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Anti-inflammatory and analgesic effects of pyeongwisan on LPS-stimulated murine macrophages and mouse models of acetic acid-induced writhing response and xylene-induced ear edema.

Oh YC, Jeong YH, Cho WK, Ha JH, Gu MJ, Ma JY - Int J Mol Sci (2015)

Bottom Line: However, its effects on inflammation-related diseases are unknown.Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema.Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance.

View Article: PubMed Central - PubMed

Affiliation: Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, 461-24, Jeonmin-dong, Yuseong, Daejeon 305-811, Korea. ulivuli@kiom.re.kr.

ABSTRACT
Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation in vivo. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW in vivo for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance.

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Effect of PW on MAPK phosphorylation in macrophages: (A) extracellular signal-regulated kinase (ERK); (B) p38 and (C) c-Jun NH2-terminal kinase (JNK). RAW 264.7 cells were treated with PW for 30 min before incubation with LPS for 30 min. Cell lysates were analyzed using Western blot analysis with specific antibodies. The experiment was repeated three times independently and similar results were obtained. Con: control; Dex: Dexamethasone. **p < 0.001 in comparisons of the LPS-stimulation value.
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ijms-16-01232-f004: Effect of PW on MAPK phosphorylation in macrophages: (A) extracellular signal-regulated kinase (ERK); (B) p38 and (C) c-Jun NH2-terminal kinase (JNK). RAW 264.7 cells were treated with PW for 30 min before incubation with LPS for 30 min. Cell lysates were analyzed using Western blot analysis with specific antibodies. The experiment was repeated three times independently and similar results were obtained. Con: control; Dex: Dexamethasone. **p < 0.001 in comparisons of the LPS-stimulation value.

Mentions: Because phosphorylation-activated MAPKs play an important role in NF-κB pathway activation and are related to iNOS expression [29], we examined the inhibitory effect of PW treatment on activation of the MAPK pathway. The phosphorylation levels of MAPKs, including ERK1/2, p38 and JNK were evaluated. When RAW 264.7 cells were stimulated with LPS in the presence of PW, the level of phosphorylated ERK MAPK was significantly decreased in a dose-dependent manner (Figure 4A). Additionally, PW inhibited p38 or JNK phosphorylation at concentrations between 100 and 1000 μg/mL (Figure 4B,C), and the full forms of ERK, p38 and JNK were not affected by PW treatment. These results indicated the inhibitory effect of PW on the phosphorylation of MAPKs was directly related to inhibition of NF-κB activation and reduction of inflammatory factor production in RAW 264.7 cells.


Anti-inflammatory and analgesic effects of pyeongwisan on LPS-stimulated murine macrophages and mouse models of acetic acid-induced writhing response and xylene-induced ear edema.

Oh YC, Jeong YH, Cho WK, Ha JH, Gu MJ, Ma JY - Int J Mol Sci (2015)

Effect of PW on MAPK phosphorylation in macrophages: (A) extracellular signal-regulated kinase (ERK); (B) p38 and (C) c-Jun NH2-terminal kinase (JNK). RAW 264.7 cells were treated with PW for 30 min before incubation with LPS for 30 min. Cell lysates were analyzed using Western blot analysis with specific antibodies. The experiment was repeated three times independently and similar results were obtained. Con: control; Dex: Dexamethasone. **p < 0.001 in comparisons of the LPS-stimulation value.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307301&req=5

ijms-16-01232-f004: Effect of PW on MAPK phosphorylation in macrophages: (A) extracellular signal-regulated kinase (ERK); (B) p38 and (C) c-Jun NH2-terminal kinase (JNK). RAW 264.7 cells were treated with PW for 30 min before incubation with LPS for 30 min. Cell lysates were analyzed using Western blot analysis with specific antibodies. The experiment was repeated three times independently and similar results were obtained. Con: control; Dex: Dexamethasone. **p < 0.001 in comparisons of the LPS-stimulation value.
Mentions: Because phosphorylation-activated MAPKs play an important role in NF-κB pathway activation and are related to iNOS expression [29], we examined the inhibitory effect of PW treatment on activation of the MAPK pathway. The phosphorylation levels of MAPKs, including ERK1/2, p38 and JNK were evaluated. When RAW 264.7 cells were stimulated with LPS in the presence of PW, the level of phosphorylated ERK MAPK was significantly decreased in a dose-dependent manner (Figure 4A). Additionally, PW inhibited p38 or JNK phosphorylation at concentrations between 100 and 1000 μg/mL (Figure 4B,C), and the full forms of ERK, p38 and JNK were not affected by PW treatment. These results indicated the inhibitory effect of PW on the phosphorylation of MAPKs was directly related to inhibition of NF-κB activation and reduction of inflammatory factor production in RAW 264.7 cells.

Bottom Line: However, its effects on inflammation-related diseases are unknown.Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema.Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance.

View Article: PubMed Central - PubMed

Affiliation: Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, 461-24, Jeonmin-dong, Yuseong, Daejeon 305-811, Korea. ulivuli@kiom.re.kr.

ABSTRACT
Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation in vivo. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW in vivo for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance.

Show MeSH
Related in: MedlinePlus