Angelica sinensis: A Novel Adjunct to Prevent Doxorubicin-Induced Chronic Cardiotoxicity

State Key Laboratory of Safety Evaluation for New Drugs, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
Basic & Clinical Pharmacology & Toxicology (Impact Factor: 2.38). 01/2008; 101(6):421-6. DOI: 10.1111/j.1742-7843.2007.00144.x
Source: PubMed


Doxorubicin is an anthracycline antibiotic agent used in the treatment of a variety of solid and haematopoietic tumours, but its use is limited by formation of metabolites that induce acute and chronic cardiac toxicities. Angelica sinensis has been widely used to treat cardiovascular and cerebrovascular diseases in China. In the present study, we used an in vivo mouse model to explore whether A. sinensis could protect against doxorubicin-induced chronic cardiotoxicity. Male ICR mice were treated with distilled water or water extraction of A. sinensis (15 g/kg, orally) daily for 4 weeks, followed by saline or doxorubicin (15 mg/kg, intravenously) treatments weekly. Cardiotoxicity was assessed by electrocardiograph, antioxidant activity in cardiac tissues, serum levels of creatine kinase, aspartate aminotransferase (AST) and histopathological change in cardiac tissues. A cumulative dose of doxorubicin (60 mg/kg) caused animal death and myocardial injury characterized by increased QT interval and decreased heart rate in electrocardiograph, decrease of heart antioxidant activity, increase of serum AST, as well as myocardial lesions. Pre-treatment with A. sinensis significantly reduced mortality and improved heart performance of the doxorubicin-treated mice as evidenced from normalization of antioxidative activity and serum AST, preventing loss of myofibrils as well as improving arrhythmias and conduction abnormalities. Furthermore, the in vitro cytotoxic study showed that A. sinensis did not compromise the antitumour activity of doxorubicin. These results suggested that A. sinensis elicited a typical cardioprotective effect on doxorubicin-related oxidative stress, and could be a novel adjunct in the combination with doxorubicin chemotherapy.

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    • "For example, different extracts or specific active ingredients from A. sinensis show potent anticancer activities [6] [7]. Extracted natural products from A. sinensis have been proved successful also against cardiovascular complications, hepatic diseases, inflammation, etc. [4] [8] [9] [10]. Although the traditional medicinal formula of A. sinensis is available in many countries, the plant is indigenous to China only. "
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    ABSTRACT: Background Angelica sinensis is a well-known traditional Chinese medicinal plant. We have aimed to assess the genetic diversity and relationships in A. sinensis cultivars collected from different locations of China, and also some other Angelica species. Results We have employed an improved random amplified polymorphic DNA (RAPD) technique for the amplification of DNA materials form ten Angelica cultivars, and the results were verified by inter-simple sequence repeat (ISSR) analysis. Twenty six RAPD primers were used for RAPD, and the amplified bands were found highly polymorphic (96%). Each primer amplified 8-14 bands with an average number of 10.25. The cluster dendrogram showed the index of similarity coefficients ranging from 0.41 to 0.92. The similarity coefficients were higher between different cultivars of A. sinensis, and lower between different species. Twenty ISSR primers were used for the amplification, and each primer had amplified 6-10 bands with an average number of 7.2 bands per primer. The cluster dendogram showed the index of similarity coefficients ranging from 0.35 to 0.89. Conclusions This study genetically characterized the Angelica species, which might have significant contribution in genetic and ecological conservation of this important medicinal plant. Also, this study indicates the improved RAPD and ISSR analysis are important and potent molecular tools for the study of genetic diversity and authentication of organisms.
    Electronic Journal of Biotechnology 03/2015; 18(2):96-102. DOI:10.1016/j.ejbt.2014.12.006 · 0.68 Impact Factor
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    • "Danggui has also been shown to promote angiogenesis [22]. Danggui is not only commonly used to treat various gynecological conditions, but recent studies have also shown that it can prevent doxorubicin-induced chronic cardiotoxicity and reduce myocardial injury in animal models [23, 24]. A range of active compounds have already been isolated and identified from Danggui [17]. "
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    ABSTRACT: Danggui (Radix Angelicae Sinensis) is an herb often used in Traditional Chinese medicine. It is used to promote blood flow and has been used in the treatment of myocardial ischemia-reperfusion injury in animal models. Angiotensin II (Ang II) has been shown to play important roles in mediating cardiovascular diseases, and may cause cardiac hypertrophy and apoptosis. This study aimed to investigate whether Danggui has protective effects on Ang II-induced apoptosis in H9c2 cardiomyoblast cells and study the mechanisms involved. We evaluated the effect of Danggui on Ang II-induced apoptosis in an in vitro model. H9c2 cardiomyoblast cells were cultured in serum-free medium for 4 hr, then treated with Danggui (50, 100 μg/ml) 1 hr pre- or post-Ang II treatment. After a further 23 hr of culture, cells were harvested for analyses with assays for apoptosis markers and cell signaling pathways. Our results showed that Ang II induced upregulation of pro-apoptotic Bad, instability of the mitochondria membrane potential, cytochrome c release, caspase-9 and caspase-3 activation and cardiomyocyte apoptosis. Pre- or post-treatment with Danggui reversed all of the above Ang II-induced apoptotic effects in H9c2 cells. Furthermore, the JNK (SP600125) inhibitor completely blocked Danggui inhibition of caspase-3 activation in Ang II-treated H9c2 cells. Our results showed that Danggui either pre-treatment or post-treatment highly attenuated the Ang II-induced apoptosis in cardiomyoblast cells. The findings demonstrated that the anti-apoptosis effect of Danggui is mediated by JNK and PI3k inhibitors.
    BMC Complementary and Alternative Medicine 09/2014; 14(1):358. DOI:10.1186/1472-6882-14-358 · 2.02 Impact Factor
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    • "A. sinensis has been used for a long time in traditional Chinese medicine for its biological activities, such as immune system regulation [32, 33], menopausal symptom relief [15, 16], and cardioprotection [34, 35]. The different extracts of A. sinensis, such as water, chloroform, and acetone extracts, have demonstrated antitumor biofunctions [36, 37]. "
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    ABSTRACT: Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.
    Evidence-based Complementary and Alternative Medicine 11/2013; 2013:394636. DOI:10.1155/2013/394636 · 1.88 Impact Factor
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