control, had similar activity as REO. Therefore, our observations indicate that REO appears to be effective against fungal brain infections caused by C. albicans.

PC-3 암세포에 대한 18β-Glycyrrhetinic Acid의 항암효과

한용문(Yongmoon Han) 대한약학회 2017 약학회지 Vol.61 No.2

In the current study, we examined anticancer activity of 18β-glycyrrhetinic acid (18β-GA) and its mechanism in a murine model bearing xenografts of PC-3 human prostate cancer cell line. For the examination, we utilized thymic mice and athymic animals as well. Results from cytotoxicity assay showed that 18β-GA caused killing of PC-3 cancer cells. The cytotoxicity was enhanced as the 18β-GA treatment was prolonged, which could be an anticancer factor of the compound. An LD50 of 18β-GA was approximately 120 μM and this efficacy appeared to be equivalent to efficacy of doxorubicin at 1 μM. Based on these in-vitro data, the anticancer activity was assessed in thymic mice (Balb/c strain) and athymice animals (Balb/c nu/nu), respectively. Xenograft tumors were generated by subcutaneous injection of PC-3 (3×106 cells/mouse) to test mice, 18β-GA (50 μg/time/mouse) was intraperitoneally given to the animals every other day for 4 times, and the tumor volumes were measured for a period of 21 days. Data displayed that the 18β-GA treatment reduced the tumor size (P < 0.01) as compared to control mice groups. The treatment increased the production of IFN-γ. However, the anticancer activity was demolished in athymic mice. These observations indicate that the anticancer activity may be associated with T lymphocyte, presumably by IFN-γ, a major cytokine of Th1-immunity. Combined all data together, 18β-GA has anticancer activity against PC-3 prostate cancer cell.