title: Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway.
abstract: Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark ofMyrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Chaoyang District, Beijing 100029, China.
authors.forename: Jing
authors.identifier: 0000-0001-7653-9481
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian District, Beijing 100193, China.
authors.forename: Guibo
authors.identifier: 0000-0002-5717-1607
authors.initials: G
authors.lastname: Sun
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Chaoyang District, Beijing 100029, China.
authors.forename: Xiaolan
authors.identifier: 0000-0002-4895-1644
authors.initials: X
authors.lastname: Cui
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian District, Beijing 100193, China.
authors.forename: Xiangbao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian District, Beijing 100193, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Qin
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian District, Beijing 100193, China.
authors.forename: Xiaobo
authors.identifier: 0000-0002-9736-0170
authors.initials: X
authors.lastname: Sun