• Title/Summary/Keyword: Prostaglandin E2 Tumor necrosis factor-$\alpha$

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Effects of plant-based Korean food extracts on lipopolysaccharide-stimulated production of inflammatory mediators in vitro

  • Lee, Sun Young;Kim, Yoo-Sun;Lim, Ji Ye;Chang, Namsoo;Kang, Myung-Hee;Oh, Se-Young;Lee, He-Jin;Kim, Hyesook;Kim, Yuri
    • Nutrition Research and Practice
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    • v.8 no.3
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    • pp.249-256
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    • 2014
  • BACKGROUND/OBJECTIVES: The traditional Korean diet is plant-based and rich in antioxidants. Previous studies have investigated the potential health benefits of individual nutrients of Korean foods. However, the cumulative effects of a Korean diet on inflammation remain poorly understood. Therefore, the aim of this study was to investigate the anti-inflammatory effects of a plant-based Korean diet. MATERIALS/METHODS: Using data from the Fifth Korean National Health and Nutrition Examination Survey, 75 individual plant food items were selected which represent over 1% of the total diet intake of the Korean diet. These items were classified into ten different food groups, and the vegetable (Veg) and fruit (Fruit) groups were studied based on their high antioxidant capacity. For comparison, a mixture of all ten groups (Mix) was prepared. To produce a model of inflammation with which to test these Veg, Fruit, and Mix plant-based Korean food extracts (PKE), RAW264.7 macrophages were treated with lipopolysaccharide (LPS). RESULTS: Levels of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), as well as protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be lower following PKE treatment. Furthermore, PKE treatment was found to suppress tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) via the nuclear transcription factor kappa-B ($NF-{\kappa}B$) signaling pathway. Overall, the Mix group exhibited the greatest anti-inflammatory effects compared with Veg and Fruit PKE group. CONCLUSIONS: Inhibition of LPS-induced pro-inflammatory mediators by the PKE tested was found to involve an inhibition of NF-kB activation. Moreover, PKE tested have the potential to ameliorate various inflammation-related diseases by limiting the excessive production of pro-inflammatory mediators.

Roots of Daucus carota sativa abrogates acute phase of Inflammation by the Inhibition of NO and Pro-Inflammatory Cytokine Production (NO와 Pro-Inflammatory Cytokine의 억제를 통한 호라복(胡蘿蔔)의 항염증효과)

  • Lee, Dong-Jin;Park, Sang-Mi;Hwangbo, Min;Jung, Tae-Young;Kim, Sang-Chan;Jee, Seon-Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.26 no.2
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    • pp.45-57
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    • 2013
  • Objectives : Daucus carota sativa has been frequently used as food supplements in many of the Asian countries, and a nutritional medical drug in traditional medicine. This research investigated the effects of Daucus carota sativa extract (DCE) on acute phases of inflammation in Raw 264.7 cells treated with lipopolysaccharide (LPS) in terms of the inhibition of nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines production. Methods : NO, $PGE_2$, tumor necrosis factor (TNF)-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6 contents were assayed by ELISA, and expressions of inflammation-related proteins such as inducible NO synthase (iNOS) were determined by immunoblot analyses. Results : DCE treatment attenuated the LPS ability to increase the productions of NO and $PGE_2$ as well as the protein level of iNOS in a concentration-dependent manner. Consistently, treatment of the cells with DCE suppressed the production of TNF-${\alpha}$, interleukin-$1{\beta}$ and interleukin-6. DCE also caused decreases of inhibitor of ${\kappa}B{\alpha}$ phosphorylation induced by LPS in the cells, which means DCE inhibition of NF-${\kappa}B$ activity. Furthermore, DCE blocked LPS-induced phosphorylation of p38 and SAPK/JNK. Conclusion : This study showing here may be of help to understand the action mechanism of DCE, and provide the information for the medical use of Daucus carota sativa for the inflammatory disease.

Effects of dietary Antrodia cinnamomea fermented product supplementation on metabolism pathways of antioxidant, inflammatory, and lipid metabolism pathways-a potential crosstalk

  • Lee, M.T.;Lin, W.C.;Lin, L.J.;Wang, S.Y.;Chang, S.C.;Lee, T.T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.7
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    • pp.1167-1179
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    • 2020
  • Objective: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. Methods: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. Results: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet. Conclusion: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Anthocyanins from Hibiscus syriacus L. Attenuate LPS-Induced Inflammation by Inhibiting the TLR4-Mediated NF-κB Signaling Pathway

  • Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga;Molagoda, Ilandarage Menu Neelaka;Lee, Kyoung Tae;Choi, Yung Hyun;Kang, Chang-Hee;Jeong, Jin-Woo;Kim, Gi-Young
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.92-92
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    • 2019
  • Excessive or chronic inflammation contributes to the pathogenesis of many inflammatory diseases such as sepsis, rheumatoid arthritis, and ulcerative colitis. Hibiscus syriacus L. has been used as a medicinal plant in many Asian countries, even though its anti-inflammatory activity has been unclear. Therefore, we investigated the anti-inflammatory effect of anthocyanin fractions from the H. syriacus L. varieties Pulsae (PS) on the lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and cytokines in RAW264.7 macrophages. PS suppressed LPS-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) secretion concomitant with downregulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, PS inhibited the production of proinflammatory cytokines such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and IL-12 in LPS-stimulated RAW264.7 macrophages. Further study showed that PS significantly decreased LPS-induced nuclear translocation of the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) subunits, p65 and p50. Molecular docking data showed that many anthocyanins from PS fit into the hydrophobic pocket of MD2 and bound to Toll-like receptor 4 (TLR4), indicating that PS inhibits the TLR4-MD2-mediated inflammatory signaling pathway. Especially, apigenin-7-O-glucoside most powerfully bound to MD2 and TLR4 through LYS122, LYS122, and SER127 at a distance of $2.205{\AA}$, $3.098{\AA}$, and $2.844{\AA}$ and SER441 at a distance of $2.873{\AA}$ (docking score: -8.4) through hydrogen bonding, respectively. Additionally, PS inhibited LPS-induced TLR4 dimerization/expression on the cell surface, which consequently decreased MyD88 recruitment and IRAK4 phosphorylation. PS completely blocked LPS-mediated mortality in zebrafish larvae by diminishing the recruitment of neutrophil and macrophages accompanied by low levels of proinflammatory cytokines. Taken together, our results indicate that PS attenuates LPS-mediated inflammation in both in vitro and in vivo by blocking the TLR4/MD2-MyD88/IRAK4-$NF-{\kappa}B$ axis. Therefore, PS might be used as a novel modulatory candidate for effective treatment of LPS-mediated inflammatory diseases.

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The anti-inflammatory effect of Lithospermum Erythrorhizon on lipopolysaccharide - induced inflammatory response in RAW 264.7 cells (LPS로 유도한 RAW 264.7 세포의 염증반응에서 자초(紫草)의 항염증 효과)

  • Choi, Sun-Bok;Bae, Gi-Sang;Jo, Il-Joo;Park, Kyoung-Chel;Seo, Seung-Hee;Kim, Dong-Goo;Shin, Joon-Yeon;Gwak, Tae-Sin;Lee, Jung-Hyun;Lee, Guem-San;Park, Sung-Joo;Song, Ho-Joon
    • The Korea Journal of Herbology
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    • v.28 no.2
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    • pp.67-73
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    • 2013
  • Objective : Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods : To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, interleukin, (IL)-$1{\beta}$ and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-${\kappa}B$) activation by western blot. Results : Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, $PGE_2$, and pro-inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK), and NF-${\kappa}B$ activation in RAW 264.7 cells. Conclusion : LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-${\kappa}B$ activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.

Anti-inflammatory Effect of Gagam-GongJin-dan in mouse peritoneal macrophages (마우스 복강대식세포에서 가감공진단(加減拱辰丹)의 항염증 효과)

  • Kim, Hong-Jun;Kim, Young-Sik;Mok, Ji-Ye;Jeong, Seung-Il;Hwang, Sung-Yeoun;Cho, Jung-Keun;Jang, Seon-Il
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.207-217
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    • 2011
  • Objectives : In a previous study, we have shown that Gagam-Gongjin-Dan(GGD) has an inhibitory effect on the ovalbumin-induced immune responses and a hepatoprotective effect on actaminophen-induced liver injury in Balb/c Mice. However, the possible anti-inflammatory effect of GGD extract for inflammatory mediators was not reported. Therefore, the purpose of this study was to investigate an inhibitory effects of GGD extract against lipopolysaccharides(LPS) induced inflammatory mediators in mouse peritoneal macrophages. Methods : GGD extract was prepared by extracting with methanol for 7 days. The extract was freeze-dried following filtration through vacuum distillation system. Accumulated nitrite, an oxidative product of nitric oxide(NO), was measured in the culture medium by the Griess reaction. The levels of prostaglandin $E_2(PGE_2)$, interleukin-$1{\beta}$(IL-$1{\beta}$), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) were measured by Western blot analysis. Results : GGD extract (50-$400\;{\mu}g$/ml) per se had no cytotoxic effect in LPS-stimulated peritoneal macrophages. GGD extract dose-dependently reduced NO, $PGE_2$, IL-$1{\beta}$ and TNF-${\alpha}$ production and COX-2 activity caused by stimulation of LPS. The levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with GGD extract in a dose dependent manner. Conclusions : These results suggest that GGD extract has an anti-inflammatory effect against LPS-induced inflammatory mediators in peritoneal macrophages, these properties may contribute to inflammation disease care.

Anti-inflammatory Effects of the Fruits of Foeniculum vulgare in Lipopolysaccharide-stimulated Macrophages (대식세포에서 LPS로 유도된 염증에 대한 회향 열매의 항염 효과)

  • Yang, In Jun;Yu, Hak Yin;Lee, Dong-Ung;Shin, Heung Mook
    • Journal of Life Science
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    • v.24 no.9
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    • pp.981-987
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    • 2014
  • Foeniculum vulgare has long been prescribed in traditional medicine for the treatment of inflammation diseases. In this study, we aimed to investigate the inhibitory effects of the fruits of F. vulgare on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells under non-cytotoxic ($100{\mu}g/ml$) conditions. The 80% methanol extract was subsequently partitioned successively with hexane, methylene chloride, ethyl acetate, and n-butanol, and the fractions so obtained were also examined for their anti-inflammatory effects. Among them, the hexane, methylene chloride, and ethyl acetate fractions inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS stimulated macrophages. The methylene chloride and ethyl acetate fractions also suppressed the productions of interleukin $(IL)-1{\beta}$ and IL-6 by down-regulating their mRNA levels in LPS stimulated RAW 264.7 cells. Furthermore, the ethyl acetate fraction strongly suppressed tumor necrosis factor (TNF)-${\alpha}$ at the protein and mRNA levels in LPS stimulated RAW 264.7 cells. These observations suggest that the anti-inflammatory actions of F. vulgare are due to inhibitions of the productions of NO, PGE2, and pro-inflammatory cytokines.

Anti-inflammatory Activity of Perilla frutescens Britton Seed in RAW 264.7 Macrophages and an Ulcerative Colitis Mouse Model (RAW 264.7 대식세포와 궤양성 대장염 마우스 모델에서의 들깨의 항염증 효과)

  • Lee, Yuna;Song, Boram;Ju, Jihyeung
    • Korean Journal of Food Science and Technology
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    • v.46 no.1
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    • pp.61-67
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    • 2014
  • This study aimed to investigate the anti-inflammatory activities of raw (P) and roasted (RP) Perilla frutescens Britton (perilla) seeds in RAW 264.7 macrophages and an ulcerative colitis mouse model. In lipopolysaccharide-treated RAW 264.7 cells, treatment with ethanol extract of P at the concentrations of 75 and $150{\mu}g/mL$ decreased nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) levels to 48-85% of the control (p<0.01). Treatment with RP extract exhibited similar effects on NO, IL-6, and TNF-${\alpha}$, decreasing those levels to 51-84% of the control (p<0.01). In dextran sulfate sodium-treated ulcerative colitis mice, dietary treatment with 1% RP for 7 days decreased the colonic levels of prostaglandin $E_2$ and leukotriene $B_4$ to 34% and 58% of the control, respectively (p<0.05). Dietary P treatment, however, did not decrease those levels significantly. These results indicate that roasted perilla seed exerts anti-inflammatory activity both in vitro and in vivo.

The Study of Anti-inflammatory Effect of Hwanggeumjakyak-tang Extract in RAW 264.7 Macrophage (황금작약탕(黃芩芍藥湯)의 RAW 264.7 대식 세포에서의 항염증 효과에 관한 연구)

  • Kim, Ma-Ryong;Kang, Ok-Hwa;Kim, Sung-Bae;Kang, Hee-Jung;Kim, Ji-Eun;Hwang, Hyeong-Chil;Kim, In-Won;Kwon, Dong-Yeul
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.43-50
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    • 2013
  • Objectives : Hwanggeumjakyak-tang (huangqin shaoyao tang, HJT) has been used to treat acute enteritis in traditional oriental medicine. However, there has been a lack of studies regarding the effects of HJT on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. So we examined the effect of HJT water extract on pro-inflammatory mediators in lipopolysaccharide (LPS) - stimulated mouse macrophage, RAW 264.7 cells. Methods : Cells were treated with 2 ug/mL of LPS 1 h prior to the addition of HJT. Cell viability was measured by MTS assay. The production of nitric oxide (NO) was determined by reacting cultured medium with Griess reagent. The expression of cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) and mitogen-activated protein kinases (MAPKs) was investigated by Western blot, RT-PCR. The content of level of cytokines (prostaglandin (PG) $E_2$, interleukin (IL)-6, IL-12, Tumor necrosis factor-alpha (TNF-${\alpha}$) and monocyte chemoattractant protein-1 (MCP-1)) in media from LPS-stimulated Raw 264.7 cells was analyed by ELISA kit. Results : HJT inhibited the production of NO, $PGE_2$, IL-6 as well as the expressions of iNOS, COX-2 but did not inhibit the production of IL-12, TNF-${\alpha}$, MCP-1 in the murine macrophage, RAW 264.7 cells. HJT also had suppression effects of LPS-induced MAPKs activation Conclusion : These results suggest that HJT has an anti-inflammatory therapeutic potential, which may result from inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

The Anti-Inflammatory Effect of Pulsatilla koreana Methanol Extract in Lipopolysaccharid-Exposed RAW 264.7 Cells (Lipopolysaccharide를 처리한 RAW 264.7 세포에서 백두옹 메탄올 추출물의 항염증 효과)

  • Lee, Gui Sun;Kim, Doo Hee;Park, Joong Hyun;Choi, Hee Seung;Heo, Seong Kyu;Cha, Yun Yeop
    • Journal of Korean Medicine for Obesity Research
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    • v.17 no.1
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    • pp.1-9
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    • 2017
  • Objectives: This study was performed to identify the anti-inflammatory effect of Pulsatilla koreana (PK) methanol extract on lipopolysaccharide (LPS) induced inflammatory. Methods: There were five groups. They were control group, LPS-exposed PK methanol extract group ($0{\mu}g/ml$, $10{\mu}g/ml$, $30{\mu}g/ml$, $100{\mu}g/ml$). To measure out cytotoxicity of PK, we performed the MTT assay. To evaluate the anti-inflammatory effect of PK, we examined the inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines (interleukin $[IL]-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ [$TNF-{\alpha}$], IL-10). Results: 1. The extract of PK (${\sim}100{\mu}g/ml$) itself did not have any cytotoxic effect in RAW 264.7 cells. 2. The concentration of plasma NO and PGE2 in PK methanol extract group showed a lower values than those of control group. 3. The concentration of plasma $IL-1{\beta}$, plasma IL-6, and plasma $TNF-{\alpha}$ in PK methanol extract group showed a lower values than those of control group. 4. The concentration of Plasma IL-10 in PK methanol extract groups showed higher than control group; however, these values showed no significantly different. Conclusions: According to this study, the extract of PK could be used as a protective agent against inflammation.