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.

Chinese Veterinary Medicine B307 Promotes Cardiac Performance and Skeletal Muscle Contraction via Enhancing Intracellular Calcium Levels and Neural Electrical Activity in Animal and Cell Models

“…The strain has complete provenance data, is easy to buy, and has been widely used in general research, safety assessment tests, embryology research, and physiological research. As described in our previous experiments [ 4 – 6 ], the dosage of the B307 extract was much lower than the dosage of IC 50 . All protocols in the oral B307 treatments in animal models were executed according to the international guidelines for care and use of laboratory animals.…”

“…Ginseng contains a complex mixture of saponins, ginsenosides, and panaxosides, ophiopogon contains homoisoflavonoids with anti-inflammatory properties, and schizandra contains abundant amounts of phytoestrogen lignans with antioxidant activity [ 26 ]. As suggested in our previous studies, we have reported that B307 can effectively alleviate oxidative stress, inflammation, and damage in the myocardial tissue [ 4 , 5 ]. In addition, our recent study also reported that B307 could be a protective and beneficial alternative treatment for thyroidectomy-induced cardiopulmonary exercise dysfunction [ 6 ].…”

“…For animal health considerations, the proportion of Chinese herbal medicines (CHMs) is usually determined based on scientific evidence and the experience of the prescriber [ 3 ]. As suggested in our previous studies, we have reported that CHM B307 can effectively enhance cardiac and motor functions for mice and rats [ 4 – 6 ]. CHM B307 with main herbal ingredients of ginseng ( Panax ginseng Radix), schizandra ( Schisandra chinensis Fructus), ophiopogon ( Ophiopogon spicata Tuber), and Danshen ( Salviae miltiorrhizae Radix) can be an appropriate CVM in protecting muscle against fatigue and strengthening the contraction of the heart muscle for animals [ 7 – 14 ].…”

“…Due to limitations of instrument function, we assessed the cardiovascular performance of mice instead of pigeons by color Doppler M-mode echocardiography. As described in our previous experiment [ 4 , 5 ], after anesthesia with 2% isoflurane gas (Baxter Healthcare, New Providence, RI, USA), mice were placed on a heated working platform for monitoring ECG and respiration gating. Echocardiography was measured by using a prospect high-resolution imaging system (S-Sharp Corporation, Taiwan) with the probe providing the central frequency ranging from 20 to 40 MHz.…”

GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling

“…These results indicated that liraglutide may reduce mHTT-induced cytotoxicity by restoring blocked neuronal insulin signaling. mHTT-induced oxidative stress plays a key role in mHTT-induced neuronal apoptosis [ 20 ]. To determine whether liraglutide protects cells from mHTT-induced oxidative stress damage, we measured intracellular ROS levels through the DHE fluorometric method.…”