PPAR Research最新文献

{"title":"Hydroxychloroquine Potentiates Apoptosis Induced by PPAR<i>α</i> Antagonist in 786-O Clear Cell Renal Cell Carcinoma Cells Associated with Inhibiting Autophagy.","authors":"Ruizhe Mao,&nbsp;Jian Shi,&nbsp;Xuyi Ma,&nbsp;Haiyan Xu","doi":"10.1155/2021/6631605","DOIUrl":"https://doi.org/10.1155/2021/6631605","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is the major pathological pattern of renal cell carcinoma. The ccRCC cells exhibit a certain degree of inherent drug resistance due to some genetic mutations. In recent years, peroxisome proliferator-activated receptor-<i>α</i> (PPAR<i>α</i>) antagonists have been reported as a targeted therapeutic drug capable of inducing apoptosis and cell cycle arrest in the ccRCC cell line. Autophagy, which can be induced by stress in eukaryotic cells, plays a complex role in the proliferation, survival, and death of tumor cells. In our study, we found that the expression of PPAR<i>α</i> was low in highly differentiated ccRCC tissues and 786-O cell line but high in poorly differentiated ccRCC tissues. The level of PPAR<i>α</i> expression in ccRCC tissues is correlated to the grade of differentiation, but not to the sex or age of ccRCC patients. The findings also revealed that the PPAR<i>α</i> antagonist GW6471 can lower cell viability and induce autophagy in the 786-O ccRCC cell line. This autophagy can be inhibited by hydroxychloroquine. When treated with a combination of hydroxychloroquine and GW6471, the viability of the 786-O cells was decreased further when compared to the treatment with GW6471 or hydroxychloroquine alone, and apoptosis was promoted. Meanwhile, when human kidney 2 cells were cotreated with hydroxychloroquine and GW6471, cell viability was only slightly influenced. Hence, our finding indicates that the combination of GW6471 and hydroxychloroquine may constitute a novel and potentially effective treatment for ccRCC. Furthermore, this approach is likely to be safe owing to its minimal effects on normal renal tissues.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6631605"},"PeriodicalIF":2.9,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38958174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fenofibrate Exerts Antitumor Effects in Colon Cancer via Regulation of DNMT1 and CDKN2A.","authors":"Rui Kong,&nbsp;Nan Wang,&nbsp;Wei Han,&nbsp;Wen Bao,&nbsp;Jie Lu","doi":"10.1155/2021/6663782","DOIUrl":"https://doi.org/10.1155/2021/6663782","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor alpha (PPARA) is the molecular target of fibrates commonly used to treat dyslipidemia and diabetes. Recently, the potential role of PPARA in other pathological conditions, such as cancers, has been recognized. Here, using bioinformatics analysis, we found that PPARA was expressed at relatively low levels in pancancers, and Kaplan-Meier analyses revealed that high PPARA protein expression was correlated with better survival of patients with colon cancer. <i>In vitro</i> experiments showed that fenofibrate regulated cell cycle distribution, promoted apoptosis, and suppressed cell proliferation and epithelial mesenchymal transition by activating PPARA. PPARA activation inhibited DNMT1 activity and abolished methylation-mediated CDKN2A repression. Downregulation of cyclin-CDK complexes led to the restoration of CDKN2A, which caused cell cycle arrest in the G1 phase via regulation of the CDKN2A/RB/E2F pathway. Finally, we demonstrated that fenofibrate administration inhibited tumor growth and DNMT1 activity <i>in vivo</i>. The PPARA agonist, fenofibrate, might serve as an applicable agent for epigenetic therapy of colon cancer patients.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6663782"},"PeriodicalIF":2.9,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38958175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of PPAR<i>β</i>/<i>δ</i> within Human Dental Pulp Cells: A Preliminary In Vitro Study.","authors":"Caroline L de Lima,&nbsp;Bruna R Amorim,&nbsp;Carine Royer,&nbsp;Augusto P Resende,&nbsp;Maria F Borin,&nbsp;Francisco A R Neves,&nbsp;Ana Carolina Acevedo","doi":"10.1155/2021/8854921","DOIUrl":"https://doi.org/10.1155/2021/8854921","url":null,"abstract":"<p><p>Controlling the inflammatory response to restore tissue homeostasis is a crucial step to maintain tooth vitality after pathogen removal from caries-affected dental tissues. The nuclear peroxisome proliferator-activated receptor beta/delta (PPAR<i>β</i>/<i>δ</i>) is a ligand-activated transcription factor with emerging anti-inflammatory roles in many cells and tissues. However, its expression and functions are poorly understood in human dental pulp cells (hDPCs). Thus, this study evaluated PPAR<i>β</i>/<i>δ</i> expression and assessed the anti-inflammatory effects evoked by activation of PPAR<i>β</i>/<i>δ</i> in lipopolysaccharide- (LPS-) induced hDPCs. Our results showed that hDPCs constitutively expressed PPAR<i>β</i>/<i>δ</i> mRNA/protein, and treatment with LPS increased <i>PPARβ/δ</i> mRNA expression. The selective PPAR<i>β</i>/<i>δ</i> agonist GW0742 significantly decreased inflammation-related mRNA expression in hDPCs (<i>IL6</i>, <i>IL1β</i>, <i>TNFα</i>, <i>MMP1</i>, and <i>MMP2</i>) and RAW264.7 cells (<i>Il6</i> and <i>Tnfα</i>). Further, PPAR<i>β</i>/<i>δ</i> agonist attenuated MMP2/9 gelatinolytic activity in hDPCs. Previously LPS-conditioned hDPCs increased the migration of RAW264.7 cells through the membrane of a Transwell coculture system. Conversely, pretreatment with GW0742 markedly decreased macrophage recruitment. These findings provide among the first evidence that hDPCs express PPAR<i>β</i>/<i>δ</i>. In addition, they suggest that activation of PPAR<i>β</i>/<i>δ</i> by GW0742 can attenuate some cellular and molecular in vitro aspects related to the inflammatory process, pointing out to investigate its potential target role in dental pulp inflammation.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"8854921"},"PeriodicalIF":2.9,"publicationDate":"2021-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25547063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Potential PPAR-Related Multigene Signature Predicting Prognosis of Patients with Hepatocellular Carcinoma.","authors":"Wenfang Xu,&nbsp;Zhen Chen,&nbsp;Gang Liu,&nbsp;Yuping Dai,&nbsp;Xuanfu Xu,&nbsp;Duan Ma,&nbsp;Lei Liu","doi":"10.1155/2021/6642939","DOIUrl":"https://doi.org/10.1155/2021/6642939","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptors (PPARs) and part of their target genes have been reported to be related to the progression of hepatocellular carcinoma (HCC). The prognosis of HCC is not optimistic, and more accurate prognostic markers are needed. This study focused on discovering potential prognostic markers from the PPAR-related gene set. The mRNA data and clinical information of HCC were collected from TCGA and GEO platforms. Univariate Cox and lasso Cox regression analyses were used to screen prognostic genes of HCC. Three genes (<i>MMP1</i>, <i>HMGCS2</i>, and <i>SLC27A5</i>) involved in the PPAR signaling pathway were selected as the prognostic signature of HCC. A formula was established based on the expression values and multivariate Cox regression coefficients of selected genes, that was, risk score = 0.1488∗expression value of <i>MMP</i>1 + (-0.0393)∗expression value of <i>HMGCS</i>2 + (-0.0479)∗expression value of <i>SLC</i>27<i>A</i>5. The prognostic ability of the three-gene signature was assessed in the TCGA HCC dataset and verified in three GEO sets (GSE14520, GSE36376, and GSE76427). The results showed that the risk score based on our signature was a risk factor with a HR (hazard ratio) of 2.72 (95%CI (Confidence Interval) = 1.87 ~ 3.95, <i>p</i> < 0.001) for HCC survival. The signature could significantly (<i>p</i> < 0.0001) distinguish high-risk and low-risk patients with poor prognosis for HCC. In addition, we further explored the independence and applicability of the signature with other clinical indicators through multivariate Cox analysis (<i>p</i> < 0.001) and nomogram analysis (C-index = 0.709). The above results indicate that the combination of <i>MMP1</i>, <i>HMGCS</i>2, and <i>SLC</i>27<i>A</i>5 selected from the PPAR signaling pathway could effectively, independently, and applicatively predict the prognosis of HCC. Our research provided new insights to the prognosis of HCC.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6642939"},"PeriodicalIF":2.9,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25524636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-22-3p/PGC1<i>β</i> Suppresses Breast Cancer Cell Tumorigenesis via PPAR<i>γ</i>.","authors":"Xuehui Wang,&nbsp;Zhilu Yao,&nbsp;Lin Fang","doi":"10.1155/2021/6661828","DOIUrl":"https://doi.org/10.1155/2021/6661828","url":null,"abstract":"<p><p>In this study, we found that miR-22-3p expression was decreased in breast cancer (BC) cell lines and tissues. Overexpression of miR-22-3p inhibited the proliferation and migration of BC cells in vitro and in vivo, while depletion of miR-22-3p exhibited the opposite effect. Importantly, miR-22-3p could directly target PGC1<i>β</i> and finally regulate the PPAR<i>γ</i> pathway in BC. In conclusion, miR-22-3p/PGC1<i>β</i> suppresses BC cell tumorigenesis via PPAR<i>γ</i>, which may become a potential biomarker and therapeutic target.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6661828"},"PeriodicalIF":2.9,"publicationDate":"2021-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25524637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pemafibrate Pretreatment Attenuates Apoptosis and Autophagy during Hepatic Ischemia-Reperfusion Injury by Modulating JAK2/STAT3<i>β</i>/PPAR<i>α</i> Pathway.","authors":"Ziqi Cheng,&nbsp;Chuanyong Guo","doi":"10.1155/2021/6632137","DOIUrl":"https://doi.org/10.1155/2021/6632137","url":null,"abstract":"<p><p>Hepatic ischemia-reperfusion injury (HIRI) is a common phenomenon in liver transplantation and liver surgery. This article is aimed at clarifying the role of pemafibrate in HIRI through JAK2/STAT3<i>β</i>/PPAR<i>α</i>. In the experiment, we divided Balb/c into seven groups, namely, normal control (NC), Sham, PEM (1.0 mg/kg), IRI, IRI + PEM (0.1 mg/kg), IRI + PEM (0.5 mg/kg), and IRI + PEM (1.0 mg/kg). We used biochemical assay, histopathological evaluation, immunohistochemistry, RT-PCR and qRT-PCR, ELISA analysis, and other methods to determine the level of serum AST, ALT, IL-1<i>β</i>, and TNF-<i>α</i> in the liver at three time points (2 h, 8 h, and 24 h) after reperfusion of apoptosis factor, autophagy factor, and the JAK2/STAT3/PPAR<i>α</i> content in tissues. Our experiment results showed that the pemafibrate can effectively reduce the level of hepatic IR injury. In addition, pemafibrate has anti-inflammatory, antiapoptotic, and antiautophagy effects, which are mediated by the JAK2/STAT3<i>β</i>/PPAR<i>α</i> pathway.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6632137"},"PeriodicalIF":2.9,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25524635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOCK4 Is a Platinum-Chemosensitive and Prognostic-Related Biomarker in Ovarian Cancer.","authors":"Qianqian Zhao,&nbsp;Jie Zhong,&nbsp;Ping Lu,&nbsp;Xiao Feng,&nbsp;Ying Han,&nbsp;Chenqi Ling,&nbsp;Wenke Guo,&nbsp;Weijin Zhou,&nbsp;Fudong Yu","doi":"10.1155/2021/6629842","DOIUrl":"https://doi.org/10.1155/2021/6629842","url":null,"abstract":"<p><p>Ovarian carcinoma (OV) is a lethal gynecological malignancy. Most OV patients develop resistance to platinum-based chemotherapy and recurrence. Peroxisome proliferator-activated receptors (PPARs) are the ligand activating transcription factor of the nuclear receptor superfamily. PPARs as important transcriptional regulators regulate important physiological processes such as lipid metabolism, inflammation, and wound healing. Several reports point out that PPARs can also have an effect on the sensitivity of tumor cells to platinum-based chemotherapy drugs. However, the role of PPAR-target related genes (PPAR-TRGs) in chemotherapeutic resistance of OV remains unclear. The present study is aimed at optimizing candidate genes by integrating platinum-chemotherapy expression data and PPAR family genes with their targets. The gene expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. A total of 4 genes (<i>AP2A2</i>, <i>DOCK4</i>, <i>HSDL2</i>, and <i>PDK4</i>) were the candidate differentially expressed genes (DEGs) of PPAR-TRGs with platinum chemosensitivity. After conducting numerous survival analyses using different cohorts, we found that only the upexpression of <i>DOCK4</i> has important significance with the poor prognosis of OV patients. Meanwhile, <i>DOCK4</i> is detected in plasma and enriched in neutrophil and monocyte cells of the blood. We further found that there were significant correlations between <i>DOCK4</i> expression and the levels of CD4+ T cell infiltration, dendritic cell infiltration, and neutrophil infiltration in OV. In addition, we verified the expression level of <i>DOCK4</i> in OV cell lines treated with platinum drugs and found that <i>DOCK4</i> is potentially responsive to platinum drugs. In conclusion, <i>DOCK4</i> is potentially associated with immune cell infiltration and represents a valuable prognostic biomarker in ovarian cancer patients.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6629842"},"PeriodicalIF":2.9,"publicationDate":"2021-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25391283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-<i>α</i> Activation.","authors":"Jie Zhang,&nbsp;Ping Cheng,&nbsp;Weiqi Dai,&nbsp;Jie Ji,&nbsp;Liwei Wu,&nbsp;Jiao Feng,&nbsp;Jianye Wu,&nbsp;Qiang Yu,&nbsp;Jingjing Li,&nbsp;Chuanyong Guo","doi":"10.1155/2021/6658944","DOIUrl":"https://doi.org/10.1155/2021/6658944","url":null,"abstract":"<p><p>Hepatic ischemia and reperfusion injury is characterized by hepatocyte apoptosis, impaired autophagy, and oxidative stress. Fenofibrate, a commonly used antilipidemic drug, has been verified to exert hepatic protective effects in other cells and animal models. The purpose of this study was to identify the function of fenofibrate on mouse hepatic IR injury and discuss the possible mechanisms. A segmental (70%) hepatic warm ischemia model was established in Balb/c mice. Serum and liver tissue samples were collected for detecting pathological changes at 2, 8, and 24 h after reperfusion, while fenofibrate (50 mg/kg, 100 mg/kg) was injected intraperitoneally 1 hour prior to surgery. Compared to the IR group, pretreatment of FF could reduce the inflammatory response and inhibit apoptosis and autophagy. Furthermore, fenofibrate can activate PPAR-<i>α</i>, which is associated with the phosphorylation of AMPK.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6658944"},"PeriodicalIF":2.9,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25382880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin Alleviates Liver Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Autophagy via TGF-<i>β</i>1/Smad3 and p38/PPAR<i>α</i> Pathways.","authors":"Jie Ji,&nbsp;Qiang Yu,&nbsp;Weiqi Dai,&nbsp;Liwei Wu,&nbsp;Jiao Feng,&nbsp;Yuanyuan Zheng,&nbsp;Yan Li,&nbsp;Chuanyong Guo","doi":"10.1155/2021/6651839","DOIUrl":"https://doi.org/10.1155/2021/6651839","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to confirm the hepatocellular protective functions of apigenin and the molecular mechanism on liver fibrosis in mice.</p><p><strong>Methods: </strong>Carbon tetrachloride (CCl₄) and bile duct ligature (BDL) mouse fibrosis models were used to investigate the effects of apigenin on liver fibrosis. Sixty-six male C57 mice were randomly divided into eight groups, including the vehicle group, CCl₄ group, CCl₄+L-apigenin (20 mg/kg) group, CCl₄+H-apigenin (40 mg/kg) group, sham group, BDL group, BDL+L-apigenin(20 mg/kg) group, and BDL+H-apigenin(40 mg/kg) group. Serum liver enzymes (ALT and AST), proteins associated with autophagy, and indicators linked with the TGF-<i>β</i>1/Smad3 and p38/PPAR<i>α</i> pathways were detected using qRT-PCR, immunohistochemical staining, and western blotting.</p><p><strong>Results: </strong>Our findings confirmed that apigenin could decrease the levels of ALT and AST, suppress the generation of ECM, inhibit the activation of HSCs, regulate the balance of MMP2 and TIMP1, reduce the expression of autophagy-linked protein, and restrain the TGF-<i>β</i>1/Smad3 and p38/PPAR<i>α</i> pathways.</p><p><strong>Conclusion: </strong>Apigenin could alleviate liver fibrosis by inhibiting hepatic stellate cell activation and autophagy via TGF-<i>β</i>1/Smad3 and p38/PPAR<i>α</i> pathways.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6651839"},"PeriodicalIF":2.9,"publicationDate":"2021-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25360431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amorfrutins Relieve Neuropathic Pain through the PPAR<i>γ</i>/CCL2 Axis in CCI Rats.","authors":"Pengfei Gao,&nbsp;Jiayu Wang,&nbsp;Zhen Su,&nbsp;Fayin Li,&nbsp;Xianlong Zhang","doi":"10.1155/2021/8894752","DOIUrl":"https://doi.org/10.1155/2021/8894752","url":null,"abstract":"<p><p>Neuropathic pain is a public health problem. Although many pharmaceuticals are used to treat neuropathic pain, effective and safe drugs do not yet exist. In this study, we tested nociceptive responses in CCI rats, and ELISA assay was performed to examine the expression of proinflammatory cytokines. We found that amorfrutins significantly reduce the pain behaviors in CCI rats and suppress the expression of proinflammatory cytokines (TNF<i>α</i>, IL-6, and IL-1<i>β</i>) and chemokines (CCL2/CCR2) in the spinal cord. However, concurrent administration of a PPAR<i>γ</i> antagonist, GW9662, reversed the antihyperalgesic effect induced by amorfrutins. The results indicate that amorfrutins inhibit the inflammation and chemokine expression by activating PPAR<i>γ</i>, thus relieving neuropathic pain in CCI rats. Therefore, PPAR<i>γ</i>-CCL2/CCR2 pathway might represent a new treatment option for neuropathic pain.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"8894752"},"PeriodicalIF":2.9,"publicationDate":"2021-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25341270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}