scholarly journals Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1685
Author(s):  
Devesh Tewari ◽  
Pawan Gupta ◽  
Sweta Bawari ◽  
Archana N. Sah ◽  
Davide Barreca ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Opioid Receptors ◽  
Analgesic Activity ◽  
In Silico ◽  
Mu Opioid Receptors ◽  
Fruit Extract ◽  
Mu Opioid ◽  
Cox 2 ◽  
Ficus Palmata

Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of Ficus palmata L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant (p < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin. The results proved that F. palmata fruits have the potential to ameliorate painful conditions.

scholarly journals 6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects

2021 ◽  
Author(s):  
Nicholas S. Akins ◽  
Nisha Mishra ◽  
Hannah M. Harris ◽  
Narendar Dudhipala ◽  
Seong Jong Kim ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Activity ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Mu Opioid ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists

Analgesia is commonly mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. Recently, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold <i>via</i> an ester linker. <i>In vitro</i> studies showed that some of these compounds have dual agonism on kappa and mu opioid receptors, while some have triple agonism on kappa, mu, and delta. <i>In vivo </i>studies on the lead dual kappa and mu opioid receptor agonist, compound <b>10</b>, showed that it<b> </b>produced analgesic activity while avoiding anxiogenic effects in murine models, thus providing further strong evidence for the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

scholarly journals Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Sandeep Dembla ◽  
Marc Behrendt ◽  
Florian Mohr ◽  
Christian Goecke ◽  
Julia Sondermann ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Opioid Receptors ◽  
Dorsal Root ◽  
Trp Channels ◽  
Signaling Cascade ◽  
Central Component ◽  
Mu Opioid Receptors ◽  
Cellular Mechanisms ◽  
Mu Opioid

Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful analgesia. The cellular mechanisms downstream of peripheral µORs are not well understood. Here, we show in neurons of murine dorsal root ganglia that pro-nociceptive TRPM3 channels, present in the peripheral parts of nociceptors, are strongly inhibited by µOR activation, much more than other TRP channels in the same compartment, like TRPV1 and TRPA1. Inhibition of TRPM3 channels occurs via a short signaling cascade involving Gβγ proteins, which form a complex with TRPM3. Accordingly, activation of peripheral µORs in vivo strongly attenuates TRPM3-dependent pain. Our data establish TRPM3 inhibition as important consequence of peripheral µOR activation indicating that pharmacologically antagonizing TRPM3 may be a useful analgesic strategy.

Structure Modifications of Pinostrobin from Temu Kunci (Boesenbergia pandurata ROXB. SCHLECHT) and Their Analgesic Activity Based on in Silico Studies

2021 ◽  
pp. 2089-2094
Author(s):  
Andy Suryadi ◽  
Siswandono Siswodihardjo ◽  
Tri Widiandani ◽  
Retno Widyowati
Keyword(s):  
Analgesic Activity ◽  
In Silico ◽  
Spectrophotometric Analysis ◽  
Acyl Chloride ◽  
In Silico Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Derivatives Of

Temu kunci (Boesenbergia pandurata ROXB. SCHLECHT) is one of Indonesia medicinal plants which contains essential oils and flavonoids and it has interesting pharmacological activities, such as antifungal, antibacterial, antioxidant, anti-inflammatory and anti-cancer. It also contains pinostrobin which potent as anti-inflammatory and analgesic activities through inhibition of COX-2 enzymes. This research was to obtain pinostrobin derivatives of acylation reactions between pinostrobin and acyl chloride derivatives. The structure modifications of pinostrobin were obtained by Schotten-Baumann method through nucleophilic substitution reactions between pinostrobin and acyl chloride derivatives. Their structure had analyzed using the spectrophotometric analysis (NMR, IR, and GC/MS). The investigation of structure modifications of pinostrobin (1) from this plant has demonstrated the presence of pinostrobin acetate (2) and new pinostrobin propionate (3). The 2 and 3 are derivatives of pinostrobin that can be synthesized using the Schotten-Baumann method to yield 84.3% and 73.9%, respectively. The results of in silico study between pinostrobin and pinostrobin acyl derivatives on the COX-2 receptor with a PDB code: 1PXX showed that pinostrobin RS value was -87.18kcal/mol, while pinostrobin propionate had a RS value of -98.61 kcal/mol. It can be predicted that the pinostrobin acyl derivative has greater analgesic activity than pinostrobin, so it is feasible to be developed and carried out research on its analgesic activity in vivo.

scholarly journals Mu-opioid receptors modulate noradrenaline release from the rat hippocampus as measured by in vivo microdialysis.

1993 ◽  
Vol 61 ◽  
pp. 67
Author(s):  
Machiko Matsumoto ◽  
Mitsuhiro Yoshioka ◽  
Hiroko Togashi ◽  
Charles B. Smith ◽  
Hideya Saito
Keyword(s):  
Opioid Receptors ◽  
Noradrenaline Release ◽  
In Vivo Microdialysis ◽  
Rat Hippocampus ◽  
Mu Opioid Receptors ◽  
Mu Opioid

scholarly journals 6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects

2021 ◽  
Author(s):  
Nicholas S. Akins ◽  
Nisha Mishra ◽  
Hannah M. Harris ◽  
Narendar Dudhipala ◽  
Seong Jong Kim ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Activity ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Mu Opioid ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists

Analgesia is commonly mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. Recently, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold <i>via</i> an ester linker. <i>In vitro</i> studies showed that some of these compounds have dual agonism on kappa and mu opioid receptors, while some have triple agonism on kappa, mu, and delta. <i>In vivo </i>studies on the lead dual kappa and mu opioid receptor agonist, compound <b>10</b>, showed that it<b> </b>produced analgesic activity while avoiding anxiogenic effects in murine models, thus providing further strong evidence for the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

Methoxyflavones fromStachys glutinosawith Binding Affinity to Opioid Receptors: In Silico, in Vitro, and in Vivo Studies

2015 ◽  
Vol 78 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Stefania Ruiu ◽  
Nicola Anzani ◽  
Alessandro Orrù ◽  
Costantino Floris ◽  
Pierluigi Caboni ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Opioid Receptors ◽  
In Silico ◽  
In Vivo Studies
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