Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway
Jin-Hua Zhang,1,2,* Zhao-Shui Shangguan,3,* Chao Chen,4 Hui-Jie Zhang,4 Yi Lin1 1College of Chemical Engineering, Huaqiao University, 2Department of Pharmacy, Xiamen Medical College, 3Central Laboratory, The First Affiliated Hospital of Xiamen University, 4Xiamen Diabetes Institute, The First Affil...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2016-06-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/anti-inflammatory-effects-of-guggulsterone-on-murine-macrophage-by-inh-peer-reviewed-article-DDDT |
| _version_ | 1819228886870786048 |
|---|---|
| author | Zhang JH Shangguan ZS Chen C Zhang HJ Lin Y |
| author_facet | Zhang JH Shangguan ZS Chen C Zhang HJ Lin Y |
| author_sort | Zhang JH |
| collection | DOAJ |
| description | Jin-Hua Zhang,1,2,* Zhao-Shui Shangguan,3,* Chao Chen,4 Hui-Jie Zhang,4 Yi Lin1 1College of Chemical Engineering, Huaqiao University, 2Department of Pharmacy, Xiamen Medical College, 3Central Laboratory, The First Affiliated Hospital of Xiamen University, 4Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China *These authors contributed equally to this work Abstract: The present study was aimed to investigate the effects of guggulsterone (GS) on proinflammatory responses as well as the underlying molecular mechanisms in macrophage upon lipopolysaccharide (LPS) stimulation. Effects of GS on viability of Raw264.7 cells were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (PCR) was employed to examine the mRNA expression of cytokines, including interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS). Phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), and inhibitor of nuclear factor kappaB (IκB) were determined using immunoblotting. The results revealed that GS was not toxic to Raw264.7 cells at designated concentrations. We demonstrated that GS significantly suppressed the elevated mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, and iNOS in a dose-dependent manner. GS treatment reduced the level of IκB phosphorylation in LPS-stimulated macrophages in a dose-dependent manner. Use of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-κB), led to significantly suppressing effects on IL-1β and TNF-α expression similar as that of GS-treated cells. Our findings suggest that GS possesses anti-inflammatory activity, which may be attributed to downregulation of iNOS and inhibition of NF-κB activity in LPS-stimulated Raw264.7 cells. Keywords: Anti-inflammatory effects, guggulsterone, lipopolysaccharides, NF-κB, IL-1β, TNF-α |
| first_indexed | 2024-12-23T11:04:25Z |
| format | Article |
| id | doaj.art-e62b9ef0b6ec4a81b3f78c5cc3e3b182 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-23T11:04:25Z |
| publishDate | 2016-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-e62b9ef0b6ec4a81b3f78c5cc3e3b1822022-12-21T17:49:33ZengDove Medical PressDrug Design, Development and Therapy1177-88812016-06-012016Issue 11829183527233Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathwayZhang JHShangguan ZSChen CZhang HJLin YJin-Hua Zhang,1,2,* Zhao-Shui Shangguan,3,* Chao Chen,4 Hui-Jie Zhang,4 Yi Lin1 1College of Chemical Engineering, Huaqiao University, 2Department of Pharmacy, Xiamen Medical College, 3Central Laboratory, The First Affiliated Hospital of Xiamen University, 4Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China *These authors contributed equally to this work Abstract: The present study was aimed to investigate the effects of guggulsterone (GS) on proinflammatory responses as well as the underlying molecular mechanisms in macrophage upon lipopolysaccharide (LPS) stimulation. Effects of GS on viability of Raw264.7 cells were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (PCR) was employed to examine the mRNA expression of cytokines, including interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS). Phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), and inhibitor of nuclear factor kappaB (IκB) were determined using immunoblotting. The results revealed that GS was not toxic to Raw264.7 cells at designated concentrations. We demonstrated that GS significantly suppressed the elevated mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, and iNOS in a dose-dependent manner. GS treatment reduced the level of IκB phosphorylation in LPS-stimulated macrophages in a dose-dependent manner. Use of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-κB), led to significantly suppressing effects on IL-1β and TNF-α expression similar as that of GS-treated cells. Our findings suggest that GS possesses anti-inflammatory activity, which may be attributed to downregulation of iNOS and inhibition of NF-κB activity in LPS-stimulated Raw264.7 cells. Keywords: Anti-inflammatory effects, guggulsterone, lipopolysaccharides, NF-κB, IL-1β, TNF-αhttps://www.dovepress.com/anti-inflammatory-effects-of-guggulsterone-on-murine-macrophage-by-inh-peer-reviewed-article-DDDTguggulsteronemacrophage: lipopolysaccharidesNF-κB |
| spellingShingle | Zhang JH Shangguan ZS Chen C Zhang HJ Lin Y Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway Drug Design, Development and Therapy guggulsterone macrophage: lipopolysaccharides NF-κB |
| title | Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway |
| title_full | Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway |
| title_fullStr | Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway |
| title_full_unstemmed | Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway |
| title_short | Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway |
| title_sort | anti inflammatory effects of guggulsterone on murine macrophage by inhibiting lps induced inflammatory cytokines in nf kappa b signaling pathway |
| topic | guggulsterone macrophage: lipopolysaccharides NF-κB |
| url | https://www.dovepress.com/anti-inflammatory-effects-of-guggulsterone-on-murine-macrophage-by-inh-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT zhangjh antiinflammatoryeffectsofguggulsteroneonmurinemacrophagebyinhibitinglpsinducedinflammatorycytokinesinnfkappabsignalingpathway AT shangguanzs antiinflammatoryeffectsofguggulsteroneonmurinemacrophagebyinhibitinglpsinducedinflammatorycytokinesinnfkappabsignalingpathway AT chenc antiinflammatoryeffectsofguggulsteroneonmurinemacrophagebyinhibitinglpsinducedinflammatorycytokinesinnfkappabsignalingpathway AT zhanghj antiinflammatoryeffectsofguggulsteroneonmurinemacrophagebyinhibitinglpsinducedinflammatorycytokinesinnfkappabsignalingpathway AT liny antiinflammatoryeffectsofguggulsteroneonmurinemacrophagebyinhibitinglpsinducedinflammatorycytokinesinnfkappabsignalingpathway |