Advertisement

Embelin and Its Role in Chronic Diseases

  • Hong Lu
  • Jun Wang
  • Youxue Wang
  • Liang Qiao
  • Yongning Zhou
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 928)

Abstract

Embelia ribes Burm of Myrsinaceae family has been widely used as an herb in the traditional medicine of India. Embelin is an active component extracted from the fruits of Embelia ribes. It has a wide spectrum of biological activities and is not toxic at low dose. This review focuses on the physical–chemical properties and bioactivities of Embelin, as well as its effects on chronic diseases such as tumors, autoimmune inflammatory diseases, parasitic infections, microbial infections, diabetes, obesity, and cardio-cerebral vascular diseases. The underlying mechanisms of the effects are also discussed. As a multiple-targeted therapeutic agent, Embelin has the potential to be used widely for the treatment of a variety of chronic diseases, including malignant tumors.

Keywords

Embelin Anticancer activity Autoimmune inflammatory diseases Anthelmintic activity Antimicrobial activity Diabetes Cardio-cerebral vascular diseases 

Notes

Acknowledgments

This work was supported by the grant “The Model for Prevention and Control of Malignant Tumor in Area with High Incidence from Wuwei Gansu Province” (National Science and Technology Program, Grant Code: 2012GS620101 to YN Zhou).

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Afzal M, Gupta G, Kazmi I, Rahman M, Upadhyay G, Ahmad K, Imam F, Pravez M, Anwar F (2012) Evaluation of anxiolytic activity of embelin isolated from Embelia ribes. Biomed Aging Pathol 2:45–47CrossRefGoogle Scholar
  2. 2.
    Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, Sung B, Ichikawa H (2006) Targeting Signal-Transducer-and-Activator-of-Transcription-3 for Prevention and Therapy of Cancer. Ann N Y Acad Sci 1091:151–169PubMedCrossRefGoogle Scholar
  3. 3.
    Ahn KS, Sethi G, Aggarwal BB (2007) Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein, blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Mol Pharmacol 71:209–219PubMedCrossRefGoogle Scholar
  4. 4.
    Ansari MN, Bhandari U (2008) Protective effect of Embelia ribes Burm on methionine-induced hyperhomocysteinemia and oxidative stress in rat brain. Indian J Exp Biol 46:521–527PubMedGoogle Scholar
  5. 5.
    Awino O, Kiprono P, Keronei K, Kaberia F, Obala A (2014) Antimicrobial Activity of 2,5-Dihydroxy-3-methyl-1,4-benzoquinone from Embelia schimperi. Zeitschrift Für Naturforschung C 63:47–50Google Scholar
  6. 6.
    B∅gh HO, Andreassen JR, Lemmich J (1996) Anthelmintic usage of extracts of Embelia schimperi from Tanzania. J Ethnopharmacol 50:35–42CrossRefGoogle Scholar
  7. 7.
    Badamaranahalli SS, Kopparam M, Bhagawati ST, Durg S (2015) Embelin lipid nanospheres for enhanced treatment of ulcerative colitis–Preparation, characterization and in vivo evaluation. Eur J Pharm Sci 76:73–82PubMedCrossRefGoogle Scholar
  8. 8.
    Baker RG, Hayden MS, Ghosh S (2011) NF-κB, inflammation, and metabolic disease. Cell Metab 13:11–22PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Bartlett JMS (2010) Biomarkers and Patient Selection for PI3K/Akt/mTOR targeted therapies: current status and future directions. Clin Breast Cancer 10:S86–S95PubMedCrossRefGoogle Scholar
  10. 10.
    Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238PubMedCrossRefGoogle Scholar
  11. 11.
    Bhandari U, Ansari MN, Islam F (2008) Cardioprotective effect of aqueous extract of Embelia ribes Burm fruits against isoproterenol-induced myocardial infarction in albino rats. Indian J Exp Biol 9:35–40Google Scholar
  12. 12.
    Bhandari U, Chaudhari HS, Bisnoi AN, Kumar V, Khanna G, Javed K (2013) Anti-obesity effect of standardized ethanol extract of Embelia ribes in murine model of high fat diet-induced obesity. PharmaNutrition 1:50–57CrossRefGoogle Scholar
  13. 13.
    Bhandari U, Jain N, Ansari MN, Pillai KK (2008) Beneficial effect of Embelia ribes ethanolic extract on blood pressure and glycosylated hemoglobin in streptozotocin-induced diabetes in rats. Fitoterapia 79:351–355PubMedCrossRefGoogle Scholar
  14. 14.
    Bhandari U, Jain N, Pillai KK (2007) Further studies on antioxidant potential and protection of pancreatic beta-cells by Embelia ribes in experimental diabetes. Exp Diabetes Res 2007 (ID: 15803)Google Scholar
  15. 15.
    Bischoff SC, Lorentz A, Schwengberg S, Weier G, Raab R, Manns MP (1999) Mast cells are an important cellular source of tumour necrosis factor alpha in human intestinal tissue. Gut 44:643–652PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Bryan VL, Zachary TB, Robert CF, Nir H, James JC, Marianne B (2011) TGF-β suppresses β-catenin-dependent tolerogenic activation program in dendritic cells. PLoS ONE 6:e20099CrossRefGoogle Scholar
  17. 17.
    Cantley LC, Neel BG (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci 96:4240–4245PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Chen J, Nikolovska-Coleska Z, Wang G, Qiu S, Wang S (2006) Design, synthesis, and characterization of new embelin derivatives as potent inhibitors of X-linked inhibitor of apoptosis protein. Bioorg Med Chem Lett 16:5805–5808PubMedCrossRefGoogle Scholar
  19. 19.
    Chitra M, Shyamala Devi CS, Sukumar E (2003) Antibacterial activity of embelin. Fitoterapia 74(4):401–403PubMedCrossRefGoogle Scholar
  20. 20.
    Chitra M, Sukumar E, Suja V, Devi CSS (1994) Antitumor, anti-Inflammatory and analgesic property of embelin, a plant product. Chemotherapy 40:109–113PubMedCrossRefGoogle Scholar
  21. 21.
    Choudhary S, Keshavarzian A, Yong S, Wade M, Bocckino S, Day BJ, Banan A (2001) Novel antioxidants zolimid and AEOL11201 ameliorate colitis in rats. Dig Dis Sci 46:2222–2230PubMedCrossRefGoogle Scholar
  22. 22.
    Coutelle O, Hornig-Do HT, Witt A, Andree M, Schiffmann LM, Piekarek M, Brinkmann K, Seeger JM, Liwschitz M, Miwa S, Hallek M, Kronke M, Trifunovic A, Eming SA, Wiesner RJ, Hacker UT, Kashkar H (2014) Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing. EMBO Mol Med 6:624–639PubMedPubMedCentralGoogle Scholar
  23. 23.
    D’Avigdor E, Wohlmuth H, Asfaw Z, Awas T (2014) The current status of knowledge of herbal medicine and medicinal plants in Fiche, Ethiopia. J Ethnobiol Ethnomed 10:1–33CrossRefGoogle Scholar
  24. 24.
    Dai Y, Jiao H, Teng G, Wang W, Zhang R, Wang Y, Hebbard L, George J, Qiao L (2014) Embelin reduces colitis-associated tumorigenesis through limiting IL-6/STAT3 signaling. Mol Cancer Ther 13:1206–1216PubMedCrossRefGoogle Scholar
  25. 25.
    Dai Y, Qiao L, Chan KW, Yang M, Ye J, Ma J, Zou B, Gu Q, Wang J, Pang R, Lan HY, Wong BC (2009) Peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of Embelin on colon carcinogenesis. Cancer Res 69:4776–4783PubMedCrossRefGoogle Scholar
  26. 26.
    Danquah M, Duke CB 3rd, Patil R, Miller DD, Mahato RI (2012) Combination therapy of antiandrogen and XIAP inhibitor for treating advanced prostate cancer. Pharm Res 29:2079–2091PubMedCrossRefGoogle Scholar
  27. 27.
    Danquah M, Li F, Duke CB 3rd, Miller DD, Mahato RI (2009) Micellar delivery of bicalutamide and embelin for treating prostate cancer. Pharm Res 26:2081–2092PubMedCrossRefGoogle Scholar
  28. 28.
    Debebe Y, Tefera M, Mekonnen W, Abebe D, Woldekidan S, Abebe A, Belete Y, Menberu T, Belayneh B, Tesfaye B, Nasir I, Yirsaw K, Basha H, Dawit A, Debella A (2015) Evaluation of anthelmintic potential of the Ethiopian medicinal plant Embelia schimperi Vatke in vivo and in vitro against some intestinal parasites. BMC Complement Altern Med 15:187PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Dhanjal JK, Nigam N, Sharma S, Chaudhary A, Kaul SC, Grover A, Wadhwa R (2014) Embelin inhibits TNF-α converting enzyme and cancer cell metastasis: molecular dynamics and experimental evidence. BMC Cancer 14:775PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Dharmapatni AA, Cantley MD, Marino V, Perilli E, Crotti TN, Smith MD, Haynes DR (2015) The X-linked inhibitor of apoptosis protein inhibitor embelin suppresses inflammation and bone erosion in collagen antibody induced arthritis mice. Mediators Inflamm 2015(2):1–10 (ID: 564042)Google Scholar
  31. 31.
    Dowling RJ, Sonenberg N (2010) Downstream of mTOR: translational control of cancer. In: mTOR pathway and mTOR inhibitors in cancer therapy. Humana Press, pp. 201–216.Google Scholar
  32. 32.
    Dwivedi D, Singh V (2015) Effects of the natural compounds embelin and piperine on the biofilm-producing property of Streptococcus mutans. J Tradit Complement Med. http://www.elsevier.com/locate/jtcme
  33. 33.
    Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E (2000) SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem 275:15985–15991PubMedCrossRefGoogle Scholar
  34. 34.
    Feresin GE, Tapia A, Sortino M, Zacchino S, Arias ARd, Inchausti A, Yaluff G, Rodriguez J, Theoduloz C, Schmeda-Hirschmann G (2003) Bioactive alkyl phenols and embelin from Oxalis erythrorhiza. J Ethnopharmacol 88:241–247PubMedCrossRefGoogle Scholar
  35. 35.
    Ferreria GM, Laddha KS (2013) Histochemical localization of embelin in fruits of Embellia Ribes Brum and its quantification. Int J Pharma Biosci Technol 1:16–19Google Scholar
  36. 36.
    Gandhi GR, Stalin A, Balakrishna K, Ignacimuthu S, Paulraj MG, Vishal R (2013) Insulin sensitization via partial agonism of PPARgamma and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats. Biochim Biophys Acta 1830:2243–2255PubMedCrossRefGoogle Scholar
  37. 37.
    Ghazi H, Hirotsugu M, Norio N, Masao H, Nobuko K, Kunitada S (2000) Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res 14:510–516CrossRefGoogle Scholar
  38. 38.
    Ghosh S, Karin M (2002) Missing pieces in the NF-κB puzzle. Cell 109:S81–S96PubMedCrossRefGoogle Scholar
  39. 39.
    Giday M, Asfaw Z, Woldu Z (2009) Medicinal plants of the Meinit ethnic group of Ethiopia: an ethnobotanical study. J Ethnopharmacol 124:513–521PubMedCrossRefGoogle Scholar
  40. 40.
    Girnun GD, Smith WM, Drori S, Sarraf P, Mueller E, Eng C, Nambiar P, Rosenberg DW, Bronson RT, Edelmann W (2002) APC-dependent suppression of colon carcinogenesis by PPARγ. Proc Natl Acad Sci 99:13771–13776PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Golan-Goldhirsh A, Gopas J (2013) Plant derived inhibitors of NF-κB. Phytochem Rev 13:107–121CrossRefGoogle Scholar
  42. 42.
    Gottlieb TM, Leal JF, Seger R, Taya Y, Oren M (2002) Cross-talk between Akt, p53 and Mdm2: possible implications for the regulation of apoptosis. Oncogene 21:1299–1303PubMedCrossRefGoogle Scholar
  43. 43.
    Gp C (2012) Anthelmintic activity of fruits of Embelia ribes Burm. Int J Pharm Chem Sci 1:1680–1681Google Scholar
  44. 44.
    Gustafson DL, Swanson JD, Pritsos CA (1993) Modulation of glutathione and glutathione dependent antioxidant enzymes in mouse heart following doxorubicin therapy. Free Radic Res Commun 19:111–120PubMedCrossRefGoogle Scholar
  45. 45.
    Harish GU, Danapur V, Jain R, Patell VM (2012) Endangered medicinal plant Embelia ribes Burm.f.—a review. Pharmacognosy Journal 4:6–19CrossRefGoogle Scholar
  46. 46.
    Hendrickson BA, Ranjana G, Cho JH (2002) Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev 15:79–94PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Heo JY, Kim HJ, Kim SM, Park KR, Park SY, Kim SW, Nam D, Jang HJ, Lee SG, Ahn KS, Kim SH, Shim BS, Choi SH, Ahn KS (2011) Embelin suppresses STAT3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase PTEN. Cancer Lett 308:71–80PubMedCrossRefGoogle Scholar
  48. 48.
    Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α-and obesity-induced insulin resistance. Science 271:665–670PubMedCrossRefGoogle Scholar
  49. 49.
    Hu R, Yang Y, Liu Z, Jiang H, Zhu K, Li J, Xu W (2015) The XIAP inhibitor Embelin enhances TRAIL-induced apoptosis in human leukemia cells by DR4 and DR5 upregulation. Tumour Biol 36:769–777PubMedCrossRefGoogle Scholar
  50. 50.
    Hu R, Zhu K, Li Y, Yao K, Zhang R, Wang H, Yang W, Liu Z (2011) Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells. Med Oncol 28:1584–1588PubMedCrossRefGoogle Scholar
  51. 51.
    Huang Y, Lu J, Gao X, Li J, Zhao W, Sun M, Stolz DB, Venkataramanan R, Rohan LC, Li S (2012) PEG-derivatized embelin as a dual functional carrier for the delivery of paclitaxel. Bioconjug Chem 23:1443–1451PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Issazadeh S, Mustafa M, Ljungdahl Å, Höjeberg B, Dagerlind Å, Elde R, Olsson T (1995) Interferon γ, interleukin 4 and transforming growth factor β in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. J Neurosci Res 40:579–590PubMedCrossRefGoogle Scholar
  53. 53.
    Ivan L, Mehran M, Jean-Daniel C, Luc-Marie J, Christian S, Bénédicte B, Alain C, Alain R, Pierre C, Simon W (2002) Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 40:2110–2116CrossRefGoogle Scholar
  54. 54.
    Jeon Y-J, Kim B-H, Kim S, Oh I, Lee S, Shin J, Kim T-Y (2013) Rhododendrin ameliorates skin inflammation through inhibition of NF-κB, MAPK, and PI3K/Akt signaling. Eur J Pharmacol 714:7–14PubMedCrossRefGoogle Scholar
  55. 55.
    Johri R, Dhar S, Pahwa G, Sharma S, Kaul J, Zutshi U (1990) Toxicity studies with potassium embelate, a new analgesic compound. Indian J Exp Biol 28:213–217PubMedGoogle Scholar
  56. 56.
    Jope RS, Johnson GVW (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29:95–102PubMedCrossRefGoogle Scholar
  57. 57.
    Joshi R, Kamat JP, Mukherjee T (2007) Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chem Biol Interact 167:125–134PubMedCrossRefGoogle Scholar
  58. 58.
    Joy B, Kumar SN, Radhika AR, Abraham A (2015) Embelin (2,5-Dihydroxy-3-undecyl-p-benzoquinone) for photodynamic therapy: study of their cytotoxicity in cancer cells. Appl Biochem Biotechnol 175:1069–1079PubMedCrossRefGoogle Scholar
  59. 59.
    Joy B, Nishanth Kumar S, Soumya MS, Radhika AR, Vibin M, Abraham A (2014) Embelin (2,5-dihydroxy-3-undecyl-p-benzoquinone): a bioactive molecule isolated from Embelia ribes as an effective photodynamic therapeutic candidate against tumor in vivo. Phytomedicine 21:1292–1297PubMedCrossRefGoogle Scholar
  60. 60.
    Kalyan Kumar G, Dhamotharan R, Kulkarni NM, Mahat MY, Gunasekaran J, Ashfaque M (2011) Embelin reduces cutaneous TNF-alpha level and ameliorates skin edema in acute and chronic model of skin inflammation in mice. Eur J Pharmacol 662:63–69PubMedCrossRefGoogle Scholar
  61. 61.
    Kane LP, Smith SV, Stokoe D, Weiss A (1999) Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol 9:601–604PubMedCrossRefGoogle Scholar
  62. 62.
    Karin M, Greten FR (2005) NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759PubMedCrossRefGoogle Scholar
  63. 63.
    Karin M, Lin A (2002) NF-κB at the crossroads of life and death. Nat Immunol 3:221–227PubMedCrossRefGoogle Scholar
  64. 64.
    Khan MI, Ahmed A, Akram M, Mohiuddin E, Khan U, Ayaz S, Shah S, Asif M, Ghazala S, Ahmed K (2010) Monograph of Embelia ribes Burm. F. Afr J Plant Sci 4:503–505Google Scholar
  65. 65.
    Kim SW, Kim SM, Bae H, Nam D, Lee JH, Lee SG, Shim BS, Kim SH, Ahn KS, Choi SH, Sethi G, Ahn KS (2013) Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades. Prostate 73:296–305PubMedCrossRefGoogle Scholar
  66. 66.
    Krishnamoorthy G, Wekerle H (2009) EAE: an immunologist’s magic eye. Eur J Immunol 39(8):2031–2035PubMedCrossRefGoogle Scholar
  67. 67.
    Kumar D, Kumar A, Prakash O (2012) Potential antifertility agents from plants: a comprehensive review. J Ethnopharmacol 140:1–32PubMedCrossRefGoogle Scholar
  68. 68.
    Kumar GK, Dhamotharan R, Kulkarni NM, Honnegowda S, Murugesan S (2011) Embelin ameliorates dextran sodium sulfate-induced colitis in mice. Int Immunopharmacol 11:724–731CrossRefGoogle Scholar
  69. 69.
    Lamblin M, Sallustrau A, Commandeur C, Cresteil T, Felpin F-X, Dessolin J (2012) Synthesis and biological evaluation of hydrophilic embelin derivatives. Tetrahedron 68:4655–4663CrossRefGoogle Scholar
  70. 70.
    Lewis K (2001) Riddle of biofilm resistance. Antimicrob Agents Chemother 45:999–1007PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Li M, Wang X, Meintzer MK, Laessig T, Birnbaum MJ, Heidenreich KA (2000) Cyclic AMP promotes neuronal survival by phosphorylation of glycogen synthase kinase 3β. Mol Cell Biol 20:9356–9363PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Li Y, Sarkar FH (2002) Inhibition of nuclear factor κB activation in PC3 cells by genistein is mediated via Akt signaling pathway. Clin Cancer Res 8:2369–2377PubMedGoogle Scholar
  73. 73.
    Liang Q, Yun D, Gu Q, Chan KW, Bing Z, Ma J, Wang J, Lan HY, Wong BCY (2008) Down-regulation of X-linked inhibitor of apoptosis synergistically enhanced peroxisome proliferator-activated receptor γ ligand-induced growth inhibition in colon cancer. Mol Cancer Ther 7:2203–2211CrossRefGoogle Scholar
  74. 74.
    Liu A, Liu Y, Li PK, Li C, Lin J (2011) LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3 phosphorylation in human pancreatic cancer cells. Anticancer Res 31:2029–2035PubMedPubMedCentralGoogle Scholar
  75. 75.
    Lopiccolo J, Blumenthal GM, Bernstein WB, Dennis PA (2008) Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updates 11:32–50CrossRefGoogle Scholar
  76. 76.
    Lu J, Huang Y, Zhao W, Marquez RT, Meng X, Li J, Gao X, Venkataramanan R, Wang Z, Li S (2013) PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. Biomaterials 34:1591–1600PubMedCrossRefGoogle Scholar
  77. 77.
    Mahendran S, Badami S, Maithili V (2011) Evaluation of antidiabetic effect of embelin from Embelia ribes in alloxan induced diabetes in rats. Biomed Prev Nutr 1:25–31CrossRefGoogle Scholar
  78. 78.
    Mahendran S, Thippeswamy BS, Veerapur VP, Badami S (2011) Anticonvulsant activity of embelin isolated from Embelia ribes. Phytomedicine 18:186–188PubMedCrossRefGoogle Scholar
  79. 79.
    Makawiti DW, Konji VN, Olowookere JO (1990) Interaction of benzoquinones with mitochondria interferes with oxidative phosphorylation characteristics. FEBS Lett 266:26–28PubMedCrossRefGoogle Scholar
  80. 80.
    Manna S, Bhattacharyya D, Basak D, Mandal T (2004) Single oral dose toxicity study of a-cypermethrin in rats. Indian J Pharmacol 36:25Google Scholar
  81. 81.
    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444PubMedCrossRefGoogle Scholar
  82. 82.
    Mcauliffe PF, Meric-Bernstam F, Mills GB, Gonzalez-Angulo AM (2010) Deciphering the role of PI3K/Akt/mTOR pathway in breast cancer biology and pathogenesis. Clin Breast Cancer 10:S59–S65PubMedCrossRefGoogle Scholar
  83. 83.
    Mencher SK, Wang LG (2005) Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin Pharmacol 5:3PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Mj VDV (2004) Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients. Br J Cancer 90:1543–1550CrossRefGoogle Scholar
  85. 85.
    Moller DE (2000) Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab TEM 11:212–217PubMedCrossRefGoogle Scholar
  86. 86.
    Mori T, Doi R, Kida A, Nagai K, Kami K, Ito D, Toyoda E, Kawaguchi Y, Uemoto S (2007) Effect of the XIAP inhibitor embelin on TRAIL-induced apoptosis of pancreatic cancer cells. J Surg Res 142:281–286PubMedCrossRefGoogle Scholar
  87. 87.
    Muris JJF, Cillessen SAGM, Wim V, Houdt IS, Kummer JA, Van Krieken JHJM, Jiwa NM, Jansen PM, Kluin-Nelemans HC, Van Ossenkoppele GJ (2005) Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas. Blood 105:2916–2923PubMedCrossRefGoogle Scholar
  88. 88.
    Naik SR, Niture NT, Ansari AA, Shah PD (2013) Anti-diabetic activity of embelin: involvement of cellular inflammatory mediators, oxidative stress and other biomarkers. Phytomedicine 20:797–804PubMedCrossRefGoogle Scholar
  89. 89.
    Narayanaswamy R, Gnanamani A (2014) 2, 5-dihydroxy-3-undecyl-1, 4-benzoquinone (Embelin)-a second solid gold of India- A review. Int J Pharm Pharm Sci 6:23–30Google Scholar
  90. 90.
    Narayanaswamy R, Shymatak M, Chatterjee S, Wai LK, Arumugam G (2014) Inhibition of angiogenesis and nitric oxide synthase (NOS), by Embelin & Vilangin using in vitro, in vivo and in silico STUDIES. Adv Pharm Bull 4:543PubMedPubMedCentralGoogle Scholar
  91. 91.
    Newton R, Solomon K, Covington M, Decicco C, Haley P, Friedman S, Vaddi K (2001) Biology of TACE inhibition. Ann Rheum Dis 60:iii25–iii32PubMedPubMedCentralGoogle Scholar
  92. 92.
    Nikolovska-Coleska Z, Xu L, Hu Z, Tomita Y, Li P, Roller PP, Wang R, Fang X, Guo R, Zhang M, Lippman ME, Yang D, Wang S (2004) Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem 47:2430–2440PubMedCrossRefGoogle Scholar
  93. 93.
    Oh K, Lee O-Y, Shon SY, Nam O, Ryu PM, Seo MW, Lee D-S (2013) A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res 15:R79PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Park N, Baek HS, Chun Y-J (2015) Embelin-induced apoptosis of human prostate cancer cells is mediated through modulation of Akt and β-catenin signaling. PLoS ONE 10:e0134760PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Parmar K, Patel J, Sheth N (2014) Fabrication and characterization of liquisolid compacts of Embelin for dissolution enhancement. J Pharm Invest 44:391–398CrossRefGoogle Scholar
  96. 96.
    Parmar K, Patel J, Sheth N (2015) Self nano-emulsifying drug delivery system for Embelin: design, characterization and in-vitro studies. Asian J Pharm Sci. http://www.elsevier.com/locate/AJPS
  97. 97.
    Patel RK, Patel VR, Patel MG (2012) Development and validation of a RP-HPLC method for the simultaneous determination of embelin, rottlerin and ellagic acid in Vidangadi churna. J Pharm Anal 2:366–371CrossRefGoogle Scholar
  98. 98.
    Pathan RA, Bhandari U (2010) Preparation & characterization of embelin–phospholipid complex as effective drug delivery tool. J Incl Phenom Macrocycl Chem 69:139–147CrossRefGoogle Scholar
  99. 99.
    Peng M, Huang B, Zhang Q, Fu S, Wang D, Cheng X, Wu X, Xue Z, Zhang L, Zhang D, Da Y, Dai Y, Yang Q, Yao Z, Qiao L, Zhang R (2014) Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells. Cancer Lett 354:407–416PubMedCrossRefGoogle Scholar
  100. 100.
    Peng M, Xu S, Zhang Y, Zhang L, Huang B, Fu S, Xue Z, Da Y, Dai Y, Qiao L, Dong A, Zhang R, Meng W (2014) Thermosensitive injectable hydrogel enhances the antitumor effect of embelin in mouse hepatocellular carcinoma. J Pharm Sci 103:965–973PubMedCrossRefGoogle Scholar
  101. 101.
    Perkins ND (2012) The diverse and complex roles of NF-κB subunits in cancer. Nat Rev Cancer 12:121–132PubMedGoogle Scholar
  102. 102.
    Phuong do T, Ma CM, Hattori M, Jin JS (2009) Inhibitory effects of antrodins A-E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease. Phytother Res 23:582–584PubMedCrossRefGoogle Scholar
  103. 103.
    Plutzky J (2003) PPARs as therapeutic targets: Reverse cardiology? Science 302:406–407PubMedCrossRefGoogle Scholar
  104. 104.
    Podolak I, Galanty A, Janeczko Z (2005) Cytotoxic activity of embelin from Lysimachia punctata. Fitoterapia 76:333–335PubMedCrossRefGoogle Scholar
  105. 105.
    Podolak I, Strzałka M (2008) Qualitative and quantitative LC profile of embelin and rapanone in selected Lysimachia species. Chromatographia 67:471–475CrossRefGoogle Scholar
  106. 106.
    Poojari R (2014) Embelin—a drug of antiquity: shifting the paradigm towards modern medicine. Expert Opin Investig Drugs 23:427–444PubMedCrossRefGoogle Scholar
  107. 107.
    Poojari RJ (2014) Embelin, a small molecule quinone with a co-clinical power for castrate-resistant prostate cancer. Front Pharmacol 5:184PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Radhakrishnan N (2011) A potential antibacterial agent Embelin, a natural benzoquinone extracted from Embelia ribes. Biol Med 3(2):1–7Google Scholar
  109. 109.
    Rani P, Khullar N (2004) Antimicrobial evaluation of some medicinal plants for their anti-enteric potential against multi-drug resistant Salmonella typhi. Phytother Res 18:670–673PubMedCrossRefGoogle Scholar
  110. 110.
    Rathi SG, Bhaskar VH, Patel PG (2010) Antifungal activity of Embelia ribes plant extracts. Int J Pharm Biol Res 1:6–10Google Scholar
  111. 111.
    Rathinam KKS, Ramiah N (1976) Studies on the antifertility activity of embelin. J Res Ind Med Yoga Homeop 11:84–90Google Scholar
  112. 112.
    Reuter S, Prasad S, Phromnoi K, Kannappan R, Yadav VR, Aggarwal BB (2010) Embelin suppresses osteoclastogenesis induced by receptor activator of NF-κB ligand and tumor cells in vitro through inhibition of the NF-κB cell signaling pathway. Mol Cancer Res 8:1425–1436PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Rhodus NLCB, Myers S, Miller L, Ho V, Ondrey F (2005) The feasibility of monitoring NF-κB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog 44:77–82PubMedCrossRefGoogle Scholar
  114. 114.
    Riedl S, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik S, Liddington R, Salvesen G (2001) Structural basis for the inhibition of caspase-3 by XIAP. Cell 104:791–800PubMedCrossRefGoogle Scholar
  115. 115.
    Rondevaldova J, Leuner O, Teka A, Lulekal E, Havlik J, Van Damme P, Kokoska L (2015) In vitro antistaphylococcal effects of Embelia schimperi extracts and their component embelin with oxacillin and tetracycline. Evid Based Complement Alternat Med 2015:1–7 (ID: 175983)Google Scholar
  116. 116.
    Ruiz-Bailén M, Hoyos EAD, Ruiz-Navarro S, Díaz-Castellanos MÁ, Rucabado-Aguilar L, Gómez-Jiménez FJ, Martínez-Escobar S, Moreno RM, Fierro-Rosón J (2005) Reversible myocardial dysfunction after cardiopulmonary resuscitation. Resuscitation 66:175–181PubMedCrossRefGoogle Scholar
  117. 117.
    Sahu AK, Gautam MK, Deshmukh PT, Kushwah LS, Silawat N, Akbar Z, Muthu MS (2012) Effect of embelin on lithium–induced nephrogenic diabetes insipidus in albino rats. Asian Pac J Trop Dis 2:S729–S733CrossRefGoogle Scholar
  118. 118.
    Sahu BD, Anubolu H, Koneru M, Kumar JM, Kuncha M, Rachamalla SS, Sistla R (2014) Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis. Life Sci 107:59–67PubMedCrossRefGoogle Scholar
  119. 119.
    Salvesen GS, Duckett CS (2002) IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 3:401–410PubMedCrossRefGoogle Scholar
  120. 120.
    Samatha S, Vasudevan TN (1996) Embelia ribes Burm. as a source of red colorant. J Sci Ind Res 55:888–889Google Scholar
  121. 121.
    Sandro A, Gabriele BP (2005) Biologic therapy for inflammatory bowel disease. Drugs 65:2253–2286CrossRefGoogle Scholar
  122. 122.
    Schaible AM, Traber H, Temml V, Noha SM, Filosa R, Peduto A, Weinigel C, Barz D, Schuster D, Werz O (2013) Potent inhibition of human 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 by the anti-carcinogenic and anti-inflammatory agent embelin. Biochem Pharmacol 86:476–486PubMedCrossRefGoogle Scholar
  123. 123.
    Schreiner SJ, Schiavone AP, Smithgall TE (2002) Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. J Biol Chem 277:45680–45687PubMedCrossRefGoogle Scholar
  124. 124.
    Shankarmurthy K, Krishna V, Maruthi K, Rahiman B (2004) Rapid adventitious organogenesis from leaf segments of Embelia ribes Burm.-a threatened medicinal plant. TAIWANIA-TAIPEI- 49:194–200Google Scholar
  125. 125.
    Shelar RMC, Tekale P, Katkar K, Naik V, Suthar A, Chauhan VS (2009) Embelin: an HPLC method for quantitative estimation in Embelia ribes Burm. F. Int J Pharm Clin Res 1:146–149Google Scholar
  126. 126.
    Shi Y (2009) Structural biology of programmed cell death. In: Essentials of apoptosis. Springer, pp. 95–118Google Scholar
  127. 127.
    Shimada T, Kojima K, Yoshiura K, Hiraishi H, Terano A (2002) Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells. Gut 50:658–664PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Singh B, Guru SK, Sharma R, Bharate SS, Khan IA, Bhushan S, Bharate SB, Vishwakarma RA (2014) Synthesis and anti-proliferative activities of new derivatives of embelin. Bioorg Med Chem Lett 24:4865–4870PubMedCrossRefGoogle Scholar
  129. 129.
    Singh D, Singh R, Singh P, Gupta RS (2009) Effects of embelin on lipid peroxidation and free radical scavenging activity against liver damage in rats. Basic Clin Pharmacol Toxicol 105:243–248PubMedCrossRefGoogle Scholar
  130. 130.
    Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang H-G, Reed JC, Nicholson DW, Alnemri ES (1999) Ordering the cytochrome c–initiated caspase cascade: hierarchical activation of caspases-2,-3,-6,-7,-8, and-10 in a caspase-9–dependent manner. J Cell Biol 144:281–292PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Sreepriya M, Bali G (2005) Chemopreventive effects of embelin and curcumin against N-nitrosodiethylamine/phenobarbital-induced hepatocarcinogenesis in Wistar rats. Fitoterapia 76:549–555PubMedCrossRefGoogle Scholar
  132. 132.
    Sreepriya M, Bali G (2006) Effects of administration of Embelin and Curcumin on lipid peroxidation, hepatic glutathione antioxidant defense and hematopoietic system during N-nitrosodiethylamine/Phenobarbital-induced hepatocarcinogenesis in Wistar rats. Mol Cell Biochem 284:49–55PubMedCrossRefGoogle Scholar
  133. 133.
    Sumalatha KR, Abiramasundari G, Chetan GK, Divya T, Sudhandiran G, Sreepriya M (2014) XIAP inhibitor and antiestrogen embelin abrogates metastasis and augments apoptosis in estrogen receptor positive human breast adenocarcinoma cell line MCF-7. Mol Biol Rep 41:935–946PubMedCrossRefGoogle Scholar
  134. 134.
    Suthar M, Patel R, Hapani K, Patel A (2009) Screening of Embelia ribes for antifungal activity. Int J Pharm Sci Drug Res 1:203–206Google Scholar
  135. 135.
    Tambekar DH, Khante BS, Chandak BR, Titare AS, Boralkar SS, Aghadte SN (2009) Screening of antibacterial potentials of some medicinal plants from Melghat forest in India. Afr J Tradit Complement Altern Med 6:228–232PubMedPubMedCentralGoogle Scholar
  136. 136.
    Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, Scudiero DA, Tudor G, Qui YH, Monks A, Andreeff M, Reed JC (2000) Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res 6:1796–1803PubMedGoogle Scholar
  137. 137.
    Thippeswamy BS, Mahendran S, Biradar MI, Raj P, Srivastava K, Badami S, Veerapur VP (2011) Protective effect of embelin against acetic acid induced ulcerative colitis in rats. Eur J Pharmacol 654:100–105PubMedCrossRefGoogle Scholar
  138. 138.
    Thippeswamy BS, Nagakannan P, Shivasharan BD, Mahendran S, Veerapur VP, Badami S (2011) Protective effect of embelin from Embelia ribes Burm. against transient global ischemia-induced brain damage in rats. Neurotox Res 20:379–386PubMedCrossRefGoogle Scholar
  139. 139.
    Varier PS (2006) Indian medicinal plants a compendium of 500 species, vol 2. Orient Longman (Pvt) Ltd., Chennai, pp 368–371Google Scholar
  140. 140.
    Vinten-Johansen J, Jiang R, Reeves JG, Mykytenko J, Deneve J, Jobe LJ (2007) Inflammation, proinflammatory mediators and myocardial ischemia-reperfusion Injury. Hematol Oncol Clin North Am 21:123–145PubMedCrossRefGoogle Scholar
  141. 141.
    Wang DG, Sun YB, Ye F, Li W, Kharbuja P, Gao L, Zhang DY, Suo J (2014) Anti-tumor activity of the X-linked inhibitor of apoptosis (XIAP) inhibitor embelin in gastric cancer cells. Mol Cell Biochem 386:143–152PubMedCrossRefGoogle Scholar
  142. 142.
    Wang L, Yi TM (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206:1431–1438Google Scholar
  143. 143.
    Watson RT, Makoto K, Pessin JE (2004) Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocr Rev 25:177–204PubMedCrossRefGoogle Scholar
  144. 144.
    Xue Z, Ge Z, Zhang K, Sun R, Yang J, Han R, Peng M, Li Y, Li W, Zhang D, Hao J, Da Y, Yao Z, Zhang R (2014) Embelin suppresses dendritic cell functions and limits autoimmune encephalomyelitis through the TGF-beta/beta-catenin and STAT3 signaling pathways. Mol Neurobiol 49:1087–1101PubMedCrossRefGoogle Scholar
  145. 145.
    Yang T, Lan J, Huang Q, Chen X, Sun X, Liu X, Yang P, Jin T, Wang S, Mou X (2015) Embelin sensitizes acute myeloid leukemia cells to TRAIL through XIAP inhibition and NF-kappaB inactivation. Cell Biochem Biophys 71:291–297PubMedCrossRefGoogle Scholar
  146. 146.
    Yasmina L, Terrence T, David J, Elise T, Yisong W, Kuchroo VK, Flavell RA (2008) TGF-β signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci USA 105:10865–10870CrossRefGoogle Scholar
  147. 147.
    Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D (2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116:1310–1316PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Yoshizumi T, Ohta TI, Terada I, Fushida S, Fujimura T, Nishimura G, Shimizu K, Yi S, Miwa K (2004) Thiazolidinedione, a peroxisome proliferator-activated receptor-gamma ligand, inhibits growth and metastasis of HT-29 human colon cancer cells through differentiation-promoting effects. Int J Oncol 25:631–639PubMedGoogle Scholar
  149. 149.
    Zhao ZG, Tang ZZ, Zhang WK, Li JG (2015) Protective effects of embelin on myocardial ischemia-reperfusion injury following cardiac arrest in a rabbit model. Inflammation 38:527–533PubMedCrossRefGoogle Scholar
  150. 150.
    Zou B, Qiao L, Wong BC (2009) Current understanding of the role of PPARgamma in gastrointestinal cancers. PPAR Res 2009(1):121-132. (ID: 816957)Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Hong Lu
    • 1
  • Jun Wang
    • 1
  • Youxue Wang
    • 2
  • Liang Qiao
    • 3
    • 1
  • Yongning Zhou
    • 1
  1. 1.Division of Gastroenterology and HepatologyThe First Hospital of Lanzhou UniversityLanzhouChina
  2. 2.Department of PhysiologyThe University of Texas Southwestern Medical CenterDallasUSA
  3. 3.Storr Liver Centre, The Westmead Institute for Medical ResearchThe University of Sydney at Westmead HospitalWestmeadAustralia

Personalised recommendations