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Jakhar, Rekha,Sharma, Chanchal,Paul, Souren,Kang, Sun Chul Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.65 No.-
<P><B>Abstract</B></P> <P>In this study, the immunomodulatory effects of astemizole (AST) against lipopolysaccharide (LPS) mediated T cell proliferation and induction of inflammation in RAW macrophages (<I>in vitro</I>), and zebrafish larvae (<I>in vivo</I>) were determined. AST significantly suppressed the phagocytic activity of macrophages (3.303 ± 0.115) and inhibited lysosomal enzyme secretion (13.27 ± 2.52) induced by LPS (100 ng/ml). Moreover, AST subdued the morphological deformities such as yolk sac edema (YSE) and spinal curvature curving (SC) by inhibiting ROS generation in zebrafish larvae 24 h after microinjection of LPS (0.5 mg/ml). AST was also shown to inhibit the production of the major cytokines TNF-α (150.8 ± 0.6), IL-1β (276.5 ± 1.6), and PGE<SUB>2</SUB> (194.6 ± 0.6) pg/ml in RAW macrophages. It also subdued the ROS induced iNOS and COX-2 generated in response to LPS mediated immune dysfunctions in zebrafish larvae. These results suggested the immunosuppression effect of AST. Furthermore, induction of immune-suppression due to AST resulted in significant down-regulation of innate immunity directed by MAPK (p38, ERK and JNK), which was found to be associated with decreased production of acute inflammatory mediators both <I>in vitro</I> and <I>in vivo</I>. To confirm its activity, splenocytes were prepared using BALB/c mice and a mitogen activated splenocyte proliferation assay was also performed. Our findings suggest that AST has the ability to inhibit T cell proliferation and cytokine secretion both <I>in vitro</I> and <I>in vivo</I> by interfering with MAPK signaling pathway. Taken together, our results showed the potential of AST as a countermeasure to immune dysfunction and suggest its use as immunosuppressant compound in inflammatory disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> T cell proliferation due to Con A was inhibited by Astemizole (AST). </LI> <LI> AST curbed the increased levels of TNF-α, IL-1β and PGE<SUB>2</SUB> resulted in response to LPS (<I>Escherichia coli</I> 055: B5) in RAW macrophages. </LI> <LI> AST subdue the ROS induced iNOS and COX-2 in zebrafish larvae. </LI> <LI> AST mediated immunosuppression results in down regulation of innate immunity <I>via</I> MAPK pathways. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
농식품 환경 분야(PF) : 말굽버섯에서 분리된 다당류의 항암활성
리카자카 ( Rekha Jakhar ),소렌폴 ( Souren Paul ),강선철 ( Sun Chul Kang ) 한국환경농학회 2014 한국환경농학회 학술대회집 Vol.2014 No.-
Mushrooms are known to complement chemotherapy and radiation therapy by countering the side-effects of cancer. Recently, a great deal of interest has been developed to isolate novel bioactive compounds from mushrooms because of their numerous health beneficial effects. Chemically water-extractable polysaccharide (MFKF-AP1β) was isolated from fruiting bodies of mushroom Fomes fomentarius. In this research, we investigated the anticancer effects of MFKF-AP1β on human lung carcinoma A549 cell. Results showed that MFKF-AP1β distinctly inhibited A549 cells growth in a dose-dependent manner and induced cell apoptosis evidenced by apoptosis assay. Besides that, MFKF-AP1β induced the LDH release and causes morphological alterations. Furthermore, the MFKF-AP1β (25.100 μg/ml) resulted in a significant single strand DNA breakage, on A549 cells as shown by comet assay. Taken together, our results demonstrate that MFKF-AP1β possesses strong antitumor activities through the induction of apoptosis. All these results suggested that MFKF-AP1β has evident anticancer activity through apoptotic induction.
농식품 환경 분야(PF) : PF-17 ; 마우스 모델을 이용한 아크릴아마이드 유도된 신독성 및 간독성에 대한 morin hydrate의 보호효과
강선철 ( Sun Chul Kang ),리카자카 ( Rekha Jakhar ),마헨드라 ( Mahendra Pal Singh ) 한국환경농학회 2014 한국환경농학회 학술대회집 Vol.2014 No.-
Acrylamide (AA) is considered as a potential carcinogen by Food and Drug Administration (United States). AA is produced during the heating of starchy foods like potato chips, french fries, and coffee at high temperature and is regarded as a potential genotoxic carcinogen. However, a number of researches going on worldwide in the field of toxicology are concerned about the carcinogenicity of AA. Morin hydrate is a potent flavonoid compound. It is a yellow color substance that can be isolated from Maclura pomifera (Osage orange). So, in this study we have used morin hydrate to abolish the AA-induced toxicity by determining the variety of hematological, biochemical and immunological parameters in the serum, urine, liver and kidney of male mice. Subcutaneous injection of morin hydrate at a concentration of 5mg and 15mg kg-1 per day for 5 days along with 10mg kg-1 AA exposure could significantly reduce the toxicity of AA. As we found a significant reduction in the level of thiobarbituric reactive substances (TBARS) in tissue and serum, also, a significant reduction in antioxidant enzymes like superoxide dismutase (SOD), glutathione S transferase (GST), glutathione (GSH), myeloperoxidase (MPO) was observed. On the other hand, level of aspartate amino transferase (AST), alinine aminotransferase (ALT) in serum was found to decrease in a concentration dependent manner of morin hydrate. On the basis of the present study we conclude that morin hydrate can potentially protect renal and hepatic toxicity induced by AA.