Norisoboldine attenuates inflammatory pain via the adenosine <scp>A</scp>1 receptor

Gao, Xinghua; Lü, Qian; Chou, Gui‐Xin; Wang, Z.; Rong, Pan; Xia, Yufeng; Hu, Hongping; Dai, Yue

doi:10.1002/j.1532-2149.2013.00439.x

Cited by 21 publications

(5 citation statements)

References 37 publications

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“…1 , 3 -D i p r o p y l -8 -cyclopentylxanthine, an A 1 receptor antagonist, abolishes the effect of CBD on the spikes frequency generated by ON cells and OFF cells in the RVM, while blockade of this receptor reverses the beneficial effect of norisoboldine, which attenuates inflammatory pain [258]. To date, there is no evidence demonstrating a direct implication of adenosine A 2 receptor in the therapeutic action of CBD in pain relief.…”

Section: Cbd Receptor Targets In Painmentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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Section: Cbd Receptor Targets In Painmentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

View full text Add to dashboard Cite

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“…Moreover, recent studies also suggest that the analgesic efficacy of some herbal preparations long utilized in traditional Chinese medicine can be at least in part due to a modulation of the adenosine system. In fact, norisoboldine (the major active alkaloid component isolated from the dry roots of Lindera aggregata often utilized for chest and abdomen pain, indigestion, cold hernia, and frequent urination) was shown to promote analgesia in both the formalin and the writhing tests in rodents through the activation of A 1 receptor subtype [102]. …”

Section: Adenosine Exerts Analgesic Effects Through Its Glial Recementioning

confidence: 99%

The Purinergic System and Glial Cells: Emerging Costars in Nociception

Magni

Ceruti

2014

BioMed Research International

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It is now well established that glial cells not only provide mechanical and trophic support to neurons but can directly contribute to neurotransmission, for example, by release and uptake of neurotransmitters and by secreting pro- and anti-inflammatory mediators. This has greatly changed our attitude towards acute and chronic disorders, paving the way for new therapeutic approaches targeting activated glial cells to indirectly modulate and/or restore neuronal functions. A deeper understanding of the molecular mechanisms and signaling pathways involved in neuron-to-glia and glia-to-glia communication that can be pharmacologically targeted is therefore a mandatory step toward the success of this new healing strategy. This holds true also in the field of pain transmission, where the key involvement of astrocytes and microglia in the central nervous system and satellite glial cells in peripheral ganglia has been clearly demonstrated, and literally hundreds of signaling molecules have been identified. Here, we shall focus on one emerging signaling system involved in the cross talk between neurons and glial cells, the purinergic system, consisting of extracellular nucleotides and nucleosides and their membrane receptors. Specifically, we shall summarize existing evidence of novel “druggable” glial purinergic targets, which could help in the development of innovative analgesic approaches to chronic pain states.

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“…Linderae radix, the dried root of Lindera aggregata (Sims) Kosterm, is a traditional Chinese folk medicine possessing anti-inflammatory, analgesic, hepatoprotective and neuroprotective effects. − Linderane (LDR), a furan sesquiterpenoid (Figure A), is the main bioactive component isolated from Linderae radix. , Previous studies have shown that LDR could suppress hepatic gluconeogenesis and protect pancreatic β cells from streptozotocin (STZ)-induced oxidative damage. , However, the effects of LDR on regulating sensation and emotion in chronic pain are still unclear. Therefore, the effects of LDR on pain and anxiety were evaluated using the complete Freund’s adjuvant (CFA)-induced inflammatory pain mouse model, and the role of LDR in microglia polarization in the ACC region was also explored in this research.…”

Section: Introductionmentioning

confidence: 99%

Linderane Attenuates Complete Freund’s Adjuvant-Induced Pain and Anxiety in Mice by Restoring Anterior Cingulate Cortex Microglia M2 Polarization through Activating Cannabinoid 2 Receptor

Chen,

Qin,

Gao

et al. 2024

ACS Pharmacol. Transl. Sci.

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Chronic pain is a common condition that causes negative emotions as the disease progresses. The anterior cingulate cortex (ACC) is a key region in the integration of nociceptive perception and emotional response in chronic pain. Linderane (LDR) is an active ingredient from Linderae radix, a traditional Chinese medicine with anti-inflammatory, analgesic, and antibacterial properties. In this study, the analgesic and antianxiety effects of LDR were evaluated using a complete Freund's adjuvant (CFA)-induced inflammatory pain model in C57BL/6 male mice. Mechanical and thermal pain sensitivity were measured through plantar mechanical analgesia and hot plate apparatus, and anxietylike behavior was evaluated by open field and elevated plus maze tests. The results showed that LDR-alleviated CFA-induced pain and anxiety, reduced the release of inflammatory cytokines, and inhibited ACC microglial activation. Target prediction, molecular docking, and cellular thermal shift assay demonstrated that LDR could bind to the cannabinoid 2 receptor (CB2R), a key component of the endocannabinoid system with an important role in regulating pain and related emotions. Moreover, both the analgesic effect of LDR and its regulation of microglia polarization were reversed by a CB2R antagonist (SR144528) treatment. Therefore, our results suggested that LDR exerted analgesic effects by regulating microglial polarization in ACC via CB2R activation.

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Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor

Abstract: Our data demonstrate that NOR produces the analgesic effect in inflammatory pain by a mechanism related to the adenosine system.

Cited by 21 publications

References 37 publications

Molecular Targets of Cannabidiol in Neurological Disorders

Molecular Targets of Cannabidiol in Neurological Disorders

The Purinergic System and Glial Cells: Emerging Costars in Nociception

Linderane Attenuates Complete Freund’s Adjuvant-Induced Pain and Anxiety in Mice by Restoring Anterior Cingulate Cortex Microglia M2 Polarization through Activating Cannabinoid 2 Receptor

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