School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
J Agric Food Chem. 2024 Mar 27;72(12):6236-6249. doi: 10.1021/acs.jafc.3c08232. Epub 2024 Mar 14.
Hypercholesterolemia poses a significant cardiovascular risk, particularly in postmenopausal women. The anti-hypercholesterolemic properties of ATCC8014 (LP) are well recognized; however, its improving symptoms on postmenopausal hypercholesterolemia and the possible mechanisms have yet to be elucidated. Here, we utilized female ApoE-deficient (ApoE) mice undergoing bilateral ovariectomy, fed a high-fat diet, and administered 10 colony-forming units (CFU) of LP for 13 consecutive weeks. LP intervention reduces total cholesterol (TC) and triglyceride (TG) accumulation in the serum and liver and accelerates their fecal excretion, which is mainly accomplished by increasing the excretion of fecal secondary bile acids (BAs), thereby facilitating cholesterol conversion. Correlation analysis revealed that lithocholic acid (LCA) is an important regulator of postmenopausal lipid abnormalities. LP can reduce LCA accumulation in the liver and serum while enhancing its fecal excretion, accomplished by elevating the relative abundances of and in the ileum. Our findings demonstrate that postmenopausal lipid dysfunction is accompanied by abnormalities in BA metabolism and dysbiosis of the intestinal microbiota. LP holds therapeutic potential for postmenopausal hypercholesterolemia. Its effectiveness in ameliorating lipid dysregulation is primarily achieved through reshaping the diversity and abundance of the intestinal microbiota to correct BA abnormalities.
高胆固醇血症会对心血管系统造成重大风险，尤其是对绝经后的女性。ATCC8014（LP）具有抗高胆固醇血症的特性，这一点已得到广泛认可；然而，其对绝经后高胆固醇血症症状的改善作用及其可能的作用机制仍有待阐明。在这里，我们利用接受双侧卵巢切除术、高脂饮食喂养并连续 13 周给予 10 个集落形成单位（CFU）LP 的雌性载脂蛋白 E 缺陷（ApoE）小鼠作为研究对象。LP 干预可减少血清和肝脏中总胆固醇（TC）和甘油三酯（TG）的积累，并加速其粪便排泄，这主要是通过增加粪便次级胆汁酸（BAs）的排泄来实现的，从而促进胆固醇转化。相关性分析表明，石胆酸（LCA）是绝经后脂质异常的重要调节因子。LP 可减少肝脏和血清中 LCA 的积累，同时增加其粪便排泄，这是通过增加回肠中 和 的相对丰度来实现的。我们的研究结果表明，绝经后脂质功能障碍伴随着胆汁酸代谢异常和肠道微生物群落失调。LP 具有治疗绝经后高胆固醇血症的潜力。其改善脂质失调的有效性主要是通过重塑肠道微生物群落的多样性和丰度来纠正 BA 异常。
