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Erschienen in: Inflammation 1/2019

21.08.2018 | ORIGINAL ARTICLE

Oridonin Ameliorates Lipopolysaccharide-Induced Endometritis in Mice via Inhibition of the TLR-4/NF-κBpathway

verfasst von: Min Zhou, Yinyi Yi, Li Hong

Erschienen in: Inflammation | Ausgabe 1/2019

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Abstract

Endometritis is a health threat to both humans and animals and poses a huge economic burden. Oridonin (Ori) is a natural diterpenoid isolated from the traditional Chinese herb Rabdosiarubescens (R. rubescens) and has multiple health-promoting effects, including antioxidant, anti-inflammatory, and antitumor effects. There is little evidence showing that Ori can effectively treat endometritis, and the relevant mechanisms need to be further clarified. In this study, we investigated the effects of Ori on LPS-induced endometritis in vivo. Additionally, we examined the effects of Ori on LPS-stimulated mouse endometrial epithelial cells (mEECs). The results showed that Ori treatment significantly alleviated LPS-induced endometritis and reduced the activity of myeloperoxidase. ELISA and qPCR results indicated that Ori dose-dependently decreased the expression of TNF-α, IL-1β, and IL-6 both in tissues and in mEECs. In addition, Ori was found to inhibit LPS-induced TLR4/NF-κB signaling pathway activation. These results suggest that Ori effectively attenuates LPS-induced endometritis by inhibiting the TLR4/NF-κB signaling pathway and that Ori might be an effective drug for the prevention and treatment of LPS-induced endometritis.
Literatur
1.
Zurück zum Zitat Cicinelli, Ettore, Maria Matteo, Raffaele Tinelli, Vincenzo Pinto, Marco Marinaccio, Ugo Indraccolo, Dominique De Ziegler, and Leonardo Resta. 2013. Chronic Endometritis Due to Common Bacteria Is Prevalent in Women With Recurrent Miscarriage as Confirmed by Improved Pregnancy Outcome After Antibiotic Treatment. Reproductive Sciences 21 (5): 640–647.CrossRefPubMed Cicinelli, Ettore, Maria Matteo, Raffaele Tinelli, Vincenzo Pinto, Marco Marinaccio, Ugo Indraccolo, Dominique De Ziegler, and Leonardo Resta. 2013. Chronic Endometritis Due to Common Bacteria Is Prevalent in Women With Recurrent Miscarriage as Confirmed by Improved Pregnancy Outcome After Antibiotic Treatment. Reproductive Sciences 21 (5): 640–647.CrossRefPubMed
2.
Zurück zum Zitat Romero, R., and M. Mazor. 1988. Infection and preterm labor. Clinical Obstetrics and Gynecology 31 (3): 553–584.CrossRefPubMed Romero, R., and M. Mazor. 1988. Infection and preterm labor. Clinical Obstetrics and Gynecology 31 (3): 553–584.CrossRefPubMed
3.
Zurück zum Zitat Espinoza, J., O. Erez, and R. Romero. 2006. Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery. American Journal of Obstetrics & Gynecology 194 (3): 630–637.CrossRef Espinoza, J., O. Erez, and R. Romero. 2006. Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery. American Journal of Obstetrics & Gynecology 194 (3): 630–637.CrossRef
4.
Zurück zum Zitat Pino, A., G. Giunta, C.L. Randazzo, S. Caruso, C. Caggia, and A. Cianci. 2017. Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial. Microbial Ecology in Health & Disease 28 (1): 1357417.CrossRef Pino, A., G. Giunta, C.L. Randazzo, S. Caruso, C. Caggia, and A. Cianci. 2017. Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial. Microbial Ecology in Health & Disease 28 (1): 1357417.CrossRef
5.
Zurück zum Zitat Swangchanuthai, Theerawat, Chloe R.M. Lavender, Zhangrui Cheng, Ali A. Fouladinashta, and D. Claire Wathes. 2012. Time Course of Defense Mechanisms in Bovine Endometrium in Response to Lipopolysaccharide1. Biology of Reproduction 87 (6): 135. Swangchanuthai, Theerawat, Chloe R.M. Lavender, Zhangrui Cheng, Ali A. Fouladinashta, and D. Claire Wathes. 2012. Time Course of Defense Mechanisms in Bovine Endometrium in Response to Lipopolysaccharide1. Biology of Reproduction 87 (6): 135.
7.
Zurück zum Zitat Jiang, K., X. Ma, S. Guo, T. Zhang, G. Zhao, H. Wu, X. Wang, and G. Deng. 2017. Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced Mastitis in Mice. Inflammation:1–12. Jiang, K., X. Ma, S. Guo, T. Zhang, G. Zhao, H. Wu, X. Wang, and G. Deng. 2017. Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced Mastitis in Mice. Inflammation:1–12.
9.
Zurück zum Zitat Barton, G.M., and R. Medzhitov. 2003. Toll-like receptor signaling pathways. Science 300 (5625): 1524–1525.CrossRefPubMed Barton, G.M., and R. Medzhitov. 2003. Toll-like receptor signaling pathways. Science 300 (5625): 1524–1525.CrossRefPubMed
10.
Zurück zum Zitat Vartanian, Keri B., Susan L. Stevens, Brenda J. Marsh, Rebecca Williamskarnesky, Nikola S. Lessov, and Mary P. Stenzelpoore. 2011. LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury. Journal of Neuroinflammation 8 (1): 140.CrossRefPubMedPubMedCentral Vartanian, Keri B., Susan L. Stevens, Brenda J. Marsh, Rebecca Williamskarnesky, Nikola S. Lessov, and Mary P. Stenzelpoore. 2011. LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury. Journal of Neuroinflammation 8 (1): 140.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Wu, Haichong, Zhao Gan, Kangfeng Jiang, Chengye Li, ChangweiQiu, and Ganzhen Deng. 2016. Engeletin Alleviates Lipopolysaccharide-Induced Endometritis in Mice by Inhibiting TLR4-mediated NF-κB Activation. Journal of Agricultural and Food Chemistry 64 (31): 6171–6178.CrossRefPubMed Wu, Haichong, Zhao Gan, Kangfeng Jiang, Chengye Li, ChangweiQiu, and Ganzhen Deng. 2016. Engeletin Alleviates Lipopolysaccharide-Induced Endometritis in Mice by Inhibiting TLR4-mediated NF-κB Activation. Journal of Agricultural and Food Chemistry 64 (31): 6171–6178.CrossRefPubMed
12.
Zurück zum Zitat Kagan, Jonathan C., and Ruslan Medzhitov. 2006. Phosphoinositide-Mediated Adaptor Recruitment Controls Toll-like Receptor Signaling. Cell 125 (5): 943–955.CrossRefPubMed Kagan, Jonathan C., and Ruslan Medzhitov. 2006. Phosphoinositide-Mediated Adaptor Recruitment Controls Toll-like Receptor Signaling. Cell 125 (5): 943–955.CrossRefPubMed
13.
Zurück zum Zitat Jung, H.W., R. Mahesh, J.H. Park, Y.C. Boo, K.M. Park, and Y.K. Park. 2010. Bisabolangelone isolated from Ostericumkoreanum inhibits the production of inflammatory mediators by down-regulation of NF-kappaB and ERK MAP kinase activity in LPS-stimulated RAW264.7 cells. International Immunopharmacology 10 (2): 155–162.CrossRefPubMed Jung, H.W., R. Mahesh, J.H. Park, Y.C. Boo, K.M. Park, and Y.K. Park. 2010. Bisabolangelone isolated from Ostericumkoreanum inhibits the production of inflammatory mediators by down-regulation of NF-kappaB and ERK MAP kinase activity in LPS-stimulated RAW264.7 cells. International Immunopharmacology 10 (2): 155–162.CrossRefPubMed
14.
Zurück zum Zitat Zheng, X.C., Q.J. Wu, Z.H. Song, H. Zhang, J.F. Zhang, L.L. Zhang, T.Y. Zhang, C. Wang, and T. Wang. 2016. Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolysaccharide. Poultry Science 95 (10): 2281–2289.CrossRefPubMed Zheng, X.C., Q.J. Wu, Z.H. Song, H. Zhang, J.F. Zhang, L.L. Zhang, T.Y. Zhang, C. Wang, and T. Wang. 2016. Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolysaccharide. Poultry Science 95 (10): 2281–2289.CrossRefPubMed
15.
Zurück zum Zitat Shi, Min, Xiao Jie Lu, Juan Zhang, Hua Diao, Guangming Li, Ling Xu, Ting Wang, Jue Wei, Wenying Meng, and Jia Li Ma. 2016. Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms. Oncotarget 7 (16): 22623–22631.PubMedPubMedCentral Shi, Min, Xiao Jie Lu, Juan Zhang, Hua Diao, Guangming Li, Ling Xu, Ting Wang, Jue Wei, Wenying Meng, and Jia Li Ma. 2016. Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms. Oncotarget 7 (16): 22623–22631.PubMedPubMedCentral
16.
Zurück zum Zitat Zhao, G., T. Zhang, X. Ma, K. Jiang, H. Wu, C. Qiu, M. Guo, and G. Deng. 2017. Oridonin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-induced RAW264.7 cells and acute lung injury. Oncotarget 8 (40). Zhao, G., T. Zhang, X. Ma, K. Jiang, H. Wu, C. Qiu, M. Guo, and G. Deng. 2017. Oridonin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-induced RAW264.7 cells and acute lung injury. Oncotarget 8 (40).
17.
Zurück zum Zitat Jiang, K., X. Chen, G. Zhao, H. Wu, J. Mi, C. Qiu, X. Peng, and G. Deng. 2016. IFN-τ Plays an Anti-Inflammatory Role in Staphylococcus aureus-Induced Endometritis in Mice Through the Suppression of NF-κB Pathway and MMP9 Expression. Journal of Interferon & Cytokine Research the Official Journal of the International Society for Interferon & Cytokine Research 37 (2). Jiang, K., X. Chen, G. Zhao, H. Wu, J. Mi, C. Qiu, X. Peng, and G. Deng. 2016. IFN-τ Plays an Anti-Inflammatory Role in Staphylococcus aureus-Induced Endometritis in Mice Through the Suppression of NF-κB Pathway and MMP9 Expression. Journal of Interferon & Cytokine Research the Official Journal of the International Society for Interferon & Cytokine Research 37 (2).
18.
Zurück zum Zitat Jiang, K., S. Guo, T. Zhang, Y. Yang, G. Zhao, A. Shaukat, H. Wu, and G. Deng. 2018. Downregulation of TLR4 by miR-181a Provides Negative Feedback Regulation to Lipopolysaccharide-Induced Inflammation. Frontiers in Pharmacology 9. Jiang, K., S. Guo, T. Zhang, Y. Yang, G. Zhao, A. Shaukat, H. Wu, and G. Deng. 2018. Downregulation of TLR4 by miR-181a Provides Negative Feedback Regulation to Lipopolysaccharide-Induced Inflammation. Frontiers in Pharmacology 9.
19.
Zurück zum Zitat Brodzki, P., K. Kostro, A. Brodzki, and U. Lisiecka. 2014. Determination of selected parameters for non-specific and specific immunity in cows with subclinical endometritis. Animal Reproduction Science 148 (3–4): 109–114.CrossRefPubMed Brodzki, P., K. Kostro, A. Brodzki, and U. Lisiecka. 2014. Determination of selected parameters for non-specific and specific immunity in cows with subclinical endometritis. Animal Reproduction Science 148 (3–4): 109–114.CrossRefPubMed
20.
Zurück zum Zitat Di Pietro, C., S. Caruso, R. Battaglia, M. IraciSareri, A. La Ferlita, F. Strino, G. Bonaventura, et al. 2018. MiR-27a-3p and miR-124-3p, upregulated in endometrium and serum from women affected by chronic Endometritis, are new potential molecular markers of endometrial receptivity. American Journal of Reproductive Immunology: e12858. https://doi.org/10.1111/aji.12858. Di Pietro, C., S. Caruso, R. Battaglia, M. IraciSareri, A. La Ferlita, F. Strino, G. Bonaventura, et al. 2018. MiR-27a-3p and miR-124-3p, upregulated in endometrium and serum from women affected by chronic Endometritis, are new potential molecular markers of endometrial receptivity. American Journal of Reproductive Immunology: e12858. https://​doi.​org/​10.​1111/​aji.​12858.
21.
Zurück zum Zitat Mishra, Bhuwan B., and Vinod K. Tiwari. 2011. Natural products: An evolving role in future drug discovery. European Journal of Medicinal Chemistry 46 (10): 4769–4807.CrossRefPubMed Mishra, Bhuwan B., and Vinod K. Tiwari. 2011. Natural products: An evolving role in future drug discovery. European Journal of Medicinal Chemistry 46 (10): 4769–4807.CrossRefPubMed
22.
Zurück zum Zitat Deng, Y., C. Chen, H. Yu, H. Diao, C. Shi, Y. Wang, G. Li, and M. Shi. 2017. Oridonin ameliorates lipopolysaccharide/D-galactosamine-induced acute liver injury in mice via inhibition of apoptosis. American Journal of Translational Research 9 (9): 4271–4279.PubMedPubMedCentral Deng, Y., C. Chen, H. Yu, H. Diao, C. Shi, Y. Wang, G. Li, and M. Shi. 2017. Oridonin ameliorates lipopolysaccharide/D-galactosamine-induced acute liver injury in mice via inhibition of apoptosis. American Journal of Translational Research 9 (9): 4271–4279.PubMedPubMedCentral
25.
Zurück zum Zitat Cao, S.Y., W. Wang, F.F. Nan, Y.N. Liu, S.Y. Wei, F.F. Li, and L. Chen. 2018. Asiatic acid inhibits LPS-induced inflammatory response in endometrial epithelial cells. Microbial Pathogenesis 116: 195–199.CrossRefPubMed Cao, S.Y., W. Wang, F.F. Nan, Y.N. Liu, S.Y. Wei, F.F. Li, and L. Chen. 2018. Asiatic acid inhibits LPS-induced inflammatory response in endometrial epithelial cells. Microbial Pathogenesis 116: 195–199.CrossRefPubMed
26.
Zurück zum Zitat Herath, S., D.P. Fischer, D. Werling, E.J. Williams, S.T. Lilly, H. Dobson, C.E. Bryant, and I.M. Sheldon. 2006. Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. Endocrinology 147: 562–570.CrossRefPubMed Herath, S., D.P. Fischer, D. Werling, E.J. Williams, S.T. Lilly, H. Dobson, C.E. Bryant, and I.M. Sheldon. 2006. Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus. Endocrinology 147: 562–570.CrossRefPubMed
28.
Zurück zum Zitat Netea, M.G., and Van Der Meer JwkullbergBj. 2004. Toll-like receptors as an escape mechanism from the host defense. Trends in Microbiology 12 (11): 484–488.CrossRefPubMed Netea, M.G., and Van Der Meer JwkullbergBj. 2004. Toll-like receptors as an escape mechanism from the host defense. Trends in Microbiology 12 (11): 484–488.CrossRefPubMed
30.
Zurück zum Zitat Tanaka, T., M. Narazaki, and T. Kishimoto. 2014. IL-6 in inflammation, immunity, and disease. Cold Spring HarbPerspect Biol 6: a016295.CrossRef Tanaka, T., M. Narazaki, and T. Kishimoto. 2014. IL-6 in inflammation, immunity, and disease. Cold Spring HarbPerspect Biol 6: a016295.CrossRef
31.
Zurück zum Zitat Yang, X., B. Shi, L. Li, Z. Xu, Y. Ge, J. Shi, Y. Liu, and D. Zheng. 2016. Death receptor 6 (DR6) is required for mouse B16 tumor angiogenesis via the NF-κB, P38 MAPK and STAT3 pathways. Oncogenesis 5: e206.CrossRefPubMedPubMedCentral Yang, X., B. Shi, L. Li, Z. Xu, Y. Ge, J. Shi, Y. Liu, and D. Zheng. 2016. Death receptor 6 (DR6) is required for mouse B16 tumor angiogenesis via the NF-κB, P38 MAPK and STAT3 pathways. Oncogenesis 5: e206.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Dinarello, C.A. 1996. Biologic basis for interleukin-1 in disease. Blood 87: 2095–2147. Dinarello, C.A. 1996. Biologic basis for interleukin-1 in disease. Blood 87: 2095–2147.
33.
Zurück zum Zitat Esposito, E., and S. Cuzzocrea. 2009. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Current Medicinal Chemistry 16: 3152–3167.CrossRefPubMed Esposito, E., and S. Cuzzocrea. 2009. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Current Medicinal Chemistry 16: 3152–3167.CrossRefPubMed
34.
Zurück zum Zitat Colotta, F., P. Allavena, A. Sica, C. Garlanda, and A. Mantovani. 2009. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30: 1073–1081.CrossRef Colotta, F., P. Allavena, A. Sica, C. Garlanda, and A. Mantovani. 2009. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30: 1073–1081.CrossRef
35.
Zurück zum Zitat Mateu, A., L. Ramudo, M.A. Manso, and I. De Dios. 2015. Cross-talk between TLR4 and PPARγ pathways in the arachidonic acid-induced inflammatory response in pancreatic acini. International Journal of Biochemistry & Cell Biology 69: 132–141.CrossRef Mateu, A., L. Ramudo, M.A. Manso, and I. De Dios. 2015. Cross-talk between TLR4 and PPARγ pathways in the arachidonic acid-induced inflammatory response in pancreatic acini. International Journal of Biochemistry & Cell Biology 69: 132–141.CrossRef
36.
Zurück zum Zitat Jiang, Q., M. Yi, Q. Guo, C. Wang, H. Wang, S. Meng, C. Liu, Y. Fu, H. Ji, and T. Chen. 2015. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway. International Immunopharmacology 29 (2): 370–376.CrossRefPubMed Jiang, Q., M. Yi, Q. Guo, C. Wang, H. Wang, S. Meng, C. Liu, Y. Fu, H. Ji, and T. Chen. 2015. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway. International Immunopharmacology 29 (2): 370–376.CrossRefPubMed
37.
Zurück zum Zitat Zhao, G., H. Wu, K. Jiang, X. Chen, X. Wang, C. Qiu, M. Guo, and G. Deng. 2016. The Anti-Inflammatory Effects of Interferon Tau by Suppressing NF-κB/MMP9 in Macrophages Stimulated with Staphylococcus aureus. Journal of Interferon & Cytokine Research the Official Journal of the International Society for Interferon & Cytokine Research 36 (8): 516–524.CrossRef Zhao, G., H. Wu, K. Jiang, X. Chen, X. Wang, C. Qiu, M. Guo, and G. Deng. 2016. The Anti-Inflammatory Effects of Interferon Tau by Suppressing NF-κB/MMP9 in Macrophages Stimulated with Staphylococcus aureus. Journal of Interferon & Cytokine Research the Official Journal of the International Society for Interferon & Cytokine Research 36 (8): 516–524.CrossRef
38.
Zurück zum Zitat Baeuerle, P.A. 1988. IκB: a specific inhibitor of the NF-κB transcription factor. Science 242 (4878): 540–546.CrossRefPubMed Baeuerle, P.A. 1988. IκB: a specific inhibitor of the NF-κB transcription factor. Science 242 (4878): 540–546.CrossRefPubMed
39.
Zurück zum Zitat Nicholas, Courtney, Sanjay Batra, Melissa A. Vargo, Oliver H. Voss, Mikhail A. Gavrilin, Mark D. Wewers, Denis C. Guttridge, Erich Grotewold, and Andrea I. Doseff. 2007. Apigenin Blocks Lipopolysaccharide-Induced Lethality In Vivo and Proinflammatory Cytokines Expression by Inactivating NF-κB through the Suppression of p65 Phosphorylation. Journal of Immunology 179 (10): 7121–7127.CrossRef Nicholas, Courtney, Sanjay Batra, Melissa A. Vargo, Oliver H. Voss, Mikhail A. Gavrilin, Mark D. Wewers, Denis C. Guttridge, Erich Grotewold, and Andrea I. Doseff. 2007. Apigenin Blocks Lipopolysaccharide-Induced Lethality In Vivo and Proinflammatory Cytokines Expression by Inactivating NF-κB through the Suppression of p65 Phosphorylation. Journal of Immunology 179 (10): 7121–7127.CrossRef
Metadaten
Titel
Oridonin Ameliorates Lipopolysaccharide-Induced Endometritis in Mice via Inhibition of the TLR-4/NF-κBpathway
verfasst von
Min Zhou
Yinyi Yi
Li Hong
Publikationsdatum
21.08.2018
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 1/2019
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-018-0874-8

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