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

Aleksandr A Artyukov; Elena A Zelepuga; Larisa N Bogdanovich; Natalia M Lupach; Vyacheslav L Novikov; Tatyana A Rutckova; Emma P Kozlovskaya

doi:10.3390/jcm9051494

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

J Clin Med. 2020 May 15;9(5):1494. doi: 10.3390/jcm9051494.

Authors

Aleksandr A Artyukov¹, Elena A Zelepuga¹, Larisa N Bogdanovich², Natalia M Lupach³, Vyacheslav L Novikov¹, Tatyana A Rutckova¹, Emma P Kozlovskaya¹

Affiliations

¹ G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Science, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, Russia.
² Medical Association of the Far Eastern Branch of the Russian Academy of Sciences (FEB RAS MO), Kirov Str., 95, Vladivostok 690022, Russia.
³ Primorye Regional Clinical Hospital No. One (SHI), Aleutskaya Str., 57, Vladivostok, Primorsky Krai 690091, Russia.

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).

Keywords: Histochrome; Thymarin; atherosclerosis; cardiovascular diseases (CVD); echinochrome A (EchA); mechanism of action; oxidative stress; polyhydroxy-1,4-naphthoquinones.