Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic  P2X Receptors

Soares‐Bezerra, Rômulo José; Calheiros, Andrea Surrage; Ferreira, Natiele Carla da Silva; Frutuoso, Valber da Silva; Alves, Luiz Anastácio

doi:10.3390/ph6050650

Cited by 34 publications

(21 citation statements)

References 48 publications

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“…192 Several natural products are shown to cause analgesia on inflammatory pain or neuropathic pain by inhibiting P2X 3 or P2X 7 mechanisms, although the selectivity of these compounds for specific P2X receptors remains unclear. Paeoniflorin ( 72 ) is a chief ingredient in the root of Paeonia lactiflora Pall, and it has been shown to be effective in relieving colorectal distension induced visceral pain and hyperalgesia in a rat model of IBS (neonatal maternal separation).…”

Section: 0 Herbal Medicines Are Natural Purinergic Drugs With Efficmentioning

confidence: 99%

Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

Ochoa-Cortés¹,

Liñán-Rico²,

Jacobson³

et al. 2014

Inflammatory Bowel Diseases

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Treatments for IBD, IBS, FD or motility disorders are not adequate, and purinergic drugs offer exciting new possibilities. GI symptoms that could be targeted for therapy include visceral pain, inflammatory pain, dysmotility, constipation and diarrhea. The focus of this review is on potential for developing purinergic drugs for clinical trials to treat GI symptoms. Purinergic receptors are divided into adenosine P1 (A1,A2A,A2B,A3), ionotropic ATP-gated P2X ion channel (P2X1–7) or metabotropic P2Y1,2,4,6,11–14 receptors. There is good experimental evidence for targeting A2A, A2B, A3, P2X7, P2X3 receptors or increasing endogenous adenosine levels to treat IBD, inflammatory pain, IBS/visceral pain, inflammatory-diarrhea and motility disorders. Purine genes are also potential biomarkers of disease. Advances in medicinal-chemistry have an accelerated pace toward clinical trials: Methotrexate and sulfasalazine, used to treat IBD, act by stimulating CD73-dependent adenosine production. ATP protects against NSAID-induced enteropathy and has pain-relieving properties in humans. A P2X7R antagonist AZD9056 is in clinical trials for CD. A3 AR drugs target inflammatory diseases (e.g. CF101; CF102). Dipyridamole, a nucleoside uptake-inhibitor, is in trials for endotoxemia. Drugs for pain in clinical-trials include P2X3/P2X2/3(AF-219) and P2X7(GSK1482160) antagonists and A1(GW493838) or A2A(BVT.115959) agonists. IberogastR is a phytopharmacon targeting purine-mechanisms with efficacy in IBS and FD. Purinergic drugs have excellent safety/efficacy profile for prospective clinical trials in IBD, IBS, FD and inflammatory-diarrhea. Genetic polymorphisms and caffeine consumption may affect susceptibility to treatment. Further studies in animals can clarify mechanisms and test new-generation drugs. Finally, there is still a huge gap in our knowledge of human pathophysiology of purinergic signaling.

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Section: 0 Herbal Medicines Are Natural Purinergic Drugs With Efficmentioning

confidence: 99%

Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

Ochoa-Cortés¹,

Liñán-Rico²,

Jacobson³

et al. 2014

Inflammatory Bowel Diseases

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“…As a neurotransmitter, ATP plays an important role in regulating the transduction of the visceral pain signal by binding to P2X receptors [15,16], and ATP participates in the regulation of intestinal movement and gastrointestinal secretion. P2X receptors are widely distributed in the body, and they play an important role in the formation, transduction, and regulation of neuropathic pain, inflammatory pain, and visceral pain [17][18][19][20]. Many studies have shown that purinergic (P2X) receptors are involved in pain signal transmission, in which the P2X 3 and P2X 2/3 receptors are the main subtypes [21,22].…”

Section: Introductionmentioning

confidence: 99%

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

Weng

Wu²,

Zhou

et al. 2015

Purinergic Signalling

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The aim of this study is to investigate the role of the purinergic receptor P2X 3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n= 8); (2) the model group (MG, n=8); and (3) the model+ electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X 3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X 3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X 3 receptor in the intercolonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X 3 receptor and ease the sensitivity to visceral pain. The P2X 3 receptor plays an important role in IBS visceral pain. The different levels of P2X 3 in the peripheral enteric nervous system and central nervous system mediate the effects of the EA treatment of the visceral hyperalgesia of IBS.

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“…Of the seven subtypes of P2XR, the types that are most related to the progression or control of pain status are the P2X3R, the heteromericeP2X2/3R, P2X4R, and the P2X7R [78].…”

Section: Purinergic P2x Receptors Inhibitorsmentioning

confidence: 99%

“…Also, purotoxin, a peptide isolated from the venom of the Asian spider Geolycosasp, also showed a potent and selective antagonist effect on P2X3R, inhibiting the ionic current in rat neurons and showing an analgesic effect on inflammatory pain [78].…”

Section: Purinergic P2x Receptors Inhibitorsmentioning

confidence: 99%

Natural Products as a Source for Novel Analgesic Compounds

Abdel-Rahman¹

2017

Pain Relief - From Analgesics to Alternative Therapies

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Natural products have an important role in the discovery of analgesic drugs along with the determining of the complex mechanisms involved in pain transmission and pain relief. Lately, several substances with antinociceptive actions have been purified from natural sources and further identified, resulting in novel structural classes and more understanding of the underlying pharmacological mechanisms of actions. Yet, natural products still hold great potential for the discovery of novel agents for treatment of pain disorders and potentially drug addictions with exciting pharmacological profiles (i.e. no side effects, no addictive potential). The aim of this chapter is to highlight some active compounds derived from natural sources that possess analgesic properties. Additionally, the identification of new compounds derived from natural sources could lead to great understanding of the underlying pharmacological mechanisms of action, which will be addressed in this chapter as well.

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Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors

Cited by 34 publications

References 48 publications

Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

Potential for Developing Purinergic Drugs for Gastrointestinal Diseases

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

Natural Products as a Source for Novel Analgesic Compounds

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