BIOMEDICINE & PHARMACOTHERAPY
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2020
·
IF 4.545
Zhishen Xie,Jianping Zhao,Hui Wang,Yali Jiang,Qiaoling Yang,Yu Fu,Huahui Zeng,Christian Hölscher,Jiangyan Xu,Zhenqiang Zhang
This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aβ) and the possible mechanisms involved. MG dose-dependently reduces Aβ deposition, toxicity and memory impairment caused by Aβ in transgenic C. elegans . More importantly, these effects are reversed by GW9662, a selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist. MG is more effective in enhancing PPAR-γ luciferase levels than honokiol (HK). Meanwhile, MG has the potential to bind with the ligand binding domain of PPAR-γ (PPAR-γ-LBD). As expected, MG inhibited the luciferase activity of NF-κB and its target genes of inflammatory cytokines, and this effect was blocked by GW9662. The luciferase activity of Nrf2-ARE expression can be activated by MG and decreased Aβ-induced reactive oxygen species (ROS). The target gene LXR of PPAR-γ is activated by MG, which upregulates ApoE and promotes microglia phagocytosis and the degradation of Aβ, and these effects were also reversed by GW9662. In summary, MG can attenuate Aβ-induced AD and the underlying mechanism is the reduction of inflammation and promotion of phagocytosis and degradation of Aβ, which is dependent on PPAR-γ.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Zhishen Xie,Gai Gao,Hui Wang,Erwen Li,Yong Yuan,Jiangyan Xu,Zhenqiang Zhang,Pan Wang,Yu Fu,Huahui Zeng,Junying Song,Christian Hölscher,Hui Chen
Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro , and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.
研究领域:
药理学
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代谢性疾病
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分子生物学
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营养学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
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IF 3.118
Lina Zhang,Jinghua Gao,Peng Tang,Li Chong,Yue Liu,Peng Liu,Xin Zhang,Li Chen,Chen Hou
Nuciferine, a bioactive component extracted from the lotus leaf , has been reported to have various anti-inflammatory effects. In the present study, we aimed to investigate the anti-inflammatory effects and mechanism of nuciferine on lipopolysaccharide (LPS)-stimulated BV2 microglia cells . The anti-inflammatory activity of nuciferine was measured by ELISA to detect the inflammatory mrdiators secretion in LPS-simulated BV2 microglia cells. The results demonstrated that nuciferine significantly inhibited LPS-induced TNF-α, IL-1β, PGE 2 and NO secretion. LPS-induced NF-κB activation was also suppressed by nuciferine. Further studies showed that nuciferine increased the expression of PPAR-γ. Functional aspects were analyzed using PPAR-γ specific inhibitor GW9662 , which attenuated the LPS-induced secretion of proinflammatory mediators, such as TNF-α, IL-1β, PGE 2 , and NO. In conclusion, these results suggested that nuciferine activated PPAR-γ, which subsequently inhibited LPS-induced inflammation in BV2 cells.
研究领域:
药理学
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免疫学
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神经科学
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细胞生物学
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PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2016
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IF 3.418
Shuai Wang,Zewei Sun,Wenting Zhao,Zhen Wang,Mingjie Wu,Yanyun Pan,Hui Yan,Jianhua Zhu
CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-κB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-α and transcription factor NF-κB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-γ, was involved in the CD97 mediated NF-κB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-γ expression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-γ expression and decreased LPS induced NF-κB activation. In conclusion, CD97 plays a negative role in LPS induced NF-κB activation and TNF-α secretion, partly through PPAR-γ upregulation.
研究领域:
免疫学
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细胞生物学
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炎症研究
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PubMed
高影响因子
International Journal of Oral Science
·
2023
·Vol. 15
·期 1
·1-13
·
IF 14.9
Lan Tingting,Bi Fei,Xu Yuchan,Yin Xiaoli,Chen Jie,Han Xue,Guo Weihua
Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H 2 O 2 )-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H 2 O 2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.
研究领域:
移植学
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再生医学
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药理学
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细胞生物学
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牙科学
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2018
·Vol. 46
·期 11
·1538-1545
·
IF 3.64
Jiangming Deng,Lianxia Guo,Baojian Wu
Human CYP2A6 (Cyp2a5 in mice) plays an important role in metabolism and detoxification of various drugs and chemicals. Here, we investigated a potential role of peroxisome proliferator-activated receptor γ (Ppar-γ) in circadian regulation of the Cyp2a5 enzyme. We first showed that Cyp2a5 mRNA and protein in mouse liver displayed robust circadian oscillations. Consistent with a circadian protein pattern, Cyp2a5-mediated 7-hydroxylation of coumarin was circadian time–dependent. Formation of 7-hydroxycoumarin was more extensive at a dosing time of Zeitgeber time 2 (ZT2) than that at ZT14. Interestingly, the nuclear receptor Ppar-γ was also a circadian gene. Circadian Ppar-γ protein level was strongly correlated with the Cyp2a5 mRNA level (r = 0.989). Furthermore, Ppar-γ activation (by a selective agonist, rosiglitazone) upregulated Cyp2a5 expression in Hepa-1c1c7 cells, whereas Ppar-γ knockdown downregulated Cyp2a5 expression. Also, Ppar-γ knockdown blunted the rhythmicity of Cyp2a5 mRNA in serum-shocked Hepa-1c1c7 cells. In addition, a combination of promoter truncation analysis, mobility shift, and chromatin immunoprecipitation assays revealed that Ppar-γ directly bound to a PPAR response element (i.e., the −1418- to −1396-bp region) within Cyp2a5 promoter and activated the gene transcription. Taken together, Ppar-γ was a transcriptional activator of Cyp2a5, and its rhythmic expression contributed to circadian expression of Cyp2a5.
研究领域:
药理学
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分子生物学
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昼夜节律生物学
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高影响因子
MOLECULAR GENETICS AND GENOMICS
·
2025
·Vol. 300
·期 1
·1-16
·
IF 2.1
Tian Xinyuan,Bai Xiaoping,Han Yunqi,Ye Yu,Peng Meiling,Cui Hongwei,Li Kai
PPAR γ, as a widely present receptor in tissues, plays a key role in lipid metabolism, energy balance, inflammatory response, and cell differentiation. It plays an important role in the occurrence and development of various tumors, including prostate cancer, gastric cancer, lung cancer, etc., by regulating lipid metabolism. However, the specific mechanism by which it affects lung cancer growth is not yet clear. To investigate how PPAR γ affects lung cancer cell growth by altering ALDH1A3 levels through its impact on lipid metabolism. Bioinformatics analysis was used to predict the correlation between PPAR γ, ALDH1A3 and lung cancer. Based on the results of bioinformatics analysis, PPAR γ activator (Pioglitazone, Pio) and ALDH1A3 inhibitor (diethylaminobenzaldehyde, DEAB) were used to act on lung cancer cells and observe their growth. After measuring the IC50 value of the drug in vitro experiments, lipid metabolomics analysis was conducted to identify the significant changes in differential metabolites and metabolic pathways under the combined influence of Pio and DEAB. Through bioinformatics analysis, it was found that there were significant differences in the levels of PPAR γ and ALDH1A3 between lung cancer and normal lung tissues, and ALDH1A3 was positively correlated with PPAR γ. AUC analysis found that PPAR γ and ALDH1A3 have good predictive value in the diagnosis and prognosis of lung cancer. GSEA enrichment analysis showed that PPAR γ and ALDH1A3 were significantly correlated with lipid oxidation. Combining relevant literature to demonstrate the inhibitory effect of PPAR γ receptors on lung cancer cells and the ability of PPAR γ activation to inhibit ALDH1A3 levels. Further in vitro CCK-8 and IC50 measurements of lung cancer cells A549 and H1299 were conducted, followed by non targeted lipidomics analysis. It was found that the metabolic pathways upregulated by activation of PPAR γ and inhibition of ALDH1A3 included glycerophospholipid metabolism, cholesterol metabolism, arachidonic acid metabolism, and fat digestion and absorption, with glycerophospholipid metabolism pathway accounting for the highest percentage. Conclusion: PPAR γ activation can inhibit the production of ALDH1A3, alter the glycerophospholipid metabolism pathway, and thus inhibit the proliferation of lung cancer cells. This study confirms that PPAR γ affects lung cancer proliferation by influencing the glycerophospholipid metabolism pathway.
研究领域:
肿瘤学
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分子生物学
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代谢学
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药理学
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PubMed
高影响因子
Journal of Functional Foods
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2016
·
IF 3.973
Limin Xiang,Yihai Wang,Xiaomin Yi,Xinluan Wang,Xiangjiu He
Chinese hickory ( Carya cathayensis Sarg.) is a common and nutritious nut. Twenty-nine phenolic compounds, together with three quinones and three triterpenoids , were isolated from Chinese hickory husks. Their structures were determined by comprehensive spectroscopic methods. The total methanolic extract, chloroform and ethyl acetate fractions and all the isolated compounds were evaluated for antioxidant activity and neuroprotective effects on SH-SY5Y cells, as well as the effects on the expression of PPAR-γ in 3T3-L1 cells. Quercetin ( 10 ) and protocatechuic acid methyl ester ( 24 ) showed pronounced antioxidant activities in all of the different antioxidant assays and neuroprotective effect against H 2 O 2 -induced oxidative stress . Some of the flavonoids could significantly decrease the mRNA expression level of PPAR-γ by approximately 70%. The present study provided supplement information for the evaluation of antioxidant activity and health benefit of Chinese hickory.
研究领域:
植物化学
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药理学
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营养学
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DOI
高影响因子
RENAL FAILURE
·
2025
·
IF 3
Neng Bao,Ming-Jia Gu,Qiu-Ya Huang,Hai-Jian Sun,Xue-Xue Zhu,Xin Gu,Jin Wang,Xiang Yu,Qing-Bo Lu,Ya-Fen Yu
Purpose This study aims to investigate the protective effect of baicalin on sepsis-associated acute kidney injury (SA-AKI) and its molecular mechanism.Materials and methods An SA-AKI mouse model was established via lipopolysaccharide (LPS) injection. Baicalin’s effects on renal function, oxidative stress, and apoptosis were evaluated using histopathology, dihydroethidium, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Bioinformatics, molecular docking, ribonucleic acid (RNA) sequencing, and Western blotting were employed to investigate the role of baicalin in regulating the peroxisome proliferator‑activated receptor‑γ (PPAR-γ)/uncoupling protein 1 (UCP1) pathway. Human kidney-2 cells were used for in vitro validation.Results In this study, baicalin significantly ameliorated LPS-induced acute kidney injury by modulating the PPAR-γ/UCP1 signaling pathway. Both in vivo and in vitro experiments revealed that baicalin attenuates inflammation, oxidative stress, and apoptosis while restoring mitochondrial function. RNA sequencing analysis revealed significant upregulation of PPAR-γ/UCP1 in the baicalin-treated group. Further molecular docking and molecular dynamics simulations confirmed a stable interaction between baicalin and UCP1. Validation via small interfering RNA-mediated knockdown of PPAR-γ and UCP1 revealed that inhibition of the PPAR-γ/UCP1 pathway abrogated baicalin’s protective effects, highlighting the critical role of this pathway in mediating baicalin’s renoprotection.Conclusion Baicalin protects against SA-AKI by activating the PPAR-γ/UCP1 signaling pathway. This study provides new insights into the mechanisms through which baicalin mitigates kidney injury in sepsis, suggesting its potential as a therapeutic agent for SA-AKI.
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Molecular Medicine Reports
·
2019
·Vol. 19
·期 6
·5417-5423
·
IF 1.851
Zhimin Wang,Fang Li,Yuan Quan,Junye Shen
Hepatocellular carcinoma (HCC) has become a global public health problem. Therefore, the development of novel and effective therapeutic agents for the treatment of HCC is considered an emergency. Avicularin, a bio‑active flavonoid from plants, has been reported to exhibit diverse pharmacological properties. The aim of the present study was to investigate the role of avicularin in HCC and the underlying mechanism of action. Huh7 cells were treated with avicularin in a concentration‑dependent manner, and the cell proliferation was examined using a 3‑(4, 5‑dimethylthiazol‑2‑yl)‑2, 5‑diphenyltetrazolium bromide assay kit. The cell migration and invasion abilities were detected using wounding‑healing assays and Transwell assays. Flow cytometric analysis was performed to investigate the cell cycle distribution and cell apoptosis. The activity of nuclear factor (NF)‑κB (p65), cyclooxygenase‑2 (COX‑2) and peroxisome proliferator‑activated receptor γ (PPAR‑γ) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that avicularin treatment markedly decreased cell proliferation concentration‑dependently in HCC, and inhibited cell migration and invasion in Huh7 cells. It was also found that the treatment of avicularin markedly inhibited the G0/G1‑phase cells and decreased the accumulation of S‑phase cells in the cell cycle and induced cell apoptosis. In addition, it was confirmed that the anticancer efficacy of avicularin in HCC was dependent on the regulation of NF‑κB (p65), COX‑2 and PPAR‑γ activities. In conclusion, the findings suggested that avicularin serves an antineoplastic role in HCC and may provide a potential therapeutic strategy for the treatment of HCC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Xinlin Zhu,Yi Dong,Ya Zhang,Chenghai Gao,Lijian Ding,Yonghong Liu,Zhiran Ju
Gouty arthritis, driven by monosodium urate (MSU) crystal deposition and dysregulated inflammation, remains a therapeutic challenge due to the limitations of current treatments. Here, we investigate Herdmanine D (HDD), a marine-derived alkaloid from the ascidian Herdmania momus. It was optimized via structure–activity relationship (SAR) studies and computational modeling to enhance its binding to peroxisome proliferator-activated receptor γ (PPAR-γ), which regulates the PPAR-γ/NF-κB signaling pathway in gout pathogenesis. The optimized HDD derivative 9a demonstrated potent PPAR-γ binding affinity and pharmacokinetic properties, effectively suppressing NF-κB-driven pro-inflammatory cytokines in vitro. In murine MSU-induced gouty arthritis models, 9a alleviated synovial inflammation and tissue damage. Mechanistically, 9a activated PPAR-γ to inhibit NF-κB and attenuate NLRP3 inflammasome assembly. This work highlights HDD as a unique marine scaffold for next-generation antigout therapeutics, merging marine natural product safety with rational design to address unmet clinical needs.
研究领域:
药理学
·
海洋天然产物
·
炎症性疾病
·
药物设计与开发
·
风湿病学
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DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Mingquan Gao,Xudong Yu,Ziqian Shang,Mengyao Tan,Xie Huang,Zaizhi Du,Xiaojiao Wang,Xinrui Yang,Ximei Luo,Weidong Wang,Rong Li,Shenglin Luo
Radiation‐induced lung injury (RILI) is a major complication of nuclear radiation exposure and thoracic radiotherapy, driven in part by a vicious cycle of oxidative stress and mitochondrial dysfunction. Peroxisome proliferator‐activated receptor gamma (PPAR‐γ), a key regulator of mitochondrial homeostasis and inflammatory resolution, therefore represents a potential therapeutic target, yet multi‐omics analyses revealed that this immunometabolic checkpoint remains functionally constrained in irradiated macrophages. To reactivate this pathway, we developed an inhalable, ROS‐responsive nanospray (HANP) by loading nicotinamide adenine dinucleotide (NAD + ) and astaxanthin (ASX) into a hollow mesoporous polydopamine (HMPDA) shell. Excess ROS in microenvironment triggers oxidative degradation of the HMPDA shell, enabling intracellular release of NAD + and ASX. Mechanistically, NAD + promotes SIRT1‐mediated deacetylation of PPAR‐γ, whereas ASX serves as an activating ligand, thereby cooperatively restoring PPAR‐γ signaling. This response re‐establishes macrophage mitochondrial homeostasis by coordinating mitochondrial biogenesis and mitophagy, which subsequently promotes a shift toward a reparative macrophage phenotype. In murine models of focal thoracic irradiation and lethal whole‐body irradiation, HANP markedly attenuated lung injury and improved survival. Collectively, these findings identify macrophage PPAR‐γ as a therapeutically actionable redox‐immunometabolic regulator and support inhaled dual‐activation of this pathway as a promising strategy for protection against RILI in both clinical and emergency settings. A nebulized nanoassembly alleviates radiation‐induced lung injury by reprogramming macrophages through coordinated ROS scavenging, NAD + replenishment, and PPAR‐γ activation. Redox balance, mitochondrial homeostasis, and immune regulation are restored, revealing a microenvironment‐centered strategy for localized radioprotection.
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