Vanicoside B

Cytotoxic Effect of Vanicosides A and B from Reynoutria sachalinensis Against Melanotic and Amelanotic Melanoma Cell Lines and in silico Evaluation for Inhibition of BRAFV600E and MEK1.[Pubmed:32610527]

Int J Mol Sci. 2020 Jun 29;21(13). pii: ijms21134611.

Vanicosides A and B are the esters of hydroxycinnamic acids with sucrose, occurring in a few plant species from the Polygonaceae family. So far, vanicosides A and B have not been evaluated for anticancer activity against human malignant melanoma. In this study, we tested these two natural products, isolated from Reynoutria sachalinensis rhizomes, against two human melanoma cell lines (amelanotic C32 cell line and melanotic A375 cell line, both bearing endogenous BRAFV600E mutation) and two normal human cell lines-keratinocytes (HaCaT) and the primary fibroblast line. Additionally, a molecular docking of vanicoside A and Vanicoside B with selected targets involved in melanoma progression was performed. Cell viability was studied using an MTT assay. A RealTime-Glo Annexin V Apoptosis and Necrosis assay was used for monitoring programmed cell death (PCD). Vanicoside A demonstrated strong cytotoxicity against the amelanotic C32 cell line (viability of the C32 cell line was decreased to 55% after 72 h incubation with 5.0 microM of vanicoside A), significantly stronger than Vanicoside B. This stronger cytotoxic activity can be attributed to an additional acetyl group in vanicoside A. No significant differences in the cytotoxicity of vanicosides were observed against the less sensitive A375 cell line. Moreover, vanicosides caused the death of melanoma cells at concentrations from 2.5 to 50 microM, without harming the primary fibroblast line. The keratinocyte cell line (HaCaT) was more sensitive to vanicosides than fibroblasts, showing a clear decrease in viability after incubation with 25 microM of vanicoside A as well as a significant phosphatidylserine (PS) exposure, but without a measurable cell death-associated fluorescence. Vanicosides induced an apoptotic death pathway in melanoma cell lines, but because of the initial loss of cell membrane integrity, an additional cell death mechanism might be involved like permeability transition pore (PTP)-mediated necrosis that needs to be explored in the future. Molecular docking indicated that both compounds bind to the active site of the BRAFV600E kinase and MEK-1 kinase; further experiments on their specific inhibitory activity of these targets should be considered.

Antitumor Activity of Vanicoside B Isolated from Persicaria dissitiflora by Targeting CDK8 in Triple-Negative Breast Cancer Cells.[Pubmed:31622095]

J Nat Prod. 2019 Nov 22;82(11):3140-3149.

A flavonoid glycoside, quercitrin (1), and two phenylpropanoyl sucrose derivatives, Vanicoside B (2) and lapathoside C (3), were isolated for the first time from the herb Persicaria dissitiflora. Vanicoside B (2) exhibited antiproliferative activity against a panel of cancer cell lines in triple-negative breast cancer (TNBC) MDA-MB-231 cells. The underlying mechanisms of the antitumor activity of 2 were investigated in TNBC cells. Upregulation of cyclin-dependent kinase 8 (CDK8) was observed in a claudin-low molecular subtype of TNBC cells. A molecular modeling study indicated that 2 showed a high affinity for CDK8. Further investigations revealed that 2 suppressed CDK8-mediated signaling pathways and the expression of epithelial-mesenchymal transition proteins and induced cell cycle arrest and apoptosis in MDA-MB-231 and HCC38 TNBC cells. Moreover, 2 inhibited tumor growth without overt toxicity in a nude mouse xenograft model implanted with MDA-MB-231 cells. Taken together, these findings demonstrate the significance of CDK8 activity in TNBC and suggest a potential use of 2 as a therapeutic candidate for the treatment of aggressive human triple-negative breast cancer.

Biological evaluation of phytoconstituents from Polygonum hydropiper.[Pubmed:28000515]

Nat Prod Res. 2017 Sep;31(17):2053-2057.

Fourteen compounds including Vanicoside B (1), vanicoside F (2), vanicoside E (3) and 5,6-dehydrokawain (4), aniba-dimer-A (5), 6,6'-((1alpha,2alpha,3beta,4beta)-2,4-diphenylcyclobutane-1,3-diyl)bis(4-methoxy- 2H-pyran-2-one) (6), (+)-ketopinoresinol (7), isorhamnetin (8), 3,7-dihydroxy-5,6-dimethoxy-flavone (9), isalpinin (10), cardamomin (11), pinosylvin (12), 2-desoxy-4-epi-pulchellin (13) and beta-sitosterol (14) were isolated from dichloromethane-soluble portion of Polygonum hydropiper. By using Alamar blue assay, compounds 2, 7, 8, 11 and 12 were found to be active against Trypanosoma brucei with IC50 values in the range of 0.49-7.77 mug/mL. Cardamomin (11) had most significant activity against T. brucei with IC50/IC90 values of 0.49/0.81 mug/mL compared to the positive control DFMO (IC50/IC90: 3.02/8.05 mug/mL). Furthermore, in antimalarial, antimicrobial, anti-inflammatory, PPAR and cytotoxic assays, some compounds have demonstrated moderate inhibitory potentials.

Antioxidant and enzyme inhibition activities and chemical profiles of Polygonum sachalinensis F.Schmidt ex Maxim (Polygonaceae).[Pubmed:19698767]

Fitoterapia. 2010 Mar;81(2):124-31.

Polygonum sachalinensis is a widespread invasive plant in Europe. Chemical profiles of its different organs were studied by HPLC-UV-ESI/MS. Seven major constituents quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-arabinopyranoside, lapathoside D, N-trans-feruloyltyramine, lapathoside C, hydropiperoside, and Vanicoside B were isolated and identified. The free radical-scavenging, alpha/beta-glucosidase, and acetylcholinesterase inhibitory activities of crude MeOH extracts and isolated compounds were studied. The structure-activity relationships were discussed. The chemical profiles revealed flavonoids and phenylpropanoids are the major compounds of all the organs of this plant. Quercetin-3-O-arabinopyranoside, lapathoside D, N-trans-feruloyltyramine, lapathoside C and hydropiperoside were isolated from this species for the first time. In the alpha-glucosidase bioassay, quercetin-3-O-beta-D-galactopyranoside, lapathoside D and N-trans-feruloyltyramine demonstrated stronger activities than the positive reference acarbose. The trend in scavenging power showed no relation to enzyme inhibition in the test models.

New phenylpropanoid esters of sucrose from Polygonum lapathifolium.[Pubmed:11678656]

J Nat Prod. 2001 Oct;64(10):1305-8.

Four new phenylpropanoid esters of sucrose, lapathosides A (1), B (2), C (3), and D (4), were isolated from the aerial parts of Polygonum lapathifolium together with known esters, Vanicoside B (5) and hydropiperoside (6). The structures of 1-4 were determined by spectral (1D and 2D NMR and MS) analysis. Lapathoside A (1) and Vanicoside B (2) showed significant inhibitory effects on the Epstein-Barr virus early antigen activation by tumor-promoters.

Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, from Polygonum lapathifolium.[Pubmed:11597787]

Cancer Lett. 2001 Nov 28;173(2):133-8.

To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, Vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, Vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.

New sucrose phenylpropanoid esters from Polygonum perfoliatum.[Pubmed:10978204]

J Nat Prod. 2000 Aug;63(8):1094-7.

Five diferuloyl esters of sucrose, 6'-acetyl-3,6-diferuloylsucrose (helonioside B) (1); 2',4',6'-triacetyl-3,6-diferuloylsucrose (2); 1, 2',4',6'-tetraacetyl-3,6-diferuloylsucro se (3); 1,2',6'-triacetyl-3, 6-diferuloylsucrose (4); and 2',6'-diacetyl-3,6-diferuloylsucrose (5), were isolated, along with the 1,3,6-tri-p-coumaroyl-6'-feruloylsucroses, vanicoside A and Vanicoside B, from the whole plant of Polygonum perfoliatum by various chromatographic methods. The structures of these phenylpropanoid glycosides were determined on the basis of their NMR and mass spectroscopic data. Compound 1 is a known compound, but 2-5 are new members of this class.

Vanicosides C-F, new phenylpropanoid glycosides from Polygonum pensylvanicum.[Pubmed:9644060]

J Nat Prod. 1998 Jun 26;61(6):762-6.

The isolation of the protein kinase C inhibitors, vanicoside A (1) and Vanicoside B (2), from Polygonum pensylvanicum prompted continued interest in the active principles of this plant. A new, more efficient isolation procedure has been developed to facilitate separation of homologues of vanicosides A and B from the complex extract. Several new phenylpropanoid glycosides have since been isolated. The structures of these principles were determined to be 2'-O-acetylhydropiperoside (4), 6'-O-p-coumarylhydropiperoside (5), 4'-O-acetylvanicoside A (6), and 3'-O-acetylVanicoside B (7) using negative ion FABMS, 1H NMR, and 2D NMR techniques.