Broccoli sprouts in analgesia : preclinical in vivo studies

©. This manuscript version is made available under the CC-BY-NC-ND license http://creativecommons.org/licenses/cc-by-nc-nd /4.0/ This document is the Acepted version of a Published Work that appeared in final form in [Food & Function]. To access the final edited and published work see [https://doi.org/10.1039/C6FO01489E]Broccoli is a rich source of health-promoting glucosinolates and phenolic compounds, minerals and vitamins, which might have potential to alleviate pain. The aim of this work was to explore the antinociceptive effects of a broccoli sprouts aqueous extract (BSE) in experimental models of pain and an opioid mechanism. BSE was administered to mice and rats that were submitted to the writhing and formalin tests, respectively. Gastric damage or sedative-like response, as adverse effects observed in anti-inflammatory non-steroidal and opioid analgesic drugs, respectively, were also explored. Antinociceptive but not sedative or gastric injury response was observed in a significant and dose-dependent manner with BSE (50-500 mg/kg, i.p. and 500-2000 mg/kg, p.o.), containing 15 µmol SFN in 1 mg of BSE, in comparison to the control group resembling the effects of the analgesic tramadol (30 mg/kg, i.p.) in writhing and formalin tests. Blockage of opioid receptors by naloxone (1 mg/kg, i.p.) produced partial inhibition in the antinociceptive effect of BSE in both tests. This study gives evidences of the potential activity of Broccoli in the pain therapy

Anticonvulsant and Antioxidant Effects of Tilia americana

Tilia genus is commonly used around the world for its central nervous system properties; it is prepared as tea and used as tranquilizing, anticonvulsant, and analgesic. In this study, anticonvulsant activity of the Tilia americana var. mexicana inflorescences and leaves was investigated by evaluating organic and aqueous extracts (100, 300, and 600 mg/kg, i.p.) and some flavonoids in the pentylenetetrazole-induced seizures in mice. Moreover, antioxidant effect of these extracts and flavonoids was examined in an in vitro study by using spectrophotometric technique. Significant activity was observed in the methanol extract from inflorescences. An HPLC analysis of the methanol extract from inflorescences and leaves of Tilia allowed demonstrating the respective presence of some partial responsible flavonoid constituents: quercetin (20.09 ± 1.20 μg/mg and 3.39 ± 0.10 μg/mg), rutin (3.52 ± 0.21 μg/mg and 8.94 ± 0.45 μg/mg), and isoquercitrin (1.74 ± 0.01 μg/mg and 1.24 ± 0.13 μg/mg). In addition, significant but different antioxidant properties were obtained among the flavonoids and the extracts investigated. Our results provide evidence of the anticonvulsant activity of Tilia reinforcing its utility for central nervous system diseases whose mechanism of action might involve partial antioxidant effects due to the presence of flavonoids

Use of Phytoestrogens for the Treatment of Psychiatric Symptoms Associated with Menopause Transition

Menopause transition is recognized as a vulnerable period in women life to develop or aggravate symptoms of psychiatric disorders. Several treatments including antidepressants and hormonal restitution with estrogens have been suggested to ameliorate the symptoms. Also, in this period of life is frequent the use of other drugs to treat is also frequent the use of other drugs to treat comorbid pathologies that might even increase the risk of drug-drug interactions. Literature reports that some phytochemicals with estrogenic activity have beneficial effects during menopausal transition without collateral events. This chapter shows evidence about the use of phytoestrogens as an alternative therapy for the treatment of some psychiatric symptoms associated with the menopausal transition. Data derived from preclinical research related to the use of classical phytoestrogens (isoflavones), considering the beneficial effects, as well as adverse events, are discussed. Also, the use of polyphenols and organosulfurate compounds as an alternative for the treatment of anxiety- and depressive-like behavior as well as fibromyalgia is included. A narrative review was conducted using bibliography reporting the use of isoflavones (genistein, daidzein, equol), coumestans or lignans for the reduction of depressive-like or anxiety-like behavior. Furthermore, it is described if the use of this compounds impact in other signs of menopause, i.e. vasomotor and osteoporosis. In addition, due to the high frequency of comorbid pathologies as diabetes mellitus, dyslipidemia or metabolic syndrome with psychiatric disorders, the use of these phytochemicals is discussed

Synergistic interaction in the analgesic-like effects of maqui berry and citrus Is antagonized by sweeteners

Although physiologically pain has a protective function, in many diseases, it is one of the most prominent symptoms. Today, new trends are focused on finding more natural alternatives to conventional treatments to alleviate it. Thereby, the purpose of this investigation was to obtain preclinical data of the antinociceptive properties of a lyophilized obtained from a newly designed maqui–citrus beverage alone and added with different sweeteners. To achieve this objective, maqui berry and citrus pharmacological activity were studied separately, as well as the interaction of both ingredients. In addition, due to the controversy generated regarding the intake of sugars, related to different metabolic diseases, the influence of different sweeteners (stevia, sucralose, or sucrose) was studied to determine their possible influence on the bioactive compounds of this product. For the attainment of our goals, a pharmacological evaluation, using the 1% formalin test, a nociceptive pain model in mice, was performed by using a sub-efficacious dosage of Maqui (25 mg/kg, i.p.) alone and combined with citrus, and then compared with the effects obtained in the presence of the different sweeteners. As a result, the antinociceptive response of the maqui was synergized in the presence of citrus in the neurogenic and inflammatory phases of the formalin test. However, this response was partially or totally reduced in the presence of the sweeteners. Our study gives preclinical evidence that a combination of maqui and citrus might exert beneficial actions to relieve pain, whereas the presence of sweeteners could reduce or avoid it.This work was partially supported by Consejo Nacional de Ciencia y Tecnología (CONACYT) grant numbers 226454 and 256448 and Institutional projects numbers INP-NC123280.0 and INP-NC17073.0. Also, was partially funded by the Spanish MINECO through Research Project AGL2016-75332-C2-1-R (AEI/FEDER, UE), the Spanish MICIN through Research Project PID2019- 104212RD-100, and VA by a FPI grant (BES-2017-079754

Antinociceptive effects of maqui-berry (Aristotelia chilensis (Mol.) Stuntz)

Maqui-berry is characterised by presenting a high concentration of (poly)phenols, accounting anthocyanins (cyanidin and delphinidin) for over 85% of the total. These coloured flavonoids have demonstrated potential neurological activity, but the evidence of their antinociceptive properties is scarce. In order to cover this gap, different doses (suitable for human administration) of a maqui-berry powder (1.6% anthocyanin), using enteral and parenteral routes of administration, were compared at central and peripheral levels using a nociceptive pain model (formalin test) in mice. Gastric damage analysis as possible adverse effects of analgesic and anti-inflammatory drugs was also explored. Dose-antinociceptive response was confirmed using both routes of administration and in both neurogenic and inflammatory phases of the formalin test, without gastric damage. In conclusion, these preliminary data provide evidence of pharmacological properties of maqui-berry to alleviate nociceptive pain.This work was partially supported by Consejo Nacional de Ciencia y Tecnología (CONACYT) grant numbers 226454 and 256448 and Institutional projects numbers INP-NC123280.0 and INP-NC17073.0. Also, was partially funded by the Spanish MINECO through Research Project AGL2016-75332-C2-1-R (AEI/FEDER, UE), the Spanish MICIN through Research Project PID2019-104212RD-100, and VA by a FPI [grant number BES-2017-079754]

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 conditionOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was partially supported by the projects CONACYT-22645419 and 256448, and the "Fundación Séneca"—Murcia Regional Agency for Science and Technology, Project 20855/PI/18. NB is granted by a “Juan de la Cierva Incorporación” (IJC-2020-044496-I) post-doctoral contract funded by MCIN/AEI/1013039/501100011033 and European Union NextGenerationEU/PRTR. Authors would also like to thank the CYTED Programme, Action 112RT0460 CORNUCOPIA Thematic NetworkPeer reviewe

Role of β-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil

Tagetes lucida Cav. (Asteraceae) is an ancient medicinal plant commonly used to alleviate pain. Nevertheless, scientific studies validating this property are lacking in the literature. Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities of T. lucida essential oil (TLEO) and a bioactive metabolite. The chemical constitution and possible toxicity of the extract and the mechanism of action of β-caryophyllene were also explored. Temporal course curves and dose–response graphics were generated using TLEO (0.1–10 mg/kg or 3.16–31.62 mg/kg) and β-caryophyllene (3.16–10 mg/kg). Metamizole (80 mg/kg) and indomethacin (20 mg/kg) were used as reference drugs in the formalin assay and writhing test in rats and mice, respectively. The β-caryophyllene mechanism of action was explored in the presence of naloxone (1 mg/kg), flumazenil (10 mg/kg), WAY100635 (0.16 mg/kg), or nitro-l-arginine methyl ester (L-NAME) (20 mg/kg) in the formalin test in rats. GC/MS analysis demonstrated the presence of geranyl acetate (49.89%), geraniol (7.92%), and β-caryophyllene (6.27%). Significant and dose-dependent antinociceptive response was produced by TLEO and β-caryophyllene without the presence of gastric damage. In conclusion, β-caryophyllene was confirmed as a bioactive compound in the T. lucida analgesic properties by involving the participation of receptors like opioids, benzodiazepines, and Serotonin 1A receptor (5-HT1A), as well as nitric oxide

Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins

Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties

Pharmacological evaluation of the anxiolytic-like effects of Lippia graveolens and bioactive compounds

Context: Lippia species (Verbenaceae) are widely used in Latin America and Africa as folk medicine for their tranquilizing properties. Objective: To evaluate the anxiolytic-like effects and safety of Lippia graveolens Kunth. by exploring its aqueous and organic leaf extracts and identifying the responsible chemical constituents. Material and methods: Aqueous and organic extracts (hexane, ethyl acetate and methanol) were pharmacologically evaluated at several doses. Chemical constituents were identified using MS, NMR and GC-MS analysis. The isolated compounds (3 mg/kg, i.p.), extracts (1, 3, 10 and 30 mg/kg, i.p.), and the reference drug diazepam (0.1 mg/kg, i.p.) were assessed in CD-1 mice using experimental behavioural models: open-field, cylinder, hole-board, plus-maze and sodium pentobarbital-induced hypnosis, as well as their acute toxicity (LD50). Results: After administration of the extracts and bioactive compounds, a significant anxiolytic-like response from 1 mg/kg, i.p. was observed, resembling the effect of diazepam. Major presence of thymol (33.40%) was observed in the hexane extract; whereas for the first time in this species a p-cymene + thymol mixture (9.78%), naringenin (0.18%) and cirsimaritin (1.16%) were obtained as bioactive constituents of the ethyl acetate crude extract. Acute toxicity was calculated to be LD50 = 1000 mg/kg for the crude hexane extract, lower in comparison to the other extracts analyzed (LD50 > 2000 mg/kg). Discussion and conclusion: Our results suggest that L. graveolens exerts anxiolytic-like activity involving many kinds of constituents, mainly of the terpenoid and flavonoid nature. These results reinforce the potential use of this species in the therapy of anxiety

Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain

Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31.6 mg/kg). UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100) in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D2, GABAA, and opioids, but not by 5-HT1A, receptors