We first took HFD-induced obese mice as an in vitro model of obese cardiomyopathy. In the group treated with Bic, it could significantly reverse myocardial inflammation, myocardial fibrosis and myocardial hypertrophy caused by HFD, and finally improve cardiac function. Bic inhibited NF-κB and MAPK pathways to achieve the above therapeutic effects. Subsequently, we used PA-stimulated H9c2 as an in vitro model of obese cardiomyopathy to further verify that Bic could inhibit the NF-κB and MAPK pathways to inhibit the PA-induced inflammation.
Obesity is a chronic disease. At the beginning, adipose tissue will produce local inflammation, which leads to long-term low-grade inflammation throughout the body. These pathological changes will cause multiple organs to be involved and eventually lead to organ dysfunction[23, 24]. It is noteworthy that studies in recent years have shown that obesity-induced chronic inflammation was related to various cardiovascular diseases. Chronic inflammation caused by obesity existed in the development of myocardial inflammation, myocardial fibrosis, and myocardial hypertrophy. which will eventually lead to myocardial dysfunction[25, 26]. Inhibition of inflammation has become an effective strategy in the treatment of obese cardiomyopathy. As previously mentioned, Bic, a traditional Chinese medicine derivative with Schisandra chinensis as raw material, is an approved clinical drug to treat chronic hepatitis . In addition, it is worth noting that Bic have anti-inflammatory effects in other inflammation-related models. Zhang et al found that Bic could regulate the oxidative stress to protect the rat brain from focal ischemia. Luo et al found that Bic can reduce TNF-α and IL-1β to alleviate acute lung injury.. Therefore, we believe that Bic may be a potential effective drug for the treatment of obesity-induced cardiomyopathy
It is known to all that the free fatty acid would generally increase in overweight people, in which the proportion of saturated fatty acid palmitate (C16:0) was the highest[30, 31]. PA is often used as an inducer for obese cardiomyopathy model in vitro, which can cause inflammation, fibrosis and myocardial damage in vitro[32, 33]. In previous studies, we found that PA induces the inflammation of cardiomyocytes by directly binding Toll-like receptor 4 (TLR4) accessory protein myeloid differentiation 2 (MD2). As the classic TRL4-related pathways, NF-κB and MAPK pathways were significantly activated by PA. Therefore, inhibiting the activation of these pathways provides important ideas for the treatment of obese-induced cardiomyopathy. Studies have found that a variety of drugs can improve obese cardiomyopathy by reducing the activation of these two pathways. Hinokinin alleviates HFD-induced cardiac injury by restraining the MAPK pathway. Curcumin analogue C66 could inhibit JNK-mediated NF-κB and MAPK pathways for treating obesity induced cardiomyopathy. As expected, in our study, PA could activate the pathway of H9c2 cells and make them produce inflammatory factors. However, Bic can reverse the activation of pathway and reduce the level of myocarditis. In vivo, Bic can also improve myocardial fibrosis, myocardial hypertrophy and myocardial injury caused by inflammation.
It is well known that in addition to inflammation, there are many other biological processes also involved in the occurrence of obese cardiomyopathy. Oxidative stress is one of the most significant mechanisms in the process of inflammation, fibrosis and hypertrophy caused by obese cardiomyopathy. It is worth noting that Bic has been reported to have antioxidant stress effects. In addition, in obese cardiomyopathy, in addition to NF-κB and MAPK pathways, Jak2 / Stat3 pathway and Tgf-1β/ Smad3 pathway were also involved. Therefore, the deficiency of this study is that it did not explore the effect of Bic on oxidative stress in obese cardiomyopathy.