A new isoprenylated stilbene, flavestinK (1) together with two known isoprenylated stilbenes, flavestin B (2), flavestin G (3), and two isoprenilated flavanones, 4-O-methyl-8-isoprenylnaringenin (4) and 8-isoprenyl-5,7-dihydroxyflavanone (5) were isolated from the leaves of Macaranga recurvata Gage. All of the structures have been determined based on HRESIMS, 1D and 2D NMR spectral data. All of the isolated compounds were evaluated for their cytotoxicity against three human cancer cells (HeLa, T47D and WiDr). Compound 1 showed higher activity than doxorubicin against HeLa cells with IC₅₀ value of 13.1 µg/mL.
Doxorubicin ; Euphorbiaceae ; Flavanones ; HeLa Cells ; Humans ; Stilbenes

In a search for novel treatments for diabetic complications from natural resources, we found that the ethyl acetate-soluble fraction from the 80% ethanol extract of the leaves of Homonoia riparia has a considerable inhibitory effect on advanced glycation end product (AGE) formation. Bioassay-guided isolation of this fraction resulted in identification of 15 phenolic compounds (1 – 15). These compounds were evaluated in vitro for inhibitory activity against the formation of AGE. The majority of tested compounds, excluding ethyl gallate (15), markedly inhibited AGE formation, with IC₅₀ values of 2.2 – 89.9 µM, compared with that of the positive control, aminoguanidine (IC₅₀ = 962.3 µM). In addition, the effects of active isolates on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish was investigated; (–)-epigallocatechin-3-O-gallate (6), corilagin (7), and desmanthine-2 (11) significantly decreased HG-induced dilation of hyaloid–retinal vessels compared with the HG-treated control group.
Diabetes Complications ; Ethanol ; Euphorbiaceae ; Glucose ; In Vitro Techniques ; Natural Resources ; Phenol* ; Zebrafish

BACKGROUND: Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases. Euphorbia lathyris L. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. METHODS: Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL. Bone resorption assays were performed using dentine slices. The expression level of mRNA was analyzed by real-time polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. Western blotting assays were performed to detect the expression or activation level of proteins. RESULTS: ELL inhibited RANKL-induced osteoclast formation without cytotoxicity. Furthermore, the RANKL-stimulated bone resorption was diminished by ELL. Mechanistically, ELL blocked the RANKL-triggered p38 mitogen-activated protein kinase (MAPK) phosphorylation, which resulted in the suppression of the expression of c-Fos and nuclear factor of activated T cells (NFATc1). In osteoblasts, ELL had little effect on the mRNA expression of RANKL and osteoprotegerin (OPG). CONCLUSIONS: The present data suggest that ELL has an inhibitory effect on osteoclast differentiation and function via downregulation of the p38/c-Fos/NFATc1 signaling pathways. Thus, ELL could be useful for the treatment of bone diseases associated with excessive bone resorption.
Animals ; Blotting, Western ; Bone Diseases ; Bone Marrow ; Bone Matrix ; Bone Resorption ; Dentin ; Down-Regulation ; Euphorbia* ; Euphorbiaceae ; Humans ; Macrophage Colony-Stimulating Factor ; Macrophages ; Methanol ; Mice ; Osteoblasts ; Osteoclasts* ; Osteoprotegerin ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Plants ; Protein Kinases ; RANK Ligand ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; T-Lymphocytes

Fourteen compounds were isolated from 95% ethanol extract by silica gel, MCI, and ODS column chromatography. These compounds were respectively identified as quercetin (1), kaempferol (2), (+)-catechin (3), fraxin (4), protocatechuic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), apocynol A (9), baccatin (10), cerevisterol (11), ellagic acid (12), 3, 3',4'-tri-0-methylellagic acid(13) and N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(14) by analyzing their spectral data and comparing with the previously reported literatures. Except for gallic acid (6), all other compounds were isolated from this plant for the first time. Compounds 1, 2 and 6 showed moderate anti-proliferation activities on tumor cells.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Euphorbiaceae ; chemistry ; Humans ; Plants, Medicinal ; chemistry ; Spectrometry, Mass, Electrospray Ionization

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, an extract of the dried whole plants of Euphorbia supina Rafin was found to significantly inhibit sEH activity in vitro. Phytochemical investigation of E. supina resulted in isolation of 17 compounds (1 - 17), including triterpenes (1 - 4), phenolic compounds (5 - 8), and flavonoid derivatives (9 - 17). The structures of the isolated compounds were established mainly by extensive analysis of the 1D and 2D NMR, and MS data. All of the isolated compounds were evaluated for their sEH inhibitory activity. Among the isolated phenolic compounds, 8 was identified as a significant inhibitor of sEH, with an IC50 value of 15.4 +/- 1.3 microM. Additionally, a kinetic analysis of isolated compounds (2, 5, 8 - 11, 13, and 17) indicated that the inhibitory effects of flavonoid derivatives 10 and 11 were of mixed-type, with inhibitory constants (Ki) ranging from 3.6 +/- 0.8 to 21.8 +/- 1.0 microM, whereas compounds 2, 5, 8, 9, 13, and 17 were non-competitive inhibitors with inhibition Ki values ranging from 3.3 +/- 0.2 to 39.5 +/- 0.0 microM.
Euphorbia* ; Euphorbiaceae ; Inhibitory Concentration 50 ; Phenol ; Triterpenes

OBJECTIVETo evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally.

METHODSBased on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively.

RESULTSIn Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group.

CONCLUSIONCo-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

Administration, Oral ; Animals ; Biological Availability ; Biological Transport ; Chromatography, High Pressure Liquid ; Euphorbiaceae ; chemistry ; Paclitaxel ; pharmacokinetics ; Permeability ; Plant Extracts ; pharmacology ; Plant Roots ; chemistry ; Rats ; Tandem Mass Spectrometry ; Verapamil

BACKGROUND: Osteoclasts are differentiated from monocytes/macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL). Croton pycnanthus Benth. (CPB) is a herbal plant that belongs to Euphorbiaceae family. The aim of this study was to investigate the effects of CPB on osteoclastogenesis and RANKL-dependent signaling pathways. METHODS: Methanol extract of CPB was obtained from International Biological Material Research Center. Osteoclast differentiation was achieved by culturing mouse bone marrow-derived macrophages (BMMs) with M-CSF and RANKL. Osteoclast numbers were evaluated by counting multinuclear cells positive for tartrate-resistant acid phosphatase (TRAP). mRNA and protein levels were analyzed by real-time polymerase chain reaction (PCR) and Western blotting, respectively. The activation of signaling molecules were assessed after acute stimulation of cells with high dose of RANKL by Western blotting with phospho-specific antibodies. RESULTS: CPB reduced the generation of TRAP-positive multinucleated cells and the activation of mitogen-activated protein kinase (MAPK) and NF-kappaB signaling pathways. The induction of the expression of c-Fos, nuclear factor-activated T cells c1 (NFATc1) and dendritic cell-specific transmembrane protein (DC-STAMP) by RANKL was also suppressed. CONCLUSIONS: CPB exerts negative effects on osteoclast differentiation in response to the RANKL. The inhibitory mechanism involves the suppression of MAPK and NF-kappaB signaling pathways and subsequently the down-regulation of c-Fos and NFATc1 transcription factors.
Acid Phosphatase ; Animals ; Antibodies, Phospho-Specific ; Blotting, Western ; Cell Differentiation ; Colony-Stimulating Factors ; Croton* ; Down-Regulation ; Euphorbiaceae ; Humans ; Macrophage Colony-Stimulating Factor ; Macrophages ; Methanol* ; Mice ; NF-kappa B* ; NFATC Transcription Factors ; Osteoclasts* ; Plants ; Protein Kinases ; RANK Ligand ; Real-Time Polymerase Chain Reaction ; Receptor Activator of Nuclear Factor-kappa B ; RNA, Messenger ; T-Lymphocytes

We investigated the anti-nociceptive effect of Excoecaria agallocha (E.agallocha) against chemically and thermally induced nociception, Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction (Alk-CF) of E.agallocha by oral administration. Compared with controls, Alk-CF decreased the writhing numbers (P<0.01) in a dose dependent manner. Further we determined that, Alk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as Rutin. Docking simulation demonstrated that Rutin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. In conclusion we have identified peripheral and central anti-nociceptive activities of E.agallocha that involve opioid receptor, and in which the active compound is Rutin.
Analgesics ; isolation & purification ; therapeutic use ; Animals ; Drug Evaluation, Preclinical ; Euphorbiaceae ; chemistry ; Female ; Male ; Mice ; Pain ; drug therapy ; Phytotherapy ; Plant Extracts ; chemistry ; therapeutic use ; Rutin ; isolation & purification ; therapeutic use

AIM: To investigate the chemical constituents in the stems of Trigonostemon heterophyllus. METHOD: The chemical constituents were isolated by column chromatography on silica gel, Rp-18, and Sephadex LH-20, and their structures were elucidated on the basis of spectroscopic analysis. RESULTS: Three compounds were isolated and identified as a new diterpene, trigonoheterene B (1), together with two known compounds, trigonostemone (2) and trigonochinene B (3). CONCLUSION Compound 1 is new. Compounds 2 and 3 showed antibacterial activities.
Diterpenes ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Euphorbiaceae ; chemistry ; Molecular Structure ; Plant Stems ; chemistry

The anti-malarial potential of different parts of Allophylus africanus P. Beauv and Tragia benthamii Baker were determined in vivo for suppressive, curative and cytotoxic activities in mice receiving 0.2 mL of a standard inoculum size of 1 × 10(7) infected erythrocytes of Plasmodium berghei (NK-65) intraperitoneally. The A. africanus extracts suppressed parasitaemia following administration to infected mice by 92.82%-97.81% on day 7 post-infection against 96.81% for chloroquine. The infected extract-treated animals had significantly moderate (P < 0.05) packed cell volume (PCV) compared with the infected, untreated animals. Phytochemical screening revealed a predominance of tannins, saponins, flavonoids and carbohydrates in all parts of A. africanus, and alkaloids instead of flavonoids in the extract of T. benthamii. The results suggest that the extract possesses considerable antimalarial activity. These results support further studies on A. africanus.
Animals ; Antimalarials ; administration & dosage ; chemistry ; Drug Evaluation, Preclinical ; Euphorbiaceae ; chemistry ; Female ; Humans ; Malaria ; drug therapy ; parasitology ; Male ; Mice ; Plant Extracts ; administration & dosage ; chemistry ; Plasmodium berghei ; drug effects ; Sapindaceae ; chemistry