Rosiglitazone Alleviates Mechanical Allodynia of Rats with Bone Cancer Pain through the Activation of PPAR-γ to Inhibit the NF-κB/NLRP3 Inflammatory Axis in Spinal Cord Neurons

Fu, Jie; Zhao, Baoxia; Ni, Chaobo; Ni, Huadong; Xu, Longsheng; He, Qing; Xu, Miao; Xu, Chengfei; Luo, Ge; Zhu, Jianjun; Tao, Jiachun; Yao, Ming

doi:10.1155/2021/6086265

Cited by 13 publications

(9 citation statements)

References 55 publications

(55 reference statements)

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“…In the daytime-feeding group, we observed that PG intake at 7 PM led to an increase in PPAR- γ level and a decrease in pNF- κ B and IL-6 levels in liver tissues. Our data support the previous report [ 60 ] that rosiglitazone activated PPAR- γ to inhibit the NF- κ B inflammatory axis.…”

Section: Discussionsupporting

confidence: 93%

PPAR-γ Agonist Pioglitazone Restored Mouse Liver mRNA Expression of Clock Genes and Inflammation-Related Genes Disrupted by Reversed Feeding

Fedchenko¹,

Izmailova²,

Shynkevych³

et al. 2022

PPAR Research

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Introduction. The master clock, which is located in the suprachiasmatic nucleus (SCN), harmonizes clock genes present in the liver to synchronize life rhythms and bioactivity with the surrounding environment. The reversed feeding disrupts the expression of clock genes in the liver. Recently, a novel role of PPAR-γ as a regulator in correlating circadian rhythm and metabolism was demonstrated. This study examined the influence of PPAR-γ agonist pioglitazone (PG) on the mRNA expression profile of principle clock genes and inflammation-related genes in the mouse liver disrupted by reverse feeding. Methods. Mice were randomly assigned to daytime-feeding and nighttime-feeding groups. Mice in daytime-feeding groups received food from 7 AM to 7 PM, and mice in nighttime-feeding groups received food from 7 PM to 7 AM. PG was administered in the dose of 20 mg/kg per os as aqueous suspension 40 μl at 7 AM or 7 PM. Each group consisted of 12 animals. On day 8 of the feeding intervention, mice were sacrificed by cervical dislocation at noon (05 hours after light onset (HALO)) and midnight (HALO 17). Liver expressions of Bmal1, Clock, Rev-erb alpha, Cry1, Cry2, Per1, Per2, Cxcl5, Nrf2, and Ppar-γ were determined by quantitative reverse transcription PCR. Liver expression of PPAR-γ, pNF-κB, and IL-6 was determined by Western blotting. Glucose, ceruloplasmin, total cholesterol, triglyceride concentrations, and ALT and AST activities were measured in sera by photometric methods. The null hypothesis tested was that PG and the time of its administration have no influence on the clock gene expression impaired by reverse feeding. Results. Administration of PG at 7 AM to nighttime-feeding mice did not reveal any influence on the expression of the clock or inflammation-related genes either at midnight or at noon. In the daytime-feeding group, PG intake at 7 PM led to an increase in Per2 and Rev-erb alpha mRNA at noon, an increase in Ppar-γ mRNA at midnight, and a decrease in Nfκb (p65) mRNA at noon. In general, PG administration at 7 PM slightly normalized the impaired expression of clock genes and increased anti-inflammatory potency impaired by reversed feeding. This pattern was supported by biochemical substrate levels—glucose, total cholesterol, ALT, and AST activities. The decrease in NF-κB led to the inhibition of serum ceruloplasmin levels as well as IL-6 in liver tissue. According to our data, PG intake at 7 PM exerts strong normalization of clock gene expression with a further increase in Nrf2 and, especially, Ppar-γ and PPAR-γ expression with inhibition of Nfκb and pNF-κB expression in daytime-feeding mice. These expression changes resulted in decreased hyperglycemia, hypercholesterolemia, ALT, and AST activities. Thus, PG had a potent chronopharmacological effect when administered at 7 PM to daytime-feeding mice. Conclusions. Our study indicates that reversed feeding induced the disruption of mouse liver circadian expression pattern of clock genes accompanied by increasing Nfκb and pNF-κB and IL-6 expression and decreasing Nrf2 and PPAR-γ. Administration of PG restored the clock gene expression profile and decreased Nfκb, pNF-κB, and IL-6, as well as increased Nrf2, Ppar-γ, and PPAR-γ expression. PG intake at 7 PM was more effective than at 7 AM in reversed feeding mice.

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Section: Discussionsupporting

confidence: 93%

PPAR-γ Agonist Pioglitazone Restored Mouse Liver mRNA Expression of Clock Genes and Inflammation-Related Genes Disrupted by Reversed Feeding

Fedchenko¹,

Izmailova²,

Shynkevych³

et al. 2022

PPAR Research

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“…Previous studies suggest that the NF-κB/NLRP3 inflammatory axis performs a crucial part in pain ( Fu et al, 2021b ). Therefore, we decided to elucidate the potential molecular mechanisms by which catalpol inhibit inflammatory pain.…”

Section: Resultsmentioning

confidence: 99%

“…The procedure for extracting proteins was similar to an earlier experiment ( Fu et al, 2021b ). Through i. p. injection of sodium pentobarbital (100 mg/kg), rats were fully sedated.…”

Section: Methodsmentioning

confidence: 99%

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Catalpol ameliorates CFA-induced inflammatory pain by targeting spinal cord and peripheral inflammation

Zhao

Fu²,

Ni³

et al. 2022

Front. Pharmacol.

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Chronic, inflammatory pain is an international health concern that severely diminishes individuals’ quality of life. Catalpol is an iridoid glycoside derived from the roots of Rehmannia glutinosa that possesses anti-inflammatory, antioxidant, and neuroprotective properties for the treating multiple kinds of disorders. Nevertheless, catalpol’s impacts on inflammatory pain and its potential methods of action are still unclear. The purpose of this investigation is to determine the mechanism of catalpol to reduce the inflammatory pain behaviors in a rat model with complete Freund’s adjuvant (CFA). Catwalk, Von-Frey, and open field testing were performed for behavioral assessment. Western blot analysis and real-time quantitative PCR (RT-PCR) were employed to identify variations in molecular expression, while immunofluorescence was utilized to identify cellular localization. Catalpol effectively reduced CFA-induced mechanical allodynia and thermal hyperalgesia when injected intrathecally. Moreover, catalpol can regulate the HDAC4/PPAR-γ-signaling pathway in CFA rat spinal cord neurons. Meanwhile catalpol significantly decreased the expression of the NF-κB/NLRP3 inflammatory axis in the spinal cord of CFA rats. In addition, both in vivo and in vitro research revealed that catalpol treatment inhibited astrocyte activation and increase inflammatory factor expression. Interestingly, we also found that catalpol could alleviate peripheral pain by inhibiting tissue inflammation. Taken together, the findings declared that catalpol may inhibit inflammatory pain in CFA rats by targeting spinal cord and peripheral inflammation.

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“…PPARγ/RXRα has been proven to negatively regulate the NF-κB signal [ 22 ]. As shown in Figure 5 A,B, the protein expression of NF-κB in 95D cells were significantly decreased in DHA-PC, DHA-TG, and DHA-EE groups by 32.8% ( p < 0.01), 21.6% ( p < 0.01), and 15.5% ( p < 0.05) compared to the control group, respectively.…”

Section: Resultsmentioning

confidence: 99%

Comparative Study of Docosahexaenoic Acid with Different Molecular Forms for Promoting Apoptosis of the 95D Non-Small-Cell Lung Cancer Cells in a PPARγ-Dependent Manner

et al. 2022

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Cancer is a leading cause of death in worldwide. Growing evidence has shown that docosahexaenoic acid (DHA) has ameliorative effects on cancer. However, the effects of DHA-enriched phosphatidylcholine (DHA-PC) and efficacy differences between DHA-PC, DHA-triglyceride (DHA-TG), and DHA- ethyl esters (DHA-EE) on cancer cells had not been studied. In this study, 95D lung cancer cells in vitro were used to determine the effects and underlying mechanisms of DHA with different molecular forms. The results showed that DHA-PC and DHA-TG treatment significantly inhibited the growth of 95D cells by 53.7% and 33.8%, whereas DHA-EE had no significantly effect. Morphological analysis showed that DHA-PC and DHA-TG prompted promoted cell contraction, increased concentration of cell heterochromatin, vacuolization of cytoplasm, and edema of endoplasmic reticulum and mitochondria. TUNEL and AO/EB staining indicated that both DHA-PC and DHA-TG promoted cell apoptosis, in which DHA-PC performed better than DHA-TG. Mechanistically, DHA-PC and DHA-TG treatment up-regulated the PPARγ and RXRα signal, inhibited the expression of NF-κB and Bcl-2, and enhanced the expression of Bax and caspase-3, thereby promoting cell apoptosis. In conclusion, DHA-PC exerted superior effects to DHA-TG and DHA-EE in promoting apoptosis in 95D non-small-cell lung cancer cells. These data provide new evidence for the application of DHA in treatment of cancer.

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Rosiglitazone Alleviates Mechanical Allodynia of Rats with Bone Cancer Pain through the Activation of PPAR-γ to Inhibit the NF-κB/NLRP3 Inflammatory Axis in Spinal Cord Neurons

Cited by 13 publications

References 55 publications

PPAR-γ Agonist Pioglitazone Restored Mouse Liver mRNA Expression of Clock Genes and Inflammation-Related Genes Disrupted by Reversed Feeding

PPAR-γ Agonist Pioglitazone Restored Mouse Liver mRNA Expression of Clock Genes and Inflammation-Related Genes Disrupted by Reversed Feeding

Catalpol ameliorates CFA-induced inflammatory pain by targeting spinal cord and peripheral inflammation

Comparative Study of Docosahexaenoic Acid with Different Molecular Forms for Promoting Apoptosis of the 95D Non-Small-Cell Lung Cancer Cells in a PPARγ-Dependent Manner

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