Korean ginseng extract ameliorates abnormal immune response through the regulation of inflammatory constituents in Sprague Dawley rat subjected to environmental heat stress

다국어 초록 (Multilingual Abstract)

Background: Increases in the average global temperature cause heat stresseinduced disorders by disrupting homeostasis. Excessive heat stress triggers an imbalance in the immune system; thus protection against heat stress is important to maintain immune homeostasis. Korean ginseng (Panax ginseng Meyer) has been used as a herbal medicine and displays beneficial biological properties.
Methods: We investigated the protective effects of Korean ginseng extracts (KGEs) against heat stress in a rat model. Following acclimatization for 1 week, rats were housed at room temperature for 2 weeks and then exposed to heat stress (40C/2 h/day) for 4 weeks. Rats were treated with three KGEs from the beginning of the second week to the end of the experiment.
Results: Heat stress dramatically increased secretion of inflammatory factors, and this was significantly reduced in the KGE-treated groups. Levels of inflammatory factors such as heat shock protein 70, interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor-alpha were increased in the spleen and muscle upon heat stress. KGEs inhibited these increases by down-regulating heat shock protein 70 and the associated nuclear factor-kB and mitogen-activated protein kinase signaling pathways.
Consequently, KGEs suppressed activation of T-cells and B-cells.
Conclusion: KGEs suppress the immune response upon heat stress and decrease the production of inflammatory cytokines in muscle and spleen. We suggest that KGEs protect against heat stress by inhibiting inflammation and maintaining immune homeostasis.

참고문헌 (Reference)

1 김성년, "흑삼(구증구포인삼)이 혈당 강하에 미치는 영향 및 증포별 ginsenoside 조성 변화" 한국식품과학회 41 (41): 77-81, 2009

2 Boyman O, "The role of interleukin-2 during homeostasis and activation of the immune system" 12 (12): 180-190, 2012

3 Snoeck V, "The IgA system : a comparison of structure and function in different species" 37 (37): 455-467, 2006

4 Sakurai H, "Targeting of TAK1 in inflammatory disorders and cancer" 33 (33): 522-530, 2012

5 Woo J, "Stress protein-induced immunosuppression : inhibition of cellular immune effector functions following overexpression of haem oxygenase(HSP 32)" 6 (6): 84-93, 1998

6 Kawai T, "Signaling to NF-kB by Toll-like receptors" 13 (13): 460-469, 2007

7 Kim K-J, "Role of the red ginseng in defense against the environmental heat stress in Sprague Dawley rats" 20 (20): 20240-20253, 2015

8 Thériault JR, "Role of scavenger receptors in the binding and internalization of heat shock protein 70" 177 (177): 8604-8611, 2006

9 Putics A, "Resveratrol induces the heat-shock response and protects human cells from severe heat stress" 10 (10): 65-76, 2008

10 Iwasaki A, "Regulation of adaptive immunity by the innate immune system" 327 (327): 291-295, 2010

11 Nathan C, "Points of control in inflammation" 420 (420): 846-852, 2002

12 Gilmore TD, "Introduction to NF-kB : players, pathways, perspectives" 25 (25): 6680-6684, 2006

13 Curtsinger JM, "Inflammatory cytokines provide a third signal for activation of naive CD4þ and CD8þ T cells" 162 (162): 3256-3262, 1999

14 Grivennikov SI, "Immunity, inflammation, and cancer" 140 (140): 883-899, 2010

15 Racine R, "IgM production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection" 186 (186): 1011-1021, 2011

16 Lewis S, "Hsp70 expression in Enteromorpha intestinalis(Chlorophyta)exposed to environmental stressors" 51 (51): 277-291, 2001

17 Mayer M, "Hsp70 chaperones : cellular functions and molecular mechanism" 62 (62): 670-, 2005

18 Knochel JP, "Heat stroke and related heat stress disorders" 35 (35): 301-377, 1989

19 Nover L, "Heat stress proteins and transcription factors" 53 (53): 80-103, 1997

20 Pockley AG, "Heat shock proteins, inflammation, and cardiovascular disease" 105 (105): 1012-1017, 2002

21 Seo-Yun Choi, "Ginsenoside Rg5 prevents apoptosis by modulating heme-oxygenase-1/nuclear factor E2-related factor 2 signaling and alters the expression of cognitive impairment-associated genes in thermal stress-exposed HT22 cells" 고려인삼학회 42 (42): 225-228, 2018

22 고은정, "Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish" 고려인삼학회 41 (41): 23-30, 2017

23 강수원, "Ginseng, the 'Immunity Boost': The Effects of Panax ginseng on Immune System" 고려인삼학회 36 (36): 354-368, 2012

24 원해단, "Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies" 고려인삼학회 36 (36): 27-39, 2012

25 Sørensen JG, "Full genome gene expression analysis of the heat stress response in Drosophila melanogaster" 10 (10): 312-328, 2005

26 Gasteiger G, "Foxp3þ regulatory T-cells and IL-2: the Moirai of T-cell fates?" 3 : 2012

27 Somensi N, "Extracellular HSP70 activates ERK1/2, NF-kB and pro-inflammatory gene transcription through binding with RAGE in A549 human lung cancer cells" 42 (42): 2507-2522, 2017

28 Zhang Y, "Differential gene expression in Festuca under heat stress conditions" 56 (56): 897-907, 2005

29 Bennouna S, "Cross-talk in the innate immune system : neutrophils instruct recruitment and activation of dendritic cells during microbial infection" 171 (171): 6052-6058, 2003

30 Lee B-Y, "Composition of saponin and free sugar of some white ginsengs with processing conditions" 28 (28): 922-927, 1996

31 Becker T, "CD40, an extracellular receptor for binding and uptake of Hsp70epeptide complexes" 158 (158): 1277-1285, 2002

32 Zheng Z, "Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke" 28 (28): 53-63, 2008