World Scientific
Skip main navigation
Close Drawer MenuOpen Drawer Menu

Cookies Notification

We use cookies on this site to enhance your user experience. By continuing to browse the site, you consent to the use of our cookies. Learn More
×
Our website is made possible by displaying certain online content using javascript.
In order to view the full content, please disable your ad blocker or whitelist our website www.worldscientific.com.

System Upgrade on Mon, Jun 21st, 2021 at 1am (EDT)

During this period, the E-commerce and registration of new users may not be available for up to 6 hours.
For online purchase, please visit us again. Contact us at [email protected] for any enquiries.
No Access

Neferine, a Bisbenzylisoquinoline Alkaloid, Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis

    https://doi.org/10.1142/S0192415X18500660Cited by:12
    Previous
    Next

    Abstract

    Both the incidence and prevalence of ulcerative colitis (UC) are increasing throughout the world. Neferine, a natural alkaloid, demonstrated a variety of biological activities. In this study, the anti-inflammatory effect of neferine was investigated. Raw264.7 cells were stimulated with lipopolysaccharide (LPS) or LPS plus Z-VAD-fmk (Z-VAD). The inhibitory effect of neferine on secretion of nitrite, cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined. The protective effect of neferine was investigated in dextran sulfate sodium (DSS)-induced UC mouse model. Neferine significantly inhibited LPS and LPS plus Z-VAD induced secretion of nitrite, cytokines, and expression of iNOS and COX-2. Oral administration of neferine (10mg/kg and 25mg/kg) significantly reduced DSS-induced mouse weight loss, decreased disease activity index (DAI) scores, improved colon pathological changes, and decreased plasma cytokines. In addition, neferine significantly inhibited the protein expression of iNOS, COX-2, receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), and increased the protein expression of caspase-8 in colon tissues. These data suggest that neferine was a potent anti-inflammatory agent against LPS and DSS induced inflammation both in vitro and in vivo.

    References

    • Bao, J., R. Ding, L. Zou, C. Zhang, K. Wang, F. Liu, P. Li, M. Chen, J.B. Wan, H. Su, Y. Wang and C. He . Forsythiae Fructus inhibits B16 melanoma growth involving MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation. Am. J. Chin. Med. 44: 1043–1061, 2016. Link, ISI, Google Scholar
    • Bao, J., R.B. Ding, Y. Liang, F. Liu, K. Wang, X. Jia, C. Zhang, M. Chen, P. Li, H. Su, J.B. Wan, Y. Wang and C. He . Differences in chemical component and anticancer activity of green and ripe Forsythiae Fructus. Am. J. Chin. Med. 45: 1513–1536, 2017. Link, Google Scholar
    • Bordoni, A., F. Danesi, D. Dardevet, D. Dupont, A.S. Fernandez, D. Gille, C. Nunes Dos Santos, P. Pinto, R. Re, D. Remond, D.R. Shahar and G. Vergeres . Dairy products and inflammation: A review of the clinical evidence. Crit. Rev. Food Sci. Nutr. 57: 2497–2525, 2017. Crossref, Medline, Google Scholar
    • Boughton-Smith, N.K., S.M. Evans, C.J. Hawkey, A.T. Cole, M. Balsitis, B.J. Whittle and S. Moncada . Nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Lancet. 342: 338–340, 1993. Crossref, Medline, Google Scholar
    • Brouwers, H., J. von Hegedus, R. Toes, M. Kloppenburg and A. Ioan-Facsinay . Lipid mediators of inflammati-on in rheumatoid arthritis and osteoarthritis. Best. Pract. Res. Clin. Rheumatol. 29: 741–755, 2015. Crossref, Medline, Google Scholar
    • Cao, J.G., X.Q. Tang and S.H. Shi . Multidrug resistance reversal in human gastric carcinoma cells by neferine. World J. Gastroenterol. 10: 3062–3064, 2004. Medline, Google Scholar
    • Choi, Y.H., J.K. Bae, H.S. Chae, Y.O. Choi, P. Nhoek, J.S. Choi and Y.W. Chin . Isoliquiritigenin ameliorates dextran sulfate sodium-induced colitis through the inhibition of MAPK pathway. Int. Immunopharmacol. 31: 223–232, 2016. Crossref, Medline, Google Scholar
    • Eguchi, K. and R. Nagai . Islet inflammation in type 2 diabetes and physiology. J. Clin. Invest. 127: 14–23, 2017. Crossref, Medline, Google Scholar
    • Fredman, G. and I. Tabas . Boosting inflammation resolution in atherosclerosis: The next frontier for therapy. Am. J. Pathol. 187: 1211–1221, 2017. Crossref, Medline, Google Scholar
    • Furukawa, H. , On the alkaloids of Nelumbo nucifera gaertn. ix. alkaloids of loti embryo (2). structure of neferine, a new biscoclaurine alkaloid. Yakugaku. Zasshi. 85: 335–338, 1965. Crossref, Medline, Google Scholar
    • Galluzzi, L., O. Kepp, F.K. Chan and G. Kroemer . Necroptosis: Mechanisms and relevance to disease. Annu. Rev. Pathol. 12: 103–130, 2017. Crossref, Medline, Google Scholar
    • Garrity-Park, M., E.V. Loftus, Jr., W.J. Sandborn and T.C. Smyrk . Myeloperoxidase immunohistochemistry as a measure of disease activity in ulcerative colitis: Association with ulcerative colitis-colorectal cancer, tumor necrosis factor polymorphism and RUNX3 methylation. Inflamm. Bowel Dis. 18: 275–283, 2012. Crossref, Medline, Google Scholar
    • Grootjans, S., T. Vanden Berghe and P. Vandenabeele . Initiation and execution mechanisms of necroptosis: An overview. Cell Death Differ. 24: 1184–1195, 2017. Crossref, Medline, Google Scholar
    • Guan, G., H. Han, Y. Yang, Y. Jin, X. Wang and X. Liu . Neferine prevented hyperglycemia-induced endothelial cell apoptosis through suppressing ROS/Akt/NF-kappaB signal. Endocrine 47: 764–771, 2014. Crossref, Medline, Google Scholar
    • Guihot, G., R. Guimbaud, V. Bertrand, B. Narcy-Lambare, D. Couturier, P.H. Duee, S. Chaussade and F. Blachier . Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: Correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn’s disease. Amino Acids 18: 229–237, 2000. Crossref, Medline, Google Scholar
    • Guimbaud, R., V. Bertrand, L. Chauvelot-Moachon, G. Quartier, N. Vidon, J.P. Giroud, D. Couturier and S. Chaussade . Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis. Am. J. Gastroenterol. 93: 2397–2404, 1998. Crossref, Medline, Google Scholar
    • Hegazy, S.K. and M.M. El-Bedewy . Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis. World J. Gastroenterol. 16: 4145–4151, 2010. Crossref, Medline, Google Scholar
    • Huang, C., Y. Li, P. Cao, Z. Xie and Z. Qin . Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells. J. Huazhong Univ. Sci. Technolog. Med. Sci. 31: 488–496, 2011. Crossref, Medline, Google Scholar
    • Huang, S., H.F. Liu, X. Quan, Y. Jin, G. Xuan, R.B. An, T. Dikye and B. Li . Rhamnella gilgitica attenuates inflammatory responses in LPS-induced murine macrophages and complete Freund’s adjuvant-induced arthritis rats. Am. J. Chin. Med. 44: 1379–1392, 2016. Link, ISI, Google Scholar
    • Jung, H.A., S.E. Jin, R.J. Choi, D.H. Kim, Y.S. Kim, J.H. Ryu, D.W. Kim, Y.K. Son, J.J. Park and J.S. Choi . Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1. Life Sci. 87: 420–430, 2010. Crossref, Medline, Google Scholar
    • Kim, D.S., S.H. Kim, J.Y. Kee, Y.H. Han, J. Park, J.G. Mun, M.J. Joo, Y.D. Jeon, S.J. Kim, S.H. Park, S.J. Park, J.Y. Um and S.H. Hong . Eclipta prostrata improves DSS-induced colitis through regulation of inflammatory response in intestinal epithelial cells. Am. J. Chin. Med. 45: 1047–1060, 2017. Link, Google Scholar
    • Kim, M.J., Y.C. Yoo, N.Y. Sung, J. Lee, S.R. Park, E.J. Shon, B.D. Lee and M.R. Kim . Anti-inflammatory effects of Liriope platyphylla in LPS-stimulated macrophages and endotoxemic mice. Am. J. Chin. Med. 44: 1127–1143, 2016. Link, ISI, Google Scholar
    • Koeberle, A. and O. Werz . Multi-target approach for natural products in inflammation. Drug Discov. Today 19: 1871–1882, 2014. Crossref, Medline, Google Scholar
    • Kuhn, F. and E. Klar . Surgical principles in the treatment of ulcerative colitis. Viszeralmedizin 31: 246–250, 2015. Medline, Google Scholar
    • Lalitha, G., P. Poornima, A. Archanah and V.V. Padma . Protective effect of neferine against isoproterenol-induced cardiac toxicity. Cardiovasc. Toxicol. 13: 168–179, 2013. Crossref, Medline, Google Scholar
    • Li, G., G. Zhu, Y. Gao, W. Xiao, H. Xu, S. Liu, G. Tu, H. Peng, C. Zheng, S. Liang and G. Li . Neferine inhibits the upregulation of CCL5 and CCR5 in vascular endothelial cells during chronic high glucose treatment. Inflammation 36: 300–308, 2013. Crossref, Medline, Google Scholar
    • Li, X.C., G.X. Tong, Y. Zhang, S.X. Liu, Q.H. Jin, H.H. Chen and P. Chen . Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1. Acta Pharmacol. Sin. 31: 679–686, 2010. Crossref, Medline, Google Scholar
    • Liu, Z.Y., B. Wu, Y.S. Guo, Y.H. Zhou, Z.G. Fu, B.Q. Xu, J.H. Li, L. Jing, J.L. Jiang, J. Tang and Z.N. Chen . Necrostatin-1 reduces intestinal inflammation and colitis-associated tumorigenesis in mice. Am. J. Cancer Res. 5: 3174–3185, 2015. Medline, Google Scholar
    • Miao, X.P., J.S. Li, Q. Ouyang, R.W. Hu, Y. Zhang and H.Y. Li . Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease. Cochrane Database Syst. Rev. 10: Cd007744, 2014. Google Scholar
    • Monie, T.P. and C.E. Bryant . Caspase-8 functions as a key mediator of inflammation and pro-IL-1beta processing via both canonical and non-canonical pathways. Immunol. Rev. 265: 181–193, 2015. Crossref, Medline, Google Scholar
    • Patil, D.T., A.C. Moss and R.D. Odze . Role of histologic inflammation in the natural history of ulcerative colitis. Gastrointest. Endosc. Clin. N. Am. 26: 629–640, 2016. Crossref, Medline, Google Scholar
    • Pawlak, M., P. Lefebvre and B. Staels . Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 62: 720–733, 2015. Crossref, Medline, Google Scholar
    • Poornima, P., R.S. Quency and V.V. Padma . Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells. Food Chem. 136: 659–667, 2013a. Crossref, Medline, Google Scholar
    • Poornima, P., C.F. Weng and V.V. Padma . Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells. Food Chem. 141: 3598–3605, 2013b. Crossref, Medline, Google Scholar
    • Poornima, P., C.F. Weng and V.V. Padma . Neferine, an alkaloid from lotus seed embryo, inhibits human lung cancer cell growth by MAPK activation and cell cycle arrest. Biofactors 40: 121–131, 2014. Crossref, Medline, Google Scholar
    • Priya, L.B., R. Baskaran, C.Y. Huang and V.V. Padma . Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: Possible role in modulating NADPH oxidase/ROS-mediated NFkappaB redox signaling cascade. Sci. Rep. 7: 12283, 2017. Crossref, Medline, Google Scholar
    • Qi, Y., F. Gao, L. Hou and C. Wan . Anti-inflammatory and immunostimulatory activities of astragalosides. Am. J. Chin. Med. 45: 1157–1167, 2017. Link, ISI, Google Scholar
    • Rickard, J.A., J.A. O’Donnell, J.M. Evans, N. Lalaoui, A.R. Poh, T. Rogers, J.E. Vince, K.E. Lawlor, R.L. Ninnis, H. Anderton, C. Hall, S.K. Spall, T.J. Phesse, H.E. Abud, L.H. Cengia, J. Corbin, S. Mifsud, L. Di Rago, D. Metcalf, M. Ernst, G. Dewson, A.W. Roberts, W.S. Alexander, J.M. Murphy, P.G. Ekert, S.L. Masters, D.L. Vaux, B.A. Croker, M. Gerlic and J. Silke . RIPK1 regulates RIPK3-MLKL-driven systemic inflammation and emergency hematopoiesis. Cell 157: 1175–1188, 2014. Crossref, Medline, Google Scholar
    • Shlomovitz, I., S. Zargrian and M. Gerlic . Mechanisms of RIPK3-induced inflammation. Immunol. Cell. Biol. 95: 166–172, 2017. Crossref, Medline, Google Scholar
    • Silva, B.C., A.C. Lyra, R. Rocha and G.O. Santana . Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis. World J. Gastroenterol. 20: 9458–9467, 2014. Crossref, Medline, Google Scholar
    • Sun, W., X. Wu, H. Gao, J. Yu, W. Zhao, J.J. Lu, J. Wang, G. Du and X. Chen . Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells. Free Radic. Biol. Med. 108: 433–444, 2017. Crossref, Medline, Google Scholar
    • Villa, F.A. and L. Gerwick . Marine natural product drug discovery: Leads for treatment of inflammation, cancer, infections, and neurological disorders. Immunopharmacol. Immunotoxicol. 32: 228–237, 2010. Crossref, Medline, Google Scholar
    • Wan, J.Y., W.H. Huang, W. Zheng, C.W. Park, S.H. Kim, D.B. Seo, K.S. Shin, J. Zeng, H. Yao, C. Sava-Segal, C.Z. Wang and C.S. Yuan . Multiple effects of ginseng berry polysaccharides: Plasma cholesterol level reduction and enteric neoplasm prevention. Am. J. Chin. Med. 45: 1293–1307, 2017. Link, Google Scholar
    • Wan, P., H. Chen, Y. Guo and A.P. Bai . Advances in treatment of ulcerative colitis with herbs: From bench to bedside. World J. Gastroenterol. 20: 14099–14104, 2014. Crossref, Medline, Google Scholar
    • Xu, L., X. Zhang, Y. Li, S. Lu, S. Lu, J. Li, Y. Wang, X. Tian, J.J. Wei, C. Shao and Z. Liu . Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Tumour Biol. 37: 8721–8729, 2016. Crossref, Medline, Google Scholar
    • Yoon, J.S., H.M. Kim, A.K. Yadunandam, N.H. Kim, H.A. Jung, J.S. Choi, C.Y. Kim and G.D. Kim . Neferine isolated from Nelumbo nucifera enhances anti-cancer activities in Hep3B cells: Molecular mechanisms of cell cycle arrest, ER stress induced apoptosis and anti-angiogenic response. Phytomedicine 20: 1013–1022, 2013. Crossref, Medline, Google Scholar
    • Zhao, L., X. Wang, Q. Chang, J. Xu, Y. Huang, Q. Guo, S. Zhang, W. Wang, X. Chen and J. Wang . Neferine, a bisbenzylisoquinline alkaloid attenuates bleomycin-induced pulmonary fibrosis. Eur. J. Pharmacol. 627: 304–312, 2010. Crossref, Medline, ISI, Google Scholar
    • Zhao, W., C. Li, H. Gao, Q. Wu, J. Shi and X. Chen . Dihydrotanshinone I attenuates atherosclerosis in ApoE-deficient mice: Role of NOX4/NF-κB mediated lectin-like oxidized LDL receptor-1 (LOX-1) of the endothelium. Front Pharmacol. 7: 418, 2016. Crossref, Medline, Google Scholar
    Published: 28 August 2018
    Remember to check out the Most Cited Articles!

    Check out our Chinese Medicine Titles today.
    Includes titles by Nobel Winner, Tu You You and more!