Marati Kavitha, Palatheeya Sujatha, Chettupalli Ananda Kumar, Naik Bukke Sarad Pawar
Department of Pharmacology, University College of pharmaceutical Sciences, Palamuru University, Mahbubnagar Rural, Mahbubnagar, Telangana, 509001, India.
Department of Pharmaceutical Sciences, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, 203201, India.
BMC Pharmacol Toxicol. 2025 Jan 14;26(1):7. doi: 10.1186/s40360-025-00836-z.
Piperine, a secondary metabolite, affects the antihyperlipidemic effect of Ezetimibe (EZ). Hyperlipidemia is one of the independent risk factors for cardiovascular disorders such as atherosclerosis. Antihyperlipidemic drugs are essential for reducing cardiovascular events and patient mortality. Our study aimed to improve the solubility of EZ, a lipid-lowering drug that belongs to BCS II and has low solubility. Piperine, a bioenhancer, can increase the bioavailability of other pharmaceuticals without modifying their fundamental characteristics or enhancing their efficacy. The objective of this study was to increase the bioavailability of EZ while also improving its potency and reducing its toxicity by using piperine as a bioenhancer. Therefore, rats were given piperine combined with EZ, and their antihyperlipidemic activity was assessed while fed a high-fat diet.
The in vivo antihyperlipidemic effect of EZ with piperine was assessed at doses of 10 and 5-20 mg/kg b.w. The evaluation was conducted using propylthiouracil-induced and triton X-100-induced hyperlipidemia in rats. Give 400 mg/kg body weight of propylthiouracil along with piperine. Serum levels of total cholesterol (TC) (p < 0.01), triglycerides (TG) (p < 0.01), low-density lipoprotein (LDL) (p < 0.01), and very low-density lipoprotein (VLDL) (p < 0.01) all went up significantly. Additionally, it led to the induction of high-density lipoprotein (HDL) (p < 0.01). Administration of Triton X-100 via intraperitoneal injection at a single dose resulted in an elevation of lipid levels.
Lower levels of high-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein (VLDL) were significantly reduced by EZ at 10 mg/kg b.w. and piperine at 20 mg/kg b.w., respectively (p < 0.01 and p < 0.05). Liver histology studies provided further evidence supporting the present findings. Areas of concentrated periportal lymphocytes and hepatocytes formed a cord pattern in rats with hyperlipidaemia. It seemed like the hepatocytes, periportal area, and centrilobular part of the liver were all normal in the group who had the treatment. An analysis of the EZ plasma drug concentration with time was carried out in a research. The medication's most effective concentration (Cmax) was determined to be within 4 h after delivery, and The quantified concentration of the active medication was detectable in the bloodstream for 24 h.
In combination with piperine, EZ has demonstrated significant antioxidant and antihyperlipidemic effects. This indicates that EZ could be further utilised for treating hyperlipidemia and atherosclerosis due to its potential to boost the bioavailability and oral absorption of the drug.
胡椒碱作为一种次生代谢产物，会影响依折麦布（EZ）的抗高血脂作用。高血脂是动脉粥样硬化等心血管疾病的独立危险因素之一。抗高血脂药物对于降低心血管事件和患者死亡率至关重要。我们的研究旨在提高EZ的溶解度，EZ是一种属于生物药剂分类系统（BCS）II类且溶解度低的降脂药物。胡椒碱作为一种生物增强剂，可以在不改变其他药物基本特性或增强其疗效的情况下提高其生物利用度。本研究的目的是通过使用胡椒碱作为生物增强剂来提高EZ的生物利用度，同时提高其效力并降低其毒性。因此，给大鼠服用胡椒碱与EZ的组合，并在喂食高脂饮食的同时评估它们的抗高血脂活性。
评估了10mg/kg体重的EZ和5 - 20mg/kg体重的胡椒碱的体内抗高血脂作用。使用丙硫氧嘧啶诱导和 Triton X - 100诱导的大鼠高血脂进行评估。给予400mg/kg体重的丙硫氧嘧啶以及胡椒碱。血清总胆固醇（TC）水平（p < 0.01）、甘油三酯（TG）水平（p < 0.01）、低密度脂蛋白（LDL）水平（p < 0.01）和极低密度脂蛋白（VLDL）水平（p < 0.01）均显著升高。此外，它还导致高密度脂蛋白（HDL）升高（p < 0.01）。单次腹腔注射Triton X - 100导致血脂水平升高。
10mg/kg体重的EZ和20mg/kg体重的胡椒碱分别显著降低了较低水平的高密度脂蛋白（LDL）、总胆固醇（TC）、甘油三酯（TG）和极低密度脂蛋白（VLDL）（p < 0.01和p < 0.05）。肝脏组织学研究提供了支持本研究结果的进一步证据。高脂血症大鼠门静脉周围淋巴细胞和肝细胞集中区域形成条索状。接受治疗的组中肝脏的肝细胞、门静脉区域和肝小叶中心部分似乎都正常。在一项研究中对EZ血浆药物浓度随时间进行了分析。确定该药物的最大有效浓度（Cmax）在给药后4小时内，并且活性药物的定量浓度在血液中可检测24小时。
与胡椒碱联合使用时，EZ已显示出显著的抗氧化和抗高血脂作用。这表明EZ因其具有提高药物生物利用度和口服吸收的潜力，可进一步用于治疗高血脂和动脉粥样硬化。
