Tang Xingkui, Yang Yi, Peng Wenxu, Xu Mengping, Fan Qitong, Li Feng, Zou Guorong, Zhu Jianlin
The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, China.
Cancer Institute of Panyu, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2024 Jul 17;15:1412453. doi: 10.3389/fphar.2024.1412453. eCollection 2024.
Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease.
Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10 mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake . In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids.
PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice.
PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.
据报道，桔梗皂苷D（PD）可治疗包括非酒精性脂肪性肝病在内的代谢性疾病。此外，据报道桔梗皂苷D可激活肠道5'-AMP激活蛋白激酶（AMPK）的磷酸化水平，从而减少脂质吸收。因此，本研究的目的是探讨PD激活肠道AMPK和减少脂质吸收是否能改善非酒精性脂肪性肝病。
将清洁级雄性C57/BL小鼠喂食高脂饮食（HFD）（含60%热量）16周，同时口服PD（10mg/kg/天）。收集肝脏和肠道，并对肠道进行检测。采用蛋白质免疫印迹分析检测肠道脂质吸收相关基因（CD36、NPC1L1和ApoB）的表达、肠道和肝脏中的血清总甘油三酯（TG）和总胆固醇（TC）水平、粪便游离脂肪酸（FFA）水平以及肠道中AMPK磷酸化蛋白的表达。采用油红O和苏木精-伊红（H&E）染色检测肝脏、肠道和脂肪中的脂质分布。使用结肠癌细胞系（Caco2）来证实PD对细胞脂质摄取的影响。此外，检测血清炎症因子和肝酶，以阐明PD对代谢综合征循环的影响。然后使用瘦素缺乏小鼠（OB）进一步探讨PD对体重和血脂的改善作用。
PD对高脂饮食诱导的代谢综合征和脂肪肝具有非常显著的治疗或预防作用。PD改善了高脂饮食喂养小鼠的体重、胰岛素敏感性和糖耐量，还预防了非酒精性脂肪性肝病，降低了血脂水平，并增加了粪便脂质排泄。此外，PD通过激活肠道AMPK蛋白减少脂质吸收，这可能涉及抑制肠道脂质吸收相关基因（CD36、NPC1L1和ApoB）的基因表达水平。这些因素的综合作用改善了肝脏脂质蓄积和脂肪组织中的脂质蓄积。进一步发现，PD还改善了瘦素缺乏小鼠（OB）的体重和血脂水平。
PD对高脂饮食下的小鼠具有很强的治疗作用。PD通过抑制肠道脂肪吸收减轻高脂饮食诱导肥胖和非酒精性脂肪性肝病。
