SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

Ubillas, R.; Jolad, Shivanand D.; Bruening, Reimar C.; Kernan, Michael R.; King, Steven R.; Sesin, David F.; Barrett, Marilyn; Stoddart, Cheryl A.; Flaster, T.; Kuo, Jacqueline; Ayala, Fabiola Garces; Meza, Ericka; Castañel, M.; Mcmeekin, D.; Rozhon, Edward J.; Tempesta, Michael S.; Barnard, Dale L.; Huffman, John H.; Smee, Donald F.; Sidwell, Robert W.; Soike, Kenneth F.; Brazier, Anne D.; Safrin, Sharon; Orlando, Raffaele; Kenny, Peter T.M.; Berova, N.; Nakanishi, Koji

doi:10.1016/s0944-7113(11)80026-7

Cited by 95 publications

(113 citation statements)

References 38 publications

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“…12,13,16,34) Twofold serial dilutions of natural products were seeded into cells monolayers cultivated in 96-well culture plates, using the MNCC as the higher concentration. An infection control was made in the absence of natural products.…”

Section: Methodsmentioning

confidence: 99%

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Wei

et al. 2003

Chem. Pharm. Bull.

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Viruses are the leading cause of respiratory infections in children and adults and are a major cause of morbidity and mortality worldwide. Respiratory viral infections contribute to be leading cause of morbidity, mortality, and economic loss throughout the world.1) Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants, in children, and even in adults.2) Ribavirin and immunoglobulin preparations with high titers of RSV-specific neutralizing antibodies are currently approved for use to treat and prevent RSV infections. However, neither of these is cost-effective and simple to administer.3) Parainfluenza type 3 virus (PIV 3) is another respiratory virus caused infections in children. No chemotherapy agents and vaccine have been used to treat PIV 3 infections. 4) Therefore, the development of new antiviral agents with different mechanisms is most desirable. Traditional medicines utilizing natural products have been shown to contain antiviral compounds. [5][6][7][8][9] The screening of plants as a possible source of antiviral has led to the discovery of potent inhibitors of in vitro viral growth and the use of the ethnopharmacological approach enhances the probability of identifying new bioactive plant compounds. 10)Our interest has focused on the treatments for respiratory viral infections. In order to find more potent inhibitors of RSV and PIV 3, we have been looking for some inhibitory substances from natural sources. 11-17)Selaginella uncinata SPRING is a Chinese herb medicine widely distributed in south China, which has been used to treat infectious diseases and tumors. Previous phytochemical studies on the constituents of genus Selaginella led to the discovery of many compounds, including flavonoids and lignans. 18,19) As part of our continuous searching for novel antivial agents from medicinal plants, ethanol extract of the whole plants of S. uncinata was found to show significant inhibitory activities against RSV. The active extract led to the isolation and characterization of two new compounds, named uncinoside A (1) and uncinoside B (2) 20) together with three known compounds. Here we report the isolation and structure elucidation of the two new chromone glycosides and their antiviral activities against RSV, PIV 3, and influenza type A virus (Flu A). Results and DiscussionAn EtOH extract of the whole plant of S. uncinata was concentrated and partitioned with CHCl 3 and EtOAc. The CHCl 3 fraction was separated by silica gel column chromatography to yield two new chromone glycosides uncinoside A (1) and uncinoside B (2), and one known 5,7-dihydroxy-2,6-8-trimethylchromone (8-methyleugenitol) (3). The EtOAc fraction was separated by silica gel and polyamide column chromatography and prepared thin-layer chromatography (TLC) to afford two known biflavonoids: amentoflavone (4) 11,21) and hinokiflavone (5) 21,22) (Chart 1). The structure of the compound 3 was determined by the Xray diffraction analysis and spectral data. The structures of the other two known biflavonoids were...

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Section: Methodsmentioning

confidence: 99%

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Wei

et al. 2003

Chem. Pharm. Bull.

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“…22,23) Twofold serial dilutions of natural products were seeded into cells monolayers cultivated in 96-well culture plates, using the MNCC as the higher concentration. An infection control was made in the absence of natural products.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Evaluation of Secoiridoid Glucosides from the Fruits of Ligustrum lucidum as Antiviral Agents.

Deng

et al. 2001

Chem. Pharm. Bull.

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Oleuropein is a phenolic secoiridoid glucoside widespread in members of the family Oleaceae. It has been shown to possess a wide range of biological activities. It increased coronary blood flow and showed antiarrhythmic and spasmolytic effects.1,2) Oleuropein exhibited hypoglycemic effect and increased tolerance of orally administered glucose. It also showed anti-oxidative and anti-inflammatory properties. [3][4][5][6][7] Other reported effects of oleuropein included the potentiation of cellular and organismal protection through the macrophage-mediated response, 4) the inhibition of platelet aggregation and eicosanoid production, 8) reduction of the low density lipoproteins (LDL) level, 9) the potent and protective antioxidant action on LDL, 10) the inhibitory effects on cytochrome P450 and 17b-hydroxysteroid dehydrogenase activity, 11) potent cytotoxic effects on tumor cell lines including P-388, L-1210. 12) inhibitory effects on of lipoxygenase activity, 13) and antibacterial functions. 14-18) Recently, oleuropein was also claimed in a U.S. patent to have potent antiviral activities against herpes mononucleosis, hepatitis virus, rotovirus, bovine rhinovirus, canine parvovirus and feline leukaemia virus. 19) On the other hand, But and his research team recently reported the isolation of oleuropein (4), lucidumoside C (1) and other secoiridoid glucosides from the fruits of Ligustrum lucidum, another member of Oleaceae.3) They demonstrated strong anti-oxidative effects in these secoiridoid glucosides (Table 1). Oleuropein and lucidumoside C were found to have stronger anti-oxidative potency than trolox, their IC 50 being 25.0, 9.3, and 55.0 mM, respectively. Based on such anti-oxidative capabilities and also the antiviral effects claimed in the U.S. patent, the authors suggested that "it would be interesting to check if oleuropein's antiviral effect is related to its anti-oxidant property and also if lucidumoside C has stronger antiviral function". 3)This suggestion actually posed two important questions: 1) is anti-oxidative potency of a compound correlated with its antiviral potency? and 2) is anti-oxidation a mechanism against viruses?In the present paper, we present the in vitro evaluation of six secoiridoid glucosides from the fruits of Ligustrum lucidum against herpes simplex type 1 virus (HSV-1), influenza type A virus (Flu A), respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3). The relationship of antiviral activities of secoiridoid glucosides with their anti-oxidative effects were analysed. Results and DiscussionThe six secoiridoid glucosides isolated from L. lucidum did not show any antiviral activities against Flu A and HSV-1, except oleoside dimethylester (2) which showed a little antiviral activity against HSV-1 (Tables 2, 3).The in vitro antiviral activities of the six isolated compounds against RSV are summarized in Table 4. Oleuropein showed potent anti-RSV activity with an IC 50 value of 23.4 mg/ml and a large therapeutic index comparable to that of ribavirin, an approved d...

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“…The sap of C. lechleri has been used in South American countries like Ecuador and Peru for many years to treat diarrheas, including dysentery and cholera, and various lung, stomach, and other conditions (Ubillas et al, 1994;Jones, 2003;Risco et al, 2003;Rossi et al, 2003). Additional pharmacological studies have shown that crofelemer reduced fluid secretion in cell culture and mouse models (Gabriel et al, 1999).…”

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confidence: 99%

Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels

Namkung²,

2009

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Crofelemer, a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri, is in clinical trials for secretory diarrheas of various etiologies. We investigated the antisecretory mechanism of crofelemer by determining its effect on the major apical membrane transport and signaling processes involved in intestinal fluid transport. Using cell lines and measurement procedures to isolate the effects on individual membrane transport proteins, crofelemer at 50 M had little or no effect on the activity of epithelial Na ϩ or K ϩ channels or on cAMP or calcium signaling. Crofelemer inhibited the cystic fibrosis transmembrane regulator (CFTR) Cl Ϫ channel with maximum inhibition of ϳ60% and an IC 50 ϳ7 M. Crofelemer action at an extracellular site on CFTR produced voltage-independent block with stabilization of the channel closed state. Crofelemer did not affect the potency of glycine hydrazide or thiazolidinone CFTR inhibitors. Crofelemer action resisted washout, with Ͻ50% reversal of CFTR inhibition after 4 h. Crofelemer was also found to strongly inhibit the intestinal calcium-activated Cl Ϫ channel TMEM16A by a voltage-independent inhibition mechanism with maximum inhibition Ͼ90% and IC 50 ϳ6.5 M. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl Ϫ channels may account for its intestinal antisecretory activity.

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SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

Cited by 95 publications

References 38 publications

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

In Vitro Evaluation of Secoiridoid Glucosides from the Fruits of Ligustrum lucidum as Antiviral Agents.

Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels

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