Patil Niharika, Patil Vishal S, Punase Nandeeni, Mapare Ghanshyam, Bhatt Shvetank, Patil Chandragouda R
Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.
School of Health Sciences and Technology, Vishwanath Karad MIT World Peace University, Kothrud, Pune, India.
J Am Nutr Assoc. 2025 Aug;44(6):529-544. doi: 10.1080/27697061.2025.2461217. Epub 2025 Feb 10.
β-carotene, a vitamin A precursor is reported to inhibit molecular pathways cardinal to pathogenesis of fibrotic tissue alterations and in this study, the effectiveness of 14 days oral administration of β-carotene (10, 20, and 40 mg/kg/day) in the cardiac fibrosis (CF) in rats was studied and explored the mechanisms through network pharmacology.
CF was induced by isoproterenol (ISO) 6 mg/kg/SC from day 1 to day 7. Losartan (LOS) 10 mg/kg/day/ served as the standard. Both β-carotene and LOS were administered from day 1 to 14. On the 15 day, ECG and blood pressure (systolic, diastolic and mean) were recorded in the anesthetized rats followed by their euthanasia. The extent of cardiac fibrosis in the isolated hearts was determined using heart coefficient, tissue levels of hydroxyproline, histological examination. The oxidative stress in cardiac tissue was estimated, as GSH, SOD, catalase, MDA and NO. β-carotene targeted proteins pathway, process, and functional enrichment analysis were explored through network pharmacology.
β-carotene dose-dependently mitigated the biochemical and histological changes induced by ISO in heart tissues. In ECG, it restored ST height, QT, and QRS intervals. Additionally, it normalized systolic, diastolic, and mean arterial pressures. The reduction in heart coefficient suggests β-carotene's potential to inhibit collagen deposition in heart tissue. β-carotene normalized oxidative stress markers, and hydroxyproline levels. All other biochemical parameters were restored to normal levels with β-carotene treatment. β-carotene 40 mg/kg dose showed comparable effect to that of LOS 10 mg/kg. β-carotene modulated IL-17, TNF, NF-kappa B, HIF-1, Sphingolipid, Relaxin, Adipocytokine, cAMP, Toll-like receptor, MAPK, PI3K-Akt, cGMP-PKG, VEGF, Ras, and PPAR signaling pathways.
β-carotene dose-dependently protects against ISO-induced CF in rats, with 40 mg/kg as an effective antifibrotic dose.
β-胡萝卜素是一种维生素A前体，据报道可抑制纤维化组织改变发病机制的关键分子途径。在本研究中，研究了连续14天口服β-胡萝卜素（10、20和40毫克/千克/天）对大鼠心脏纤维化（CF）的有效性，并通过网络药理学探索其作用机制。
从第1天至第7天，皮下注射异丙肾上腺素（ISO）6毫克/千克诱导CF。氯沙坦（LOS）10毫克/千克/天作为标准对照。β-胡萝卜素和LOS均从第1天给药至第14天。在第15天，记录麻醉大鼠的心电图和血压（收缩压、舒张压和平均压），随后对其实施安乐死。使用心脏系数、羟脯氨酸组织水平、组织学检查确定离体心脏的心脏纤维化程度。评估心脏组织中的氧化应激，包括谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、过氧化氢酶、丙二醛（MDA）和一氧化氮（NO）。通过网络药理学探索β-胡萝卜素靶向的蛋白质途径、过程和功能富集分析。
β-胡萝卜素剂量依赖性地减轻了ISO诱导的心脏组织生化和组织学变化。在心电图方面，它恢复了ST段高度、QT间期和QRS间期。此外，它使收缩压、舒张压和平均动脉压恢复正常。心脏系数的降低表明β-胡萝卜素具有抑制心脏组织中胶原蛋白沉积的潜力。β-胡萝卜素使氧化应激标志物和羟脯氨酸水平恢复正常。经β-胡萝卜素治疗后，所有其他生化参数均恢复至正常水平。40毫克/千克剂量的β-胡萝卜素显示出与10毫克/千克的LOS相当的效果。β-胡萝卜素调节白细胞介素-17（IL-17）、肿瘤坏死因子（TNF）、核因子κB（NF-κB）、缺氧诱导因子-1（HIF-1）、鞘脂、松弛素、脂肪细胞因子、环磷酸腺苷（cAMP）、Toll样受体、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）、环磷酸鸟苷-蛋白激酶G（cGMP-PKG）、血管内皮生长因子（VEGF）、Ras和过氧化物酶体增殖物激活受体（PPAR）信号通路。
β-胡萝卜素剂量依赖性地保护大鼠免受ISO诱导的CF，40毫克/千克为有效抗纤维化剂量。
