ABSTRACT
Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A-C (1-3), with distinctive C-C and C-O-C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.
ABSTRACT
Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.
ABSTRACT
Compared with conventional methods for organic pollutant degradation, photocatalysis is a promising treatment technology with broad application prospects. Bi2O2CO3 is often used for organic pollutants degradation but greatly restricted by having drawbacks of large band gap and high electron-hole recombination rate. Herein, heterostructured Bi2O2CO3 (BOC)/reduced graphene oxide (rGO)/polydopamine (PDA) (BGP) photocatalysts were first designed through a green chemical method. By incorporating rGO and PDA in BOC, the kinetic constant of BGP to catalytically degrade methyl orange (MO) was significantly increased; over fourfold elevated rather than that of BOC (kapp/BOC = 0.0019, kapp/BGP = 0.0089) due to the high electron transfer capability of rGO and superior adhesive force and semiconducting properties of PDA. DRS and photoelectrochemical results confirmed the improvement of the light absorption range and charge transfer capability because of the synergistic effect of rGO and PDA. Results of trapping experiment and ESR unraveled the catalytic mechanism that both holes (h+) and superoxide radicals (â¢O2-) were the main oxidative species for MO degradation. Economic assessment results demonstrated that Bi2O2CO3/rGO/PDA heterojunctions have great potentials in the field of organic wastewater purification. This study developed a low-cost and highly efficient BGP material and provided a deep understanding of the structure-performance relationships of materials for organic pollutant degradation.
Subject(s)
Photochemical Processes , Waste Disposal, Fluid/methods , Azo Compounds , Catalysis , Environmental Pollutants , Graphite , Green Chemistry Technology , Indoles , Oxidation-Reduction , Polymers , WastewaterABSTRACT
In this study, Fe-Mn binary oxides, which harbor the strong oxidative power of manganese dioxide and the high adsorption capacity of iron oxides, were synthesized for Tl(I) removal using a concurrent chemical oxidation and precipitation method. The adsorption of Tl onto the Fe-Mn adsorbent was fast, effective, and selective, with equilibrium sorption reaching over 95% under a broad operating pH (3-12), and high ionic strength (0.1-0.5mol/L). The adsorption can be well fitted with both Langmuir and Freundlich isotherms, and the kinetics can be well described by the pseudo-second-order model. Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) spectra suggest that surface complexation, oxidation and precipitation were the main mechanisms for the removal of Tl. This study shows that the Fe-Mn binary oxides could be a promising adsorbent for Tl removal.
