Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

Abstract

Abstract. The present study aimed to explore the role of Rhein lysinate (RHL) in neonatal rat ventricular myocytes (NRVMs) and congestive heart failure induced by co-arctation of the abdominal aorta. Male Sprague-Dawley rats were divided into 3 groups randomly: co-arctation of abdominal aorta group (A group, n=10), sham operation group (SH group, n=10) and RHL treatment rats (A+RHL group, n=10). To establish an in vitro oxidative stressed cardiomyocyte model, NRVMs were treated with 10 µM H 2 O 2 for 24 h. MTT assay indicated that H 2 O 2 treatment reduced primary cardiomyocyte viability in a time-and dose-dependent manner, whereas RHL abolished the detrimental effects of H 2 O 2 , indicating a protective role of RHL. Further study demonstrated that H 2 O 2 -induced reactive oxygen species (ROS) production was reversed by RHL. Then, TUNEL staining was carried out and the results revealed that H 2 O 2 markedly enhanced primary cardiomyocyte apoptosis. Conversely, RHL incubation decreased H 2 O 2 -induced cell apoptosis, indicating the protective role of RHL in primary cardiomyocytes. Furthermore, abnormal p38 activation was identified in the failed heart. Notably, treatment with RHL reduced p38 activation. In addition, RHL significantly enhanced the expression of anti-apoptotic protein, B cell lymphoma (Bcl)-2, however markedly reduced the protein level of Bcl-2 associated X, apoptosis regulator in primary cardiomyocytes, indicating its anti-apoptotic role in the cardiac setting. Overall, RHL protects heart failure primarily by reducing ROS production and cardiomyocyte apoptosis via suppressing p38 mitogen activated protein kinase activation.

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

“…Rhein is one of the effective components of rhubarb, and its protective effects on cerebrovascular conditions and tumors have been reported . RHL is a new compound produced by the reaction of lysine and rhein, which can dissolve in water and is convenient for drug administration . In this study, for the first time, we explored the effects of RHL on SCI in rats and evaluated the specific molecular mechanisms.…”

“…29,30 RHL is a new compound produced by the reaction of lysine and rhein, which can dissolve in water and is convenient for drug administration. 18 In this study, for the first time, we explored the effects of RHL on SCI in rats and evaluated the specific molecular mechanisms.…”

“…Its water solubility was significantly improved, and its clinical application was expanded . Studies have shown that RHL is characterized by anti‐inflammatory and antitumor features . In human glioma U87 cells, RHL is shown to induce cell apoptosis via suppressing Bcl‐2 and increasing Bax expression .…”

“…17 Studies have shown that RHL is characterized by anti-inflammatory and antitumor features. 17,18 In human glioma U87 cells, RHL is shown to induce cell apoptosis via suppressing Bcl-2 and increasing Bax expression. 19 In cervical cancer cells, RHL is found to suppress HeLa cell growth via p38 MAPK and JNK signaling pathway.…”

The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation

“…Rhein is a bioactive molecule isolated from rhizomes of medicinal plants such as Rheum L. As a substance in the anthraquinone group, rhein is commonly used as a cathartic (9). It not only sensitizes the carcinoma cells to chemotherapy or radiotherapy (10)(11)(12)(13), but also exhibits excellent antiinflammatory activities (14) and plays significant roles in the protection of the myocardial cells from hypoxia-induced injury (15,16). Additionally, the phytochemical rhein is involved in the regulation of the adipogenesis process in the cultured cells (17,18).…”