Quercetin: Further Investigation of its Antinociceptive Properties and Mechanisms of Action

Arnaldo Willain Filho,Valdir Cechinel Filho,Leonardo Olinger,Marcia Maria de Souza 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6

The antinociceptive action of quercetin, a common bioactive flavonoid present in many medicinal plants, was assessed in different models of chemical and thermal nociception in mice. Quercetin (10-60 mg/kg, i.p. or 100-500 mg/kg, p.o.) dose-dependently inhibited nociceptive behavior in the acetic acid-induced pain test. Moreover, quercetin (10-60 mg/kg, i.p.) inhibited both phases of formalin-induced pain, with ID50 values of 374.1 (68.0-402.0) mmol/kg and 103.0 (45.0-201.0) mmol/kg, for the neurogenic and inflammatory phases, respectively. Quercetin (10-60 mg/kg) also inhibited the nociception induced by glutamate and capsaicin by 68.2% and 75.5%, respectively. Its analgesic action was significantly reversed by p-chlorophenylalanine methyl ester, katanserin, methysergide, a GABAA antagonist (bicuculline), or a GABAB antagonists (baclofen). Its action was also modulated by tachykinins, but was not affected by adrenal-gland hormones. Furthermore, the antinociceptive effects did not result from muscle-relaxant or sedative action. Together, these results indicate that quercetin produces dose-related anti-nociception in several models of chemical pain, through mechanisms that involve interaction with L-arginine-nitric oxide, serotonin, and GABAergic systems. These results confirm and extend other investigations on the analgesic effect of quercetin and its mechanisms of action.

Quercetin: Further Investigation of its Antinociceptive Properties and Mechanisms of Action

Filho, Arnaldo Willain,Filho, Valdir Cechinel,Olinger, Leonardo,Souza, Marcia Maria de 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6

The antinociceptive action of quercetin, a common bioactive flavonoid present in many medicinal plants, was assessed in different models of chemical and thermal nociception in mice. Quercetin (10-60 mg/kg, i.p. or 100-500 mg/kg, p.o.) dose-dependently inhibited nociceptive behavior in the acetic acid-induced pain test. Moreover, quercetin (10-60 mg/kg, i.p.) inhibited both phases of formalin-induced pain, with $ID_{50}$ values of 374.1 (68.0-402.0) mmol/kg and 103.0 (45.0-201.0) mmol/kg, for the neurogenic and inflammatory phases, respectively. Quercetin (10-60 mg/kg) also inhibited the nociception induced by glutamate and capsaicin by 68.2% and 75.5%, respectively. Its analgesic action was significantly reversed by p-chlorophenylalanine methyl ester, katanserin, methysergide, a $GABA_A$ antagonist (bicuculline), or a $GABA_B$ antagonists (baclofen). Its action was also modulated by tachykinins, but was not affected by adrenal-gland hormones. Furthermore, the antinociceptive effects did not result from muscle-relaxant or sedative action. Together, these results indicate that quercetin produces dose-related anti-nociception in several models of chemical pain, through mechanisms that involve interaction with L-arginine-nitric oxide, serotonin, and GABAergic systems. These results confirm and extend other investigations on the analgesic effect of quercetin and its mechanisms of action.

Antiulcerogenic Activity of Fractions and 3,15-Dioxo-21α-hydroxyFriedelane Isolated from Maytenus robusta (Celastraceae)

Sergio Faloni de Andrade,Vânia Floriani Noldin,Franco Delle Monache,Valdir Cechinel Filho,Eros Comunello,Rivaldo Niero 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.1

The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3,15-dioxo-21α-hydroxy friedelane. The triterpene was evaluated in the HCl/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3,15-dioxo-21α-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant reduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.

Topical and Systemic Anti-Inflammatory Effects of Echinodorus macrophyllus (Kunth) Micheli (Alismataceae)

Ellen Tanus-Rangel,Scheila R. Santos,Lousa˜ Lopes,Vaˆnia Noldin,Franco D. Monache,Valdir Cechinel-Filho,Domingos T.O. Martins 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.5

Echinodorus macrophyllus leaf has been used in Brazilian folk medicine to treat inflammatory conditions and kidney dysfunctions. The present study evaluated the effects of leaf ethanolic extract from E. macrophyllus (EEEm) in acute and subchronic models of inflammation. The EEEm was found to cause significant and potent inhibition of carrageenan- and dextran-induced paw edema in rats and marked decreases in the exudate volume and leukocyte migration in rats with carrageenan-induced pleurisy, the vascular permeability increase induced by intraperitoneal acetic acid, and the croton oil-induced topical ear edema in mice. On the other hand, the EEEm was not active in the test model of cotton pellet-induced granuloma in rats. Phytochemical analysis with E. macrophyllus leaves revealed the presence of triterpenoids, steroids, flavones, flavonols, and xanthones. Two flavonoids were isolated from the ethyl acetate fraction and identified as isovitexin and vitexin. Our results support the traditional use of E. macrophyllus leaves in the treatment of acute inflammatory conditions

Antiulcerogenic Activity of Fractions and 3,15-Dioxo-21${\alpha}$-hydroxy Friedelane Isolated from Maytenus robusta (Celastraceae)

Deandrade, Sergio Faloni,Comunello, Eros,Noldin, Vania Floriani,Monache, Franco Delle,Filho, Valdir Cechinel,Niero, Rivaldo 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.1

The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3, 15-dioxo-21${\alpha}$-hydroxy friedelane. The triterpene was evaluated in the HCI/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3, 15-dioxo-21${\alpha}$-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant redduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.

Chemical Composition and Antinociceptive Potential of Campomanesia reitziana Fruits

Luciane Angela Nottar Nesello,Adriana Campos,Theodoro Wagner,Arturo San Feliciano,Fatima de Campos Buzzi,Valdir Cechinel Filho 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.5

The methanolic extract from Campomanesia reitziana fruits and the main active principle, identified as 4',6'-dihydroxy-3',5'-dimethyl-2'-methoxy chalcone or dimethyl cardamonin (1), exhibited pronounced antinociceptive effects against two models of pain in mice. Compound 1 caused dose-dependent inhibition of abdominal constrictions, with a calculated ID50 value of 8.1 (6.5–10.1) μmol/kg (i.p.), being about 16-fold more potent than two reference analgesic drugs. Methanolic extract and 1 were also effective against the formalin model, inhibiting both phases of pain, causing reductions of 39.9% and 26.8% (extract, 10 mg/kg) and 52.9% and 57.6% (compound 1, 5 mg/kg) for the first and second phases, respectively.

Phytochemical Analysis and Antinociceptive Properties of the Seeds of Garcinia achachairu

Marlova Manhabosco Dal Molin,Rivaldo Niero,Suellen Silva,Douglas Rafael Alves,Nara Lins Meira Quintão,Franco Delle Monache,Valdir Cechinel Filho 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.4

In a search for new and effective analgesic substances from the Brazilian biodiversity, the present study evaluates the chemical composition and antinociceptive potential of the methanol extract and a pure compound obtained from the seeds of Garcinia achachairu Rusby (Clusiaceae). The methanolic seed extract was directly subjected to purification by column chromatography and the purification was monitored by thin-layer chromatography. The main isolated compound was identified as Guttiferone A by comparison of conventional spectroscopic data (IR, NMR-1H and 13C) to the literature data which was isolated for the first time from this plant. When evaluated in the acetic acid-induced nociception model in mice, the methanolic seed extract had an ID50 (Inhibitory dose) of 13.1 (11.23-14.91) mg/kg and a maximal inhibition of 72 ± 4%. In the same model, Guttiferone A had an ID50 of 4.54 (3.29-6.24) mg/kg and a maximal inhibition of 73 ± 5%. The methanolic seed extract and Guttiferone A were also active in pain models induced by formalin, capsaicin, glutamate and carrageenan. These data suggest that the antinociceptive effect of Guttiferone A partly depends on its interference with the synthesis or activity of the cytokine TNF-α, the keratinocyte-derived chemokine KC, and/or PGE2. These data support, at least in part, the use of G. achachairu in folk medicine and suggest that this plant is an important source of compounds with a suitable profile for development as new and effective medicinal agents to treat pain processes.