Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets

Abstract

The effect of low doses of echinochrome A (EchA), a natural polyhydroxy-1,4-naphthoquinone pigment from the sea urchin Scaphechinus mirabilis, has been studied in clinical trials, when it was used as an active substance of the drug Histochrome® and biologically active supplement Thymarin. Several parameters of lipid metabolism, antioxidant status, and the state of the immune system were analyzed in patients with cardiovascular diseases (CVD), including contaminating atherosclerosis. It has been shown that EchA effectively normalizes lipid metabolism, recovers antioxidant status and reduces atherosclerotic inflammation, regardless of the method of these preparations’ administrations. Treatment of EchA has led to the stabilization of patients, improved function of the intracellular matrix and decreased epithelial dysfunction. The increased expression of surface human leukocyte antigen DR isotype (HLA-DR) receptors reflects the intensification of intercellular cooperation of immune cells, as well as an increase in the efficiency of processing and presentation of antigens, while the regulation of CD95 + expression levels suggests the stimulation of cell renewal processes. The immune system goes to a different level of functioning. Computer simulations suggest that EchA, with its aromatic structure of the naphthoquinone nucleus, may be a suitable ligand of the cytosolic aryl cell receptor, which affects the response of the immune system and causes the rapid expression of detoxification enzymes such as CYP and DT diaphorase, which play a protective role with CVD. Therefore, EchA possesses not only an antiradical effect and antioxidant activity, but is also a SOD3 mimetic, producing hydrogen peroxide and controlling the expression of cell enzymes through hypoxia-inducible factors (HIF), peroxisome proliferator-activated receptors (PPARs) and aryl hydrocarbon receptor (AhR).

Sea Urchin Pigments: Echinochrome A and Its Potential Implication in the Cytokine Storm Syndrome

“…Echinochrome A Cardioprotective activity Human [17] Echinochrome A Acetylcholinesterase inhibition H9c2 and A7r5 cells [18] Echinochrome A Antistress effect Bone marrow cells in SHK mice [19] Echinochrome A Amelioration of intraocular inflammation (uveitis) caused by endotoxins Lewis rats [20] Echinochrome A Decreased risk of atherogenesis and improvement of glutathione metabolism Human [21] Echinochrome A Cardiomyocyte protection against toxic agents Rat cardiac myoblast H9c2 cells and isolated rat cardiomyocytes. [1] Echinochrome A Reduction in diabetic complications in liver Wistar albino rats [22] Echinochrome A Improvement of the musculoskeletal system and the metabolism of lipids and proteins in both types of diabetes mellitus Wistar albino rats [23] Echinochrome A Improvement in the renal function and ameliorating renal histopathological Winstar albino rats [3] Echinochrome A Enhancement in exercise capacity Sprague-Dawley rats [24] Echinochrome A Prevention and/or deceleration of PD-like neurodegeneration Rats [25] Echinochrome A Hepatoprotective effect against intrahepatic cholestasis induced by toxic agents Rats [26] Echinochrome A Enhancing cardiomyocyte differentiation Mouse embryonic stem cells [27] Echinochrome A Potentiating the effectiveness of antitumor therapy Ehrlich ascites carcinoma model [28] Echinochrome A Cardioprotective against the cytotoxicity of doxorubicin Human cardiomyocyte cell line (AC16) and human breast cancer cell line (MCF-7) [29] Echinochrome A Liver antiseptic Albino rats [30] Echinochrome A Improvement in lipid profile, liver functions, kidney functions, and antioxidant markers Rats [31] Echinochrome A Cardioprotective against the cytotoxicity of doxorubicin AC16 human cardiomyocyte cells [4] Echinochrome A Hypolipidemia in obesity Rats [31] Echinochrome A Prevention of atherosclerotic inflammation, SOD3 mimetic, improves the response of the immune system Human [12] Echinochrome A Protective effects on the extracellular matrix of vocal folds in Ovariectomized rats [32] Echinochrome A Antitumor activity, decreases lipid peroxidation, and improves antioxidant status Ehrlich ascites carcinoma tumor model in mice [33] Echinochrome A Anti-inflammatory effect Rats [34]…”

“…77.99.03.935.Á.000138.06.04 dated 14 June 2004, TU 9350-064-02698170-2004; RU2340216C1). The chemistry and pharmacokinetics of EchA [ 11 ] were investigated and EchA was used in orally ingested formulations [ 12 ], complying with the Lipinski Rule of five for orally available compounds (data not published). We summarize the focus of our investigation in terms of pharmacological effects in Table 1 .…”

“…In cardiomyocytes treated with doxorubicin, EchA produced a decrease in ROS [ 1 ], whereas spinochrome D, a structural analog to EchA, showed an increase in the ATP production, the oxygenation of cells, and increased GSH levels [ 1 , 29 ]. In humans, EchA treatments have resulted in improvements in glucose metabolism, inhibition of lipid peroxidation processes, and an increase in CAT activity and GSH concentration [ 12 , 21 ]. The increase in hydrogen peroxide by EchA generates increases in peroxisomes and mitochondria in cells, leading to an increase in CAT activity [ 12 , 21 , 43 ].…”

“…In humans, EchA treatments have resulted in improvements in glucose metabolism, inhibition of lipid peroxidation processes, and an increase in CAT activity and GSH concentration [ 12 , 21 ]. The increase in hydrogen peroxide by EchA generates increases in peroxisomes and mitochondria in cells, leading to an increase in CAT activity [ 12 , 21 , 43 ]. In humans, EchA showed nitric-oxide- and hydrogen-peroxide-mimicking effects in endothelial and smooth muscle vascular cells.…”

Blue Growth: Sea Urchin Sustainable Aquaculture, Innovative Approaches

“…However, this is still based on harvesting sea urchin. Still, on the positive side, it would appear that it has been evidenced that there are real benefits for human health (Shikov et al, 2018;Itoh et al, 2016;Vasileva et al, 2017;Yoon et al, 2019;Artyukov et al, 2020), and marketable products have been developed to meet the increasing demand for these pigments.…”