JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Ruyi Li,Gongcan Chen,Yizhuo Li,Haiyan Liu,Lu Huang,Chao Yang,Yifei Rao
Ethnopharmacological relevance Gardenia jasminoides Ellis (GJE) is a traditional Chinese medicine widely used for metabolic disorders. However, its efficacy against hyperuricemia, the responsible active fraction, and the underlying mechanisms of its effect remains to be clarified. Aim of the study To investigate the material basis and urate-lowering activity of the 70% ethanolic fraction of GJE (GJE70), and to elucidate its molecular mechanism. Materials and methods UPLC-Q-TOF-MS characterized the chemical composition of GJE70. Hyperuricemia was induced in rats by potassium oxonate and yeast extract. Serum and urinary uric acid, uric acid clearance, renal function, and histopathology were assessed for anti-hyperuricemia efficacy and urate excretion. Hepatic function and histology were examined for safety. To explore mechanisms, kidney transcriptomics and metabolomics were performed; molecular docking predicted compound-target binding, which was validated by IF, WB, qRT-PCR and rescue experiments in HK-2 cells. Results UPLC-Q-TOF-MS identified 18 major compounds in GJE70, with crocins predominant. In hyperuricemia rats, GJE70 significantly reduced serum uric acid and increased urinary uric acid excretion and clearance, indicating enhanced renal urate elimination. Renal function and histopathology showed alleviated renal injury without obvious hepatotoxicity, with normal liver enzymes and histology. Transcriptomic and metabolomic analyses revealed that GJE70 mainly modulated PPAR signaling pathways. Molecular docking and MD Analysis demonstrated strong binding affinities of compounds to PPARγ. Subsequent IF, WB, and qRT-PCR confirmed that GJE70 upregulated PPARγ expression and its downstream urate transporters (ABCG2, OAT1, and OAT3), and suppressed NF-κB signaling levels. In HK-2 cells, GJE70 reduced supernatant uric acid, upregulated ABCG2/OAT1/OAT3, and inhibited NF-κB activation; GW9662 attenuated these effects, confirming PPARγ dependence. Conclusion GJE70 exerts potent urate-lowering and renoprotective effects via PPARγ-mediated regulation of urate transporters and anti-inflammatory pathways, suggesting its potential as a therapeutic candidate for hyperuricemia. Download: Download high-res image (445KB) Download: Download full-size image
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高影响因子
Nutrients
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2022
·Vol. 14
·期 12
·2411
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IF 6.706
Zhuohui Zhao,Zhen-Tao Deng,Suling Huang,Mengmeng Ning,Ying Feng,Yu Shen,Qin-Shi Zhao,Ying Leng
Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease worldwide, with no effective therapies available. Discovering lead compounds from herb medicine might be a valuable strategy for the treatment of NASH. Here, we discovered Alisol B, a natural compound isolated fromAlisma orientalis(Sam.), that attenuated hepatic steatosis, inflammation, and fibrosis in high-fat diet plus carbon tetrachloride (DIO+CCl4)-induced and choline-deficient and amino acid-defined (CDA)-diet-induced NASH mice. RNA-seq showed Alisol B significantly suppressed CD36 expression and regulated retinol metabolism in NASH mice. In mouse primary hepatocytes, Alisol B decreased palmitate-induced lipid accumulation and lipotoxicity, which were dependent on CD36 suppression. Further study revealed that Alisol B enhanced the gene expression of RARα with no direct RARα agonistic activity. The upregulation of RARα by Alisol B reduced HNF4α and PPARγ expression and further decreased CD36 expression. This effect was fully abrogated after RARα knockdown, suggesting Alisol B suppressed CD36 via regulating RARα-HNF4α-PPARγ cascade. Moreover, the hepatic gene expression of RARα was obviously decreased in murine NASH models, whereas Alisol B significantly increased RARα expression and decreased CD36 expression, along with the downregulation of HNF4α and PPARγ. Therefore, this study showed the unrecognized therapeutic effects of Alisol B against NASH with a novel mechanism by regulating RARα-PPARγ-CD36 cascade and highlighted Alisol B as a promising lead compound for the treatment of NASH.Keywords:Alisol B;non-alcoholic steatohepatitis;RARα;CD36
研究领域:
药理学
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分子生物学
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肝病学
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PubMed
高影响因子
Experimental and Therapeutic Medicine
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2023
·Vol. 27
·期 1
·1-13
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IF 2.7
Qiankun Quan,Xinxin Ma,Ming Li,Xi Li,Haifeng Yuan
β‑Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin‑degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator‑activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE, and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ1‑42, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra‑ and extracellular Aβ1‑42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co‑expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ1‑42 treatment, reduce the levels of intra‑ and extraneuronal Aβ1‑42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co‑expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.
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高影响因子
Chinese Herbal Medicines
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2024
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IF 4.7
Shuang He,Xiaoling Liang,Weixiong Chen,Yangji Nima,Yi Li,Zihui Gu,Siyue Lai,Fei Zhong,Caixiong Qiu,Yuying Mo,Jiajun Tang,Guanyi Wu
Objective This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. Methods In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated human immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. Results Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness in AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells. Conclusion These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.
研究领域:
药理学
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免疫学
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皮肤病学
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高影响因子
AQUATIC TOXICOLOGY
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2024
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IF 4.1
Jinyun Li,Lu Fang,Miaocui Xi,Anyu Ni,Qiuhui Qian,Zejun Wang,Huili Wang,Jin Yan
Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid—a methyl donor for m6A-RNA methylation—on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.
研究领域:
环境毒理学
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分子生物学
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脂质代谢
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斑马鱼研究
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表观遗传学
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PubMed
高影响因子
PHYTOMEDICINE
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2022
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IF 6.656
Zheng Wang,Ying Chen,Mingming Gu,Zhen Wu,Baoping Ding,Wenwen Yang,Xue Wu,Changyu Wang,Xuhui Gao,Yang Yang,Guilin Yin
Background Adriamycin (ADR), a high-efficiency, broad-spectrum anthraquinone chemotherapeutic agent, is currently used to treat various malignant tumors and can lead to cumulative, dose-dependent, and irreversible cardiotoxicity . Lycorine (LYC) is a benzyl phenethylamine alkaloid that exerts remarkable therapeutic effects on cancers and sepsis . Purpose However, researchers have not yet elucidated whether LYC exerts protective effects against cardiotoxicity induced by ADR and the possible molecular mechanisms. Design This study established ADR injury models in vitro and in vivo to explore the effects of LYC against cardiotoxicity induced by ADR. The effects of LYC on blood biochemical parameters, cardiac parameters and structure, ADR-related pathophysiological processes, and the SIRT1/PPARγ signal pathway in ADR-injured models, were analyzed using a series of experimental methods. Results LYC significantly improved survival rate, blood biochemical parameters (LDH, CK , and BUN), cardiac parameters (SV and CO), mitochondrial dysfunction, and ameliorated oxidative stress , apoptosis , and myocardial fibrosis in ADR-injured mice ( p<0.05 ). Moreover, LYC obviously increased cell viability and reduced oxidative stress, apoptosis, and mitochondrial dysfunction in ADR-injured cells ( p<0.05 ). Furthermore, this study confirmed that the protective effect of LYC on ADR-induced cardiotoxicitymight be mediated by the SIRT1/PPARγ signaling pathway . These results revealed that the beneficial role of LYC on cardiotoxicity induced by ADR were mediated via regulating SIRT1/PPARγ signaling for the first time. Conclusion These discoveries may provide a theoretical basis for the exploitation of LYC as a potential cardioprotective drug candidate due to its multiple biological functions to reduce ADR-induced cardiotoxicity, but further preclinical and clinical studies are still needed.
研究领域:
药理学
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毒理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
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2021
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IF 3.905
Lili Tan,Jie Lu,Limin Liu,Lu Li
Atherosclerosis is the underlying contributing factor of cardiovascular disease, which is a process of inflammation and lipid-rich lesion. Macrophage-derived foam cell is a key hallmark of atherosclerosis and connected with various factors of lipid metabolism. Here, we showed that fatty acid binding protein 3 (FABP3) was upregulated in the aorta of ApoE −/- mice with high-fat-diet (HFD) feeding. Knockdown of FABP3 in HFD-fed ApoE −/- mice notably facilitated cholesterol efflux, inhibited macrophage foam cell formation, and thus prevented atherogenesis. Furthermore, FABP3 silencing decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ). Mechanistic studies had disclosed the involvement of PPARγ signaling in balancing cholesterol uptake and efflux and diminishing foam cell formation. These findings firstly revealed an anti-atherogenic role of FABP3 silencing in preventing foamy macrophage formation partly through PPARγ, which might be a beneficial approach for therapying atherosclerosis.
研究领域:
心血管疾病
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脂质代谢
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炎症
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PubMed
高影响因子
Adipocyte
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2022
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IF 3.553
Shuai Chen,Yicheng Jiang,Xiaoyang Qi,Peng Song,Liming Tang,Hanyang Liu
Bariatric surgery (BS) is a dependable method for managing obesity and metabolic diseases, however, the regulatory processes of lipid metabolism are still not well elucidated. Differentially expressed genes (DEGs) were analysed through three transcriptomic datasets of GSE29409, GSE59034 and GSE72158 from the GEO database regarding subcutaneous adipose tissue (SAT) after BS, and 37 DEGs were identified. The weighted gene co-expression network analysis (WGCNA), last absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms further screened four key genes involved in the regulation of STMN2, SFRP4, APOE and MXRA5. The GSE53376 dataset was used to further confirm the differential expression of SFRP4, APOE and MXRA5 in the postoperative period. GSEA analysis reveals activation of immune-related regulatory pathways after surgery. Finally, the silencing of MXRA5 was found by experimental methods to affect the expression of PPARγ and CEBPα during the differentiation of preadipocytes, as well as to affect the formation of lipid droplets. In conclusion, SAT immunoregulation was mobilized after BS, while MXRA5 was involved in the regulation of lipid metabolism.
研究领域:
生物信息学
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分子生物学
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代谢
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肥胖
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
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2024
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IF 4.4
Xuening Ma,Qianchao Shao,Shuxian Huang,Weigao Zhang,Hu Liu,Xu Jiayi,Xunan Zhao,Peiqi Li,Da Shao,YuanQing Bu,Dan Weng
The increasing incidence of cancer underscore the necessity of investigating contributors such as endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA). Although BPA's risks are well-documented, comprehensive studies on its substitutes, such as bisphenol B (BPB), are limited. Dysregulated lipid metabolism is a hallmark of cancer progression. Our previous work demonstrated that BPA and bisphenol S (BPS) disrupt lipid metabolism via the peroxisome proliferator-activated receptor γ (PPARγ) pathway. We hence hypothesized that BPB might similarly perturb lipid metabolism and promote tumor growth. BPB's impact on lipid metabolism was investigated in vitro and in vivo using B16 melanoma cancer cells. Our findings indicate BPB exposure significantly increased lipid metabolism in B16 cells, enhancing cell proliferation and migration, and promoting tumor development in mice. Utilizing siRNA transfection or chemical inhibitor, we found that stearoyl-CoA desaturase-1 (SCD1), a key enzyme in lipid synthesis pathway, was required for BPB-induced lipid accumulation and cancer cell migration. Docking analysis revealed BPB may activate gene expression related to lipid metabolism and angiogenesis by interacting with PPARγ and hypoxia-inducible factor-1α (HIF-1α). This study illuminates BPB's potential role in advancing melanoma through lipid metabolism manipulation, highlighting the need for further research into the safety of BPA substitutes and their impact on cancer development.
研究领域:
肿瘤学
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分子生物学
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环境健康
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细胞生物学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2020
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IF 2.985
Peng Ma,Rongrong Huang,Jingyao Jiang,Yuan Ding,Tingting Li,Yu Ou
C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα , which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36 , IL6 and TNFα . These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.
研究领域:
药理学
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肝病学
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营养保健品
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分子生物学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Zhiwei Bao,Dou Wang,Yao Zhao,Ting Luo,Guilin Yang,Yuanxiang Jin
Carbendazim (CBZ) and procymidone (PRO) are two widely used fungicides in agriculture. However, there are still gaps in knowledge regarding about the potential hazards of joint exposure to CBZ and PRO in animals. Here, 6-week-old ICR mice were exposed to CBZ, PRO and CBZ + PRO for 30 days, and metabolomics were performed to discover the mechanism by which the mixture enhanced the effects on lipid metabolism. Co-exposure to CBZ + PRO elevated the body weights, relative liver weights and relative epididymis fat weights, but not in the single exposure groups. Molecular docking analysis suggested that CBZ and PRO combined with peroxisome proliferator-activated receptor (PPARγ) at the same amino acid site as the agonist rosiglitazone. The RT-qPCR and WB results demonstrated that the levels of PPARγ were higher in the co-exposure group than in the single exposure groups. In addition, hundreds of differential metabolites were discovered by metabolomics and enriched in different pathways, such as pentose phosphate pathway and purine metabolism. A unique effect, a decrease in glucose-6-phosphate (G6P) that promoted more NADPH production, was observed in the CBZ + PRO group. These results demonstrated that exposure to CBZ + PRO caused more serious lipid metabolism disorder in the liver than exposure to a single fungicide, which could provide some new insight for the toxic effects after fungicides joint exposure.
研究领域:
毒理学
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药理学
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代谢组学
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环境科学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Hongyi Xian,Ruobing Bai,Yu Feng,Shiyue Tang,Zhiming Li,Chudan Gao,Kaiwei Li,Boxuan Liang,Yizhou Zhong,Yuji Huang,Hao Li,Yanhong Deng,Xiaohong Yang,Xiyun Huang,Xiaoqing Chen,Xingfen Yang,Zhenlie Huang
Polylactic acid (PLA), a biodegradable plastic, is increasingly promoted as a sustainable alternative to conventional plastics. However, its degradation under non-composting conditions and associated toxicological impacts remain insufficiently understood. This study aimed to compare the toxicity of PLA microplastics (MPs) at different degradation stages, including PLA polymers, oligomers, and aged polymers, in zebrafish larvae. Zebrafish were exposed to environmentally relevant concentrations (0.1, 1, and 10 mg/L), and morphological, biochemical, and transcriptomic analyses were performed. PLA MPs disrupted lipid metabolism, decreased ATP levels, and elevated reactive oxygen species production, ultimately leading to cardiac malformations. Mechanistically, PLA MPs activated the peroxisome proliferator-activated receptor γ (PPARγ), upregulating genes related to lipid storage and cardiac development. Co-exposure with a PPARγ antagonist GW9662 partially alleviated these effects, confirming the role of PPARγ-mediated pathways in PLA MP-induced lipid disruption and cardiotoxicity. Notably, PLA polymers showing stronger cardiac dysfunction than PLA oligomers and ultraviolet (UV)-aged PLA polymers. These findings provided critical evidence that PLA MPs impair energy homeostasis and cardiac development in zebrafish, underscoring the urgent need for comprehensive ecological risk assessments of PLA-based materials under realistic environmental conditions.
研究领域:
环境毒理学
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海洋污染
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生态毒理学
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发育生物学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）