Asian Journal of Pharmaceutical Sciences
·
2017
·Vol. 12
·期 6
·580-585
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IF 0
Shijie Wei,Jingbo Ren,Ning Li,Wuzhen Huo,Chongkai Gao
An LCC delivery system for Fenofibrate (Fen) was developed to improve its poorly oral bioavailability. Fen-LCC preparation methods were screened, and the prepared Fen-LCC was then characterized by a polarizing microscope and transmission electron microscopy (TEM). The spray drying technique was selected to dry and solidify particles into powder. The in vitro release of Fen-LCC was measured and in vivo pharmacokinetic experiments were carried out on rats after oral administration. Particles prepared through the high-temperature input method exhibited structural characteristics of LCC, and re-dissolved particles maintained the same features. The LCC delivery system can significantly improve in vitro release outcomes. After oral administration, AUCs of the suspension and LCC systems were measured at 131.6853 µg⋅h/ml and 1435.72893 µg⋅h/ml, respectively. The spray drying process presented here better maintains cubic structures, and the LCC system significantly improves bioavailability levels.
研究领域:
药剂学
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药物递送系统
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纳米医学
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药代动力学
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药物代谢
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Wei Ye,Lei Wang,Ye Fan,Li Ma,Zaohong Chen,Jinmeng Zhang,Rong Zeng,Xiang Liu
Metabolic dysfunction-associated steatotic liver disease (MASLD) progression closely involves ferroptosis. Using high-fat diet-challenged mice and free fatty acid (FFA)-treated HepG2 cells, we demonstrate that oleanolic acid (OA) ameliorates MASLD and suppresses ferroptosis─an effect validated by the ferroptosis activator Erastin. Supported by network pharmacology, mechanistic analyses reveal that OA exerts synergistic efficacy via a dual-axis network. First, molecular docking, cellular thermal shift assay (CETSA), and molecular dynamics (MD) simulations confirm that OA directly binds PTGS2, mitigating lipid peroxidation and inflammatory mediator release. Second, OA activates the AMPK/ACC metabolic signaling pathway, inhibiting ACC through phosphorylation to correct lipid metabolism disorders, and its antiferroptotic effect can be blocked by AMPK inhibitors. This study first elucidates OA’s therapeutic mechanism against MASLD via “metabolic correction + oxidative inhibition,” outlining a novel strategy for targeting hepatic ferroptosis.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2026
·Vol. 60
·期 30
·20740-20756
·
IF 12.2
Yan Jin,Fang Lu,Xi Miaocui,Liu Ziqi,Zhang Shihan,Zhang Yuning,Zhang Yuwei,Xue Ting,Li Jiahang,Huang Yue,Chang Runfeng,Qian Qiuhui,Wang Zejun,Teng Miaomiao,Wang Huili
2-Ethylhexyl diphenyl phosphate (EHDPP), a widely used
alternative
flame retardant, raised increasing concern due to its potential developmental
and metabolic toxicity. This study evaluated the toxicity of EHDPP
on early zebrafish development within a concentration range of 5–500
μg/L, with a particular emphasis on metabolic disturbances and
their underlying mechanisms. Exposure to EHDPP induced developmental
abnormalities and disturbances in glucose and lipid homeostasis, accompanied
by mitochondrial dysfunction, excessive reactive oxygen species generation,
and ATP depletion. Transcriptomic analysis identified significant
enrichment of pathways associated with glucose and lipid metabolism,
mitochondrial function, and peroxisome proliferator-activated receptor
(PPAR) signaling. Integrated mRNA, protein, and dual-luciferase reporter
analyses demonstrated that EHDPP at 50 and 500 μg/L altered
PPAR transcriptional activity, with suppression of PPARα and
activation of PPARγ. Pharmacological and genetic interventions
further revealed distinct subtype-specific roles of PPAR signaling
in regulating lipid accumulation, glucose metabolism, mitochondrial
function, and oxidative stress. A deleterious feedback loop, in which
oxidative stress and mitochondrial dysfunction further exacerbated
metabolic disturbances, culminated in ATP depletion and energy deficiency,
ultimately contributing to developmental toxicity. These findings
demonstrated that EHDPP disrupted metabolic homeostasis through interference
with PPAR signaling, providing novel insights into its toxicological
mechanisms and potential environmental health risks.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.2
Cong Zhang,Yingxi Luo,Yangkun Xiong,Liang Chen,Haixia Zhao,Zhenpeng Qiu,Yuan Yang
Gigantol, a naturally active molecule derived from the edible plant Dendrobium, has been demonstrated to have hepatoprotective potential, but its effect in the treatment of metabolic dysfunction-associated steatohepatitis (MASH) remains unclear. Here, we found that gigantol treatment greatly corrected dyslipidemia, hepatic dysfunction, and hepatic histological changes that arrested MASH occurrence in high-fat and high-fructose-diet (HFFD)-fed mice. Mechanistically, gigantol promoted the nuclear translocation of the transcription factor EB (TFEB) to regulate the key factors of lipophagy and fatty acid oxidation to maintain hepatic lipid metabolism homeostasis. Consistent results were observed in palmitic acid-induced cell models. Notably, silencing TFEB reversed the effect of gigantol in enhancing lipophagy and fatty acid oxidation in vivo and in vitro. In summary, this study provides strong evidence to demonstrate that gigantol attenuates HFFD-induced MASH by promoting TFEB-dependent lipophagy and fatty acid oxidation, suggesting that gigantol, an edible plant-derived compound, is promising to be developed as a therapeutic drug for MASH in the future.
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DEVELOPMENTAL CELL
·
2026
·
IF 8.7
Man Wang,Yi Chen,Ming Guo,Pengzhi Xie,Xinzhe Zhao,Shulin Chen,Yian Deng,Rui Hu,Qianyi Wan,Juanyu Zhou,Zhuzhen Zhang,Ke Lan,Haiyang Chen,Yuan Liu
Long COVID has emerged as a significant public health challenge with no effective treatments currently available, yet the pathophysiological mechanisms underlying its persistent gastrointestinal (GI) symptoms remain poorly understood. Here, integrating clinical data with transgenic animal models, we discover a critical role for impaired intestinal epithelial repair in the local intestinal etiology of long COVID. Mechanistically, we show that intestinal SARS-CoV-2 reservoirs disrupt very-long-chain fatty acid (VLCFA) metabolism, suppressing activation of peroxisome proliferator-activated receptor (PPAR) signaling and reducing peroxisome abundance. This disruption impairs intestinal stem cell differentiation and epithelial regeneration, resulting in prolonged GI symptoms including diarrhea, inflammation, and microbiota dysbiosis. Importantly, the FDA-approved sodium phenylbutyrate (NaPB) and fenofibrate alleviate these symptoms by promoting peroxisome proliferation and restoring epithelial repair. These findings provide insights into the GI pathogenesis of long COVID and highlight the therapeutic potential of enhancing the VLCFA-PPAR-peroxisome axis to mitigate persistent GI complications.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Xueyun Liu,Man Hu,Chen Ye,Lihong Liao,Chang Ding,Lijuan Sun,Jichao Liang,Yong Chen
It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid , 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting . Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas , as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor , compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.
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MOLECULES
·
2022
·Vol. 27
·期 10
·3127
·
IF 4.927
Miaomiao Chi,Kunming Qin,Lei Cao,Min Zhang,Yingying Su,Xun Gao
Coronary heart disease (CHD), which has developed into one of the major diseases, was reported to be treated by the target of peroxisome proliferators-activate receptor γ (PPAR-γ). As a natural medicine long used in the treatment of CHD, there are few studies on how to screen the target active compounds with high specific activity fromChoerospondias axillaris. To advance the pace of research on target-specific active compounds in natural medicines, we have combined magnetic ligand fishing and functionalized nano-microspheres to investigate the active ingredients of PPAR-γ targets inChoerospondias axillaris. The PPAR-γ functionalized magnetic nano-microspheres have been successfully synthesized and characterized by vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The specificity, reusability, and reproducibility of the nano-microspheres were investigated with the help of the specific binding of rosiglitazone to PPAR-γ. In addition, the incubation temperature and the pH of the buffer solution in the magnetic ligand fishing were optimized to improve the specific adsorption efficiency of the analytes. Finally, with the aid of ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS/MS), the 16 active ligands including 9 organic acids, 5 flavonoids, and 2 phenols were found in the ethanolic extracts ofChoerospondias axillaris. Therefore, the study can provide a successful precedent for realizing the designated extraction and rapid isolation of target-specific active ingredient groups in the complex mixtures.Keywords:PPAR-γ;magnetic ligand fishing;Choerospondias axillaris;UHPLC-Q-Exactive orbitrap-MS/MS
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Frontiers in Pharmacology
·
2022
·
IF 5.988
Qin Yeyu,Xie Jing,Zheng Ruihe,Li Yuhang,Wang Haixia
Doxorubicin (DOX) is one of the most common chemotherapeutic anti-cancer drugs. However, its clinical use is restricted by serious cardiotoxicity. Oleoylethanolamide (OEA), a structural congener of endocannabinoid anandamide, is the endogenous agonist of peroxisome proliferator activated-receptor α (PPARα) and transient receptor potential cation channel vanilloid-1 (TRPV1), and involved in many physiological processes. The present study aimed to determine whether OEA treatment protects against DOX-induced cytotoxicity (DIC) and gain insights into the underlying mechanism that mediate these effects. Our data revealed that Oleoylethanolamide treatment improved the myocardial structure in DOX-challenged mice by attenuating cardiac oxidative stress and cell apoptosis. OEA also alleviated DOX-induced oxidative stress and apoptosis dysregulation in HL-1 cardiomyocyte. These effects were mediated by activation of TRPV1 and upregulation of PI3K/ Akt signaling pathway. Inhibition of TRPV1 and PI3K reversed the protective effects of OEA. Taken together, our data suggested that OEA protects against DIC through a TRPV1- mediated PI3K/ Akt pathway.
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Frontiers in Pharmacology
·
2022
·
IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
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AQUACULTURE NUTRITION
·
2021
·Vol. 27
·期 6
·2749-2758
·
IF 3.497
Yan-Yu Zhang,Jun-Xian Wang,Jiong Ren,Jie Wang,Fang Qiao,Mei-Ling Zhang,Zhen-Yu Du
In aquaculture, excess lipid deposition in liver is a health damage in largemouth bass ( Micropterus salmoides ). Activation of peroxisome proliferator-activated receptor-α (PPARα) has been proved to stimulate lipid catabolism and alleviate fatty liver in rodents and human. Our present study was conducted to investigate the effects of Pparα activation via dietary fenofibrate stimulation on hepatic lipid catabolism in largemouth bass. Total 240 fish (10.7 ± 0.2 g) were randomly divided into eight tanks and fed two diets (control and control containing 5 g/kg fenofibrate), respectively, for 4 weeks. Dietary fenofibrate increased Pparα protein and mitochondrial DNA amounts. The weight gain rate and carcass ratio of fish with Pparα activation decreased, but viscerosomatic index and hepatosomatic index were higher in the fenofibrate-fed fish than the control. Pparα activation significantly reduced triglyceride levels in the serum and liver but did not change the lipid composition in liver. Moreover, hepatic glycogen accumulation was found in the fish with Pparα activation. The Pparα activation also had health benefits for liver, as reflected by reducing serum ALT and AST activities, and increasing antioxidative ability in liver. Our results showed that in largemouth bass, Pparα can be activated and the Pparα activation could efficiently stimulate lipid catabolism and reduce hepatic fat deposition, and promote health in liver.
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Lipids in Health and Disease
·
2023
·Vol. 22
·期 1
·1-16
·
IF 4.5
Zhang Li,Tong Yingying,Fang Yan,Pei Jinjin,Wang Qilan,Li Gang
Objective The goal of this study was to explore the hypolipidemic effects of bergenin extracted from Saxifraga melanocentra Franch ( S. melanocentra ), which is a frequently utilized Tibetan medicinal plant known for its diverse bioactivities. Establishing a quality control system for black stem saxifrage is crucial to ensure the rational utilization of its medicinal resources. Methods A one-step polyamide medium-pressure liquid chromatography technique was applied to isolate and prepare bergenin from a methanol extract of S. melanocentra . A zebrafish model of hyperlipidemia was used to investigate the potential hypolipidemic effects of bergenin. Results The results revealed that bergenin exhibited substantial hypo efficacy in vivo. Specifically, bergenin significantly reduced the levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) while simultaneously increasing high-density lipoprotein cholesterol (HDL-c) levels. At the molecular level, bergenin exerted its effects by inhibiting the expression of FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-1β, and TNF while promoting the expression of IL-4 at the transcriptional level. Molecular docking analysis further demonstrated the strong binding affinity of bergenin to proteins such as FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-4, IL-1β, and TNF. Conclusions Findings indicate that bergenin modulates lipid metabolism by regulating lipid and cholesterol synthesis as well as inflammatory responses through signaling pathways associated with FASN, SREBF1, and RORα. These results position bergenin as a potential candidate for the treatment of hyperlipidemia.
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Particuology
·
2025
·
IF 4.3
Shuyu Li,Di Wu,Hui Yu,Xin Huang,Na Wang,Ting Wang,Hongxun Hao
In this work, API nanoscale drugs loaded onto solid lipid microspheres (ND@SLMs) were successfully prepared by combining in-situ crystallization technology and liquid-liquid phase separation (LLPS). This method is characterized by its low energy consumption and the absence of a requirement for high concentrations of surfactants. Tristearin (SSS) was used as the drug carriers, and fenofibrate (FEN) was used as API to verify the feasibility of this method. Characterization was performed using SEM, PXRD, and DSC, while in-situ Raman and EasyViewer enabled real-time monitoring of the particle formation process. The results show that the obtained Active Pharmaceutical Ingredient (API) nanoscale crystals exhibited uniform distribution in the solid lipid carrier and enhanced release rates compared to the bulk ingredients. API droplets prepared by LLPS adhered to the surface of the FEN + SSS droplets played the role of dispersant. Response surface analysis was employed to analyze the independent variables and their interactions, and the optimum value of the processing parameters was obtained. Finally, the expandability of this method to other hydrophobic drugs was verified by ibuprofen (IBU).
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危险品化学品经营许可证（带存储）