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壳聚糖微球(CTMS)和壳聚糖-辣椒素微球(CCMS)对油酸诱导的脂质积累的抑制作用及其药代动力学

inhibition of lipid accumulation induced by oleic acid and pharmacokinetics of chitosan microspheres (CTMS) and chitosan-capsaicin microspheres (CCMS).

作者信息

Wu Sihui, Pan Haitao, Tan Sirong, Ding Chen, Huang Guidong, Liu Guihua, Guo Jiao, Su Zhengquan

机构信息

Guangdong Food and Drug Vocational-Technical School, Guangzhou, China.

Key Research Center of Liver Regulation for Hyperlipidemia SATCM/Class III Laboratory of Metabolism SATCM, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Food Nutr Res. 2017 Jun 14;61(1):1331658. doi: 10.1080/16546628.2017.1331658. eCollection 2017.

Abstract

Chitosan and capsaicin are compounds extracted from natural products and have been indicated to lower body weight and prevent fatty liver. However, their applications are limited by poor oral bioavailability, low compliance and some serious side effects. To solve these problems, we successfully prepared chitosan microspheres (CTMS) and chitosan-capsaicin microspheres (CCMS) in previous study. Therefore, in the present study, we evaluated the ability of CTMS and CCMS to eliminate lipid accumulation in hepatocytesand also characterized their pharmacokinetic parameters after administration. The results showed that the two microspheres could significantly reduce intracellular lipid accumulation and dose-dependently improve the triglyceride (TG) content in HepG2 cells. A pharmacokinetic study indicated that CTMS and CCMS were distributed in almost all of the measured tissues, especially liver and kidney, and that their absorption was better than those of chitosan and capsaicin. Simultaneously, the prolonged circulating half-lives, the lower clearance and higher plasma concentration of CTMS and CCMS showed that their bioavailability was effectively enhanced. All of the results indicated that the lipid accumulation inhibition of CTMS and CCMS was better than that of chitosan and capsaicin, and that these microspheres can be developed as preventive agents for fatty liver or obesity.

摘要

壳聚糖和辣椒素是从天然产物中提取的化合物,已被证明具有降低体重和预防脂肪肝的作用。然而,它们的应用受到口服生物利用度差、依从性低和一些严重副作用的限制。为了解决这些问题,我们在先前的研究中成功制备了壳聚糖微球(CTMS)和壳聚糖-辣椒素微球(CCMS)。因此,在本研究中,我们评估了CTMS和CCMS消除肝细胞脂质积累的能力,并对给药后的药代动力学参数进行了表征。结果表明,这两种微球可显著减少细胞内脂质积累,并剂量依赖性地提高HepG2细胞中的甘油三酯(TG)含量。药代动力学研究表明,CTMS和CCMS几乎分布在所有测量组织中,尤其是肝脏和肾脏,并且它们的吸收优于壳聚糖和辣椒素。同时,CTMS和CCMS延长的循环半衰期、较低的清除率和较高的血浆浓度表明它们的生物利用度得到了有效提高。所有结果表明,CTMS和CCMS对脂质积累的抑制作用优于壳聚糖和辣椒素,并且这些微球可开发为脂肪肝或肥胖症的预防剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33cb/5475299/afbb0ef65cd7/zfnr_a_1331658_f0001_b.jpg

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