ABSTRACT The present study assessed the possible antinociceptive action of the hydroalcoholic ext... more ABSTRACT The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
The present study describes the occurrence of two ellagitannins in the ethanolic extract of the l... more The present study describes the occurrence of two ellagitannins in the ethanolic extract of the leaves and stems of Phyllanthus sellowianus (Euphorbiaceae). Their preliminary antinociceptive properties were also evaluated. The two ellagitannins were identified on the basis of 1H- and 13C-NMR spectra data and by mixed co-TLC and co-HPLC injection with an authentic sample of furosin and geraniin. Preliminary pharmacological analysis revealed that both furosin and geraniin (3 to 30 mg/kg, i.p.), given 30 min before testing, exhibited significant and dose-related antinociceptive properties against acetic acid-induced abdominal constrictions in mice. Geraniin and furosin were about six- to seven-fold more potent at the ID50 level (micromol/kg) as analgesics than aspirin and acetaminophen, respectively, although they were less efficacious when compared with the standard drugs. These data extend our previous studies and indicate that the two ellagitannins isolated from P.sellowianus, identified as furosin and geraniin are, at least in part, responsible for the antinociceptive actions reported previously for the hydroalcoholic extract of P.sellowianus and other plants belonging to the genus Phyllanthus.
A wide variety of noxious stimuli are known to induce a sensation of pain evoked in a remote regi... more A wide variety of noxious stimuli are known to induce a sensation of pain evoked in a remote region of the body. Here, we show that chalcones can inhibit the pain provoked by the administration of an intraperitoneal acetic acid (AA). This study investigates the effects of 17 synthetic chalcones in the writhing test, a visceral pain model in mice. The majority of these compounds proved more active than some analgesic drugs, such as aspirin and acetaminophen, two reference drugs used here for comparison. Four chalcones, 9, 10, 16, and 17, were selected for more detailed studies, since they exhibited significant antinociceptive activities and chemical structures of interest. They caused dose-related inhibitions, proving about 15-, 10-, 9-, and 8-fold more active than the standard drugs. When administrated orally, only chalcone 9 proved to be effective. These chalcones might be further used as a model to obtain new and more potent analgesic drugs.
Recently, we reported small-molecule chalcones as a novel class of HIV-1 integrase (IN) inhibitor... more Recently, we reported small-molecule chalcones as a novel class of HIV-1 integrase (IN) inhibitors. The most potent compound showed an IC50 value of 2 microM for both IN-mediated 3'-processing and strand transfer reactions. To further utilize the chalcones, we developed pharmacophore models to identify chemical signatures important for biological activity. The derived models were validated with a collection of published inhibitors, and then were applied to screen a subset of our small molecule database. We tested 71 compounds in an in vitro assay specific for IN enzymatic activity. Forty-four compounds showed inhibitory potency<100 microM, and four of them exhibited IC50 values<10 microM. One compound, 62, with an IC50 value of 0.6 microM, displayed better potency than the original chalcone 2 against the strand transfer process. This study demonstrates the systematic use of pharmacophore technologies to discover novel structurally diverse inhibitors based on lead molecules that would exhibit poor characteristics in vivo. The identified compounds have the potential to exhibit favorable pharmacokinetic and pharmacodynamic profiles.
... Vilma EF Heinzen and Rosendo A. Yunes Corresponding Author Contact Information. Departmento d... more ... Vilma EF Heinzen and Rosendo A. Yunes Corresponding Author Contact Information. Departmento de Química, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil. Received 21 March 1995; revised 13 June 1995; accepted 22 June 1995. ...
ABSTRACT The present study assessed the possible antinociceptive action of the hydroalcoholic ext... more ABSTRACT The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
The present study describes the occurrence of two ellagitannins in the ethanolic extract of the l... more The present study describes the occurrence of two ellagitannins in the ethanolic extract of the leaves and stems of Phyllanthus sellowianus (Euphorbiaceae). Their preliminary antinociceptive properties were also evaluated. The two ellagitannins were identified on the basis of 1H- and 13C-NMR spectra data and by mixed co-TLC and co-HPLC injection with an authentic sample of furosin and geraniin. Preliminary pharmacological analysis revealed that both furosin and geraniin (3 to 30 mg/kg, i.p.), given 30 min before testing, exhibited significant and dose-related antinociceptive properties against acetic acid-induced abdominal constrictions in mice. Geraniin and furosin were about six- to seven-fold more potent at the ID50 level (micromol/kg) as analgesics than aspirin and acetaminophen, respectively, although they were less efficacious when compared with the standard drugs. These data extend our previous studies and indicate that the two ellagitannins isolated from P.sellowianus, identified as furosin and geraniin are, at least in part, responsible for the antinociceptive actions reported previously for the hydroalcoholic extract of P.sellowianus and other plants belonging to the genus Phyllanthus.
A wide variety of noxious stimuli are known to induce a sensation of pain evoked in a remote regi... more A wide variety of noxious stimuli are known to induce a sensation of pain evoked in a remote region of the body. Here, we show that chalcones can inhibit the pain provoked by the administration of an intraperitoneal acetic acid (AA). This study investigates the effects of 17 synthetic chalcones in the writhing test, a visceral pain model in mice. The majority of these compounds proved more active than some analgesic drugs, such as aspirin and acetaminophen, two reference drugs used here for comparison. Four chalcones, 9, 10, 16, and 17, were selected for more detailed studies, since they exhibited significant antinociceptive activities and chemical structures of interest. They caused dose-related inhibitions, proving about 15-, 10-, 9-, and 8-fold more active than the standard drugs. When administrated orally, only chalcone 9 proved to be effective. These chalcones might be further used as a model to obtain new and more potent analgesic drugs.
Recently, we reported small-molecule chalcones as a novel class of HIV-1 integrase (IN) inhibitor... more Recently, we reported small-molecule chalcones as a novel class of HIV-1 integrase (IN) inhibitors. The most potent compound showed an IC50 value of 2 microM for both IN-mediated 3'-processing and strand transfer reactions. To further utilize the chalcones, we developed pharmacophore models to identify chemical signatures important for biological activity. The derived models were validated with a collection of published inhibitors, and then were applied to screen a subset of our small molecule database. We tested 71 compounds in an in vitro assay specific for IN enzymatic activity. Forty-four compounds showed inhibitory potency<100 microM, and four of them exhibited IC50 values<10 microM. One compound, 62, with an IC50 value of 0.6 microM, displayed better potency than the original chalcone 2 against the strand transfer process. This study demonstrates the systematic use of pharmacophore technologies to discover novel structurally diverse inhibitors based on lead molecules that would exhibit poor characteristics in vivo. The identified compounds have the potential to exhibit favorable pharmacokinetic and pharmacodynamic profiles.
... Vilma EF Heinzen and Rosendo A. Yunes Corresponding Author Contact Information. Departmento d... more ... Vilma EF Heinzen and Rosendo A. Yunes Corresponding Author Contact Information. Departmento de Química, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil. Received 21 March 1995; revised 13 June 1995; accepted 22 June 1995. ...
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