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Chemical Compound Review

hispidin     2-[(E)-2-(3,4- dihydroxyphenyl)ethenyl]-6...

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Disease relevance of hispidin

  • Synthetic hispidin was found to inhibit isoform beta of protein kinase C (IC50 of 2 x 10(-6) mol/L), but not E. coli and placental type XV alkaline phosphatases [1].
  • Ethanolic extracts, hispidin and hispolon showed considerable antiviral activity against influenza viruses type A and B [2].

High impact information on hispidin

  • Lamin B1 phosphorylation was partly reduced, but its cleavage was completely prevented, despite the presence of active caspase-6, by adding a selective PKC-betas inhibitor, hispidin, to the apoptotic cytoplasms [3].
  • Preferential PKCdelta and PKCbeta translocation was in accordance with other results showing that rottlerin and hispidin have the highest efficacy in suppressing EGF-induced CCE augmentation [4].
  • Blocking PKC beta translocation with hispidin resulted in more rapid uptake of wild-type bacteria and greatly reduced escape from the primary phagocytic vacuoles of J774 cells [5].
  • Rottlerin, an inhibitor of PKC delta in J774 cells, also inhibited the activation of PLD, but hispidin, an inhibitor of PKC betaI and betaII, did not [6].
  • A possible biogenesis of 1 mediated by the fungal metabolite hispidin was postulated [7].

Biological context of hispidin

  • In this study, we used two inflammatory agents, IL-1beta and phorbol myristic acetate, to activate PKC isozymes and specific inhibitors of PKCalpha (Gö6976) and PKCbeta (hispidin) to distinguish how each of these isoform(s) controls angiogenesis, wound healing, and permeability [8].

Anatomical context of hispidin

  • The enhanced activity of hispidin toward the cancerous cell lines is discussed [1].
  • Hispidin synthesized in our laboratory to a high degree of purity (checked by 1H and 13C NMR spectroscopy) was shown to be cytotoxic (between 10(-3) mol/L and 10(-7) mol/L) toward normal human MRC-5 fibroblasts, human cancerous keratinocytes (SCL-1 cell line), and human cancerous pancreatic duct cells (Capan-1 cell line) [1].
  • Inhibition of chemiluminescence response of human mononuclear cells and suppression of mitogen-induced proliferation of spleen lymphocytes of mice by hispolon and hispidin [9].
  • The antiviral activity of two phenolic compounds, hispolon and hispidin, isolated from the fruit bodies of the basidiomycete Inonotus hispidus as well as of some extracts prepared from fruit bodies and mycelial cultures of this fungus was investigated in allantois on the shell-test system [2].
  • However, hispidin, an inhibitor of PKCbeta, inhibited the release of superoxide anion from circulating leukocytes in all groups of animals. feG prevented the increased expression of the beta1-integrin CD49d on the circulating neutrophils elicited by antigen challenge [10].

Gene context of hispidin

  • A beta-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus [11].
  • Hispidin derivatives from the mushroom Inonotus xeranticus and their antioxidant activity [12].
  • Interestingly, addition of hispidin in three successive doses (between 10(-5) mol/L and 10(-7) mol/L) led to a 100-fold increase in activity with an enhanced activity on cancer cells compared to normal cells (50%) [1].
  • Stimulation by PMA but not Ca2+ was inhibited by the protein kinase C (PKC) inhibitors staurosporine and hispidin [13].
  • The effects of two phenolic compounds, hispolon and hispidin isolated from fruit bodies of the basidiomycete Inonotus hispidus (Bull. ex Fr.) Karst, were investigated on the chemiluminescence response by LPS- or zymosan-activated human mononuclear cells (MNC) and on the concanavalin A-induced proliferation of spleen lymphocytes of mouse in vitro [9].


  1. Synthetic hispidin, a PKC inhibitor, is more cytotoxic toward cancer cells than normal cells in vitro. Gonindard, C., Bergonzi, C., Denier, C., Sergheraert, C., Klaebe, A., Chavant, L., Hollande, E. Cell Biol. Toxicol. (1997) [Pubmed]
  2. Antiviral activity of Inonotus hispidus. Awadh Ali, N.A., Mothana, R.A., Lesnau, A., Pilgrim, H., Lindequist, U. Fitoterapia (2003) [Pubmed]
  3. Protein kinase C-beta II Is an apoptotic lamin kinase in polyomavirus-transformed, etoposide-treated pyF111 rat fibroblasts. Chiarini, A., Whitfield, J.F., Armato, U., Dal Pra, I. J. Biol. Chem. (2002) [Pubmed]
  4. PKC isoform-specific enhancement of capacitative calcium entry in human corneal epithelial cells. Zhang, F., Wen, Q., Mergler, S., Yang, H., Wang, Z., Bildin, V.N., Reinach, P.S. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  5. Mobilization of protein kinase C in macrophages induced by Listeria monocytogenes affects its internalization and escape from the phagosome. Wadsworth, S.J., Goldfine, H. Infect. Immun. (2002) [Pubmed]
  6. Activation of host phospholipases C and D in macrophages after infection with Listeria monocytogenes. Goldfine, H., Wadsworth, S.J., Johnston, N.C. Infect. Immun. (2000) [Pubmed]
  7. Phelligridimer A, a highly oxygenated and unsaturated 26-membered macrocyclic metabolite with antioxidant activity from the fungus Phellinus igniarius. Wang, Y., Wang, S.J., Mo, S.Y., Li, S., Yang, Y.C., Shi, J.G. Org. Lett. (2005) [Pubmed]
  8. Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha. Bokhari, S.M., Zhou, L., Karasek, M.A., Paturi, S.G., Chaudhuri, V. J. Invest. Dermatol. (2006) [Pubmed]
  9. Inhibition of chemiluminescence response of human mononuclear cells and suppression of mitogen-induced proliferation of spleen lymphocytes of mice by hispolon and hispidin. Ali, N.A., Lüdtke, J., Pilgrim, H., Lindequist, U. Die Pharmazie. (1996) [Pubmed]
  10. The tripeptide feG regulates the production of intracellular reactive oxygen species by neutrophils. Mathison, R.D., Davison, J.S. Journal of inflammation (London, England) (2006) [Pubmed]
  11. A beta-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus. Park, I.H., Jeon, S.Y., Lee, H.J., Kim, S.I., Song, K.S. Planta Med. (2004) [Pubmed]
  12. Hispidin derivatives from the mushroom Inonotus xeranticus and their antioxidant activity. Lee, I.K., Seok, S.J., Kim, W.K., Yun, B.S. J. Nat. Prod. (2006) [Pubmed]
  13. Expression and modulation of an NADPH oxidase in mammalian astrocytes. Abramov, A.Y., Jacobson, J., Wientjes, F., Hothersall, J., Canevari, L., Duchen, M.R. J. Neurosci. (2005) [Pubmed]
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