PHARMACEUTICAL BIOLOGY
·
2017
·
IF 1.916
Xin Yang,Qian Wang,Zeng-run Pang,Meng-ran Pan,Wen Zhang
Context: Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited.Objective: We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved.Materials and methods: C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism.Results: FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01–47.70%).Conclusion: This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.
研究领域:
药理学
·
营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 9
·e13898
·
IF 2.72
Jing-Yu Duan,Wei Chen,Yang-Qi Zhao,Liang-Liang He,En-Chao Li,Zhong-Hui Bai,Yong-Jian Wang,Chun-Ping Zhang
Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n -dotriacontanol ( 1 ), shikimic acid ( 2 ), 1- O -caffeoylquinic acid methyl ester ( 3 ), 5- O -caffeoylquinic acid methyl ester ( 4 ), 5- O -coumaroylquinic acid methyl ester ( 5 ), 5- O -caffeoylquinic acid butyl ester ( 6 ), quercetin-3- O - α - L -rhamnoside ( 7 ), quercetin ( 8 ), quercetin-3- O -(4״-methoxy) -α-L -rahmnopyranosyl ( 9 ), hyperoside ( 10 ), and rutin ( 11 ). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 μM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 μM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. Practical applications Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1 , 2 , 3 , 5 , 6 , 9 , 10 , and 11 were isolated from the plant for the first time. Quercetin-3- O -(4"-methoxy)- α - L -rahmnopyranosyl ( 9 ) and hyperoside ( 10 ) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum .
研究领域:
药理学
·
生物化学
·
细胞生物学
·
药用植物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Can Wang,Ruina Cui,Congying Niu,Xiali Zhong,Qicheng Zhu,Di Ji,Xianjie Li,Hongxia Zhang,Chunqiao Liu,Lina Zhou,Yanli Li,Guowang Xu,Yanhong Wei
The residue of polychlorinated biphenyls (PCBs) exists throughout the environment and humans are subject to long-term exposure. As such, the potential environmental and health risk caused by low-dose exposure to PCBs has attracted much attention. 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB126), the highest toxicity compound among dioxin-like-PCBs, has been widely used and mass-produced. Cardiotoxicity is PCB126's crucial adverse effect. Maintaining proper metabolism underlies heart health, whereas the impact of PCB126 exposure on cardiac metabolic patterns has yet to be elucidated. In this study, we administered 0.5 and 50 μg/kg bw of PCB126 to adult male mice weekly by gavage for eight weeks. Pathological results showed that low-dose PCB126 exposure induced heart injury. Metabolomic analysis of the heart tissue exposed to low-dose PCB126 identified 59 differential metabolites that were involved in lipid metabolism , amino acid metabolism, and the tricarboxylic acid (TCA) cycle. Typical metabolomic characteristic of cardiac hypertrophy was reflected by accumulation of fatty acids (e.g. palmitic, palmitoleic, and linoleic acid), and disturbance of carbohydrates including D-glucose and intermediates in TCA cycle (fumaric, succinic, and citric acid). Low-dose PCB126 exposure increased glycine and threonine, the amino acids necessary for the productions of collagen and elastin . Besides, PCB126-exposed mice exhibited upregulation of collagen synthesis enzymes and extracellular matrix proteins, indicative of cardiac fibrosis. Moreover, the expression of genes related to TGFβ/PPARγ/MMP-2 signaling pathway was perturbed in the PCB126-treated hearts. Together, our results reveal that low-dose PCB126 exposure disrupts cardiac metabolism correlated with hypertrophy and fibrosis. This study sheds light on the underlying mechanism of PCBs' cardiotoxicity and identifies potential sensitive biomarkers for environmental monitoring.
研究领域:
毒理学
·
心脏病学
·
环境健康
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2020
·
IF 4.831
Zhenteng Liu,Fenghua Li,Jingwen Xue,Meimei Wang,Shoucui Lai,Hongchu Bao,Shunzhi He
Follicular atresia is one of the main processes for the loss of granulosa cells and oocytes from the mammalian ovary and any impairment to premature ovarian failure. Large numbers of studies have demonstrated that granulosa cell apoptosis causes follicular atresia, yet the rescue of these cells remains elusive. We aimed to use Esculentoside A (3-O-b-D-glucopyranosyl-1, 4-b-D-xylopyranosyl) phytolaccagenin, a saponin extracted from Phytolacca esculenta roots, as a potential rescue agent for the apoptosis of granulosa cells. Our results revealed the rescue of normal body and ovary weights, normal ovarian histo-architecture of ovaries, and hormones levels with regular estrus cycle. Consistently, the expression of proliferating and anti-apoptotic markers, i.e. KI67 and BCL-2 in granulosa cells, was enhanced. Meanwhile, the expressions of pro-apoptotic markers, which were BAX and CASPASEs (CASPASE-9 and CASPASE-3), were prominently reduced in Esculentoside A-induced premature ovarian failure mice. Additionally, PPARγ, a potential therapeutic target, has also rescued its expression by treating the premature ovarian failure mice with Esculentoside A. Our results advocated that Esculentoside A could restore folliculogenesis in premature ovarian failure mice. Furthermore, it has the potential to be investigated as a therapeutic agent for premature ovarian failure.
研究领域:
生殖生物学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2022
·
IF 4.52
Long Zhu,Mingrong Wang,Shuo Fu,Kaiqi Li,Jialin Liu,Zaizhao Wang
Bisphenol A (BPA) is a widely used endocrine disruptor , which has attracted much attention due to its harmful effects on male reproduction. To investigate the interference of BPA on steroid synthesis in males, male rare minnows ( Gobiocypris rarus ) were exposed to 15 μg L −1 BPA for 7, 14 and 21 d. Meanwhile, a positive control group was performed with 25 ng L −1 17α-ethynyl estradiol (EE2). Results showed that BPA exposure induced lower testosterone (T) levels, while affecting the transcripts of steroidogenic gene StAR . Moreover, BPA induced abnormal germ cells proliferation in the testis in rare minnow. Transcriptome analysis showed that 354 transcripts significantly differentially expressed after BPA exposure for 14 d, several of them were enriched in the signaling pathways of cell cycle process, PPAR signaling pathway, the steroid synthesis pathway and estrogen signaling pathway. BPA significantly increased estrogen receptor (ER) levels and induced abnormal protein levels of PPARγ. BPA disrupted the StAR expression by interfering ER enrichments within StAR 5′ flanking region . Additionally, our study also revealed that BPA and EE2 might have different mechanisms for interfering with steroid hormone levels and germ cells proliferation in the testis.
研究领域:
环境科学
·
内分泌学
·
分子生物学
·
生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Jie Cao,Xiaoxuan Du,Hui Zhao,Chenhong Zhu,Chenchen Li,Xin Zhang,Libin Wei,Xue Ke
Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs) are thought to be the major cause of failure in cancer therapy due to their considerable resistance to most chemotherapeutic agents, resulting in tumor recurrence and eventually metastasis. Here, we report a treatment strategy for osteosarcoma using hydrogel−microspheres (Gel−Mps) complex mainly composed of collagenase (Col) and PLGA microspheres (Mps) carrying Pioglitazone (Pio) and Doxorubicin (Dox). Col was encapsulated in the thermosensitive gel to preferentially degrade tumor extracellular matrix (ECM), ensuring subsequent drug penetration, while Mps with Pio and Dox were co-delivered to synergistically inhibit tumor growth and metastasis. Our results showed that the Gel−Mps dyad functions as a highly biodegradable, extremely efficient, and low-toxic reservoir for sustained drug release, displaying potent inhibition of tumor proliferation and subsequent lung metastasis. Selective PPARγ agonist Pio reversed drug resistance to Dox by significantly down-regulating the expression of stemness markers and P-glycoprotein (P-gp) in osteosarcoma cells. The [email protected] @Dox/Pio exhibited advanced therapeutic efficacy in vivo , demonstrating its great potential to serve a novel osteosarcoma therapy, which not only inhibits the growth of, but also attenuates the stemness of osteosarcoma. The dual effects reinforce the sensitivity and efficacy of chemotherapy.
研究领域:
药理学
·
肿瘤学
·
生物材料科学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Xi Lu,Xirui Cheng,Guohua Li
Hyperlipidemia impose a substantial burden on human health. Recent studies have demonstrated that probiotics can regulate lipid metabolism by modulating gut microbiota composition or producing bioactive metabolites, with human-derived strains potentially exhibiting superior host colonization capacity. This study isolated Lactobacillus gasseri LG 2361 from 84 healthy infant fecal samples. Safety assessments confirmed non-hemolytic activity, antibiotic susceptibility (except natural resistance), and gastrointestinal adaption (81 % survival at pH 3.0; 60 % survival at 0.1 % bile). The strain demonstrated lipid-lowering capacity in vitro , degrading 43.0 % cholesterol and 34.6 % triglycerides. In high-fat diet mice, LG 2361 reduced hepatic lipid accumulation (11.6 % total cholesterol, p < 0.05), attenuated abdominal adiposity (32.9 % subcutaneous fat reduction, p < 0.01), and may enhance antioxidant status (22.5 % glutathione peroxidase increase, p < 0.01). Synergy with L . acidophilus ATCC 43121 amplified efficacy, achieving 61.6 % abdominal fat reduction (p < 0.01) while suppressing TNF-α (0.46-fold) and IL-1β (0.29-fold, p < 0.001). Mechanistically, LG 2361 downregulated PPARγ (0.59-fold, p < 0.01) and modulated FAT/CD36 pathways, indicating dual regulation of lipogenesis and lipid transport. These findings suggest that LG 2361 may be a probiotic candidate for hyperlipidemia management.
研究领域:
微生物学
·
益生菌研究
·
代谢紊乱
·
胃肠健康
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Chinese Journal of Natural Medicines
·
2025
·
IF 4.9
Yongsheng Fang,Zhiyun Zhu,Chun Xie,Dazhen Xia,Huimin Zhao,Zihui Wang,Qian Lu,Caimei Zhang,Wenyong Xiong,Xiaodong Yang
Saponins associated with Panax notoginseng ( P. notoginseng ) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro . The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro , accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
研究领域:
药物化学
·
药理学
·
天然产物
·
生物有机化学
·
代谢性疾病研究
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Meiyu Yuan,Ruijuan Fan,Kaitao Peng,Xian Cui,Xiaoxiao Song
Low-temperature plasma (LP) is an emerging advanced oxidation technology that can rapidly and efficiently degrade refractory organic compounds without introducing secondary pollutants. Further investigation is required into the mechanisms of polysaccharide degradation via plasma technology and the enhancement of the bioactivity of the resulting degradation products. In this study, we systematically investigated the degradation mechanisms, structural transformations, and functional potential of fucoidan (Fuc) using LP technology. The critical parameters of the LP treatment were optimized based on the Box–Behnken design, leading to the successful preparation of Fuo-30 T. Kinetic analysis revealed that the degradation process of Fuc followed second-order reaction kinetics. Structural characterization demonstrated that the active radicals generated by LP preferentially cleave glycosidic bonds in glucuronic acid (Glc p A) residues and β-1,6-linked side chains. Fuo-30 T significantly improves DSS-induced colitis. Mechanistically, it inhibits the activation of the NF-κB and MAPK pathways, enhances the stability of Nrf2 and PPARγ, and effectively reduces oxidative stress and inflammatory responses. Another possible mechanism involves lipid metabolism, particularly that of arachidonic acid. Fuo-30 T intervention significantly decreased the production of proinflammatory factors (PGE2, TXB2, and Hete) by inhibiting the cyclooxygenase and lipoxygenase pathways, thereby improving the TCA cycle. Finally, Fuo-30 T significantly upregulated the expression of tight junction proteins in the intestinal epithelium by reshaping the gut microbiota structure, which synergistically improved intestinal microecology and mucosal immune homeostasis.
研究领域:
食品科学
·
生物化学
·
生物技术
·
免疫学
·
微生物学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2019
·
IF 7.149
Wei Guo,Jian Han,Shengmin Wu,Xiongjie Shi,Qiangwei Wang,Bingsheng Zhou
Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is a ubiquitous environmental contaminant, but its toxicity is not fully understood. Accordingly, we investigated the effects of TBPH and its metabolite, mono-(2-ethyhexyl)tetrabromophthalate (TBMEHP), on lipid metabolism using a zebrafish model. The molecular docking study revealed that TBPH and TBMEHP bind to zebrafish peroxisome proliferator-activated receptor γ (PPARγ), with binding energies similar to rosiglitazone, a PPARγ agonist. Zebrafish embryos 0.75 hpf were exposed to TBPH (0.2–2000 nM) or TBMEHP (0.2–2000 nM) until 72 hpf, and their effects on PPARγ-mediated lipid metabolism were evaluated. Significant regional DNA demethylation of the PPARγ promoter was observed in the larvae at 72 hpf. Demethylation of the PPARγ promoter accompanied by upregulation of tet1 and tet2 transcription caused upregulation of PPARγ transcription and certain downstream genes involved in lipid lipolysis, transport, and metabolism. The triglyceride and total cholesterol concentrations in the larvae were significantly reduced following exposure to TBPH or TBMEHP. Furthermore, significant increases in the whole ATP content and locomotor activity in the 120 hpf larvae were observed. The overall results suggest that both TBPH and TBMEHP affect methylation of the PPARγ promoter, subsequently influencing larvae lipid metabolism via the PPARγ signaling pathway and disrupting energy homeostasis.
研究领域:
环境毒理学
·
分子生物学
·
发育生物学
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
·
2019
·Vol. 9
·期 1
·1-15
·
IF 3.355
Tan Jianxin,Wang Yajun,Wang Siliang,Wu Simeng,Yuan Zhe,Zhu Xike
Background Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify key regulators in thymic adipogenesis. We used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor β1 (TGF-β1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated. Results Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-β1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-β1 treatment. TGF-β1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-β1 enhanced the binding of Smad2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-β1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and β-catenin protein levels. TGF-β1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/β-catenin signaling pathway. Conclusion Taken together, activation of TGF-β pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.
研究领域:
免疫学
·
细胞生物学
·
蛋白质组学
·
分子生物学
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yanmei Zhong,Yingying Xu,Yongzhen Tan,Xuanxuan Zhang,Ruolun Wang,Danmin Chen,Zhaotao Wang,Xunlong Zhong
Mangiferin , a natural C-glucoside xanthone , is one of the major bioactive ingredients derived from the dry rhizome of Anemarrhenae rhizome , which has been reported to exhibit various pharmacological effects , including anti-oxidant, anti-inflammatory, anti-fatty liver, anti-metabolic syndrome, and anti-diabetic. However, the precise molecular mechanisms underlying its impact on phospholipid metabolism in the erythrocyte membrane of type 2 diabetes mellitus (T2DM) remain unclear. The present research aimed to evaluate the effects of mangiferin on glucose and lipid metabolism in T2DM model rats and discuss the relationship between lipid metabolites and potential targets involved in the hypoglycemic effects by integrating lipidomics and network pharmacology method. After 8 consecutive weeks of treatment with mangiferin, the T2DM model rats exhibited significant improvements in several biochemical indices and cytokines, including fasting blood glucose (FBG) levels after 12 h of fasting, fasting insulin level (FINS), total cholesterol (T-CHO), triacylglycerols (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HMOA-IR), TNF-α and IL-6. A total of 22 differential lipid metabolites were selected from erythrocyte membrane phospholipids, which were closely associated with the processes of T2DM. These metabolites mainly belonged to glycerophospholipid metabolism and sphingolipid metabolism. Based on network pharmacology analysis, 22 genes were recognized as the potential targets of mangiferin against diabetes. Moreover, molecular docking analysis revealed that the targets of TNF, CASP3, PTGS2, MMP9 , RELA, PLA2G2A, PPARA, and NOS3 could be involved in the modulation of inflammatory signaling pathways and arachidonic acid (AA) metabolism to improve IR and hyperglycemia . The combination of immunohistochemical staining and PCR showed that mangiferin could treat T2DM by regulating the expression of PPARγ protein and NF-κB mRNA expression to impact glycerophospholipids (GPs) and AA metabolism. The present study showed that mangiferin might alleviate IR and hyperglycemia of T2DM model rats via multiple targets and multiple pathways to adjust their phospholipid metabolism, which may be the underlying mechanism for mangiferin in the treatment of T2DM.
研究领域:
药理学
·
糖尿病研究
·
脂质代谢
·
网络药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）