1. (CSDB ID: 47107) | ![]() |
-4)-a-D-Glcp-(1- | Show graphically |
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Phoma herbarum YS4108
(Ancestor NCBI TaxID 73001,
species name lookup)
Various natural polysaccharides are capable of activating the immune system and therefore can be employed as biological response modifiers in anti-tumor therapy. We previously found a homogenous polysaccharide from the mycelium of marine fungus Phoma herbarum YS4108, named YCP, exhibiting strong in vivo antitumor ability via enhancement of the host immune responses. To further elucidate the role of YCP as a biological response modifier, the immunomodulating activities of YCP in B cells was investigated in the current study. We demonstrated that stimulation of YCP with murine splenic B cells resulted in cell proliferation and generation of IgM antibody response. Binding of YCP to B cells was a direct, saturable and reversible event and required TLR2 and TLR4 involvement. TLR2 and TLR4 defunctionalization by either antibody blocking or allele-specific mutation significantly impaired the B-cell proliferative and IgM responses to YCP. YCP interaction with TLR2 and TLR4 led to the activation of intracellular p38, ERK and JNK, as well as the translocation of transcriptional factor NF-κB into nucleus. Furthermore, specific inhibitors of p38, ERK, JNK and NF-κB could attenuate the ability of YCP to induce B cell proliferation and IgM production. Taken together, this study has indicated for the first time the immunostimulating properties of YCP on B cells through a receptor-mediated mechanism, which involves TLR2 and TLR4 and resultant activation of MAPK and NF-κB signaling pathways, thereby highlighting the role of YCP as an efficacious biological response modifier in oncologic immunotherapy.
anti-tumor therapy
Structure type: homopolymer ; 250000
2. (CSDB ID: 63051) | ![]() |
b-D-Glcp-(1-14)-Subst Subst = 14-hydroxycretenolide = SMILES C=C1C(=O)O[C@]23C[C@H]1CCC({14}CO)=C2C(=O)C=C3C | Show graphically |
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Leontodon hispidus
(NCBI TaxID 58660,
species name lookup)
Hypocretenolides, a small group of sesquiterpene lactones with an unusual ring structure, are constituents of a small number of species from the Lactuceae tribe (Asteraceae). Three biogenetically closely related 14-hypocretenolides from Leontodon hispidus L were investigated for a putative anti-inflammatory activity. 14-Hydroxyhypocretenolide-β-D-glucoside-4'-14"-hydroxyhypocretenoate significantly exhibited in vivo anti-inflammatory activity in the croton oil-induced mouse ear edema. To obtain first information regarding the molecular targets which might be affected by this constituent, two in vitro bioassays were performed: (i) DNA binding activity of the transcription factor NF-κB was evaluated by electrophoretic mobility shift assay (EMSA) using TNF-α-activated Jurkat T cells and (ii) nitrite accumulation in cell culture supernatants of LPS-activated RAW 264.7 macrophages was determined as a parameter for inducible nitric oxide synthase (iNOS)-dependent nitric oxide release. In order to gain information about structure-activity relationships, additionally the aglycone 14-hydroxyhypocretenolide and its D-glycoside were investigated in these in vitro systems. 14-Hydroxyhypocretenolide-β-D-glucoside-4'-14'-hydroxyhypocretenoate as well as its aglycone exhibited activity in both test systems, whereas the D-glucoside was not or only weakly active.
anti-inflammatory activity, NF-κB, inducible nitric oxide synthase, Asteraceae, sesquiterpene lactones, Leontodon hispidus L., croton oil-induced mouse ear edema
Structure type: monomer
3. (CSDB ID: 63052) | ![]() |
Subst1-(11-4)-b-D-Glcp-(1-14)-Subst2 Subst1 = 4,14-dihydroxyhypocretenoic acid = SMILES CC1=CC(=O)C2=C({14}CO)CC[C@@H](C{11}C(=O)O)C{4}[C@]12O; Subst2 = 14-hydroxycretenolide = SMILES C=C1C(=O)O[C@]23C[C@H]1CCC({14}CO)=C2C(=O)C=C3C | Show graphically |
Show legend Show as text |
Leontodon hispidus
(NCBI TaxID 58660,
species name lookup)
Hypocretenolides, a small group of sesquiterpene lactones with an unusual ring structure, are constituents of a small number of species from the Lactuceae tribe (Asteraceae). Three biogenetically closely related 14-hypocretenolides from Leontodon hispidus L were investigated for a putative anti-inflammatory activity. 14-Hydroxyhypocretenolide-β-D-glucoside-4'-14"-hydroxyhypocretenoate significantly exhibited in vivo anti-inflammatory activity in the croton oil-induced mouse ear edema. To obtain first information regarding the molecular targets which might be affected by this constituent, two in vitro bioassays were performed: (i) DNA binding activity of the transcription factor NF-κB was evaluated by electrophoretic mobility shift assay (EMSA) using TNF-α-activated Jurkat T cells and (ii) nitrite accumulation in cell culture supernatants of LPS-activated RAW 264.7 macrophages was determined as a parameter for inducible nitric oxide synthase (iNOS)-dependent nitric oxide release. In order to gain information about structure-activity relationships, additionally the aglycone 14-hydroxyhypocretenolide and its D-glycoside were investigated in these in vitro systems. 14-Hydroxyhypocretenolide-β-D-glucoside-4'-14'-hydroxyhypocretenoate as well as its aglycone exhibited activity in both test systems, whereas the D-glucoside was not or only weakly active.
anti-inflammatory activity, NF-κB, inducible nitric oxide synthase, Asteraceae, sesquiterpene lactones, Leontodon hispidus L., croton oil-induced mouse ear edema
Structure type: monomerNew query | Export IDs | Home | Help |
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