Similar articles

Abstract: catalpol is the main active ingredient of an extract from Radix rehmanniae, which in a previous study showed a protective effect against various types of tissue injury. However, a protective effect of catalpol on uterine inflammation has not been reported. In this study, to investigate the protective mechanism of catalpol on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and mouse endometritis, in vitro and in vivo inflammation models were established. The toll-like receptor 4 (TLR4)/nuclear factor-κ;b (NF-κ;b) signaling pathway and its downstream inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot (Wb), and immunofluorescence techniques. The results from ELISA and qRT-PCR showed that catalpol dose-dependently reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, and chemokines such as C-X-C motif chemokine ligand 8 (CXCL8) and CXCL5, both in bEECs and in uterine tissue. From the experimental results of WB, qRT-PCR, and immunofluorescence, the expression of TLR4 and the phosphorylation of NF-κB p65 were markedly inhibited by catalpol compared with the LPS group. The inflammatory damage to the mouse uterus caused by LPS was greatly reduced and was accompanied by a decline in myeloperoxidase (MPO) activity. The results of this study suggest that catalpol can exert an anti-inflammatory impact on LPS-induced bEECs and mouse endometritis by inhibiting inflammation and activation of the TLR4/NF-κB signaling pathway.

梓醇通过抑制炎症反应和TLR4/NF-κB 信号通路改善脂多糖诱导的小鼠子宫内膜炎

[1]Angrisano T, Pero R, Peluso S, et al., 2010. LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes. BMC Microbiol, 10:172.

[2]Begley LA, Kasina S, Mehra R, et al., 2008. CXCL5 promotes prostate cancer progression. Neoplasia, 10(3):244-254.

[3]Brodzki P, Kostro K, Brodzki A, et al., 2015. Inflammatory cytokines and acute-phase proteins concentrations in the peripheral blood and uterus of cows that developed endometritis during early postpartum. Theriogenology, 84(1):11-18.

[4]Brown K, Park S, Kanno T, et al., 1993. Mutual regulation of the transcriptional activator NF-κB and its inhibitor, IκBα. Proc Natl Acad Sci USA, 90(6):2532-2536.

[5]Chen BY, Jiang LX, Hao K, et al., 2018. Protection of plasma transfusion against lipopolysaccharide/D-galactosamine-induced fulminant hepatic failure through inhibiting apoptosis of hepatic cells in mice. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(6):436-444.

[6]Chen Z, Deng S, Yuan DC, et al., 2018. Novel nano-microspheres containing chitosan, hyaluronic acid, and chondroitin sulfate deliver growth and differentiation factor-5 plasmid for osteoarthritis gene therapy. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(12):910-923.

[7]Chensue SW, 2001. Molecular machinations: chemokine signals in host-pathogen interactions. Clin Microbiol Rev, 14(4):821-835.

[8]de Vries MA, Klop B, Eskes SA, et al., 2014. The postprandial situation as a pro-inflammatory condition. Clin Investig Arterioscler, 26(4):184-192.

[9]Feng XN, Zhang DF, Li XY, et al., 2018. CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells. Biomed Pharmacother, 107:1496-1504.

[10]Guo S, Jiang KF, Wu HC, et al., 2018. Magnoflorine ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation. Front Pharmacol, 9:982.

[11]Haas M, Kaup FJ, Neumann S, 2016. Canine pyometra: a model for the analysis of serum CXCL8 in inflammation. J Vet Med Sci, 78(3):375-381.

[12]Herath S, Lilly ST, Santos NR, et al., 2009. Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reprod Biol Endocrinol, 7:55.

[13]Huang CL, Cui YL, Ji LL, et al., 2013. Catalpol decreases peroxynitrite formation and consequently exerts cardioprotective effects against ischemia/reperfusion insult. Pharm Biol, 51(4):463-473.

[14]Israël A, 2010. The IKK complex, a central regulator of NF-κB activation. Cold Spring Harb Perspect Biol, 2(3):a000158.

[15]Jiang KF, Chen XY, Zhao G, et al., 2017. IFN-τ plays an anti-inflammatory role in Staphylococcus aureus-induced endometritis in mice through the suppression of NF-κB pathway and MMP9 expression. J Interferon Cytokine Res, 37(2):81-89.

[16]Karlsson I, Hagman R, Guo YZ, et al., 2015. Pathogenic Escherichia coli and lipopolysaccharide enhance the expression of IL-8, CXCL5, and CXCL10 in canine endometrial stromal cells. Theriogenology, 84(1):34-42.

[17]Kawamura M, Toiyama Y, Tanaka K, et al., 2012. CXCL5, a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer. Eur J Cancer, 48(14):2244-2251.

[18]Koyama T, Omori R, Koyama K, et al., 2018. Optimization of diagnostic methods and criteria of endometritis for various postpartum days to evaluate infertility in dairy cows. Theriogenology, 119:225-232.

[19]Li QT, Verma IM, 2002. NF-κB regulation in the immune system. Nat Rev Immunol, 2(10):725-734.

[20]Liu J, He QJ, Zou W, et al., 2006. Catalpol increases hippocampal neuroplasticity and up-regulates PKC and BDNF in the aged rats. Brain Res, 1123(1):68-79.

[21]Lyu A, Chen JJ, Wang HC, et al., 2017. Punicalagin protects bovine endometrial epithelial cells against lipopolysaccharide-induced inflammatory injury. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(6):481-491.

[22]Machado Pfeifer LF, de Souza Andrade J, Moreira EM, et al., 2018. Uterine inflammation and fertility of beef cows subjected to timed AI at different days postpartum. Anim Reprod Sci, 197:268-277.

[23]Nicholas C, Batra S, Vargo MA, et al., 2007. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-κB through the suppression of p65 phosphorylation. J Immunol, 179(10):7121-7127.

[24]Sheldon IM, Williams EJ, Miller ANA, et al., 2008. Uterine diseases in cattle after parturition. Vet J, 176(1):115-121.

[25]Shen Y, Liu B, Mao W, et al., 2018. PGE₂ downregulates LPS-induced inflammatory responses via the TLR4-NF-κB signaling pathway in bovine endometrial epithelial cells. Prostaglandins Leukot Essent Fatty Acids, 129:25-31.

[26]Sicsic R, Goshen T, Dutta R, et al., 2018. Microbial communities and inflammatory response in the endometrium differ between normal and metritic dairy cows at 5–10 days post-partum. Vet Res, 49:77.

[27]Socha BM, Lada P, et al., 2018. The influence of experimentally induced endometritis on the PPAR expression profile in the bovine endometrium. Theriogenology, 122: 74-83.

[28]Turner ML, Cronin JG, et al., 2014. Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1, and TLR6. Endocrinology, 155(4):1453-1465.

[29]van Schyndel SJ, Pascottini OB, et al., 2018. Comparison of cow-side diagnostic techniques for subclinical endometritis in dairy cows. Theriogenology, 120:117-122.

[30]Wagener K, Gabler C, Drillich M, 2017. A review of the ongoing discussion about definition, diagnosis and pathomechanism of subclinical endometritis in dairy cows. Theriogenology, 94:21-30.

[31]Wang J, Yan XX, Nesengani LT, et al., 2018. LPS-induces IL-6 and IL-8 gene expression in bovine endometrial cells “through DNA methylation”. Gene, 677:266-272.

[32]Wu HC, Zhao G, Jiang KF, et al., 2016. IFN-τ alleviates lipopolysaccharide-induced inflammation by suppressing NF-κB and MAPKs pathway activation in mice. Inflammation, 39(3):1141-1150.

[33]Yang C, Liu P, Wang S, et al., 2018. Shikonin exerts anti-inflammatory effects in LPS-induced mastitis by inhibiting NF-κB signaling pathway. Biochem Biophys Res Commun, 505(1):1-6.

[34]Ye GY, Wang KY, Gui QD, et al., 2018. Ureaplasma urealyticum-derived lipid-associated membrane proteins introduce IL-6, IL-8, and TNF-α cytokines into human amniotic epithelial cells via Toll-like receptor 2. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(8):654-661.

[35]Zhang AH, Hao S, Bi J, et al., 2009. Effects of catalpol on mitochondrial function and working memory in mice after lipopolysaccharide-induced acute systemic inflammation. Exp Toxicol Pathol, 61(5):461-469.

[36]Zhang XL, Liu WD, Niu XH, et al., 2010. Systemic administration of catalpol prevents D-galactose induced mitochondrial dysfunction in mice. Neurosci Lett, 473(3):224-228.

[37]Zhao G, Zhang T, Wu HC, et al., 2019. MicroRNA let-7c improves LPS-induced outcomes of endometritis by suppressing NF-κB signaling. Inflammation, 42(2):650-657.