Evodiamine via targeting nNOS and AMPA receptor GluA1 inhibits nitroglycerin-induced migraine-like response

Lin, Jiacheng; Zhang, Xu; Li, Chaotong; Zhang, Yingyan; Lu, Hanzhi; Chen, Jiwei; Li, Zeyu; Yang, Xuejun; Wu, Zhongping

doi:10.1016/j.jep.2020.112727

Cited by 8 publications

(5 citation statements)

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“…Previous research has proven that the GLUA1 subunit is critical for the development of chronic migraine [ 43 ]; therefore, we next determined whether the pain-relieving effect of DRD2 is linked to GLUA1. First, we determined that DRD2 largely colocalized with GLUA1 in the TNC region in CM rats using double immunofluorescence staining (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Postsynaptic membrane recruitment of GLUA1-containing AMPARs but not GLUA2/3-containing AMPARs is a crucial step in the transmission of nociceptive messages and central sensitization [ 8 , 52 ]. It has been previously reported that GLUA1-containing AMPARs in the TNC contribute greatly to chronic migraine [ 9 , 43 ]. In this study, we confirmed that inhibition of GLUA1 trafficking attenuates central sensitization and pain hyperesthesia in CM rats.…”

Section: Discussionmentioning

confidence: 99%

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Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

et al. 2022

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Background The pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking. Methods A chronic migraine model was established by repeated inflammatory soup stimulation. Mechanical, periorbital, and thermal pain thresholds were assessed by the application of von Frey filaments and radiant heat. The mRNA and protein expression levels of the dopamine D2 receptor were analyzed by qRT‒PCR and western blotting. Colocalization of the dopamine D2 receptor and the GLUA1-containing AMPAR was observed by immunofluorescence. A dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride), a PI3K inhibitor (LY294002), a PI3K pathway agonist (740YP), and a GLUA1-containing AMPAR antagonist (NASPM) were administered to confirm the effects of the dopamine D2 receptor, the PI3K pathway and GULA1 on central sensitization and the GLUA1-containing AMPAR trafficking. Transmission electron microscopy and Golgi-Cox staining were applied to assess the impact of the dopamine D2 receptor and PI3K pathway on synaptic morphology. Fluo-4-AM was used to clarify the role of the dopamine D2 receptor and PI3K signaling on neuronal calcium influx. The Src family kinase (SFK) inhibitor PP2 was used to explore the effect of Src kinase on GLUA1-containing AMPAR trafficking and the PI3K signaling pathway. Results Inflammatory soup stimulation significantly reduced pain thresholds in rats, accompanied by an increase in PI3K-P110β subunit expression, loss of dopamine receptor D2 expression, and enhanced GLUA1-containing AMPA receptor trafficking in the trigeminal nucleus caudalis (TNC). The dopamine D2 receptor colocalized with the GLUA1-containing AMPA receptor in the TNC; quinpirole, LY294002, and NASPM alleviated pain hypersensitivity and reduced GLUA1-containing AMPA receptor trafficking in chronic migraine rats. Sulpiride aggravated pain hypersensitivity and enhanced GLUA1 trafficking in CM rats. Importantly, the anti-injury and central sensitization-mitigating effects of quinpirole were reversed by 740YP. Both quinpirole and LY294002 inhibited calcium influx to neurons and modulated the synaptic morphology in the TNC. Additional results suggested that DRD2 may regulate PI3K signaling through Src family kinases. Conclusion Modulation of GLUA1-containing AMPA receptor trafficking and central sensitization by the dopamine D2 receptor via the PI3K signaling pathway may contribute to the pathogenesis of chronic migraine in rats, and the dopamine D2 receptor could be a valuable candidate for chronic migraine treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

et al. 2022

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“…In vivo, limonin (30 or 100 mg/kg) possessed an antinociceptive effect and the effect may be accompanied by an anti-inflammatory action [ 69 ]. In other studies, evodiamine could reduce capsaicin-induced currents significantly in vitro and suppress capsaicin-induced thermal hyperalgesia in rats, which may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons [ 212 ], and it could also inhibit the migraine-like pain response possibly due to the regulation of nNOS and suppression of the AMPA receptor GluA1 [ 126 ].…”

Section: Pharmacologymentioning

confidence: 99%

Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control

Xiao¹,

Xu²,

Chen³

et al. 2023

Nat. Prod. Bioprospect.

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Euodiae Fructus, referred to as “Wuzhuyu” in Chinese, has been used as local and traditional herbal medicines in many regions, especially in China, Japan and Korea, for the treatment of gastrointestinal disorders, headache, emesis, aphtha, dermatophytosis, dysentery, etc. Substantial investigations into their chemical and pharmacological properties have been performed. Recently, interest in this plant has been focused on the different structural types of alkaloids like evodiamine, rutaecarpine, dehydroevodiamine and 1-methyl-2-undecyl-4(1H)-quinolone, which exhibit a wide range of pharmacological activities in preclinical models, such as anticancer, antibacterial, anti-inflammatory, anti-cardiovascular disease, etc. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional uses, phytochemistry, pharmacology of Euodiae Fructus together with the toxicology and quality control, and discusses the possible direction and scope for future research on this plant.

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“…Intragastrical administration of evodiamine at 45 and 90 mg/kg/day for 9 days also robustly reduced the time of licking foot and shaking response, as well as maintained the shortened tail withdrawal latent time under the thermal stimulus. A high dosage of evodiamine (90 mg/kg) exerted similar effects to positive control flunarizine (i.g., 0.9 mg/kg), indicating its potential in the management of migraine (Lin et al, 2020). The downregulated nNOS expression attenuates the occurrence of migraine, which is worth to be further studied.…”

Section: Herbal Medicine In Migrainementioning

confidence: 99%

“…Another herbal prescription, Du Liang soft capsule, was reported to show analgesic actions in the behavioral performance of migraine rats by adjusting vital neurotransmitters and vasoactive substances (Hou et al, 2017). In particular bioactive constitutes of Euodiae Fructus, evodiamine could suppress the levels of AMPA receptor GluA1 and serum NO, as well as increase the pain threshold, which displayed its potential antimigraine activities in animal studies (Lin et al, 2020). Therefore, herbal therapies have significant advantages in the treatment of migraine based on multiple regulated processes.…”

mentioning

confidence: 99%

Role of herbal medicine for prevention and treatment of migraine

Chen

Wang

2021

Phytotherapy Research

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Migraine is a disabling neurovascular disease with unilateral or bilateral pulsatile headache, which intensively affects human health and quality of life due to high morbidity worldwide. Migraine is commonly accompanied by abnormal pain sensitization, neuroinflammatory response, and vasomotor dysfunction. Owing to the management dilemmas of migraine, there is an urgent need to develop effective and low-cost therapies. In recent years, herbal medicines as a promising strategy with analgesic activity and minor side effect, have been proposed for the prevention and treatment of migraine. Considering the lack of a review integrating experimental studies regarding the herbal treatment of migraine, this review systematically summarizes the important potential applications of herbal medicines in ameliorating migraine via multiple therapeutic targets and pathways, as well as provides a reference for further development of novel antimigraine drugs.

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Evodiamine via targeting nNOS and AMPA receptor GluA1 inhibits nitroglycerin-induced migraine-like response

Cited by 8 publications

References 41 publications

Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control

Role of herbal medicine for prevention and treatment of migraine

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