Modulation of the mTOR Pathway by Curcumin in the Heart of Septic Mice.

mTOR is a signaling pathway involved in cell survival, cell stress response, and protein synthesis that may be a key point in sepsis-induced cardiac dysfunction. Curcumin has been reported in vitro as an mTOR inhibitor compound; however, there are no studies demonstrating this effect in experimental sepsis. Thus, this study aimed to evaluate the action of curcumin on the mTOR pathway in the heart of septic mice. Free curcumin (FC) and nanocurcumin (NC) were used, and samples were obtained at 24 and 120 h after sepsis. Histopathological and ultrastructural analysis showed that treatments with FC and NC reduced cardiac lesions caused by sepsis. Our main results demonstrated that curcumin reduced mTORC1 and Raptor mRNA at 24 and 120 h compared with the septic group; in contrast, mTORC2 mRNA increased at 24 h. Additionally, the total mTOR mRNA expression was reduced at 24 h compared with the septic group. Our results indicate that treatment with curcumin and nanocurcumin promoted a cardioprotective response that could be related to the modulation of the mTOR pathway.

Curcumin as a Potential Treatment for COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease that rapidly spread throughout the world leading to high mortality rates. Despite the knowledge of previous diseases caused by viruses of the same family, such as MERS and SARS-CoV, management and treatment of patients with COVID-19 is a challenge. One of the best strategies around the world to help combat the COVID-19 has been directed to drug repositioning; however, these drugs are not specific to this new virus. Additionally, the pathophysiology of COVID-19 is highly heterogeneous, and the way of SARS-CoV-2 modulates the different systems in the host remains unidentified, despite recent discoveries. This complex and multifactorial response requires a comprehensive therapeutic approach, enabling the integration and refinement of therapeutic responses of a given single compound that has several action potentials. In this context, natural compounds, such as Curcumin, have shown beneficial effects on the progression of inflammatory diseases due to its numerous action mechanisms: antiviral, anti-inflammatory, anticoagulant, antiplatelet, and cytoprotective. These and many other effects of curcumin make it a promising target in the adjuvant treatment of COVID-19. Hence, the purpose of this review is to specifically point out how curcumin could interfere at different times/points during the infection caused by SARS-CoV-2, providing a substantial contribution of curcumin as a new adjuvant therapy for the treatment of COVID-19.

Effect of Verapamil, an L-Type Calcium Channel Inhibitor, on Caveolin-3 Expression in Septic Mouse Hearts.

Sepsis-induced myocardial dysfunction considerably increases mortality risk in patients with sepsis. Previous studies from our group have shown that sepsis alters the expression of structural proteins in cardiac cells, resulting in cardiomyocyte degeneration and impaired communication between cardiac cells. Caveolin-3 (CAV3) is a structural protein present in caveolae, located in the membrane of cardiac muscle cells, which regulates physiological processes such as calcium homeostasis. In sepsis, there is a disruption of calcium homeostasis, which increases the concentration of intracellular calcium, which can lead to the activation of potent cellular enzymes/proteases which cause severe cellular injury and death. The purpose of the present study was to test the hypotheses that sepsis induces CAV3 overexpression in the heart, and the regulation of L-type calcium channels directly relates to the regulation of CAV3 expression. Severe sepsis increases the expression of CAV3 in the heart, as immunostaining in our study showed CAV3 presence in the cardiomyocyte membrane and cytoplasm, in comparison with our control groups (without sepsis) that showed CAV3 presence predominantly in the plasma membrane. The administration of verapamil, an L-type calcium channel inhibitor, resulted in a decrease in mortality rates of septic mice. This effect was accompanied by a reduction in the expression of CAV3 and attenuation of cardiac lesions in septic mice treated with verapamil. Our results indicate that CAV3 has a vital role in cardiac dysfunction development in sepsis and that the regulation of L-type calcium channels may be related to its expression.