Polymers
·
2025
·Vol. 17
·期 5
·574
·
IF 4.9
Lin Fu,Hengxin Ren,Chaoxing Wang,Yaxin Zhao,Bohang Zou,Xiangyu Zhang
Polymer-based drug-controlled release systems offer greater efficacy and potency than conventional therapies. However, prominent drug side effects, lower circulation, and low drug loading capabilities limit their application range. In this work, the combination of Simvastatin (SIV) and Carvacrol (CAV) into PEG-PLGA microspheres (SIV-CAV-PP-MS) was achieved via an emulsification-solvent evaporation technique, resulting in microspheres characterized by high encapsulation efficiency and reduced particle size. In vitro studies demonstrated that the cumulative drug release increased with higher SIV and CAV levels in the release medium, reaching 88.91% and 89.35% at 25 days. Pharmacokinetic analysis revealed that the concentrations of SIV and CAV reached their maximum levels at approximately seven days in the SIV-CAV-PP-MS group, which indicates that using PEG-PLGA as a carrier significantly delays drug release. In vivo, evaluation demonstrated that the SIV-CAV-PP-MS high-dose group and positive drug control group showed reductions in low-density lipoprotein cholesterol levels by 0.39-fold and 0.36-fold compared to the Hyperlipidemia model group, and the addition of CAV significantly enhanced the lipid-lowering effects of SIV. Histological examinations indicated that the SIV-CAV-PP-MS medium-dose group displayed histological features more closely resembling those of normal mice compared to the Simvastatin control group, with a well-organized hepatocyte structure, a significant reduction in lipids, and improved liver health. The prepared polymeric microsphere utilizing SIV and SAV will be a promising dosage form for hyperlipidemia disease patients, with superior lipid-lowering efficacy and improved patient compliance.
研究领域:
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Qianyun Zhao,Yubin Liu,Mingxing Li,Long Zhao,Tiangang Wang,Yaqin Xiao,Shulin Wei,Ke Wu,Jiayue Yang,Yaqiu Wang,Yueshui Zhao,Fukuan Du,Yu Chen,Shuai Deng,Jing Shen,Zhangang Xiao,Zhi Li,Shengpeng Wang,Xu Wu
Hawthorn fruit is rich in pectins; however, the gut microbiota-modulating effects of hawthorn pectin remain unclear. In this study, enzyme-extracted hawthorn pectin ( M w : 126.24 kDa; HG/RG-I ratio: 55.64 %/37.93 %; branching degree: 2.44) was fractionated into two components: D1 (spherical, 345.76 kDa, HG/RG-I 57.48 %/37.25 %, branching degree 2.16) and D2 (flexible, 17.20 kDa, HG/RG-I 78.24 %/21.76 %, branching degree 1.33). Hawthorn pectin directly stimulated Dubosiella newyorkensis and Bifidobacterium bifidum growth in vitro . In hyperlipidemic mice, it alleviated dyslipidemia and enriched Lactobacillus and Dubosiella . Parallel experiments confirmed that D. newyorkensis supplementation similarly reduced dyslipidemia and enhanced Lactobacillus abundance, mediated by bacterial acetate production. Only D1 mimicked the pectin's prebiotic activity, promoting D. newyorkensis and B. bifidum growth. The high-RG-I D1, with elevated branching and larger M w , was identified as the key driver of hawthorn pectin's prebiotic effect. These findings highlight that hawthorn pectin and D1 specifically target probiotic D. newyorkensis to synergize with Lactobacillus against hyperlipidemia.
研究领域:
营养学
·
微生物学
·
代谢疾病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·Vol. 397
·期 8
·6037-6050
·
IF 3.1
She Cheng-Ye,Deng Yuan-Xiong,Wu Qin-Yu,Li Jing
Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.
研究领域:
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Kun Miao,Yawei Zhao,Ning Xue
The prevalence of obesity and its primary associated comorbidities, such as type 2 diabetes and fatty liver disease, has reached epidemic proportions, with no successful treatment available at present. Heat shock protein 90 (HSP90), a crucial chaperone, plays a key role in de novo lipogenesis (DNL) by stabilizing and maintaining sterol regulatory element binding protein (SREBP) activity. Kongensin A (KA), derived from Croton kongensis , inhibits RIP3-mediated necrosis, showing promise as an anti-necrotic and anti-inflammatory agent. It is not yet clear if KA, acting as an HSP90 inhibitor, can enhance hyperlipidemia, hepatic steatosis, and insulin resistance in obese individuals by controlling lipid metabolism. In this study, we first found that KA can potentially decrease lipid content at the cellular level. C57BL/6J mice were given a high-fat diet (HFD) and received KA and lovastatin through oral administration for 7 weeks. KA improved hyperlipidemia, fatty liver, and insulin resistance, as well as reduced body weight in diet-induced obese (DIO) mice, with no significant alteration in food intake. In vitro , KA suppressed DNL and reduced the amounts of mSREBPs. KA promoted mSREBP degradation via the FBW7-mediated ubiquitin-proteasome pathway. KA decreased the level of p -Akt Ser308, and p -GSK3β Ser9 by inhibiting the interaction between HSP90β and Akt. Overall, KA enhanced hyperlipidemia, hepatic steatosis, and insulin resistance by blocking SREBP activity, thereby impacting the FBW7-controlled ubiquitin-proteasome pathway.
研究领域:
药理学
·
代谢生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2023
·Vol. 37
·期 10
·e5707
·
IF 1.8
Qingxin Shi,Yuqi Lin,Lu Huang,Shuna Jin,Rongzeng Huang,Lijun Zhang,Chengwu Song,Lei Xu,Shiying Zhang
Hyperlipidemia is a chronic metabolic disorder characterized by alterations in lipid metabolism as well as other pathways. Laportea bulbifera , an indigenous medicinal plant of Chinese herbal medicine, exhibits therapeutic effects on hyperlipidemia, but the mechanisms remain unclear. This study investigated the potential mechanisms underlying the anti-hyperlipidemic effects of L. bulbifera using an integrated strategy based on metabolomics and network pharmacology methods that were established to investigate the potential mechanism of anti-hyperlipidemia effect of L. bulbifera . First, the therapeutic effects of L. bulbifera on body weight reduction and biochemical indices were assessed. Next, 18 significant metabolites distinguishing the control and model groups were identified based on serum metabolomics and multivariate analyses. Then, a compound–target network was constructed by linking L. bulbifera and hyperlipidemia using network pharmacology. Three metabolic pathways involved in treating hyperlipidemia were identified. Finally, five crucial targets were selected by constructing a bionetwork starting from the compounds and ending in the metabolites. This study established an integrated strategy based on metabolomics coupled with network pharmacology and revealed the mechanism underlying the protective effects of L. bulbifera against hyperlipidemia for the first time.
研究领域:
药理学
·
代谢组学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Junling Ren,Heng Fang,Le Yang,Hui Sun,Hongwei Song,Guangli Yan,Ying Han,Xijun Wang
Ethnopharmacological relevance Qizhi capsule (QZC), a Chinese patent drug, has been utilized to treat hyperlipidemia . Aim of study The present study aims to investigate the lipid-lowering effect of QZC, as well as the mechanism of action for treating hyperlipidemia. Materials and methods High-fat diet (HFD) induced hyperlipidemia rats were administrated with different doses of QZC for 28 days, and atorvastatin calcium tablets was used as the positive control. Serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were used to evaluate the effectiveness of QZC treatment. The metabolic profiles of feces were analyzed by UPLC-MS-based metabolomics approach coupled with multivariate data analysis. Results The levels of serum TC, TG, LDL-C, and HDL-C were significantly reversed in QZC treatment groups, showing a similar or even better treatment effect compared with the atorvastatin calcium group. Thirty-two potential fecal biomarkers related to hyperlipidemia were identified. QZC could partially recover the disturbed metabolic pathways of alpha-linolenic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. Meanwhile, the signal pathways of regulation of lipid metabolism by peroxisome proliferator-activated receptor α (PPARα), PPARα activates gene expression, and transcriptional regulation of white adipocyte differentiation can be also regulated by QZC. Conclusion The lipid-lowering effect of QZC was confirmed by both serum biochemistry and metabolomics analysis. The beneficial effects of QZC were mainly attributed to the correction of metabolic disorders and the maintenance of the dynamic balance of metabolites.
研究领域:
药理学
·
代谢组学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lu Liu,Suzhen Lei,Xiaoli Lin,David Mahoudjro Bodjrenou,Yi Zhang,Baodong Zheng,Hongliang Zeng
Type 3 resistant starch (RS3) regulates diet-related metabolic diseases by promoting intestinal short-chain fatty acids (SCFAs) and lactate production, and facilitating microbial lactate-to-butyrate fermentation. However, its precise in vivo mechanism remains unclear. Therefore, we studied the effects of type 3 lotus seed resistant starch (LRS3) and sodium lactate (SL) on colonic microbiota composition, metabolism, and lipid parameters. This study aimed to elucidate the mechanism by which LRS3 and SL modulate colonic microbiota and metabolism to mitigate hyperlipidemia in rats induced by a high-fat diet. Results showed LRS3 increased colonic microbial diversity, shifting the composition towards that of healthy rats. LRS3 intake reduced lactic acid-producing bacteria such as Allobaculum, Collinsella , and Blautia in the colon while promoting SCFAs-producing Ruminococcaceae. SL alone stimulated Lachnospiraceae growth. When both were administered, there was a significant increase in Treponema and Ruminococcaceae. The co-intervention of LRS3 and SL significantly affected lipid metabolism-related metabolites, up-regulating palmitic acid while down-regulating androsterone and phosphatidylcholine (PC) substances PC (14:0/20:4(8Z,11Z,14Z,17Z)), influencing unsaturated fatty acid biosynthesis pathways and inhibiting steroid hormone biosynthesis. Finally, via the microbial-metabolism-lipid correlation network, we identified that LRS3 and SL increased SCFAs production through Treponema and Ruminococcaceae metabolism, influencing organic acid and lipid composition in the colon. This indirectly reduced blood lipid levels in hyperlipidemic rats by modulating intestinal microecology.
研究领域:
营养学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
·
2014
·
IF 2.15
Juan Zhou,Yi-Qiao Xu,Sheng-Ya Guo,Chun-Qi Li
Introduction Hyperlipidemia is the most common form of dyslipidemia , which is the key risk factor for cardiovascular disease and stroke. The development of effective and safe drug treatments for hyperlipidemia has been proven challenging. Methods In this study, taking advantage of the transparency of larval zebrafish, we developed a zebrafish hyperlipidemia model for drug screening and efficacy assessment. Zebrafish at 5 d.p.f (days post fertilization) were fed with 0.1% egg yolk for 48 h (hours), followed by drug treatment for 24 h or 48 h. Tested drugs were administered into the zebrafish by direct soaking. Drug effect was evaluated based on quantitative analysis of Oil Red O (ORO) in zebrafish vena caudalis. Results All 5 human hypolipidemic drugs (simvastatin, lovastatin , ezetimibe , bezafibrate and hyodesoxycholic acid) showed significant hypolipidemic effects ( p < 0.01) in a dose-dependent manner in the zebrafish hyperlipidemia model. 'We also found a well-known Chinese tea Pu-erh tea significantly reduced lipids in this model ( p < 0.001 and p < 0.01). Discussion Our results demonstrate that the zebrafish hyperlipidemia model developed and validated in this study could be used for in vivo hyperlipidemia studies and drug screening and for assessing hypolipidemic drugs with different mechanisms.
研究领域:
药理学
·
心血管疾病研究
·
药物筛选
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANTICANCER RESEARCH
·
2021
·Vol. 41
·期 3
·1213-1218
·
IF 2.48
SHUIMING WANG,XIAOFENG WANG,YU WANG,QIANG LENG,YU SUN,ROBERT M. HOFFMAN,HEIYING JIN
Background/Aim: Overexpression of inflammatory cytokines and oxidative stress increase the risk of colorectal cancer (CRC) in obesity and hyperlipidemia. The aim of this study was to investigate whether the monoterpene antioxidant p-cymene would reduce the incidence of CRC in a rat model of hyperlipidemia. Materials and Methods: The hyperlipidemic CRC rat model was established by a high-fat diet and dimethyl hydrazine (DMH) induction. All rats received 30 mg/kg DMH to induce CRC, and were then assigned to groups with a normal diet or high-fat diet with/without 30 mg/kg/day p-cymene orally during the entire experimental period. Tumor incidence in each group, and the level of serum inflammatory cytokines and oxidative stress-related markers in intestinal tissues were measured. Results: p-Cymene significantly inhibited CRC occurrence in hyperlipemic rats (p=0.024) by reducing the expression of serum inflammatory cytokines (interleukin-1 by 54.5%; interleukin-6 by 28.3%; adiponectin by 26.3%; cyclo-oxygenase-2 by 48.4%) and intestinal oxidative-stress cytokines (total antioxidant capacity by 30.4%; superoxide dismutase by 30.3%; malondialdehyde by 47.1%). Conclusion: p-Cymene has clinical potential to reduce the incidence of CRC in hyperlipemia.
研究领域:
医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Materials Advances
·
2024
·
IF 5.2
Kepei Zhang,Junlan Chen,Faisal Raza,Hajra Zafar,Ye Xu,Ran Li,Kamran Hidayat Ullah,Shigao Zhou
Polydatin, a monomer derived from the dried roots and stems of traditional Chinese medicinal herb, Polygonum cuspidatum, boasts extensive pharmacological activities. Existing nanocarriers of polydatin have not been able to prolong the circulation time for enhanced antidiabetic potential of the stilbenoid polyphenol. This study aims to improve the sustained release and antidiabetic potential of polydatin by fabricating long circulating liposomes (PLLs) via a membrane dispersion method. An orthogonal optimized PLL composed of lecithin, DSPE-PEG2000, and cholesterol was produced, wherein evaluation of the physical properties showed that the prepared PLL had a spherical shape with uniform size, small particle size, and even distribution as well as high encapsulation efficiency and drug loading, along with good physical stability at 4 and 25 °C for 30 days. In vivo release experiments in different buffers via the dialysis bag method suggested that the PLL provided a sustained release of polydatin. Also, in vitro cell uptake and in vivo pharmacokinetics studies of the PLL respectively demonstrated improved cellular uptake and prolonged in vivo circulation time and bioavailability. Using a high-fat diet-induced obese type 2 diabetes mellitus (T2DM) mouse model, it was observed that the PLL could lower blood sugar, improve weight loss, reduce antioxidant stress, lower blood lipids, and ameliorate liver, spleen, and pancreatic tissue damage. This study successfully prepared long-circulating liposomes of polydatin, which sustained in vitro release of polydatin, improved bioavailability in vivo, and enhanced the activity of the drug in treating obese diabetic mice.
研究领域:
药理学
·
纳米医学
·
代谢疾病研究
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Dan-dan Zhi,Xi-ying He,Lin-fu Yang,Yun-fei Xue,Yi-qiu Liu,Dan Yue,Yi-nan Feng,Kun Dong,Ya-kai Tian
Royal jelly acid is a unique unsaturated fatty acid isolated from royal jelly. Recently, royal jelly acid was proposed to have potential therapeutic effects on hyperlipidemia. However, its effect on hyperlipidemia and the underlying molecular mechanism remains unclear. Therefore, in this study, we analyzed the mechanism of anti-hyperlipidemia of royal jelly acid through animal experiments and plasma metabolomics in conjunction with human network pharmacology and molecular docking analyses. We found that royal jelly acid could significantly decrease the serum lipid levels, ameliorate hepatic pathological injury, and reduce the level of oxidative stress in the experimental rats. A total of 41 key metabolites and 10 hub targets played key roles in the exertion of anti-hyperlipidemic effects, including tumor necrosis factor (TNF), insulin (INS) and epidermal growth factor receptor (EGFR). A total of 24 pathways, including tryptophan, citrate cycle, and arachidonic acid metabolisms, were identified as the key pathways involved in royal jelly acid-alleviated hyperlipidemia. The present findings provide new insights into the pathogenesis, diagnosis, and treatment targets of hyperlipidemia as well as contribute to the development and utilization of royal jelly acid related products.
研究领域:
药理学
·
代谢组学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2025
·Vol. 2025
·期 1
·8349248
·
IF 4.2
Yuanjie Wu,Yuntian Zhang,Xike Wu,Ziyan Zhang,Junhui Shen,Nan Tian,Chunlei Fan
This study investigated the effects of tanshinone IIA combined with rutin and squalene (RTS) on atherosclerosis (AS) associated with hyperlipidemia and the underlying mechanisms. Female New Zealand rabbits were subjected to a hyperlipidemia and AS model. Treatment with RTS for 4 weeks reduced the weight, and some serum lipid levels include serum TC, serum TG, serum LDL-C. RTS also improved lesions of the liver and aorta. In vitro analyses showed that RTS significantly activated LDLR-mediated hepatic lipid endocytosis, but blocking LDLR activation with si-SREBP2 attenuated the therapeutic effect, which demonstrated that RTS can activate the SREBP2/LDLR pathway mediating liver clearance of blood lipids. This study highlights the therapeutic potential of RTS in hyperlipidemia and AS. As a convenient form of a combination drug, RTS has shown considerable potential in the improvement of hyperlipidemia combined with AS.
研究领域:
药理学
·
心血管病学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）