Antiprotozoal and Antimycobacterial Activities of Pure Compounds from Aristolochia elegans Rhizomes.

We analyzed the antimycobacterial activity of the hexane extract of rhizomes from Aristolochia elegans. Some compounds of this extract were purified and tested against a group of drug-resistant Mycobacterium tuberculosis strains. We also evaluated their antiprotozoal activities. The hexane extract was active against M. tuberculosis H37Rv at a MIC = 100 µg mL(-1); the pure compounds eupomatenoid-1, fargesin, and (8R,8'R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50 µg mL(-1)), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50 µg mL(-1)). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC(50) < 0.624 µg mL(-1)); in contrast, fargesin and (8R,8'R,9R)-cubebin were moderately active (IC(50) < 275 µg mL(-1)). In this context, two compounds responsible for the antimycobacterial presented by A. elegans are fargesin and cubebin, although others may exert this activity also. In addition to the antimycobacterial activity, the hexane extract has important activity against E. histolytica and G. lamblia, and eupomatenoid-1 is one of the compounds responsible for the antiparasite activity.

Antimycobacterial neolignans isolated from Aristolochia taliscana.

Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 microg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.

Antimycobacterial neolignans isolated from Aristolochia taliscana

Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 ìg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.

Antimycobacterial triterpenoids from Lantana hispida (Verbenaceae).

As the Mycobacterium tuberculosis strains resistant to multiple drugs are increasing at an alarming rate, there is an urgent need for alternative anti-tuberculosis drugs. In a bioassay-guided search for antimycobacterial compounds obtained from higher plants, the study of the hexane extract from the aerial parts of Lantana hispida was performed and the biological activity of the plant products were tested against Mycobacterium tuberculosis H37Rv strain by microdilution alamar blue assay. Activity of the primary fractions led to the isolation of three pentacyclic triterpenoids with oleanane nucleous, together with beta-sitosterol. The molecular structures of the compounds were characterized as 3-acetoxy-22-(2'-methyl-2Z-butenyloxy)-12-oleanen-28-oic acid (1), 3-hydroxy-22 beta-(2'-methyl-2Z-butenoyloxy)-12-oleanen-28-oic acid (reduced lantadene A) (2) and oleanolic acid (3). MIC values for compounds 1 and 2 were 50 microg/ml, and for compound 3 the MIC=25 microg/ml.

Relaxant effect of xanthomicrol and 3alpha-angeloyloxy-2alpha-hydroxy-13,14z-dehydrocativic acid from Brickellia paniculata on rat uterus.

Brickellia paniculata has been used as spasmolytic in Mexican traditional medicine. Xanthomicrol and 3alpha-angeloyloxy-2alpha-hydroxy-13,14Z-dehydrocativic acid (AAHDD) are two of the main leaf components with antispasmodic activity. However, their mechanism of action remains unknown. An in vitro comparative study between xanthomicrol and AAHDD on rat uterus precontracted by either KCl (60 mM) or oxytocin (10 mIU/ml) was carried out to investigate the mechanism of action of these compounds on smooth muscle. Relaxant effect was measured as median inhibitory concentration (IC(50)) and maximal effect as maximal relaxant response (R(max)). Xanthomicrol was significantly more potent than AAHDD in inhibiting contractions induced by KCl 60 mM, whereas AAHDD was more potent than xanthomicrol in inhibiting contractions induced by oxytocin 10 mIU/ml. These results suggest that xanthomicrol induces a greater blocking effect on voltage-operated calcium channels than on receptor-operated gates.

Secondary metabolites from Chamaedora tepejilote (Palmae) are active against Mycobacterium tuberculosis.

Due to the emergence of multi-drug resistant Mycobacterium tuberculosis strains, there is an urgent need to search for new antimycobacterial drugs. The present work describes the bioactivity-guided fractionation of Chamaedora tepejilote hexane extract which led to the isolation and the characterization of squalene, farnesol, methylic ester of hexadecanoic acid, beta-sitosterol and ursolic acid. Activity against Mycobacterium tuberculosis H37Rv, determined by radiorespirometric Bactec assay, showed ursolic acid, squalene and farnesol to produce a M. tuberculosis growth inhibition of 99% at a concentration of 100 microg/mL.

Hypotensive effect of the hydroalcoholic extract from Jacaranda mimosaefolia leaves in rats.

Hypothermic and cardiovascular activities of the methanol extract of Jacaranda mimosaefolia leaves were tested. To evaluate the hypotensive properties, anesthetized rats were used and temperature, blood pressure, and cardiac frequency were recorded. In addition, the in vitro effect produced by the extract on induced contraction with norepinephrine (NE) in rat aorta rings was evaluated. The extract produced a significant hypothermic effect with a maximum at 2 h, an effect which was accompanied by hypotension and low cardiac frequency, physiological conditions that were again re-established to the following 2 h. In isolated aorta preparations norepinephrine antagonistic effect was not correlated with the presence of Ca2+, pD2 for NE was modified by the extract, an effect that could explain a blockade of the adrenergic receptors.

Activity against multidrug-resistant Mycobacterium tuberculosis in Mexican plants used to treat respiratory diseases.

The increase of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) demands the search for alternative antimycobacterial drugs. The aim of this study was to evaluate plants used in Mexican traditional medicine to treat respiratory diseases for activity against MDR-TB. A group of 22 plants was screened for activity against Mycobacterium tuberculosis H37Rv and Mycobacterium avium at concentrations from 50 to 200 microg/mL. The antimycobacterial effect was determined by a microcolorimetric assay with Alamar blue dye. None of the aqueous extracts had antimycobacterial activity. Hexane extracts from Artemisia ludoviciana, Chamaedora tepejilote, Lantana hispida, Juniperus communis and Malva parviflora, and methanol extracts from Artemisia ludoviciana and Juniperus communis inhibited the growth of Mycobacterium tuberculosis. Mycobacterium avium was inhibited by Juniperus communis hexane extract and by Malva parviflora methanol extract. The active extracts were tested against monoresistant variants of Mycobacterium tuberculosis H37Rv (isoniazid, rifampin, streptomycin and ethambutol resistant) and the hexane extract of Lantana hispida showed the best activity. Lantana hispida hexane extract was also active against a group of MDR-TB clinical isolates. In contrast, it did not inhibit the growth of non-tuberculous mycobacteria. The hexane extract of Lantana hispida was fractionated by column chromatography and one of its fractions (FVI) inhibited the growth of all the MDR-TB clinical isolates at concentrations up to 25 microg/mL. This study supports the fact that selecting plants by ethnobotanical criteria enhances the probability of finding species with activity against mycobacteria, and our results point to Lantana hispida as an important source of potential compounds against MDR-TB.

Antiprotozoal activity of the constituents of Rubus coriifolius.

Extraction of the aerial parts of Rubus coriifolius, a medicinal plant used by the Maya communities in Southern Mexico to treat bloody diarrhoea, resulted in the isolation of seven known compounds (-)-epicatechin, (+)-catechin, hyperin, nigaichigoside F1, beta-sitosterol 3-O-beta-d-glucopyranoside, gallic acid and ellagic acid. All compounds were tested for their antiprotozoal activity against Entamoeba histolytica and Giardia lambia. Epicatechin was the main responsible for the antiprotozoal activity of the extract against both protozoa, its activity was comparable to emetine, but no exceeded that of metronidazole.

Antiviral activity of Spirulina maxima against herpes simplex virus type 2.

Spirulina has been used in a variety of practical applications in biotechnology and medical sciences. This paper presents the antiviral activity found in a hot water extract (HWE) of a commercial preparation of Spirulina maxima, studied by a microplate inhibition assay, using several viruses. The HWE inhibited the infection for: herpes simplex virus type 2 (HSV-2), pseudorabies virus (PRV), human cytomegalovirus (HCMV), and HSV-1, and the 50% effective inhibition doses (ED(50)) were 0.069, 0.103, 0.142, and 0.333 mg/ml for each virus, respectively. For adenovirus the inhibition was less than 20%, and no inhibition was found for measles virus, subacute sclerosing panencephalitis virus (SSPE), vesicular stomatitis virus (VSV), poliovirus 1 and rotavirus SA-11, at concentrations of 2 mg/ml of the HWE. The highest antiviral activity was for HSV-2, with a selectivity index of 128. The antiviral activity was not due to a virucidal effect. Herpesvirus infection was inhibited at the initial events (adsorption and penetration) of the viral cycle. To initiate the isolation and identification of the compound that exhibits the antiviral activity of S. maxima, some extracts made by using several solvents with different polarity were evaluated by microplate inhibition assay using HSV-2. The highest antiviral activity was detected in the methanol-water 3:1, which suggests that the antiviral activity is probably due to highly polar compounds.

Effects of a labdane diterpene isolated from Brickellia paniculata on intracellular Ca2+ deposit of guinea-pig ileal longitudinal muscle.

The labdane diterpene 3alpha-angeloyloxy-2alpha-hydroxy-13,14Z-dehydrocativic acid (AAHDD) isolated from Brickellia paniculata leaves, produces relaxation of the guinea-pig ileum in vitro by Ca2+ antagonistic effects. In the longitudinal ileal muscle the compound inhibited the tonic contractions induced with 60 mM K+(IC50 = 15.52 +/- 1.93 microM) with half the potency than that of papaverine (IC50 = 6.70 +/- 1.31 MM). Phasic response to high K+ was also blocked by AAHDD, with the ratio IC50 phasic/IC50 to-nic = 7.11. In Ca2+-free, high K+ (60 mM) solution, AAHDD inhibited the contractions induced with 2 mM Ca2+ and pretreatment of the tissues with 10 uM cyclopiazonic acid or 30 pM ryanodine failed to influence the blockade of AAHDD on Ca2+ induced contractions. In muscles loaded with 45Ca, after washing the preparations with AAHDD in high K+ (60 mM) solution, determined 45Ca efflux was similar to that of the control without the diterpene. As the relaxant effect of AAHDD was not influenced by cyclopiazonic acid and by ryanodine, two agents which have been described as modulators of Ca2+ uptake and Ca2+ release from intracellular stores, the obtained results suggest that tension inhibitory effects produced by AAHDD do not involve the mobilization of Ca2+ at intracellular deposits.

Inhibitory effect of xanthomicrol and 3 alpha-angeloyloxy-2 alpha-hydroxy-13,14Z-dehydrocativic acid from Brickellia paniculata on the contractility of guinea-pig ileum.

Chemical fractionation of Brickellia paniculata methanolic extract by monitoring its inhibitory effect on K(+)-induced contraction in guinea-pig ileum in vitro led to the isolation of 5,4'-dihydroxy-6,7,8-trimethoxyflavone (xanthomicrol) and the labdane-diterpene 3 alpha-angeloyloxy-2 alpha-hydroxy-13,14 Z-dehydrocativic acid (AAHDD). Both compounds inhibited the tonic contraction the effect being highly potent when a mixture in a proportion of 3 : 1 (xanthomicrol/AAHDD) was assayed. The phasic component of the contractile response with K(+) was also reduced by the compounds. Xanthomicrol depressed the spasms induced with ACh, Hist, and BaCl(2) and its effect on Ca (2+) concentration-response curve showed a type of non-surmountable calcium blocking action; unlike the flavonoid, AAHDD produced a parallel rightward shift of the concentration-response curve to calcium, suggesting a competitive antagonism with an estimated pA(2) of 4.66. Obtained results support, in part, the popular use of B. paniculata as a spasmolytic remedy.

Quercetin glycosides in Psidium guajava L: leaves and determination of a spasmolytic principle

The traditional herbal remedy from Psidium guajava leaves had been medically proposed in mexico as effective treatment of acute diarrhea. A methanolic leaf extract was subjected to a bioassay-guided isolation of spasmolytic constituents. Six fractions were separated on a polyvinylpolypyrrolidine (PVPP) columm using a water methanol-gradient. The fraction containing flavonols inhibited peristalsis of guinea pig ileum in vitro. A trace of quercetin aglycone together with five glycosides was isolated from this active fraction and identified as quercentin 3-O-alpha-L-arabinoside (guajaravin); quercetin 3-O-ß-D-glucoside (isoquercetin); quercetin 3-O-ß-D-galactoside (hyperin); quercetin 3-O-ß-L-rhamnoside (quercitrin) and quercetin 3-O-gentobioside. Biological activity of each pure compound was studied in the same bioassay. Obtained results suggets that the spasmolytic activity of the Psidium guajava leaf remedy is mainly due to the aglycone quercetin, present in the leaf and in the extract mainly in the form of live flavonols, and whose effect is produced when these products are hydrolyzed by gastrointestinal fluid

Calcium-antagonist effect of quercetin and its relation with the spasmolytic properties of Psidium guajava L

The antidiarrheal properties of water ad methanolic extracts of Psidium guajava leaves have been demonstrated with anteriority and their spasmolytic effect was attributed to quercetin, a flavonoid conatined in this plant. The present paper reports the intestinal smooth muscle relaxation produced by quercetin on isolated guinea pig ileum previously contracted by a depolarizing KCl solution. Quercetin also inhibited intestinal contraction induced by different concentrations of calcium, shifting the contraction curve to the right showing a clear clacium-antagonistic efecct. Quercetin effect on ileal and aortic smooth muscles ar compared, the ileum being more sensitive to this flavonoid. The clacium antagonist property of quercetin is discussed and also its contribution to explain the spasmolytic effect of this popular herbal remedy