Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models

Chia, Jasmine Siew Min; Farouk, Ahmad Akira Omar; Mohamad, Tengku Azam Shah Tengku; Sulaiman, Mohd Roslan; Zakaria, Hanis; Hassan, Nurul Izzaty; Perimal, Enoch Kumar

doi:10.3390/molecules26133849

Cited by 12 publications

(8 citation statements)

References 77 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, in a neuropathic pain model, miR-7a has been observed to be the most greatly decreased miRNA in the dorsal root ganglion, and upregulation of miR-7a resulted in recovery from neuropathic pain [37]. It has been experimentally shown that miR-137-3p regulates CDK6 [38] and KIT [39], while miR-378a-3p regulates specific pain-related genes including casp9 [40][41][42], IGF1R, MAPKAPK2, ODC1 [43], PPARA [44,45], and TP53 [46][47][48][49]. The miRNAs identified in this study are potential therapeutic targets and treatments for neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Analysis of the Rat Brain During Neuropathic Pain Development

Pando,

Misganaw,

Dimitrov

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Approximately 40% of Service Members deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) and an astounding 80% of Veterans overall report experiencing pain. Currently, drugs that adequately treat pain may result in addiction and substance abuse or negative side effects such as nausea, vomiting, renal and cardiovascular issues, among other physiological and cognitive problems. Inadequate acute pain management can lead to the development of chronic pain. Combat and non-combat injuries, acute and chronic pain all have the potential to impact return-to-duty rates/decisions, thereby negatively affecting the Fighting Force. To develop more effective pain therapeutics, the molecular mechanisms contributing to the development of neuropathic pain are under intense investigation and further research is needed to fully understand neuropathic pain induction and maintenance. The overarching objective of this study is to identify microRNA (miRNA) changes in key brain regions during the onset and progression of neuropathic pain in a rodent model. Results Changes in miRNA expression were observed at day 15 post-SNL in the amygdala and thalamus. The majority of changes were observed in the left side of the brain, contralateral to the right-sided SNL injury. The DE miRNAs identified mainly in the amygdala and thalamus did not overlap between brain regions. The altered miRNAs regulate key signaling pathways and genes important in pain development. Discussion The majority of epigenetic studies investigating altered miRNA expression in the pain field have explored the peripheral nervous system. Very few studies have evaluated miRNA dynamics in the brain following neuropathic pain development. This study provides key insights into changes occurring in the brain following peripheral nerve injury. Our lab has previously identified circulating extracellular vesicle (EV) miRNAs that are altered in the blood post-SNL. There is some overlap between the blood and brain miRNAs that may serve as key biomarkers in prognosis and/or diagnosis of a peripheral nerve injury and the development of chronic pain.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Analysis of the Rat Brain During Neuropathic Pain Development

Pando,

Misganaw,

Dimitrov

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The clinically used daily dosages of 10 mg up to 80 mg/d have proven lipid lowering ability [ 31 ] and reflect doses of ~150–1200 µg/kg (orally administered) with an oral bioavailability of ~20% [ 32 ]. The dosage of PPAR-α antagonist GW6471 (1 mg/kg) was also chosen based on the literature [ 18 , 33 , 34 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, to our best knowledge, no study has examined the successful PPAR-α inhibition by reduced transcription levels of its target proteins so far. As a proven inhibition of PPAR-α enables a clear conclusion regarding the dependency or independency of the observed pravastatin-mediated effects, this should be the subject of further studies [ 18 , 33 , 34 , 35 , 36 ].…”

Section: Limitationsmentioning

confidence: 99%

Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats

Kuebart

Groß

Ripkens

et al. 2023

IJMS

View full text Add to dashboard Cite

Microcirculatory and mitochondrial dysfunction are considered the main mechanisms of septic shock. Studies suggest that statins modulate inflammatory response, microcirculation, and mitochondrial function, possibly through their action on peroxisome proliferator-activated receptor alpha (PPAR-α). The aim of this study was to examine the effects of pravastatin on microcirculation and mitochondrial function in the liver and colon and the role of PPAR-α under septic conditions. This study was performed with the approval of the local animal care and use committee. Forty Wistar rats were randomly divided into 4 groups: sepsis (colon ascendens stent peritonitis, CASP) without treatment as control, sepsis + pravastatin, sepsis + PPAR-α-blocker GW6471, and sepsis + pravastatin + GW6471. Pravastatin (200 µg/kg s.c.) and GW6471 (1 mg/kg) were applied 18 h before CASP-operation. 24 h after initial surgery, a relaparotomy was performed, followed by a 90 min observation period for assessment of microcirculatory oxygenation (μHbO2) of the liver and colon. At the end of the experiments, animals were euthanized, and the colon and liver were harvested. Mitochondrial function was measured in tissue homogenates using oximetry. The ADP/O ratio and respiratory control index (RCI) for complexes I and II were calculated. Reactive oxygen species (ROS) production was assessed using the malondialdehyde (MDA)-Assay. Statistics: two-way analysis of variance (ANOVA) + Tukey’s/Dunnett’s post hoc test for microcirculatory data, Kruskal–Wallis test + Dunn’s post hoc test for all other data. In control septic animals µHbO2 in liver and colon deteriorated over time (µHbO2: −9.8 ± 7.5%* and −7.6 ± 3.3%* vs. baseline, respectively), whereas after pravastatin and pravastatin + GW6471 treatment μHbO2 remained constant (liver: µHbO2 pravastatin: −4.21 ± 11.7%, pravastatin + GW6471: −0.08 ± 10.3%; colon: µHbO2 pravastatin: −0.13 ± 7.6%, pravastatin + GW6471: −3.00 ± 11.24%). In both organs, RCI and ADP/O were similar across all groups. The MDA concentration remained unchanged in all groups. Therefore, we conclude that under septic conditions pravastatin improves microcirculation in the colon and liver, and this seems independent of PPAR-α and without affecting mitochondrial function.

show abstract

“…In addition to the compounds mentioned above, other natural phytochemicals showed potential PPARs ligand activity in research studies ( Table 1 ). Terpenoids such as 1,8-cineole [ 7 , 179 ], gingerol [ 7 ], cinnamaldehyde [ 180 ], carvacrol [ 181 ], zerumbone [ 182 ], oridonin [ 183 ], tanshinone IIA [ 184 ], pedunculoside [ 185 ], and lycopene and β -carotene [ 186 ] acted as dual PPARs activators for exhibiting antiatherosclerotic, antiadipogenic, anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemia effects. Interestingly, betulinic acid (a triterpenoid) had PPAR γ and PPAR α antagonist activity in 3T3-L1 cells to boost glucose uptake and osteogenesis, along with adipogenesis inhibition [ 187 ].…”

Section: Phytochemicals With Ppar Modulation Activitiesmentioning

confidence: 99%

Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments

et al. 2022

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) are members of the ligand-dependent nuclear receptor family. PPARs have attracted wide attention as pharmacologic mediators to manage multiple diseases and their underlying signaling targets. They mediate a broad range of specific biological activities and multiple organ toxicity, including cellular differentiation, metabolic syndrome, cancer, atherosclerosis, neurodegeneration, cardiovascular diseases, and inflammation related to their up/downstream signaling pathways. Consequently, several types of selective PPAR ligands, such as fibrates and thiazolidinediones (TZDs), have been approved as their pharmacological agonists. Despite these advances, the use of PPAR agonists is known to cause adverse effects in various systems. Conversely, some naturally occurring PPAR agonists, including polyunsaturated fatty acids and natural endogenous PPAR agonists curcumin and resveratrol, have been introduced as safe agonists as a result of their clinical evidence or preclinical experiments. This review focuses on research on plant-derived active ingredients (natural phytochemicals) as potential safe and promising PPAR agonists. Moreover, it provides a comprehensive review and critique of the role of phytochemicals in PPARs-related diseases and provides an understanding of phytochemical-mediated PPAR-dependent and -independent cascades. The findings of this research will help to define the functions of phytochemicals as potent PPAR pharmacological agonists in underlying disease mechanisms and their related complications.

show abstract

Zerumbone Ameliorates Neuropathic Pain Symptoms via Cannabinoid and PPAR Receptors Using In Vivo and In Silico Models

Cited by 12 publications

References 77 publications

MicroRNA Expression Analysis of the Rat Brain During Neuropathic Pain Development

MicroRNA Expression Analysis of the Rat Brain During Neuropathic Pain Development

Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats

Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments

Contact Info

Product

Resources

About