NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·Vol. 397
·期 8
·6037-6050
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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
JOURNAL OF PHARMACEUTICAL SCIENCES
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2016
·
IF 2.641
Nanxi Xiang,Xu Zhou,Xinyi He,Yu Zhang,Jinjie Zhang,Zhi-Rong Zhang,Xun Sun,Tao Gong,Yao Fu
In this study, an injectable in situ –forming gel has been designed and fabricated for the controlled and prolonged release of pitavastatin calcium (Pit) for treating hyperlipidemia . By mixing phospholipids and soybean oil with ethanol, the phospholipid-based platform material (PSE) displayed in a sol state with low viscosity in vitro . After subcutaneous injection , pregel solution underwent rapid-phase separation and gelation in situ thus forming a drug release depot. Pit was loaded within PSE (PSE-P), which achieved prolonged release profiles for 15 consecutive days in vitro . Correspondingly, the pharmacokinetic study in rats demonstrated that PSE-P achieved sustained in vivo release for 15 days after 1 subcutaneous injection. The pharmacodynamic study in hyperlipidemia rats further revealed that the levels of total cholesterol, total triglyceride , and low-density lipoprotein decreased remarkably, and the in vivo therapeutic effect was well maintained for over 20 days. Additionally, PSE-P showed mild tissue inflammatory responses and excellent degradability in vivo . Thus, in situ –forming PSE-P gel represents a viable and promising drug delivery platform to achieve long-term therapeutic effects in the management of hyperlipidemia.
研究领域:
药剂学
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生物医学工程
·
代谢疾病研究
✓ 已验证
DOI
高影响因子
Bioactive Carbohydrates and Dietary Fibre
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2020
·
IF 0
Jinxia Meng,Zhouya Bai,Wenqi Huang,Ying Liu,Peilin Wang,Shaoping Nie,Xiaojun Huang
Type 2 diabetes (T2D), as the most common type of diabetes, has become the public problem in the world for increasing prevalence. In this study, the effects of polysaccharide from white kidney bean (WKBP) on streptozotocin-induced diabetic rats were investigated. Administration of WKBP decreased the levels of blood glucose , glycated serum protein and increased the level of insulin of diabetic rats. Treatment of WKBP reduced the concentration of total cholesterol and raised the ratio of high and low-density lipoprotein cholesterol related to serum lipids . WKBP also can lessen damage of pancreas, kidney and liver, and contribute to their function restoration. The results found that WKBP exhibited high potential on helping with hyperglycemia , hyperlipidemia and alleviating the damage of pancreas, kidney and liver of T2D.
研究领域:
生物化学
·
药理学
·
内分泌学
✓ 已验证
DOI
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Geer Chen,Yunfeng Huang,Haohui Yu,Junru Wang,Haobing Li,Shuqi Shen,Xingjian Zhou,Keqing Shi,Hongwei Sun
Hyperlipidemic acute pancreatitis (HAP) is a serious inflammatory pancreatic disease commonly seen in patients with disorders of lipid metabolism. Decreasing blood triglyceride levels and proinflammatory factors can alleviate hyperlipidemic pancreatitis. The lipase that enhanced the Brownian motion of mesoporous silica in triglyceride solutions could accelerate decomposition of the lipid and improve the efficiency of absorption. In this study, we developed a mesoporous silica nanoparticle with dual modification of IL-6 aptamer and lipase for the treatment of HAP. The nanoparticle could increase the ability of particles to absorb inflammatory factor IL-6 and decompose triglycerides. For every 10 mg of the dual-modified nanoparticles, the efficiency of capturing IL-6 was approximately 9.67 pg/mL and of decomposing triglycerides was approximately 3.88 mg/mL in the plasma of HAP patients within 2 h. In summary, the mesoporous silica nanoparticle could absorb the IL-6 inflammatory factor through IL-6 aptamers and decompose triglycerides through lipase. Furthermore, based on clinically available plasma exchange technology, combined with our developed dual-modified nanoparticles, we designed an absorption device for the treatment of hyperlipidemic pancreatitis; it works to promote the treatment of hyperlipidemic pancreatitis.
研究领域:
医学
·
纳米技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
APOPTOSIS
·
2024
·
IF 6.1
Gu Boyuan,Yu Wenhao,Huang Zhiwei,Bai Junjie,Liu Shenglu,Ren Bingyu,Wang Pengru,Sun Lei,Wen Jian,Zheng Yang,Tan Peng,Fu Wenguang
Hyperlipidemia is a common cause of acute pancreatitis (AP), often leading to more severe clinical symptoms. The mortality factor 4-like protein 1 (MORF4L1, also called MRG15) plays a crucial role in regulating lipid metabolism. Therefore, this study aimed to explore the mechanism of MRG15 in hyperlipidemic acute pancreatitis (HAP). Mendelian randomization, transcriptome analysis, and single-cell analysis were employed to explore the association between MRG15 and AP by utilizing publicly available databases. In vivo, hypertriglyceridemia mouse models were created by intraperitoneal injection of P407 or using APOE-deficient mice. Subsequently, the HAP model was induced by cerulean. In vitro, a cell model of HAP was established by initially exposing cells to palmitic acid to simulate a high-fat environment, followed by cerulein treatment. Subsequently, MRG15-related indicators were measured. Through Mendelian randomization, it was discovered that there is a positive correlation between genetic expression of MRG15 and the risk of AP. Transcriptome and single-cell analysis revealed that elevated MRG15 expression in AP contributes to lipid metabolism disorders and the activation of apoptosis pathways in pancreatic acinar cells. MRG15 is found to be significantly upregulated in cases of HAP. Knocking down MRG15 led to an increase in mitophagy and a decrease in apoptosis in pancreatic cells, and this effect was reversed when the mitochondrial Tu translation elongation factor (TUFM) was simultaneously knocked down. MRG15 inhibits mitophagy by degrading TUFM, ultimately promoting cell apoptosis and worsening the progression of HAP.
研究领域:
胃肠病学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
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