Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China.
Department of Obstetric, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Oxid Med Cell Longev. 2021 Nov 11;2021:1210675. doi: 10.1155/2021/1210675. eCollection 2021.
Fibrosis is the final common pathology of most chronic diseases as seen in the heart, liver, lung, kidney, and skin and contributes to nearly half of death in the developed countries. Fibrosis, or scarring, is mainly characterized by the transdifferentiation of fibroblasts into myofibroblasts and the excessive accumulation of extracellular matrix (ECM) secreted by myofibroblasts. Despite immense efforts made in the field of organ fibrosis over the past decades and considerable understanding of the occurrence and development of fibrosis gained, there is still lack of an effective treatment for fibrotic diseases. Therefore, identifying a new therapeutic strategy against organ fibrosis is an unmet clinical need. Naringenin, a flavonoid that occurs naturally in citrus fruits, has been found to confer a wide range of pharmacological effects including antioxidant, anti-inflammatory, and anticancer benefits and thus potentially exerting preventive and curative effects on numerous diseases. In addition, emerging evidence has revealed that naringenin can prevent the pathogenesis of fibrosis in vivo and in vitro via the regulation of various pathways that involved signaling molecules such as transforming growth factor-1/small mother against decapentaplegic protein 3 (TGF-1/Smad3), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), sirtuin1 (SIRT1), nuclear factor-kappa B (NF-B), or reactive oxygen species (ROS). Targeting these profibrotic pathways by naringenin could potentially become a novel therapeutic approach for the management of fibrotic disorders. In this review, we present a comprehensive summary of the antifibrotic roles of naringenin in vivo and in vitro and their underlying mechanisms of action. As a food derived compound, naringenin may serve as a promising drug candidate for the treatment of fibrotic disorders.
纤维化是大多数慢性疾病的最终共同病理，如心脏、肝脏、肺、肾脏和皮肤疾病，并导致发达国家近一半的死亡。纤维化或瘢痕形成主要特征是成纤维细胞向肌成纤维细胞的转分化和肌成纤维细胞分泌的细胞外基质（ECM）的过度积累。尽管在过去几十年中，在器官纤维化领域做出了巨大努力，并对纤维化的发生和发展有了相当的了解，但仍然缺乏有效的纤维化疾病治疗方法。因此，确定针对器官纤维化的新治疗策略是未满足的临床需求。柚皮素是一种存在于柑橘类水果中的类黄酮，已被发现具有广泛的药理作用，包括抗氧化、抗炎和抗癌作用，因此可能对许多疾病具有预防和治疗作用。此外，新出现的证据表明，柚皮素可以通过调节涉及转化生长因子-1/小母亲对抗 decapentaplegic 蛋白 3（TGF-1/Smad3）、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）、沉默调节蛋白 1（SIRT1）、核因子-κB（NF-B）或活性氧（ROS）等信号分子的各种途径，在体内和体外预防纤维化的发病机制。通过柚皮素靶向这些致纤维化途径可能成为纤维化疾病管理的新治疗方法。在这篇综述中，我们全面总结了柚皮素在体内和体外的抗纤维化作用及其作用机制。作为一种源自食物的化合物，柚皮素可能成为治疗纤维化疾病的有前途的药物候选物。
