Antinociceptive effect of natural and synthetic alkamides involves TRPV1 receptors

Rosa-Lugo, Vianey de la; Acevedo-Quiroz, Macdiel; Déciga-Campos, Myrna; Rios, Marı́a Yolanda

doi:10.1111/jphp.12721

Cited by 21 publications

(19 citation statements)

References 30 publications

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“…COX catalyzes the conversion of arachidonic acid to prostaglandin ( Williams et al, 1999 ), leading to the activation and sensitization of peripheral nociceptors. Since the vast majority of studies of alkamides shows their peripheral antinociception effects ( de la Rosa-Lugo et al, 2017 ), on the basis of the Rimbau et al (1999) study and our current findings, we suggest that the peripheral anti-nociception activity of AEAPR and MEAPR may be due to their alkamides.…”

Section: Discussionsupporting

confidence: 61%

Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots

et al. 2017

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Anacyclus pyrethrum (L.) is a plant widely used in Moroccan traditional medicine to treat inflammatory and painful diseases. The objective of the present study was to evaluate the antinociceptive, anti-inflammatory and antioxidant activities of aqueous and methanol extracts of Anacyclus pyrethrum roots (AEAPR and MEAPR). The anti-inflammatory effect of AEAPR and MEAPR was determined in xylene–induced ear edema and Complete Freund’s Adjuvant (CFA)-induced paw edema. The antinociceptive activity of AEAPR and MEAPR (125, 250, and 500 mg/kg) administered by gavage was examined in mice by using acetic acid-induced writhing, hot plate, and formalin tests, and the mechanical allodynia were assessed in CFA-induced paw edema. In addition, the in vitro antioxidant activities of the extracts were determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, ferric reducing power and β-carotene-linoleic acid assay systems. AEAPR and MEAPR produced significant reductions in CFA-induced paw edema and xylene-induced ear edema. A single oral administration of these extracts at 250 and 500 mg/kg significantly reduced mechanical hypersensitivity induced by CFA, which had begun 1 h 30 after the treatment, and was maintained till 7 h. Chronic treatment with both extracts significantly reduced mechanical hypersensitivity in persistent pain conditions induced by CFA. Acute pretreatment with AEAPR or MEAPR at high dose caused a significant decrease in the number of abdominal writhes induced by acetic acid injection (52.2 and 56.7%, respectively), a marked increase of the paw withdrawal latency in the hot plate test, and also a significant inhibition of both phases of the formalin test. This antinociceptive effect was partially reversed by naloxone pretreatment in the hot plate and formalin tests. Additionally, a significant scavenging activity in DPPH, reducing power and protection capacity of β-carotene was observed in testing antioxidant assays. The present study suggests that AEAPR and MEAPR possess potent anti-inflammatory, antinociceptive and antioxidant effects which could be related to the presence of alkaloids and phenols in the plant. In addition, the antinociceptive effect of APR extracts seems to partly involve the opioid system. Taken together, these results suggest that Anacylcus pyrethrum may indeed be useful in the treatment of pain and inflammatory disorders in humans.

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Section: Discussionsupporting

confidence: 61%

Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots

et al. 2017

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“…Therefore, the partial inhibition of the α-sanshool-induced convulsions by the TRPV1-antagonist capsazepine suggests that this alkamide induces the seizures, at least in part, by stimulating the TRPV1 channels (▶Table 2). It is possible that convulsions induced by affinin, capsaicin, and the synthetic alkamide reported by de la Rosa et al [7] also occur via the same mechanism. Additional experimental data are required to assess this statement.…”

Section: Discussionmentioning

confidence: 87%

“…and the synthetic alkamide N-isobutyl-dihydroferuloylamide (180 mg/kg, i.p.) in mice [7]. In that work, the authors found that affinin did not induce seizures at doses lower than 90 mg/kg (i.p.…”

Section: Discussionmentioning

confidence: 91%

“…In that work, we also noticed that the intraperitoneal injection of this compound induced tonic-clonic seizures in mice. Although low toxicity is generally associated with natural and synthetic alkamides, their convulsive effect in mice was recently reported [7]. This is of great significance due to the growing medical and cosmetic interest in plant extracts containing these compounds, even though little is known about their toxic effects.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for Involvement of TRPV1 Receptors and Potassium Channels in the Seizures Induced by α-Sanshool

Reyes-Trejo

Morales-Hernández

González-Anduaga

et al. 2019

PMIO

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α-Sanshool is an alkamide isolated from the stem bark of Zanthoxylum liebmannianum, a Mexican medicinal plant known as Colopahtle. Our research group has reported that the intraperitoneal administration of α-sanshool induces tonic-clonic seizures in mice. In the present study, we investigated the convulsive effect of this alkamide and elucidated its mechanism of action by comparing with well-known convulsive and anticonvulsive drugs in an in vivo approach. α-Sanshool showed a potent (ED50 [CL 95%]=3.06 [2.92–3.22] mg/kg) and immediate (2±2 s) seizure effect after the intraperitoneal administration in mice. The convulsive effect of this alkamide was only observed for intraperitoneal administration; the oral route did not show any effect. α-Sanshool was less potent than strychnine (ED50 [CL 95%]=1.53 [1.44–1.62] mg/kg), but more effective than bicuculline, 4-aminopyridine, affinin, and pentylenetetrazol, in that order. The seizures induced by α-sanshool were reduced by capsazepine and diazoxide, suggesting the involvement of TRPV1 and potassium channels in the mechanism of action of this compound.

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“…For pharmacological assays, the alkamide samples were prepared with saline solution, DMSO (10%), Tween 80 (5%), and ethanol (1%). capsaicin (420 mg) obtained according to previous reports (de la Rosa-Lugo et al, 2017;Déciga-Campos et al, 2010;Rios et al, 2007). In summary, affinin was isolated from an H. longipes acetone extract and capsaicin was obtained from a Capsicum chinese dichloromethane extract.…”

Section: Chemical Agents (Abbreviation Pubchem Cid)mentioning

confidence: 98%

Affinin and hexahydroaffinin: Chemistry and toxicological profile

Rosa-Lugo

Déciga-Campos

Rios

et al. 2020

Drug Development Research

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The present work aimed to determine the safety parameters of two new alkamides, affinin and hexahydroaffinin, with antinociceptive activity. To predict the preliminary acute toxicity, we used the acute and subchronic toxicity (50 mg/kg, orally [po]) in Swiss Webster mice. Genotoxicity assayed via analysis of cell micronuclei of the femoral bone marrow in mice; at the same time, metabolic parameters determined from peripheral blood samples. Furthermore, to discard the neuropharmacological effects, we assessed the ambulatory activity in mice to determine the possible effects in the central nervous system. Finally, we used capsaicin as a positive control of alkamides. According to our results, hexahydroaffinin (LD 50 ≥ 5,000 mg/kg, po) is significantly less noxious than affinin (LD 50 = 1,442.2 mg/kg, po) or capsaicin (LD 50 = 489.9 mg/kg, po). In subchronic administration, we did not observe any changes in hematological or biochemical parameters in any compound analyzed from peripheral blood samples. Finally, the data from the genotoxicity assay showed micronuclei formation in 28%, 5%, and 3% of mice in the capsaicin, affinin, and hexahydroaffinin groups, respectively. With the results obtained in the present investigation, we suggest that affinin and hexahydroaffinin are not only useful candidates for possible new drugs but also safe compounds.

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Antinociceptive effect of natural and synthetic alkamides involves TRPV1 receptors

Cited by 21 publications

References 30 publications

Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots

Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots

Evidence for Involvement of TRPV1 Receptors and Potassium Channels in the Seizures Induced by α-Sanshool

Affinin and hexahydroaffinin: Chemistry and toxicological profile

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