Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice

Piccinelli, Ana Claudia; Morato, Priscila Neder; Barbosa, Marcelo dos Santos; Croda, Júlio; Sampson, Jared M.; Kong, Xiang‐Peng; Konkiewitz, Elisabete Castelon; Ziff, Edward B.; Amaya-Farfán, Jaime; Kassuya, Cândida Aparecida Leite

doi:10.1016/j.lfs.2016.11.017

Cited by 34 publications

(22 citation statements)

References 44 publications

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“…This finding revealed that RT modulated the neuro-inflammation in peripheral nerve through its anti-TNF-α action and it could be one of its anti-nociceptive mechanisms. IL-1β is known to be expressed in nociceptive neurons and it has important role in several pain models 52 , 53 . The IL-1β increases the neuropathic pain sensitization through its action on the adjacent neurons 34 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

Magar

Nayak

Mahajan

et al. 2018

Sci Rep

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Despite the availability of multiple therapeutic agents, the search for novel pain management of neuropathic pain is still a challenge. Oxidative stress and inflammatory signaling are prominently involved in clinical manifestation of neuropathic pain. Toxicodendron pubescens, popularly known as Rhus Tox (RT) is recommended in alternative medicines as an anti-inflammatory and analgesic remedy. Earlier, we reported anti-inflammatory, anti-arthritic and immunomodulatory activities of Rhus Tox. In continuation, we evaluated antinociceptive efficacy of Rhus Tox in the neuropathic pain and delineated its underlying mechanism. Initially, in-vitro assay using LPS-mediated ROS-induced U-87 glioblastoma cells was performed to study the effect of Rhus Tox on reactive oxygen species (ROS), anti-oxidant status and cytokine profile. Rhus Tox decreased oxidative stress and cytokine release with restoration of anti-oxidant systems. Chronic treatment with Rhus Tox ultra dilutions for 14 days ameliorated neuropathic pain revealed as inhibition of cold, warm and mechanical allodynia along with improved motor nerve conduction velocity (MNCV) in constricted nerve. Rhus Tox decreased the oxidative and nitrosative stress by reducing malondialdehyde (MDA) and nitric oxide (NO) content, respectively along with up regulated glutathione (GSH), superoxide dismutase (SOD) and catalase activity in sciatic nerve of rats. Notably, Rhus Tox treatment caused significant reductions in the levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) as compared with CCI-control group. Protective effect of Rhus Tox against CCI-induced sciatic nerve injury in histopathology study was exhibited through maintenance of normal nerve architecture and inhibition of inflammatory changes. Overall, neuroprotective effect of Rhus Tox in CCI-induced neuropathic pain suggests the involvement of anti-oxidative and anti-inflammatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

Magar

Nayak

Mahajan

et al. 2018

Sci Rep

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“…HIV CCR5-tropic gp120 (JRFL) was obtained from Dr. C.A.L. Kassuya at the Federal University of Grande Dourados, Brazil [ 104 ]. The following inhibitors were used in this study: 200-nM AMD3100 (Tocris), 25-μM 2APB (Abcam), 10-μM Dantrolene (Abcam), 25-μM or 50-μM DL-APV (Abcam), 2-μM NPA (Tocris), 1-μM or 10-μM Rp8-Br-PET-cGMPS (Tocris) for cultured mouse or feline neurons, respectively, 10-μM or 30-μM CNQX (Abcam), 1-μM TTX (Tocris), 10-μM nifedipine (Abcam), and 20-nM human SDF-1 (Abcam).…”

Section: Methodsmentioning

confidence: 99%

HIV induces synaptic hyperexcitation via cGMP-dependent protein kinase II activation in the FIV infection model

et al. 2018

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Over half of individuals infected with human immunodeficiency virus (HIV) suffer from HIV-associated neurocognitive disorders (HANDs), yet the molecular mechanisms leading to neuronal dysfunction are poorly understood. Feline immunodeficiency virus (FIV) naturally infects cats and shares its structure, cell tropism, and pathology with HIV, including wide-ranging neurological deficits. We employ FIV as a model to elucidate the molecular pathways underlying HIV-induced neuronal dysfunction, in particular, synaptic alteration. Among HIV-induced neuron-damaging products, HIV envelope glycoprotein gp120 triggers elevation of intracellular Ca2+ activity in neurons, stimulating various pathways to damage synaptic functions. We quantify neuronal Ca2+ activity using intracellular Ca2+ imaging in cultured hippocampal neurons and confirm that FIV envelope glycoprotein gp95 also elevates neuronal Ca2+ activity. In addition, we reveal that gp95 interacts with the chemokine receptor, CXCR4, and facilitates the release of intracellular Ca2+ by the activation of the endoplasmic reticulum (ER)-associated Ca2+ channels, inositol triphosphate receptors (IP3Rs), and synaptic NMDA receptors (NMDARs), similar to HIV gp120. This suggests that HIV gp120 and FIV gp95 share a core pathological process in neurons. Significantly, gp95’s stimulation of NMDARs activates cGMP-dependent protein kinase II (cGKII) through the activation of the neuronal nitric oxide synthase (nNOS)-cGMP pathway, which increases Ca2+ release from the ER and promotes surface expression of AMPA receptors, leading to an increase in synaptic activity. Moreover, we culture feline hippocampal neurons and confirm that gp95-induced neuronal Ca2+ overactivation is mediated by CXCR4 and cGKII. Finally, cGKII activation is also required for HIV gp120-induced Ca2+ hyperactivation. These results thus provide a novel neurobiological mechanism of cGKII-mediated synaptic hyperexcitation in HAND.

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“…Normal group in which rats administered saline for 21 days orally then saline subcutaneously (s.c.) on 20th and 21st day. Limonene control group in which the animals were managed with D-Limonene purchased from Sigma Company, (50 mg/kg, orally) [7,12] for 21 days and then injected with saline (s.c.) on 20th and 21st day day. ISO control group in which animals were administered saline orally for 21 days then administered ISO (85 mg/kg, s.c.) [19,23] on 20th and 21st day for myocardial infraction induction.…”

Section: Experimental Designmentioning

confidence: 99%

“…D-Limonene, monocyclic monoterpene, is a main component in numerous citrus oils (orange, lemon, mandarin, lime, and grapefruit) [1]. D-Limonene demonstrated various pharmacological actions include anti-inflammatory [2][3][4][5][6][7], antioxidant [7][8][9][10][11], lipid-lowering [11], anti-atherogenic [11], anti-nociceptive [12], anti-diabetic [13] anti-fibrotic [14], chemo-preventive [1] and im-munosuppressive [15] actions. Also D-Limonene managed metabolic syndrome [16,17], and decreased of serum lipid levels via modulating liver X receptors signaling [16].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, D-Limonene exerted healing effects in the gastrointestinal tract [6,7,18], relieving occasional heartburn and gastroesophageal reflux disorder therefore; has been clinically used to dissolve cholesterolcontaining gallstones [1]. As for the anti-inflammatory effects, D-Limonene demonstrated anti-inflammatory effect specifically Younis NS through reducing the levels of tumor necrosis factor (TNF)-α [2,3,6,12], interleukin (IL)-6 [2], IL-1β [2,12] and NF-κB [2,4,6].…”

Section: Introductionmentioning

confidence: 99%

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D-Limonene mitigate myocardial injury in rats through MAPK/ERK/NF-κB pathway inhibition

Younis

2020

Korean J Physiol Pharmacol

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Cardiovascular diseases are the primary reason of mortality, among which myocardial infarction (MI) is the most dominant and prevalent. This study was considered to examine D-Limonene protective action against isoproterenol (ISO) induced MI. Wister male rats were dispersed into four groups. Normal and D-Limonene control group in which rats administered saline or D-Limonene. ISO control animals were administered saline for 21 days then challenged with ISO (85 mg/kg, subcutaneously) on 20th and 21st day for MI induction. D-Limonene pretreated group in which animals were pretreated with D-Limonene 50 mg/kg orally for 21 days then administered ISO on 20th and 21st day. MI prompted variations were assessed by myocardial infarction area determination, blood pressure (BP) alterations, cardiac injury biomarkers and inflammatory mediators measurements. For more depth investigation, both the apoptotic status was evaluated via measuring mRNA expression of Bcl-2 and Bax as well as mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signal transduction were investigated via Western blotting. MI group revealed significant infarcted area, blood pressure alterations, myocardial injury enzymes intensification together with inflammatory cytokines amplification. MI was associated with activation of MAPK-ERK signal pathway and apoptotic status within the myocardium. On the other hand, pretreated with D-Limonene demonstrated deterred infracted area, reduced myocardial enzymes, improved BP indices, lessened inflammatory levels. Furthermore, D-Limonene pretreatment caused a decline in MAPK proteins pathway and Bax relative mRNA expression, while intensifying Bcl-2 mRNA expression promoting that D-Limonene may constrain MI induced myocardial apoptosis. D-Limonene mitigated MI injury through MAPK/NF-κB pathway inhibition and anti-apoptotic effect.

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Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice

Cited by 34 publications

References 44 publications

RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

HIV induces synaptic hyperexcitation via cGMP-dependent protein kinase II activation in the FIV infection model

D-Limonene mitigate myocardial injury in rats through MAPK/ERK/NF-κB pathway inhibition

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