Anti‑inflammatory effects of Daehwangmokdantang, a traditional herbal formulation, in lipopolysaccharide‑stimulated RAW 264.7 macrophages

Lee,Moon  Hee; Hong,Su  Hyun; Park,Cheol; Han,Min‑Ho; Kim,Sung  Ok; Hong,Sang  Hoon; Kim,Gi‑Young; Choi,Yung  Hyun

doi:10.3892/etm.2017.5296

December-2017 Volume 14 Issue 6

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December-2017 Volume 14 Issue 6

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Article Open Access

Anti‑inflammatory effects of Daehwangmokdantang, a traditional herbal formulation, in lipopolysaccharide‑stimulated RAW 264.7 macrophages

Authors:
- Moon Hee Lee
- Su Hyun Hong
- Cheol Park
- Min‑Ho Han
- Sung Ok Kim
- Sang Hoon Hong
- Gi‑Young Kim
- Yung Hyun Choi
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Affiliations: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614‑714, Republic of Korea, Natural Products Research Team, National Marine Biodiversity Institute of Korea, Seocheon 325‑902, Republic of Korea, Department of Food Science and Biotechnology, College of Engineering, Kyungsung University, Busan 608‑736, Republic of Korea, Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690‑756, Republic of Korea

Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 5809-5816
|
Published online on: October 12, 2017

https://doi.org/10.3892/etm.2017.5296
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Abstract

Daehwangmokdantang (DHMDT) is a traditional polyherbal formulation that has known antidiarrheal and anti‑inflammatory activities. However, the underlying mechanisms of these activities are poorly understood. In the present study, the inhibitory effects of DHMDT on the production of proinflammatory mediators and cytokines in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages were investigated. The inhibitory effects of DHMDT on LPS‑induced nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β production were examined using Griess reagent and ELISA detection kits. The effects of DHMDT on the expression of inducible NO synthase (iNOS), cyclooxygenase (COX)‑2, IL‑1β and TNF‑α, and their upstream signal proteins, including nuclear factor (NF)‑κB, mitogen‑activated protein kinases (MAPKs) and RAC‑α serine/threonine‑protein kinase (Akt), a phosphatidylinositol 3‑kinase (PI3K) downstream effector, were investigated using western blotting and immunofluorescence staining. The results revealed the pretreatment with DHMDT significantly inhibited the LPS‑induced production of NO, PGE2, TNF‑α, and IL‑1β, and expression of iNOS, COX‑2 TNF‑α, and IL‑1β, without any significant cytotoxicity. DHMDT also efficiently prevented the translocation of the NF‑κB subunit p65 into the nucleus by interrupting the activation of the upstream mediator inhibitor of NF‑κB kinase α/β. Furthermore, the anti‑inflammatory effects of DHMDT were associated with the suppression of LPS‑induced phosphorylation of Akt and MAPKs in RAW 264.7 macrophages. Therefore, the results of the present study indicate that DHMDT exhibited anti‑inflammatory activity via the inhibition of proinflammatory mediators and cytokines, in which the inactivation of NF‑κB, PI3K/Akt, and MAPKs may be involved. These results suggest that DHMDT may be a potential anti‑inflammatory drug candidate.

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1	Conti B, Tabarean I, Andrei C and Bartfai T: Cytokines and fever. Front Biosci. 9:1433–1449. 2004. View Article : Google Scholar : PubMed/NCBI
2	Amin AR, Attur M and Abramson SB: Nitric oxide synthase and cyclooxygenases: Distribution, regulation, and intervention in arthritis. Curr Opin Rheumatol. 11:202–209. 1999. View Article : Google Scholar : PubMed/NCBI
3	Zhang X and Mosser DM: Macrophage activation by endogenous danger signals. J Pathol. 214:161–178. 2008. View Article : Google Scholar : PubMed/NCBI
4	Muralidharan S and Mandrekar P: Cellular stress response and innate immune signaling: Integrating pathways in host defense and inflammation. J Leukoc Biol. 94:1167–1184. 2013. View Article : Google Scholar : PubMed/NCBI
5	Verstrepen L, Adib-Conquy M, Kreike M, Carpentier I, Adrie C, Cavaillon JM and Beyaert R: Expression of the NF-kappaB inhibitor ABIN-3 in response to TNF and toll-like receptor 4 stimulation is itself regulated by NF-kappaB. J Cell Mol Med. 12:316–329. 2008. View Article : Google Scholar : PubMed/NCBI
6	Buchanan MM, Hutchinson M, Watkins LR and Yin H: Toll-like receptor 4 in CNS pathologies. J Neurochem. 114:13–27. 2010.PubMed/NCBI
7	Li L, Jacinto R, Yoza B and McCall CE: Distinct post-receptor alterations generate gene- and signal-selective adaptation and cross-adaptation of TLR4 and TLR2 in human leukocytes. J Endotoxin Res. 9:39–44. 2003. View Article : Google Scholar : PubMed/NCBI
8	Broom OJ, Widjaya B, Troelsen J, Olsen J and Nielsen OH: Mitogen activated protein kinases: A role in inflammatory bowel disease? Clin Exp Immunol. 158:272–280. 2009. View Article : Google Scholar : PubMed/NCBI
9	del Zoppo G, Ginis I, Hallenbeck JM, Iadecola C, Wang X and Feuerstein GZ: Inflammation and stroke: Putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol. 10:95–112. 2000. View Article : Google Scholar : PubMed/NCBI
10	McDaniel ML, Kwon G, Hill JR, Marshall CA and Corbett JA: Cytokines and nitric oxide in islet inflammation and diabetes. Proc Soc Exp Biol Med. 211:pp. 24–32. 1996, View Article : Google Scholar : PubMed/NCBI
11	Li Q and Verma IM: NF-kappaB regulation in the immune system. Nat Rev Immunol. 2:725–734. 2002. View Article : Google Scholar : PubMed/NCBI
12	Yenari MA and Han HS: Influence of hypothermia on post-ischemic inflammation: Role of nuclear factor kappa B (NFkappaB). Neurochem Int. 49:164–169. 2006. View Article : Google Scholar : PubMed/NCBI
13	Caivano M: Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW264 macrophages. FEBS Lett. 429:249–253. 1998. View Article : Google Scholar : PubMed/NCBI
14	Li X, Jiang S and Tapping RI: Toll-like receptor signaling in cell proliferation and survival. Cytokine. 49:1–9. 2010. View Article : Google Scholar : PubMed/NCBI
15	Heo J and Kim KJ: Dongui Bogam. Beopinmunhwasa Publishing Corp.; Seoul: 1999, (In Korean).
16	Fujihara M, Muroi M, Tanamoto K, Suzuki T, Azuma H and Ikeda H: Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide: Roles of the receptor complex. Pharmacol Ther. 100:171–194. 2003. View Article : Google Scholar : PubMed/NCBI
17	Laveti D, Kumar M, Hemalatha R, Sistla R, Naidu VG, Talla V, Verma V, Kaur N and Nagpal R: Anti-inflammatory treatments for chronic diseases: A review. Inflamm Allergy Drug Targets. 12:349–361. 2013. View Article : Google Scholar : PubMed/NCBI
18	Haddad JJ: The role of inflammatory cytokines and NF-kappaB/MAPK signaling pathways in the evolution of familial Mediterranean fever: Current clinical perspectives and potential therapeutic approaches. Cell Immunol. 260:6–13. 2009. View Article : Google Scholar : PubMed/NCBI
19	Saklatvala J: Inflammatory signaling in cartilage: MAPK and NF-kappaB pathways in chondrocytes and the use of inhibitors for research into pathogenesis and therapy of osteoarthritis. Curr Drug Targets. 8:305–313. 2007. View Article : Google Scholar : PubMed/NCBI
20	Wei J and Feng J: Signaling pathways associated with inflammatory bowel disease. Recent Pat Inflamm Allergy Drug Discov. 4:105–117. 2010. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Anti‑inflammatory effects of Daehwangmokdantang, a traditional herbal formulation, in lipopolysaccharide‑stimulated RAW 264.7 macrophages

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