Akomolafe Seun Funmilola, Akinjiyan Moses Orimoloye, Asogwa Nnaemeka Tobechukwu, Elekofehinti Olusola Olalekan
Department of Biochemistry, Ekiti State University, P.M.B. 5363, Ado Ekiti, Ekiti State, Nigeria.
Microbiota Lab, Centre for Preclinical Studies, Medical University of Warsaw, Ul. Banacha 1b, 02-097, Warsaw, Poland.
J Mol Histol. 2025 May 19;56(3):157. doi: 10.1007/s10735-025-10432-4.
Cardiovascular diseases are among the top killer diseases globally. This work assessed the cardioprotective ability of raw and roasted pumpkin (Cucurbita pepo L.) seed-supplemented diets on cisplatin-induced heart damage in rats. The cardiotoxicity was induced with cisplatin (7 mg/kg) intraperitoneally. The rats' six groups were treated for 14 days: control rats fed a normal diet; group 2: cisplatin-induced (CIS) untreated; groups 3 and 4: CIS + 5% raw pumpkin seed (RW) and CIS + 10% RW; groups 5 and 6: CIS + 5% and 10% roasted pumpkin seed (RT). The biochemical assays were done using standard procedures, and Schrödinger suites were used for in silico studies of C. pepo phytocompounds with phosphodiesterase 5. There was a significant (p < 0.05) elevation in arginase, phosphodiesterase-5, adenosine deaminase, acetylcholinesterase, and butyrylcholinesterase activities, ROS and TBARS in cisplatin-induced rats relative to control. Cisplatin-induced rats also have their nitric oxide, antioxidant (catalase, GST, and GSH) levels reduced, and the heart's histoarchitectural structure degenerated relative to control. These conditions were reversed upon treatment with raw and roasted pumpkin seeds (5% and 10%). Molecular docking of C. pepo phytocompounds like chlorogenic acid (-11.4 kcal/mol), beta-sitosterol (-11.013 kcal/mol), quercetin (-10.323 kcal/mol), and epicatechin (-10.168 kcal/mol) suggests that they are potent inhibitors of phosphodiesterase 5, better than standard drug pravastatin (-9.809 kcal/mol), with a good pharmacotoxicity profile. The study suggests that the cardioprotective effect of raw and roasted pumpkin seeds could be via their ability to inhibit phosphodiesterase 5, improve vasodilation, increase antioxidant levels, and alleviate oxidative stress.
心血管疾病是全球头号致命疾病之一。本研究评估了添加生南瓜籽和烤南瓜籽（西葫芦）的饮食对顺铂诱导的大鼠心脏损伤的心脏保护能力。通过腹腔注射顺铂（7毫克/千克）诱导心脏毒性。将大鼠分为六组，治疗14天：对照组大鼠喂食正常饮食；第2组：顺铂诱导（CIS）但未治疗；第3组和第4组：CIS + 5%生南瓜籽（RW）和CIS + 10% RW；第5组和第6组：CIS + 5%和10%烤南瓜籽（RT）。生化分析采用标准程序进行，使用薛定谔软件包对西葫芦植物化合物与磷酸二酯酶5进行计算机模拟研究。与对照组相比，顺铂诱导的大鼠精氨酸酶、磷酸二酯酶-5、腺苷脱氨酶、乙酰胆碱酯酶和丁酰胆碱酯酶活性、活性氧和丙二醛水平显著升高（p < 0.05）。顺铂诱导的大鼠一氧化氮、抗氧化剂（过氧化氢酶、谷胱甘肽S-转移酶和谷胱甘肽）水平也降低，且心脏组织架构相对于对照组发生退化。用生南瓜籽和烤南瓜籽（5%和10%）治疗后，这些情况得到逆转。西葫芦植物化合物如绿原酸（-11.4千卡/摩尔）、β-谷甾醇（-11.013千卡/摩尔）、槲皮素（-10.323千卡/摩尔）和表儿茶素（-10.168千卡/摩尔）的分子对接表明，它们是磷酸二酯酶5的有效抑制剂，比标准药物普伐他汀（-9.809千卡/摩尔）更好，具有良好的药物毒性特征。该研究表明，生南瓜籽和烤南瓜籽的心脏保护作用可能是通过其抑制磷酸二酯酶5、改善血管舒张、提高抗氧化剂水平和减轻氧化应激的能力来实现的。
