Cedrol protects against chronic constriction injury-induced neuropathic pain through inhibiting oxidative stress and inflammation

Sakhaee, Mohammad Hossein; Sayyadi, Seyed Amir Hossein; Sakhaee, Nader; Sadeghnia, Hamid Reza; Hosseinzadeh, Hossein; Nourbakhsh, Fahimeh; Forouzanfar, Fatemeh

doi:10.1007/s11011-020-00581-8

Cited by 21 publications

(9 citation statements)

References 45 publications

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“…These results are in accordance with the previous study reported that administration of cedrol (20 and 40 mg/kg, i.p.) once a day for 14 days postchronic constriction injury model of neuropathic pain attenuated nociception pain behaviors in rats by inhibition of inflammatory response and reduction of oxidative stress markers [ 12 ]. Another study showed cedrol reduced collagen-induced arthritis in mice and modulates the inflammatory response in lipopolysaccharide-mediated fibroblast-like synoviocytes [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies showed that sesquiterpenes have various therapeutic effects, such as being effective in pain management [ 9 ], protection against stroke [ 10 ], and RA [ 11 ]. Cedrol, a natural sesquiterpene, is known to carry many pharmacological effects, including antioxidant [ 12 ], anti-inflammatory [ 13 ], antibacterial [ 14 ], analgesic [ 12 ], sedative [ 15 ], hair growth inducer [ 16 ], platelet-activating factor (PAF) antagonist [ 17 ], and antitumor effects [ 18 ]. The present investigation is aimed at evaluating the potential antiarthritic effect of cedrol on complete Freund's adjuvant- (CFA-) induced experimental arthritis in rats.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis

Forouzanfar

Pourbagher‐Shahri

Ghazavi

2022

Oxidative Medicine and Cellular Longevity

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Pharmacological studies revealed that cedrol, a natural sesquiterpene, has antioxidant, anti-inflammatory, and analgesic properties. This study is aimed at evaluating the potential antiarthritic activity of cedrol in a rat experimental model of arthritis induced by using complete Freund’s adjuvant (CFA). Arthritis was induced in Wistar rats by CFA (0.1 ml) injection. Cedrol (10 and 20 mg/kg) and indomethacin (5 mg/kg) were orally administered from day one and continued for 21 days. The antiarthritic activity was assessed through mechanical allodynia and thermal hyperalgesia responses, paw edema assessment, and arthritis scores. Serum TNF-α and IL-1β levels were measured for the evaluation of inflammation. Furthermore, serum oxidative stress markers, including malondialdehyde (MDA) and thiol levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were also assessed. Oral administration of cedrol and indomethacin significantly decreased paw edema and arthritis score. Besides, cedrol and indomethacin significantly decreased pain responses. In the serum of the CFA group, TNF-α, IL-1β, and MDA were higher, while thiol and SOD and GPx were lower than the control group. Treatment by cedrol and indomethacin corrected the biochemical parameters in the serum. In this study, cedrol offers potential antiarthritic properties through its anti-inflammatory and antioxidant effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis

Forouzanfar

Pourbagher‐Shahri

Ghazavi

2022

Oxidative Medicine and Cellular Longevity

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“…Hence, we detected the inflammation and found elevated TNF-α, IL-1β, and IL-6 levels, and decreased IL-10 in CCI rats as expected. TNF-α is imperative in regulating immediate and ongoing stages of NP and the administration of TNF-α or IL-6 evokes thermal hyperalgesia and mechanical allodynia in rats [ 56 ]. Due to the substantial involvement of DNMT1 in NP as existing research reported [ 57 ], we measured the expression of DNMT1 and noted an upregulated DNMT1 in activated microglia of CCI rats, which was similar to the findings of Sarah L et al [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

RNA interference-mediated silencing of DNA methyltransferase 1 attenuates neuropathic pain by accelerating microglia M2 polarization

et al. 2022

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Background DNA methyltransferase 1 (DNMT1) exerts imperative functions in neuropathic pain (NP). This study explored the action of RNA interference-mediated DNMT1 silencing in NP by regulating microglial M2 polarization. Methods NP rat models were established using chronic constriction injury (CCI) and highly aggressive proliferating immortalized (HAPI) microglia were treated with lipopolysaccharide (LPS) to induce microglia M1 polarization, followed by treatment of DNMT1 siRNA or si-DNMT1/oe-DNMT1, respectively. The pain threshold of CCI rats was assessed by determining mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Levels of inflammatory factors (TNF-α/IL-1β/IL-6/IL-10) and DNMT1 in rat L4-L6 spinal cord samples and HAPI cells were measured using ELISA, RT-qPCR, and Western blot. iNOS and Arg-1 mRNA levels were measured via RT-qPCR. DNMT1, M1 marker (iNOS), and M2 marker (Arg-1) levels in microglia of CCI rats were detected by immunofluorescence. Percentages of M1 microglia phenotype (CD16) and M2 microglia phenotype (CD206) were detected by flow cytometry. The phosphorylation of PI3K/Akt pathway-related proteins was determined by Western blot. Results CCI rats exhibited diminished MWT and TWL values, increased pro-inflammatory cytokines, and decreased anti-inflammatory cytokine IL-10. Additionally, DNMT1 was upregulated in CCI rat microglia. DNMT1 siRNA alleviated CCI-induced NP and facilitated M2 polarization of microglia in CCI rats. DNMT1 knockdown inhibited LPS-induced M1 polarization of HAPI cells and promoted M2 polarization by blocking the PI3K/Akt pathway, but DNMT1 overexpression inhibited the M1-to-M2 polarization of microglia. Conclusion RNA interference-mediated DNMT1 silencing accelerates microglia M2 polarization by impeding the PI3K/Akt pathway, thereby alleviating CCI-induced NP.

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“…The chronic constriction injury-induced neuropathic pain (NP) model is a reproducible model for determining the effects of any pharmacological agents [ 20 , 21 , 22 ]. It has been already established and well explained [ 2 ] that the level of inflammatory mediators including IL-6, TNF, and IL-10 markedly increase in a damaged or constricted sciatic nerve.…”

Section: Discussionmentioning

confidence: 99%

1,3,4-Oxadiazole Derivative Attenuates Chronic Constriction Injury Induced Neuropathic Pain: A Computational, Behavioral, and Molecular Approach

et al. 2020

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The production and up-regulation of inflammatory mediators are contributing factors for the development and maintenance of neuropathic pain. In the present study, the post-treatment of synthetic 1,3,4 oxadiazole derivative (B3) for its neuroprotective potential in chronic constriction injury-induced neuropathic pain was applied. In-silico studies were carried out through Auto Dock, PyRx, and DSV to obtain the possible binding and interactions of the ligands (B3) with COX-2, IL-6, and iNOS. The sciatic nerve of the anesthetized rat was constricted with sutures 3/0. Treatment with 1,3,4-oxadiazole derivative was started a day after surgery and continued until the 14th day. All behavioral studies were executed on day 0, 3rd, 7th, 10th, and 14th. The sciatic nerve and spinal cord were collected for further molecular analysis. The interactions in the form of hydrogen bonding stabilizes the ligand target complex. B3 showed three hydrogen bonds with IL-6. B3, in addition to correcting paw posture/deformation induced by CCI, attenuates hyperalgesia (p < 0.001) and allodynia (p < 0.001). B3 significantly raised the level of GST and GSH in both the sciatic nerve and spinal cord and reduced the LPO and iNOS (p < 0.001). B3 attenuates the pathological changes induced by nerve injury, which was confirmed by H&E staining and IHC examination. B3 down-regulates the over-expression of the inflammatory mediator IL-6 and hence provides neuroprotective effects in CCI-induced pain. The results demonstrate that B3 possess anti-nociceptive and anti-hyperalgesic effects and thus minimizes pain perception and inflammation. The possible underlying mechanism for the neuroprotective effect of B3 probably may be mediated through IL-6.

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Cedrol protects against chronic constriction injury-induced neuropathic pain through inhibiting oxidative stress and inflammation

Cited by 21 publications

References 45 publications

Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis

Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis

RNA interference-mediated silencing of DNA methyltransferase 1 attenuates neuropathic pain by accelerating microglia M2 polarization

1,3,4-Oxadiazole Derivative Attenuates Chronic Constriction Injury Induced Neuropathic Pain: A Computational, Behavioral, and Molecular Approach

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