Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

Abstract

Cardiac failure is often observed in aging patients with Huntington’s disease (HD). However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT) were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01). Cardiac expressions of superoxide dismutase 2 (SOD2) and B-cell lymphoma 2 (Bcl-2) in aging R6/2 HD mice were significantly lower than their WT (P<0.01), but cardiac expressions of tumor necrosis factor alpha (TNF-α), neurotrophin-3 (3-NT), 4-hydroxynonenal (4-HNE), Bcl-2-associated X protein (Bax), calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05). Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05). Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01), but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly reduced under oral B307 treatment (P<0.05). Oral B307 treatment may briefly alleviate cardiac failure in aging HD R6/2 mice via suppressing cardiac oxidative stress, inflammation, and apoptosis. We suggested that the herbal formula B307 may be further developed as a potential health supplement for ameliorating cardiac failure associated with aging.

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Keywords:

• Chinese herbal medicines
• cardiomyocytes
• echocardiography
• aging
• transgenic mouse model

Acknowledgments

We thank Prof Chiung-Mei Chen (Department of Neurology, College of Medicine, Chang-Gung University, Taoyuan, Taiwan) for providing R6/2 HD mice. We acknowledge Sun-Ten Pharmaceutical Company for the technical assistance. This work was supported by the Industry-University Cooperative Grant of Brion Research Institute of Taiwan, Top University Project of NTNU, and Transnational Research Centers Grant (103T3040B04) from NTNU. The funding agency had no role in the study design, data collection/analysis, and the decision to publish the manuscript.

Disclosure

The authors report no conflicts of interest in this work.