The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin

Bánki, Eszter; Hajna, Zs; Kemény, Ágnes; Botz, Bálint; Nagy, P.; Bölcskei, Kata; Tóth, Gábor; Reglődi, Dóra; Helyes, Zsuzsanna

doi:10.1016/j.neuropharm.2014.06.019

Cited by 24 publications

(13 citation statements)

References 73 publications

(68 reference statements)

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“…This model is widely used to evaluate anti-inflammatory topical steroids and non-steroidal anti-inflammatory agents, especially those that inhibit phospholipase A2 ( Zanini et al, 1992 ; Núñez Guillén et al, 1997 ). In addition, several studies have shown that the xylene increases vascular permeability, which causes edema that indicates inflammation, due to the release of inflammatory agents such as bradykinin, prostaglandin, histamine and serotonin, which in turn release neuropeptides that activate their receptors, producing neurogenic inflammation ( Carlson et al, 1985 ; Banki et al, 2014 ). Substance P is one of these neuropeptides, which allows the release of nitric oxide from endothelial cells, triggering vasodilation and plasma exudation, which is the origin of edema formation ( Barry et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…And we first demonstrated PAC1R expression in hADSCs by gene testing and protein assay. In this study, it was revealed that maxadilan, a specific PAC1R agonist [28][29][30][31]54], could increase hADSC proliferation and promoted migration. It could also counteract hADSC apoptosis.…”

Section: Discussionmentioning

confidence: 83%

“…Maxadilan, isolated from the salivary glands of the sand fly Lutzomyia longipalpis, is a 61-amino acid vasodilatory peptide [28]. Although it has no prominent sequence homology with PACAP, maxadilan is a PAC1R-specific agonist and is used to assay the diverse physiological functions of PAC1R [29][30][31]. For example, maxadilan is used to determine that PAC1R activation prevents TNFmediated cell death in olfactory placode cells [22].…”

Section: Introductionmentioning

confidence: 99%

PAC1R agonist maxadilan enhances hADSC viability and neural differentiation potential

Guo

et al. 2016

J Cellular Molecular Medi

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Pituitary adenylate cyclase‐activating polypeptide (PACAP) is a structurally endogenous peptide with many biological roles. However, little is known about its presence or effects in human adipose‐derived stem cells (hADSCs). In this study, the expression of PACAP type I receptor (PAC1R) was first confirmed in hADSCs. Maxadilan, a specific agonist of PAC1R, could increase hADSC proliferation as determined by Cell Counting Kit‐8 and cell cycle analysis and promote migration as shown in wound‐healing assays. Maxadilan also showed anti‐apoptotic activity in hADSCs against serum withdrawal‐induced apoptosis based on Annexin V/propidium iodide analysis and mitochondrial membrane potential assays. The anti‐apoptotic effects of maxadilan correlated with the down‐regulation of Cleaved Caspase 3 and Caspase 9 as well as up‐regulation of Bcl‐2. The chemical neural differentiation potential could be enhanced by maxadilan as indicated through quantitative PCR, Western blot and cell morphology analysis. Moreover, cytokine neural redifferentiation of hADSCs treated with maxadilan acquired stronger neuron‐like functions with higher voltage‐dependent tetrodotoxin‐sensitive sodium currents, higher outward potassium currents and partial electrical impulses as determined using whole‐cell patch clamp recordings. Maxadilan up‐regulated the Wnt/β‐catenin signalling pathway associated with dimer‐dependent activity of PAC1R, promoting cell viability that was inhibited by XAV939, and it also activated the protein kinase A (PKA) signalling pathway associated with ligand‐dependent activity of PAC1R, enhancing cell viability and neural differentiation potential that was inhibited by H‐89. In summary, these results demonstrated that PAC1R is present in hADSCs, and maxadilan could enhance hADSC viability and neural differentiation potential in neural differentiation medium.

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“…This stimulates not only the central nerves but also descends to the peripheral nerves, inducing the peptide from the sensory nerve terminal. It has been explained that as a result of the above process, the mast cells and the internal smooth muscles widen the blood vessels23 ) . The authors believe it to be necessary to start substantiating the study of these effects.…”

Section: Discussionmentioning

confidence: 99%

Effects of friction massage of the popliteal fossa on blood flow velocity of the popliteal vein

et al. 2017

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[Purpose] Friction massage (friction) of the popliteal fossa is provided for the purpose of relieving pain related to circulatory disorders by improving venous flow in the lower legs. The purpose of this study is to verify the effects of enhancing the venous flow based on measuring the blood flow velocity of the popliteal vein before and after providing friction to the patients. [Subjects and Methods] Fifteen healthy male university students participated in the study. The Doppler ultrasonography (DU) was used to measure the blood flow velocity of the popliteal vein, in order to verify the effects of enhancing the venous flow by comparing the measured values before and after a friction massage. [Results] The result of comparing the blood flow velocity before and after providing friction showed that there was a significant increase after friction. [Conclusion] This study proved that friction to the popliteal fossa is effectively enhances venous flow by increasing the blood flow velocity in the popliteal vein.

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The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin

Cited by 24 publications

References 73 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

PAC1R agonist maxadilan enhances hADSC viability and neural differentiation potential

Effects of friction massage of the popliteal fossa on blood flow velocity of the popliteal vein

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