Antinociceptive and antiedema effects produced in rats by Brassica oleracea var. italica sprouts involving sulforaphane.

Natural products are recognized as potential analgesics since many of them are part of modern medicine to relieve pain without serious adverse effects. The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of an aqueous extract of Brassica oleracea var. italica sprouts (AEBS) and one of its main reported bioactive metabolites sulforaphane (SFN). Antinociceptive activity of the AEBS (30, 100, and 300 mg/kg, i.p. or 1000 and 2000 mg/kg, p.o.) and SFN (0.1 mg/kg, i.p.) was evaluated in the plantar test in rats to reinforce its analgesic-like activity at central level using the reference drug tramadol (TR, 50 mg/kg, i.p.). The anti-inflammatory-like response was determined in the carrageenan-induced oedema at the same dosages for comparison with ketorolac (KET, 20 mg/kg, i.p.) or indomethacin (INDO, 20 mg/kg, p.o.). A histological analysis of the swollen paw was included to complement the anti-inflammatory response. Additionally, acute toxicity observed in clinical analgesics as the most common adverse effects, such as sedation and/or gastric damage, was also explored. As a result, central and peripheral action of the AEBS was confirmed using enteral and parenteral administration, in which significant reduction of the nociceptive and inflammatory responses resembled the effects of TR, KET, or INDO, respectively, involving the presence of SFN. No adverse or toxic effects were observed in the presence of the AEBS or SFN. In conclusion, this study supports that Brassica oleracea var. italica sprouts are a potential source of antinociceptive natural products such as SFN for therapy of pain alone and associated to an inflammation condition.

Antinociceptive effect of Mansoa alliacea polar extracts involves opioid receptors and nitric oxide in experimental nociception in mice.

To evaluate the antinociceptive effect and the possible mechanism of action of two polar extracts of Mansoa alliacea, a medicinal plant used in Perú, Brazil, and Mexico to treat rheumatic pain, we used the formalin and hot-plate tests in mice. We found that ethanolic (MA-EtOH) and aqueous (MA-AQ) extracts of M. alliacea induced antinociceptive effects in both nociceptive tests. The antinociceptive efficacy of the highest dosage (300 mg/kg) of both extracts were also compared by using intraperitoneal and oral administration in the formalin test. Results showed that intraperitoneal injection of the two extracts produced better antinociceptive effects than that obtained by their oral administration. The mechanism of action involved in their antinociceptive activity was determined in the formalin test. Results showed that the presence of A784168 (TRPV1 antagonist) did not alter the antinociceptive effect induced by any of the M. alliacea extracts, whereas naltrexone (opioid antagonist) partially prevented the antinociceptive effect only of MA-EtOH in both phases of the formalin test. Furthermore, the effects of the extracts were diminished by L-NAME (inhibitor of nitric oxide synthase), but not by ODQ (inhibitor of the soluble guanylyl cyclase) or glibenclamide (blocker of K+ATP channels) in the neurogenic phase. However, the effect of MA-AQ was diminished by all the inhibitors in the inflammatory phase. These results support the use of M. alliacea as a potential natural product with efficacy for pain relief depending on the form of preparation and the route of administration by involving opioid receptors and the production of nitric oxide.

Synergistic Herb-Herb Interaction of the Antinociceptive and Anti-Inflammatory Effects of Syzygium aromaticum and Rosmarinus officinalis Combination.

The use of alternative medicine to treat pain has been increased, and the combination of several medicinal plants for its relief is a common practice in traditional medicine. The present study is aimed at determining whether a combination of Syzygium aromaticum (S. aromaticum) and Rosmarinus officinalis L. (R. officinalis) potentiates their antinociceptive and anti-inflammatory effects. These effects were explored using the formalin and carrageenan assays in rats, respectively. Animals received local pretreatment with S. aromaticum oil or R. officinalis ethanolic extract (0.1-100 µg/paw) alone or combined in a 1 : 1 rate. Concentration-response curves were built to compare pharmacological responses after an individual administration of S. aromaticum, R. officinalis, or their combination. The pharmacological interaction was investigated by an isobolographic study using the EC50 of each component in a fixed 1 : 1 ratio. S. aromaticum and R. officinalis administered alone showed significant and concentration-dependent antinociceptive and anti-inflammatory effects, but R. officinalis was more potent than S. aromaticum in both the antinociceptive and anti-inflammatory effects (EC50 = 7.96 ± 0.6 µg/paw vs. EC50 = 41.6 ± 1.7 µg/paw; EC50 = 1.97 ± 0.3 µg/paw vs. EC50 = 26.9 ± 2.5 µg/paw, respectively). The isobolographic analysis of the combination of these species in a 1 : 1 ratio showed a synergistic interaction between S. aromaticum and R. officinalis since Z mix (experimental value) was lower than Z add (theoretical value) for both the antinociceptive effect (Z mix = 0.45 ± 0.1 < Z add = 24.8 ± 1.3) and the anti-inflammatory effect (Z mix = 5.2 ± 0.6 < Z add = 14.4 ± 2.2), suggesting a potentiation for both pharmacological effects. These results prove evidence of the efficacy of mixture herb-herb used in folk medicine for pain therapy. It also emphasizes the requirement of pharmacological studies to explore the efficacy and safety of herb interactions.

Quercetin decreases the antinociceptive effect of diclofenac in an arthritic gout-pain model in rats.

OBJECTIVE: To analyse the antinociceptive interaction between quercetin (QUER) and diclofenac (DIC) in experimental arthritic gout-pain. METHODS: The antinociceptive effect of DIC and QUER alone and in combination were evaluated using an arthritic gout-pain model. Pain was induced through intra-articular administration of uric acid in the rats and the treatments were administered 2 h later. Additionally, the cyclooxygenase (COX) activity was determined in rats treated with DIC, QUER and their combination. KEY FINDINGS: DIC induced a maximal effect of 69.7 ± 2.7% with 3.1 mg/kg; whereas QUER only produced 17.6 ± 2.6% with the maximal dose (316 mg/kg). Ten of twelve DIC + QUER combinations showed a lesser antinociceptive effect than DIC alone did (P < 0.05). Moreover, DIC reduced total-COX (70.4 ± 1.3 versus 52.4 ± 1.8 and 77.4 ± 9.0 versus 56.1 ± 1.3, P < 0.05) and COX-2 (60.1 ± 1.0 versus 42.4 ± 1.8 and 58.1 ± 2.4 versus 48.7 ± 1.3, P < 0.05) activity after 1 and 3 h, respectively. Nevertheless, only the COX-2 activity induced by DIC was prevented in the presence of QUER (63.2 ± 3.0 versus 60.1 ± 1.0 and 56.6 ± 1.3 versus 58.1 ± 2.4 at 1 and 3 h, respectively). CONCLUSIONS: All these data demonstrated that the simultaneous administration of QUER + DIC produces an unfavorable interaction on the antinociceptive effect of DIC. Therefore, this combination might not be recommendable to relieve arthritic gout-pain.

Study of Antispasmodic and Antidiarrheal Activities of Tagetes lucida (Mexican Tarragon) in Experimental Models and Its Mechanism of Action.

Tagetes lucida has been used in traditional medicine as a remedy to alleviate several gastrointestinal disorders that provoke stomachaches, abdominal cramps, and diarrhea. However, there is not enough scientific evidence that supports these effects. Therefore, the purpose of this study was to evaluate antispasmodic and antidiarrheal activities of aqueous extract of T. lucida (AqExt-TL) as well as its mechanism of action in experimental models. Antispasmodic activity and the mechanism of action of AqExt-TL were assessed on segments of the guinea pig ileum precontracted with KCl, acetylcholine (ACh), or electrical field stimulation (EFS). Furthermore, the antispasmodic effect of two coumarins (umbelliferone and herniarin) previously identified in this species was evaluated. Antidiarrheal activity of AqExt-TL was determined using the charcoal meal test in mice. AqExt-TL showed antispasmodic activity in segments of the guinea pig ileum precontracted with KCl (83.7 ± 1.9%) and ACh (77.2 ± 5.3%) at the maximal concentration; however, practically, it did not alter the contractions induced by EFS (10.1 ± 2.2%). Antispasmodic activity of AqExt-TL was not significantly altered by hexamethonium (a ganglionic blocker) or L-NAME (an inhibitor of nitric oxide synthase). However, this extract decreased the maximal contractile response to calcium (82.7 ± 8.5%), serotonin (68.1 ± 8.5%), and histamine (63.9 ± 5.9%) in their concentration-response curves. Umbelliferone and herniarin also induced an antispasmodic effect on tissues precontracted with KCl. In addition, low doses of AqExt-TL reduced to 50% the distance traveled by charcoal meal in the gastrointestinal transit model in mice as loperamide, an antidiarrheal agent, did. These results provided evidence of the antispasmodic and antidiarrheal activity of T. lucida, which supports its use in the folk medicine in relieving symptoms in some gastrointestinal disorders. In the antispasmodic effect, the blockade of histaminergic and serotoninergic pathway as well as the calcium channels seems to be involved. Finally, umbelliferone and herniarin could be partially responsible for the antispasmodic activity induced by T. lucida.

Preclinical evidence of the anxiolytic and sedative-like activities of Tagetes erecta L. reinforces its ethnobotanical approach.

Morelos State is one of the regions of Mexico where several plant species are used in traditional medicine. Species from Tagetes genus (Asteraceae) are reported as useful in infusion to treat stomachache and intestinal diseases, but also as tranquilizers. In this study, medicinal uses of T. erecta including its depressant effect on the central nervous system (CNS) were explored by interviewing healers and merchants of local markets of Morelos State, and by investigation of the phytochemical and pharmacological tranquilizing properties. Specific anxiolytic and/or sedative-like responses of different doses of T. erecta (10, 30 and 100 or 300mg/kg, i.p.) were investigated using experimental models in mice such as: open-field, exploration cylinder, hole-board, and the barbituric-induced hypnosis potentiation. The possible anxiolytic mechanism of action was assessed in the presence of WAY100635 (0.32mg/kg, i.p.) and flumazenil (10mg/kg, i.p.), antagonists of 5-HT1A and GABA/BDZs receptors, respectively. Individual flavonoids reported in this species were also evaluated in these experimental models. As a result of this study, healers and merchants from ten local regions of Morelos State recommended T. erecta flowers as an infusion or as a tincture for several culture-bound syndromes associated with CNS, among others. Anxiolytic and sedative-like activities of the T. erecta aqueous and organic polar extracts were corroborated in these models associated to a participation of rutin, kaempferol, quercetin, kaempferitrin, and ß-sitosterol constituents; where 5-HT1A, but not BDZs, receptors were involved as anxiolytic mechanism of action. These data support the anxiolytic and sedative-like properties of T. erecta in traditional medicine by involving mainly serotonergic neurotransmission because of the presence in part of flavonoids and the terpenoid ß-sitosterol.

Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia.