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Nasturtium officinale (watercress) is a perennial dicotyledonous plant, rich in vitamins, minerals and chemical compounds. The leaves of this plant, which contain glucosinolate, are used for its diuretic and hypoglycemic effects. The purpose of the study was to investigate the safety of the standardized extract of Nasturtium officinale (SENO) with phenylethyl glucosinolate 5.0 mg/ml -1 , using acute and sub-acute oral dosage in Wistar rats. High-Performance Liquid Chromatography (HPLC) analyzed the chemical composition, from aerial parts of watercress. In the acute toxicity study, dose estimated was LD 50 in the range of 2000-5000 mg/kg, signs of mortality and toxicity on female rats were observed for 14 days, after single doses of 2000 and 5000 mg/kg. In the sub-acute study, female and male rats, age 10 weeks, were supplemented at doses of 250, 500 and 1000 mg/kg for 28 days. On the 29th day, rats were fasted, anesthetized, euthanized, then their blood used for hematological and biochemical evaluation. No significant changes in general behavior were reported regarding the acute study, while the sub-acute study demonstrated no toxicity of the hematopoietic and biochemical systems. The results showed that SENO at dosage up to 5000 mg/kg in acute study was safe, and NOAEL (no-observed-adverse-effect levels) in the sub-acute, was up to 1000 mg/kg., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: In Brazil, Erythrina velutina (Fabaceae) is widely used as a tranquilizer and/or sedative, and its extract exerts an anxiolytic-like effect profile in animal models, although these results may be caused by its sedative or amnesic effects. AIMS, MATERIALS AND METHODS: Thus, this study evaluated the effect of acute and chronic (23-26 days) administrations of the hydroalcoholic extract of the stem bark of Erythrina velutina (orally) in mice submitted to the following tests: elevated plus-maze, forced swim, spontaneous locomotor activity, and habituation to active chamber. Chlordiazepoxide and imipramine were used as standard drugs., Results: In the elevated plus-maze test, chronic, but not acute, Erythrina velutina (100mg/kg) administration increased the percentage of open arm entries, an effect also seen in both acute and chronic treatments with chlordiazepoxide (7.5mg/kg). In the forced swim test, only imipramine (25mg/kg) decreased immobility time. Impairment of habituation was seen only with acute imipramine administration and with the lowest doses of Erythrina velutina extract tested in acute (10mg/kg) and chronic (50mg/kg) administrations., Conclusions: These results suggest that chronic administration of the hydroalcoholic extract of the stem bark of Erythrina velutina exerts an anxiolytic-like effect on mice, and it could serve as a new approach for the treatment anxiety, although it may have an amnesic effect at low doses.

The anti-hyperalgesic action, antinociception, and also the possible mechanisms involved in the action of gallic acid ethyl ester (GAEE) isolated from the aerial part of Phyllanthus urinaria, have been investigated in different models of chemical, mechanical and thermal nociception in mice and rats. GAEE given by intraperitoneal (i.p.), oral (p.o.), intrathecal (i.t.) or by intracerebroventricular (i.c.v.) routes produced dose-related antinociception when assessed against chemical nociception in mice. GAEE significantly inhibited the hyperalgesia induced by bradykinin or substance P in rat paw, but did not affect the hyperalgesia caused by carrageenan or prostaglandin E2. Furthermore, GAEE, in contrast to morphine, was completely ineffective in the hot-plate test in mice. The antinociception produced by GAEE (i.p.) in the formalin test was significantly reversed by i.c.v. treatment of animals with pertussis toxin and by i.t. administration of K+ channel blockers such as apamin, charybdotoxin or glibenclamide, but not by tetraethylammonium. In contrast, GAEE (i.p.) antinociception was unaffected by i.p. treatment of animals with naloxone or by nitric oxide precursor, L-arginine, and this action was not secondary to its anti-inflammatory effect, nor was it associated with non-specific effects such as muscle relaxation or sedation. Thus, GAEE produces dose-dependent and pronounced systemic, spinal and supraspinal antinociception in mice, probably via activation of K + channels and by a Gi/o pertussis toxin-sensitive mechanism.

The antinociceptive action of the alkaloid cis-8, 10-di-n-propyllobelidiol hydrochloride dehydrate (DPHD), isolated from Siphocampylus verticillatus, given i.p., p.o., i.t., or i.c.v., was assessed in chemical and thermal models of nociception in mice, such as acetic acid-induced abdominal constriction, formalin- and capsaicin-induced licking, and hot-plate and tail-flick tests. DPHD given by i.p., p.o., i.t., or i.c.v. elicited significant and dose-related antinociception. At the ID50 level, DPHD was about 2- to 39-fold more potent than aspirin and dipyrone, but it was about 14- to 119-fold less potent than morphine. Its analgesic action was reversed by treatment of animals with p-chlorophenylalanine, naloxone, cyprodime, naltrindole, nor-binaltrorphimine, L-arginine, or pertussis toxin. Its action was also modulated by adrenal-gland hormones but was not affected by gamma-aminobutyric acid type A or type B antagonist, bicuculine, or phaclofen, nor was it affected by glibenclamide. DPHD, given daily for up to 7 days, did not develop tolerance to itself nor did it induce cross-tolerance to morphine. However, animals rendered tolerant to morphine presented cross-tolerance to DPHD. The antinociception of DPHD was not secondary to its anti-inflammatory effect, nor was it associated with nonspecific effects such as muscle relaxation or sedation. DPHD, in contrast to morphine, did not decrease charcoal meal transit in mice, nor did it inhibit electrical field stimulation of the guinea pig ileum or mouse vas deferens in vitro. Thus, DPHD produces dose-dependent and pronounced systemic, spinal, and supraspinal antinociception in mice, including against the neurogenic nociception induced by formalin and capsaicin. Its antinociceptive effect involves multiple mechanisms of action, namely interaction with mu, delta, or kappa opioid systems, L-arginine-nitric oxide and serotonin pathways, activation of Gi protein sensitive to pertussis toxin, and modulation by endogenous glucocorticoids.

The antinociception caused by the hydroalcoholic extract of Siphocampylus verticillatus (Campanulaceae) has been investigated in chemical and thermal models of nociception in mice. We have also assessed some of the mechanisms underlying the antinociceptive effect of the extract. The hydroalcoholic extract of S. verticillatus (60-1000 mg kg-1, i.p. or p.o.) produced dose-related, significant and long-lasting (6 to 8 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 204 and approximately 1000 mg kg-1, respectively. In the formalin test, the extract (100-1000 mg kg-1), given either intraperitoneally or orally, resulted in graded inhibition of both phases of formalin-induced pain, being about 2- to 4-fold more potent in attenuating the second phase of the pain. The calculated mean ID50 (mg kg-1) values for the earlier and the later phases were: 491 and 186 and 640 and 441, respectively. In addition, the extract (60-1000 mg kg-1, i.p. or p.o.) caused marked and dose-related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 420 and 485 mg kg-1, respectively. The hydroalcoholic extract, at the same doses, did not significantly affect the performance of animals in the rota-rod test, nor did it have any analgesic effect in the tail-flick or hot-plate tests. The treatment of animals with naloxone (5 mg kg-1, s.c.) significantly reversed the analgesic effect of both morphine (5 mg kg-1, s.c.) and the extract (300 mg kg-1, i.p.) when assessed against acetic acid-induced abdominal constrictions. The treatment of animals with L-arginine (600 mg kg-1, i.p.) significantly attenuated the antinociceptive effects of NG-nitro-L-arginine (L-NOARG) (75 mg kg-1, i.p.), of the hydroalcoholic extract (600 mg kg-1, i.p.) or of morphine (5 mg kg-1, s.c.), when analysed against the formalin test. In addition, adrenalectomy of animals 7 days before the tests significantly reversed the antinociception caused by the hydroalcoholic extract (300 mg kg-1, i.p.) in the formalin-induced pain. These data show that the hydroalcoholic extract of S. verticillatus has significant and long-lasting oral antinociception when assessed against both neurogenic and inflammatory models of nociception in mice. The precise mechanism responsible for the analgesic effect of the extract still remains unclear, but a great part of this effect seems to be partly related to an opioid-like action and involvement of the L-arginine-nitric oxide pathway. Finally, the antinociception caused by the hydroalcoholic extract of S. verticillatus is modulated by adrenal hormones.

The aim of this study was to isolate and characterize the constituents of the hydroalcoholic extract (HE) of the leaves, stems and roots from P. caroliniensis, and also to evaluate the preliminary antinociceptive action of the HE and purified compounds in mice. Phytosterols, quercetin, gallic acid ethyl ester and geraniin were identified in P. caroliniensis on the basis of 1H and 13C NMR spectral data and by mixed co-TLC and co-HPLC injection with authentic samples. The HE of P. caroliniensis (10-100 mg kg-1, i.p.) inhibited, in a dose-related manner, acetic acid-induced abdominal constrictions in mice, with a mean ID50 value of 23.7 mg kg-1. In the formalin test, the HE given intraperitoneally (1-30 mg kg-1) or orally (25-600 mg kg-1) caused graded inhibitions of both the neurogenic (first phase) and the inflammatory response (late phase) of formalin-induced licking. The HE was 54-fold more effective in inhibiting the late phase than it was in inhibiting the first phase of the formalin test, with mean ID50 values of 3.6 and 196.4 mg kg-1, respectively. The HE failed, however, to affect the oedematogenic response associated with the late phase of formalin-induced pain. In addition, the reference drug, aspirin, given intraperitoneally (1-100 mg kg-1) or orally (100-600 mg kg-1), caused significant inhibition of the late but not the first phase of the formalin test. Pharmacological analysis also revealed that quercetin, gallic acid ethyl ester and a semi-purified fraction of flavonoids (1-100 mg kg-1, i.p.) exhibited graded and significant antinociception against acetic acid-induced abdominal constriction. The mean ID50 values (mg kg-1) for these effects were: 18.8, 34.7 and 5.3, respectively. It is concluded that quercetin, gallic acid ethyl ester and some as yet unidentified flavonoids might account for the antinociceptive action reported for the HE of P. caroliniensis.

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.