OBJECTIVETo deal with the correlation between phylogeny, chemical constituents and pharmaceutical aspects of Ranunculaceae, namely a pharmaphylogenic study of this taxon.

METHODBased on chemical, pharmaceutical (both ethnopharmacologic and pharmacological) information, linking with different plant systems of Ranunculaceae.

RESULTChemical constituents of this taxon included several natural groups: benzylisoquinoline alkaloid, ranunculin, triterpenoid glycoside and diterpene alkaloid etc. Ranunculin and magoflorine were found to present simultaneously in some plants of this taxon.

CONCLUSIONCombining with therapeutic information, pharmaphylogenic research were in accordance with the phylogenetic system presented by Tamura that Ranunculaceae was proposed to be divided into six sub-families: Helleboroideae, Ranunculoideae, Cimicfugoideae, Isopyroideae, Thalictroideae and Coptidoideae. Results also supported the establishment of Cimicifugoideae.

Benzylisoquinolines ; isolation & purification ; Cimicifuga ; chemistry ; Diterpenes ; isolation & purification ; Furans ; isolation & purification ; Helleborus ; chemistry ; Methylglycosides ; isolation & purification ; Pharmacognosy ; classification ; Phylogeny ; Plants, Medicinal ; chemistry ; classification ; Ranunculaceae ; chemistry ; classification ; Triterpenes ; isolation & purification

This paper reports a pharmacophylogenetic study of a medicinal plant family, Ranunculaceae, investigating the correlations between their phylogeny, chemical constituents, and pharmaceutical properties. Phytochemical, ethnopharmacological, and pharmacological data were integrated in the context of the systematics and molecular phylogeny of the Ranunculaceae. The chemical components of this family included several representative metabolic groups: benzylisoquinoline alkaloids, ranunculin, triterpenoid saponin, and diterpene alkaloids, among others. Ranunculin and magnoflorine were found to coexist in some genera. The pharmacophylogenetic analysis, integrated with therapeutic information, agreed with the taxonomy proposed previously, in which the family Ranunculaceae was divided into five sub-families: Ranunculoideae, Thalictroideae, Coptidoideae, Hydrastidoideae, and Glaucidioideae. It was plausible to organize the sub-family Ranunculoideae into ten tribes. The chemical constituents and therapeutic efficacy of each taxonomic group were reviewed, revealing the underlying connections between phylogeny, chemical diversity, and clinical use, which should facilitate the conservation and sustainable utilization of the pharmaceutical resources derived from the Ranunculaceae.
Alkaloids ; analysis ; therapeutic use ; Aporphines ; analysis ; therapeutic use ; Biodiversity ; Furans ; analysis ; Humans ; Methylglycosides ; analysis ; Phylogeny ; Phytotherapy ; Plant Extracts ; chemistry ; therapeutic use ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Saponins ; analysis ; therapeutic use ; Terpenes ; analysis ; therapeutic use

This report describes surface properties of several cell membranes tested by lectininduced agglutination reactions which were quantitated using the microquantitative particle counter agglutination assay of Davis et al. (1976). The quantitative assays of concanavaalin A (con A) induced agglutination were performed for rabbit erythrocyte, rat erythrocyte, human erythrocyte, and sarcoma 180 mouse ascites cells. The percent agglutination versus the con A concentration revealed a sigmoid curve in all cases, but the steepness of the sigmoid curve is variable depending on the cell types. It varies even with the same cell but in different species. Optimum cell concentration was (0.92-0.95) x 10(7) cells/ml final concentration in the hanging drop, for rabbit erythrocytes, (0.77-1.64) x 10(7) cells/ml for rat erythrocytes, (1.59-2.7) x 10(7) cells/ml for human erythrocytes and (0.23-0.39) x 10(7) cells/ml for sarcoma 180 mouse ascites cells. When minimal and maximal agglutination percentages were defined as the concentration of con A/ml/1 x 10(6) cells corresponding to 10% and 95% agglutination, minimal and maximal agglutination occured at 0.56 ug, 19.98 ug for human erythrocytes at 0.56 ug, 224 ug for rat erythrocytes at 0.08 ug, 1.43ug for rabbit erythrocytes at 0.12 ug, 14.8 ug for sarcoma 180-mouse ascites cells respectively. The order of inhibitory activity of alpha-methyl-D-mannopyranoside (alphaMM) for each corresponding cells from the highest inhibition was human erythrocytes, rat erythrocytes, sarcoma 180 mouse ascites cells and rabbit erythrocytes. The concentrations of alphaMM required for 50% inhibition per ml of the final concentration in the hanging drop per 1 x 10(7) cells were 0.565 umoles for rabbit erythrocytes, 0.072 umoles for rat erythrocytes, 0.018 umoles for human erythrocytes and 3.677 umoles for sarcoma 180 mouse ascites cells, respectively. From our experimental results we conclude that the cytoagglutination activity was increased with con A, the inhibitory activity with alphaMM in the presence of con A was decreased, however the sarcoma 180 mouse ascites cells revealed a contradictory result, and might be due to the topological distribution of agglutination site changes to a distribution more favorable for agglutination.
Agglutination ; Agglutination Tests ; Animal ; Cell Membrane/immunology* ; Concanavalin A/pharmacology* ; Erythrocytes/immunology ; Human ; Methylmannosides/pharmacology ; Mice ; Rabbits ; Rats ; Sarcoma 180/immunology ; Surface Properties

D-glucose is an essential fuel for metabolism in mammalian cells and the predominant fuel source for the brain. Transport of glucose across tissue barriers is mediated by stereospecific transporter proteins. Glut-1 is a major glucose transporter expressed on vascular endothelial cells comprising the blood brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood brain barrier results in Glut-1 deficiency syndrome(DS). It is caused by haploinsufficiency of the blood brain barrier hexose carrier. Heterozygous mutations or hemizygosity of the GLUT-1 gene cause Glut-1 DS. It is characterized by infantile seizures refractory to anticonvulsants, developmental delay, acquired microcephaly, spasticity, ataxia, opsoclonus and other paroxysmal neurological phenomena, often occurring prior to meals. The diagnosis of Glut-1 DS is established in neurologically impaired patients with reduced cerebrospinal glucose concentration(hypoglycorrhachia) and lactate concentration in the absence of hypoglycemia. Decreased 3-O-methyl-D-glucose uptake in erythrocytes also supports the diagnosis of Glut-1 DS. Several treatment strategies have been pursued, none optimal, as it relates to the developmental encephalopahty associated with this clinical syndrome. Ketogenic diet has been effective in controlling seizures but has had little measurable effects on the associated cognitive impairments and behavioral disturbance. Current treatment is inadequate, and future studies should be directed at the mechanisms designed to upreglulate GLUT-1 expression, thereby increasing residual Glut-1 activity to 75 to 100%.
3-O-Methylglucose ; Anticonvulsants ; Ataxia ; Blood-Brain Barrier ; Brain ; Diagnosis ; Endothelial Cells ; Epilepsy ; Erythrocytes ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1* ; Glucose* ; Haploinsufficiency ; Humans ; Hypoglycemia ; Ketogenic Diet ; Lactic Acid ; Meals ; Metabolism ; Microcephaly ; Muscle Spasticity ; Ocular Motility Disorders ; Seizures

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by impaired glucose transport across the blood-brain barrier (BBB) and characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low cerebrospinal glucose concentration (hypoglycorrhachia). A diagnosis of GLUT1-DS is biochemically established in neurologically impaired patients with hypoglycorrhachia in the normoglycemia. GLUT1-DS can be confirmed by mutation analysis of the solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) gene or reduced 3-O-methyl-D-glucose uptake into erythrocytes. The patient was a 12-year-old boy born at term. He had experienced seizures from 4 months of age. Electroencephalography (EEG) did not show epileptiform activity. Brain magnetic resonance imaging (MRI) revealed mild diffuse cortical atrophy and ventricular dilatation. Furthermore, he showed developmental delay, mental retardation, and ataxia, which all became more apparent with age progression. For 7 years, he had experienced paroxysmal episodes of atonic behavioral changes that were aggravated before meals or when he became tired. When he was 12 years old, cerebrospinal fluid (CSF) analysis revealed a low glucose concentration in the normal serum glucose and lactate levels. Under the impression of GLUT1-DS, mutation analysis of the SLC2A1 gene by direct sequencing was performed using white blood cells, and c.680-2delA of intron 5 was found. We describe a GLUT1-DS patient with a typical natural history of GLUT1-DS through a long term follow-up visits, with a novel splice site mutation (SLC2A1: c.6802delA).
3-O-Methylglucose ; Ataxia ; Atrophy ; Blood Glucose ; Blood-Brain Barrier ; Brain ; Cerebrospinal Fluid ; Child ; Diagnosis ; Dilatation ; Electroencephalography ; Erythrocytes ; Follow-Up Studies ; Glucose ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1 ; Humans ; Intellectual Disability ; Introns ; Lactic Acid ; Leukocytes ; Magnetic Resonance Imaging ; Male ; Meals ; Microcephaly ; Muscle Spasticity ; Natural History ; Seizures