Anti‑inflammatory potential of total saponins derived from the roots of Panax ginseng in lipopolysaccharide‑activated RAW 264.7 macrophages

Jang,Kyung‑Jun; Choi,Sang Hoon; Yu,Gyeong  Jin; Hong,Su  Hyun; Chung,Yoon Ho; Kim,Cheol‑Hong; Yoon,Hyun‑Min; Kim,Gi‑Young; Kim,Byung  Woo; Choi,Yung  Hyun

doi:10.3892/etm.2015.2965

March-2016 Volume 11 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

March-2016 Volume 11 Issue 3

Full Size Image

Article

Anti‑inflammatory potential of total saponins derived from the roots of Panax ginseng in lipopolysaccharide‑activated RAW 264.7 macrophages

Authors:
- Kyung‑Jun Jang
- Sang Hoon Choi
- Gyeong Jin Yu
- Su Hyun Hong
- Yoon Ho Chung
- Cheol‑Hong Kim
- Hyun‑Min Yoon
- Gi‑Young Kim
- Byung Woo Kim
- Yung Hyun Choi
View Affiliations / Copyright

Affiliations: Department of Acupuncture and Moxibustion, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, NamHaeGun Black Garlic Co., Ltd., Busan 614‑853, Republic of Korea, Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690‑756, Republic of Korea, Anti‑Aging Research Center and Blue‑Bio Industry RIC, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614‑714, Republic of Korea
Pages: 1109-1115
|
Published online on: December 29, 2015

https://doi.org/10.3892/etm.2015.2965
Expand metrics +

Abstract

Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a widely known traditional medicine that has been utilized throughout Asia for several thousand years. Ginseng saponins exert various important pharmacological effects regarding the control of a number of diseases. The aim of the present study was to identify the anti‑inflammatory effects of total saponins extracted from ginseng (TSG) on lipopolysaccharide (LPS)‑stimulated mouse RAW 264.7 macrophages. The inhibitory effects of TSG on LPS‑induced nitric oxide (NO) production and LPS‑induced tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) protein expression were determined by measuring the levels of nitrite and enzyme‑linked immunosorbent assays, respectively. Furthermore, the effects of TSG on the mRNA expression levels and localizations of inducible NO synthase (iNOS), IL‑1β and TNF‑α, and their upstream signaling proteins, including nuclear factor‑κB (NF‑κB) and mitogen‑activated protein kinases (MAPKs), were investigated by reverse transcription‑polymerase chain reaction and western blotting, respectively. Following stimulation with LPS, elevated levels of NO production were detected in RAW 264.7 cells; however, TSG pretreatment significantly inhibited the production of NO (P<0.05), by suppressing the expression of iNOS. In addition, LPS‑stimulated TNF‑α and IL‑1β production was significantly reduced by TSG (P<0.05). In the LPS‑stimulated RAW 264.7 cells, NF‑κB was translocated from the cytosol to the nucleus, whilst TSG pretreatment induced the sequestration of NF‑κB in the cytosol by inhibiting inhibitor of κB degradation. TSG also contributed to downregulation of MAPKs in LPS‑stimulated RAW 264.7 cells. These results suggested that TSG may exert anti‑inflammatory activity, and that TSG may be considered a potential therapeutic for the treatment of inflammatory diseases associated with macrophage activation.

View Figures

View References

1	Zhang X and Mosser DM: Macrophage activation by endogenous danger signals. J Pathol. 214:161–178. 2008. View Article : Google Scholar : PubMed/NCBI
2	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
3	Park BS and Lee JO: Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 45:e662013. View Article : Google Scholar : PubMed/NCBI
4	Kapadia M and Sakic B: Autoimmune and inflammatory mechanisms of CNS damage. Prog Neurobiol. 95:301–333. 2011. View Article : Google Scholar : PubMed/NCBI
5	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
6	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
7	Guha M and Mackman N: LPS induction of gene expression in human monocytes. Cell Signal. 13:85–94. 2001. View Article : Google Scholar : PubMed/NCBI
8	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
9	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
10	Uto T, Fujii M and Hou DX: 6-(Methylsulfinyl)hexyl isothiocyanate suppresses inducible nitric oxide synthase expression through the inhibition of Janus kinase 2-mediated JNK pathway in lipopolysaccharide-activated murine macrophages. Biochem Pharmacol. 70:1211–1221. 2005. View Article : Google Scholar : PubMed/NCBI
11	Choi J, Kim TH, Choi TY and Lee MS: Ginseng for health care: A systematic review of randomized controlled trials in Korean literature. PLoS One. 8:e599782013. View Article : Google Scholar : PubMed/NCBI
12	Coleman CI, Hebert JH and Reddy P: The effects of Panax ginseng on quality of life. J Clin Pharm Ther. 28:5–15. 2003. View Article : Google Scholar : PubMed/NCBI
13	Kitts D and Hu C: Efficacy and safety of ginseng. Public Health Nutr. 3(4A): 473–485. 2000. View Article : Google Scholar : PubMed/NCBI
14	Shibata S: Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci. 16:S28–37. 2001. View Article : Google Scholar : PubMed/NCBI
15	Chen RJ, Chung TY, Li FY, Lin NH and Tzen JT: Effect of sugar positions in ginsenosides and their inhibitory potency on Na⁺/K⁺-ATPase activity. Acta Pharmacol Sin. 30:61–69. 2009. View Article : Google Scholar : PubMed/NCBI
16	Lü JM, Yao Q and Chen C: Ginseng compounds: An update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol. 7:293–302. 2009. View Article : Google Scholar : PubMed/NCBI
17	Kim JY, Lee HJ, Kim JS and Ryu JH: Induction of nitric oxide synthase by saponins of heat-processed ginseng. Biosci Biotechnol Biochem. 69:891–895. 2005. View Article : Google Scholar : PubMed/NCBI
18	Park JS, Park EM, Kim DH, Jung K, Jung JS, Lee EJ, Hyun JW, Kang JL and Kim HS: Anti-inflammatory mechanism of ginseng saponins in activated microglia. J Neuroimmunol. 209:40–49. 2009. View Article : Google Scholar : PubMed/NCBI
19	Kang A, Hao H, Zheng X, Liang Y, Xie Y, Xie T, Dai C, Zhao Q, Wu X, Xie L and Wang G: Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy. J Neuroinflammation. 8:1002011. View Article : Google Scholar : PubMed/NCBI
20	Sugimoto S, Nakamura S, Matsuda H, Kitagawa N and Yoshikawa M: Chemical constituents from seeds of Panax ginseng: Structure of new dammarane-type triterpene ketone, panaxadione, and hplc comparisons of seeds and flesh. Chem Pharm Bull (Tokyo). 57:283–287. 2009. View Article : Google Scholar : PubMed/NCBI
21	Dinarello CA: Proinflammatory cytokines. Chest. 118:503–508. 2000. View Article : Google Scholar : PubMed/NCBI
22	Koppula S, Kumar H, Kim IS and Choi DK: Reactive oxygen species and inhibitors of inflammatory enzymes, NADPH oxidase, and iNOS in experimental models of Parkinson's disease. Mediators Inflamm. 823902:20122012.
23	Martinon F: Signaling by ROS drives inflammasome activation. Eur J Immunol. 40:616–619. 2010. View Article : Google Scholar : PubMed/NCBI
24	Korbecki J, Baranowska-Bosiacka I, Gutowska I and Chlubek D: The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol. 64:409–421. 2013.PubMed/NCBI
25	Marcus JS, Karackattu SL, Fleegal MA and Sumners C: Cytokine-stimulated inducible nitric oxide synthase expression in astroglia: role of Erk mitogen-activated protein kinase and NF-kappaB. Glia. 41:152–160. 2003. View Article : Google Scholar : PubMed/NCBI
26	Mercurio F and Manning AM: NF-kappaB as a primary regulator of the stress response. Oncogene. 18:6163–6171. 1999. View Article : Google Scholar : PubMed/NCBI
27	Klemm S and Ruland J: Inflammatory signal transduction from the Fc epsilon RI to NF-kappa B. Immunobiology. 211:815–820. 2006. View Article : Google Scholar : PubMed/NCBI
28	Sonis ST: The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med. 13:380–389. 2002. View Article : Google Scholar : PubMed/NCBI
29	Kim EK and Choi EJ: Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 1802:396–405. 2010. View Article : Google Scholar : PubMed/NCBI
30	Huang P, Han J and Hui L: MAPK signaling in inflammation-associated cancer development. Protein Cell. 1:218–226. 2010. View Article : Google Scholar : PubMed/NCBI
31	Kaminska B, Gozdz A, Zawadzka M, Ellert-Miklaszewska A and Lipko M: MAPK signal transduction underlying brain inflammation and gliosis as therapeutic target. Anat Rec (Hoboken). 292:1902–1913. 2009. 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 potential of total saponins derived from the roots of Panax ginseng in lipopolysaccharide‑activated RAW 264.7 macrophages

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Related Articles